research on asthma patients

Diagnosis and Management of Asthma in Adults: A Review

Affiliations.

• 1 Division of Allergy and Clinical Immunology, University of Texas Medical Branch, Galveston.
• 2 Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston.
• 3 Division of Pulmonary Critical Care and Sleep, Department of Internal Medicine, University of Texas Medical Branch, Galveston.
• PMID: 28719697
• DOI: 10.1001/jama.2017.8372

Importance: Asthma affects about 7.5% of the adult population. Evidence-based diagnosis, monitoring, and treatment can improve functioning and quality of life in adult patients with asthma.

Observations: Asthma is a heterogeneous clinical syndrome primarily affecting the lower respiratory tract, characterized by episodic or persistent symptoms of wheezing, dyspnea, and cough. The diagnosis of asthma requires these symptoms and demonstration of reversible airway obstruction using spirometry. Identifying clinically important allergen sensitivities is useful. Inhaled short-acting β2-agonists provide rapid relief of acute symptoms, but maintenance with daily inhaled corticosteroids is the standard of care for persistent asthma. Combination therapy, including inhaled corticosteroids and long-acting β2-agonists, is effective in patients for whom inhaled corticosteroids alone are insufficient. The use of inhaled long-acting β2-agonists alone is not appropriate. Other controller approaches include long-acting muscarinic antagonists (eg, tiotropium), and biological agents directed against proteins involved in the pathogenesis of asthma (eg, omalizumab, mepolizumab, reslizumab).

Conclusions and relevance: Asthma is characterized by variable airway obstruction, airway hyperresponsiveness, and airway inflammation. Management of persistent asthma requires avoidance of aggravating environmental factors, use of short-acting β2-agonists for rapid relief of symptoms, and daily use of inhaled corticosteroids. Other controller medications, such as long-acting bronchodilators and biologics, may be required in moderate and severe asthma. Patients with severe asthma generally benefit from consultation with an asthma specialist for consideration of additional treatment, including injectable biologic agents.

Publication types

• Administration, Inhalation
• Adrenal Cortex Hormones / adverse effects
• Adrenal Cortex Hormones / therapeutic use
• Adrenergic beta-Agonists / adverse effects
• Adrenergic beta-Agonists / therapeutic use
• Airway Obstruction / physiopathology
• Anti-Asthmatic Agents / adverse effects
• Anti-Asthmatic Agents / therapeutic use*
• Asthma / diagnosis*
• Asthma / drug therapy*
• Asthma / physiopathology
• Biological Products / therapeutic use
• Bronchial Hyperreactivity / physiopathology
• Drug Therapy, Combination
• Inflammation
• Muscarinic Antagonists / therapeutic use
• Adrenal Cortex Hormones
• Adrenergic beta-Agonists
• Anti-Asthmatic Agents
• Biological Products
• Muscarinic Antagonists

Grants and funding

• UL1 TR000071/TR/NCATS NIH HHS/United States

• - Google Chrome

Intended for healthcare professionals

• Access provided by Google Indexer
• My email alerts
• BMA member login
• Username * Password * Forgot your log in details? Need to activate BMA Member Log In Log in via OpenAthens Log in via your institution

Search form

• Advanced search
• Search responses
• Search blogs
• Assessment and...

Assessment and management of adults with asthma during the covid-19 pandemic

Read our latest coverage of the coronavirus pandemic.

• Related content
• Peer review
• Thomas Beaney , academic clinical fellow in primary care 1 ,
• David Salman , academic clinical fellow in primary care 1 ,
• Tahseen Samee , specialist registrar in emergency medicine 2 ,
• Vincent Mak , consultant in respiratory community integrated care 3
• 1 Department of Primary Care and Public Health, Imperial College London, London, UK
• 2 Barts Health NHS Trust, London, UK
• 3 Imperial College Healthcare NHS Trust, London, UK
• Correspondence to: T Beaney Thomas.beaney{at}imperial.ac.uk

What you need to know

In patients with pre-existing asthma, a thorough history and structured review can help distinguish an asthma exacerbation from covid-19 and guide management

In those with symptoms of acute asthma, corticosteroids can and should be used if indicated and not withheld on the basis of suspected covid-19 as a trigger

Assessment can be carried out remotely, ideally via video, but have a low threshold for face-to-face assessment, according to local arrangements

A 35 year old man contacts his general practice reporting a dry cough and increased shortness of breath for the past three days. He has a history of asthma, for which he uses an inhaled corticosteroid twice daily and is now using his salbutamol four times a day. Because of the covid-19 outbreak, he is booked in for a telephone consultation with a general practitioner that morning.

Asthma is a condition commonly encountered in primary care, with over five million people in the UK prescribed active treatment. 1 While seemingly a routine part of general practice, asthma assessment is a particular challenge in the context of the covid-19 pandemic, given the overlap in respiratory symptoms between the two conditions and the need to minimise face-to-face assessment. Over 1400 people died from asthma in 2018 in England and Wales, 2 while analyses of non-covid-19 deaths during the covid-19 outbreak have shown an increase in deaths due to asthma, 31 highlighting the need to distinguish the symptoms of acute asthma from those of covid-19 and manage them accordingly.

This article outlines how to assess and manage adults with exacerbations of asthma in the context of the covid-19 outbreak ( box 1 ). We focus on the features differentiating acute asthma from covid-19, the challenges of remote assessment, and the importance of corticosteroids in patients with an asthma exacerbation.

Asthma and covid-19: what does the evidence tell us?

Are patients with asthma at higher risk from covid-19.

Some studies, mostly from China, found lower than expected numbers of patients with asthma admitted to hospital, suggesting they are not at increased risk of developing severe covid-19. 3 4 5 However, these reports should be viewed cautiously, as confounding by demographic, behavioural, or lifestyle factors may explain the lower than expected numbers. Recent pre-print data from the UK suggest that patients with asthma, and particularly severe asthma, are at higher risk of in-hospital mortality from covid-19. 6 In the absence of more conclusive evidence to indicate otherwise, those with asthma, particularly severe asthma, should be regarded as at higher risk of developing complications from covid-19. 7

Can SARS-CoV-2 virus cause asthma exacerbations?

Some mild seasonal coronaviruses are associated with exacerbations of asthma, but the coronaviruses causing the SARS and MERS outbreaks were not found to be. 8 9 In the case of SARS-CoV-2 virus, causing covid-19, data from hospitalised patients in China did not report symptoms of bronchospasm such as wheeze, but the number of patients with pre-existing asthma was not reported. 10 More recent pre-print data from hospitalised patients in the UK identified wheeze in a minority of patients with Covid-19. 11 Given the overlap of symptoms, such as cough and shortness of breath, until further published data emerges, SARS-CoV-2 may be considered as a possible viral trigger in patients with an asthma attack.

What you should cover

Challenges of remote consultations.

Primary care services have moved towards telephone triage and remote care wherever possible to minimise the risk of covid-19 transmission. This brings challenges to assessment as visual cues are missing, and, unless the patient has their own equipment, tests involving objective measurement, such as oxygen saturation and peak expiratory flow, are not possible. In mild cases, assessment via telephone may be adequate, but, whenever possible, we recommend augmenting the consultation with video for additional visual cues and examination. 12 However, many patients, particularly the elderly, may not have a phone with video capability. If you are relying on telephone consultation alone, a lower threshold may be needed for face-to-face assessment.

Presenting symptoms

Start by asking the patient to describe their symptoms in their own words. Note whether they sound breathless or struggle to complete sentences and, if so, determine whether immediate action is required. If not, explore what has changed, and why the patient has called now. The three questions recommended by the Royal College of Physicians—asking about impact on sleep, daytime symptoms, and impact on activity—are a useful screening tool for uncontrolled asthma. 13 Alternative validated scores, such as the Asthma Control Questionnaire and Asthma Control Test, which include reliever use, are also recommended. 14 In assessing breathlessness, the NHS 111 symptom checker contains three questions—the answers may arise organically from the consultation, but are a useful aide memoire:

Are you so breathless that you are unable to speak more than a few words?

Are you breathing harder or faster than usual when doing nothing at all?

Are you so ill that you’ve stopped doing all of your usual daily activities?

Consider whether an exacerbation of asthma or covid-19 is more likely. Both can present with cough and breathlessness, but specific features may indicate one over the other (see box 2 ). Do the patient’s current symptoms feel like an asthma attack they have had before? Do symptoms improve with their reliever inhaler? Do they also have symptoms of allergic rhinitis? Pollen may be a trigger for some people with asthma during hay fever season.

History and examination features helping distinguish asthma exacerbation from covid-19 10 11 14 15 16

Exacerbation of asthma*.

Improvement in symptoms with reliever inhaler

Diurnal variation

Absence of fever

Coexisting hay fever symptoms

Examination:

Reduced peak expiratory flow

Close contact of known or suspected case

Dry continuous cough

Onset of dyspnoea 4-8 days into illness

Flu-like symptoms including fatigue, myalgia, headache

Symptoms not relieved by inhaler

Absence of wheeze

Peak expiratory flow may be normal

*Note SARS-CoV-2 infection may be a trigger for an asthma exacerbation

Risk factors and medications

To assess the risk of deterioration, ask specifically about any previous hospital admissions for asthma and about oral corticosteroid use over the past 12 months. Does the patient have any other high risk conditions or are they taking immunosuppressive drugs? Ask the patient if they smoke and take the opportunity to offer support to quit.

Are they prescribed an inhaled corticosteroid (ICS) or a long acting β agonist (LABA) and ICS combination inhaler? Are they using this regularly? Are they using a spacer device, and do they have a personal asthma action plan to guide management?

Psychosocial factors

Taking a psychosocial history can be more challenging over the telephone, where cues are harder to spot. Lessons from asthma deaths have shown that adverse psychosocial factors are strongly associated with mortality. 14 17 These include a history of mental health problems, lack of engagement with healthcare services, and alcohol or drug misuse, along with employment and income problems. Social isolation is also a risk factor, which may be exacerbated during social distancing measures. 17 The covid-19 outbreak is an anxious time for many patients, and symptoms of anxiety can contribute to the overall presentation.

Examination

In remote assessment, video can help guide decision making, and we recommend its use in asthmatic patients presenting with acute symptoms. First, assess the general appearance of the patient. A fatigued patient sitting up in bed, visibly breathless, and anchoring their chest will raise immediate concerns, as opposed to someone who is walking around while talking. Vocal tone and behaviour may indicate any contributing anxiety. Observe if the patient can speak in complete sentences, listen for audible wheeze, and count the respiratory rate. Assess the work of breathing, including the use of accessory muscles, and consider the use of a chaperone where appropriate. The Roth score is not advocated for assessment of covid-19 or asthma. 18

Further objective assessment can be made, such as measuring peak expiratory flow (PEF). If the patient does not have a PEF device at home, one can be prescribed, though this may not be feasible in an acute scenario. We recommend that PEF technique be witnessed via video to assess reliability. Silent hypoxia may be a feature of covid-19, and oxygen saturations should be measured if this is a concern. 19 In some regions, oxygen saturation probe delivery services are being implemented, which may facilitate this. Heart rate can also be provided by the patient if they use conventional “wearable” technology, although, given the potential inaccuracies with different devices, the results should not be relied on. 20 If time allows, inhaler technique can also be checked.

What you should do

Determine the most likely diagnosis.

Decide on the most likely diagnosis on the basis of the history and clinical features (see box 2 and fig 1 ) or consider whether an alternative or coexisting diagnosis is likely, such as a bacterial pneumonia or pulmonary embolus. If you suspect covid-19 without asthmatic features, manage the patient as per local covid-19 guidance.

Assessment and management of patients with known asthma during the covid-19 outbreak 14

• Download figure
• Open in new tab
• Download powerpoint

Determine severity and decide if face-to-face assessment is necessary

If asthmatic features are predominant, determine severity and treat according to Scottish Intercollegiate Guidelines Network (SIGN) and British Thoracic Society (BTS) guidance ( fig 1 ). 14 If the patient cannot complete sentences or has a respiratory rate ≥25 breaths/min, treat the case as severe or life threatening asthma and organise emergency admission. A peak expiratory flow (PEF) <50% of best or predicted or a heart rate ≥110 beats/min also indicate severe or life threatening asthma. If the patient does not meet these criteria, treat as a moderate asthma attack—a PEF of 50-75% of best or predicted helps confirm this. If they do not have a PEF meter, or if you are unsure as to severity, brief face-to-face assessment to auscultate for wheeze and assess oxygen saturations can help confirm the degree of severity and determine if the patient may be suitable for treatment at home with follow-up. Do not rely solely on objective tests and use clinical judgment to decide on the need for face-to-face assessment, based on knowledge of the patient, risk factors, and any adverse psychosocial circumstances.

Wheeze has been reported as a presenting symptom in a minority of patients with confirmed covid-19, and it may be difficult to rule out the presence of SARS-CoV-2 via remote assessment. 11 We recommend that, when a face-to-face assessment is needed, it should take place via local pathways in place to safely assess patients with suspected or possible covid-19—for example, at a local “hot” clinic. At present, performing a peak flow test is not considered to be an aerosol generating procedure, but the cough it may produce could be, so individual risk assessment is advised. 21 Consider performing PEF in an open space or remotely in another room via video link. Any PEF meter should be single-patient use only and can be given to the patient for future use.

Initial management when face-to-face assessment is not required

For moderate asthma exacerbations, advise up to 10 puffs of a short acting β agonist (SABA) inhaler via a spacer, administered one puff at a time. There is no evidence that nebulisers are more effective: 4-6 puffs of salbutamol via a spacer is as effective as 2.5 mg via a nebuliser. 22 Alternatively, if the patient takes a combined inhaled corticosteroid and long acting β agonist (LABA) preparation, then maintenance and reliever therapy (MART) can be used according to their action plan. 14 Management of an acute exacerbation should not rely solely on SABA monotherapy, so advise patients to follow their personal asthma action plan and continue corticosteroid treatment (or start it if they were not taking it previously) unless advised otherwise ( box 3 ). Antibiotics are not routinely recommended in asthma exacerbations.

Risks and benefits of inhaled and oral corticosteroids in asthma and covid-19

There is substantial evidence for the benefits of steroids in asthma. Regular use of inhaled steroids reduces severe exacerbations of asthma 23 and the need for bronchodilators, 24 while the prompt use of systemic corticosteroids during an exacerbation reduces the need for hospital admissions, use of β agonists, 25 and relapses. 26

The evidence for corticosteroid use in early covid-19 is still emerging. A systematic review of steroid use in SARS reported on 29 studies, 25 of which were inconclusive and four of which suggested possible harm (diabetes, osteoporosis, and avascular necrosis) but no reported effects on mortality. 27 WHO have cautioned against the use of systemic corticosteroids for the treatment of covid-19 unless indicated for other diseases. 28

In light of the strong evidence of benefits in patients with asthma, inhaled and oral corticosteroids should be prescribed if indicated in patients with symptoms of bronchoconstriction. Steroids should not be withheld on the theoretical risk of covid-19 infection, in line with guidance from the Primary Care Respiratory Society (PCRS), British Thoracic Society (BTS), and Global Initiative for Asthma (GINA). 15 22 29

Response to initial SABA or MART treatment can be assessed with a follow-up call at 20 minutes. If there is no improvement, further treatment may be necessary at a local hot clinic for reviewing possible covid-19, emergency department, or direct admission to an acute medical or respiratory unit depending on local pathways. For those who do respond, BTS-SIGN and GINA advise starting oral corticosteroids in patients presenting with an acute asthma exacerbation (such as prednisolone 40-50 mg for 5-7 days). 14 15 There is an increasing move in personalised asthma action plans to early quadrupling of the inhaled corticosteroid dose in patients with deteriorating control for up to 14 days to reduce the risk of severe exacerbations and the need for oral steroids. 15 30 However, there may be a ceiling effect on those who are already on a high dose of inhaled corticosteroid (see BTS table 14 ), so quadrupling the dose may not be effective in this group of patients. A personalised asthma action plan is an extremely helpful guide to treatment and should be completed or updated for all patients.

Follow-up and safety-netting

We recommend that all patients with moderate symptoms are followed up via remote assessment within 24 hours. Asthma attacks requiring hospital admission tend to develop relatively slowly over 6-48 hours. 14 However, deterioration can be more rapid, and symptoms can worsen overnight. Patients should be advised to look out for any worsening breathing or wheeze, lack of response to their inhalers, or worsening PEF. They should receive clear advice on what to do, including use of their reliever, and who to contact (such as the local out-of-hours GP provider, 111, or 999). With potential long waits for remote assessment, particularly out of hours, they should be advised to have a low threshold to call 999 if their symptoms deteriorate. If covid-19 infection is also suspected, advise them to isolate for seven days from onset of symptoms and arrange testing, according to the latest guidance. 7

How this article was created

We performed a literature search using Ovid, Medline, and Global Health databases using the search terms (asthma OR lung disease OR respiratory disease) AND (coronavirus OR covid-19)). Articles from 2019-20 were screened. We also searched for specific guidelines, including NICE, British Thoracic Society, Scottish Intercollegiate Guidelines Network, Primary Care Respiratory Society, European Respiratory Society, International Primary Care Respiratory Group, Global Initiative for Asthma, and the American Academy of Allergy, Asthma and Immunology.

Education into practice

Do you feel confident in completing personalised asthma plans in collaboration with patients?

How often do you start or increase inhaled corticosteroids in patients at initial presentation with an exacerbation of asthma?

If you manage a patient with acute asthma remotely, what safety netting advice would you give and how could you check understanding?

How patients were involved in the creation of this article

No patients were involved in the creation of this article.

This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.

Contributors: TB and TS conceived the article. TB, DS, and TS carried out the literature review and wrote the initial drafts. All four authors contributed to editing and revision, and VM provided expert advice as a respiratory specialist. All authors are guarantors of the work.

Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Provenance and peer review: Commissioned, based on an idea from the author; externally peer reviewed.

• Mukherjee M ,
• Stoddart A ,
• ↵ Asthma UK. Asthma facts and statistics. https://www.asthma.org.uk/about/media/facts-and-statistics/ .
• Scabini S ,
• Mornese Pinna S ,
• Di Perri G ,
• De Rosa FG ,
• Williamson E. ,
• Walker AJ ,
• Bhaskaran KJ ,
• ↵ Public Health England. Guidance on social distancing for everyone in the UK [Withdrawn]. 2020. https://www.gov.uk/government/publications/covid-19-guidance-on-social-distancing-and-for-vulnerable-people/guidance-on-social-distancing-for-everyone-in-the-uk-and-protecting-older-people-and-vulnerable-adults .
• Shaker MS ,
• Oppenheimer J ,
• Grayson M ,
• China Medical Treatment Expert Group for Covid-19
• Docherty AB ,
• Harrison EM ,
• Greenhalgh T ,
• Pinnock H ,
• Campbell S ,
• ↵ Scottish Intercollegiate Guidelines Network & British Thoracic Society. Sign 158 British guideline on the management of asthma. 2019. https://www.sign.ac.uk/sign-158-british-guideline-on-the-management-of-asthma .
• ↵ Primary Care Respiratory Society. PCRS Pragmatic Guidance: Diagnosing and managing asthma attacks and people with COPD presenting in crisis during the UK Covid 19 epidemic. 2020. https://www.pcrs-uk.org/sites/pcrs-uk.org/files/resources/COVID19/PCRS-Covid-19-Pragmatic-Guidance-v2-02-April-2020.pdf .
• Rapoport AB
• Royal College of Physicians
• ↵ Centre for Evidence-Based Medicine. Question: Should the Roth score be used in the remote assessment of patients with possible COVID-19? Answer: No. 2020. https://www.cebm.net/covid-19/roth-score-not-recommended-to-assess-breathlessness-over-the-phone/ .
• Goldstein BA ,
• ↵ Public Health England. Guidance: COVID-19 personal protective equipment (PPE). 2020. https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/covid-19-personal-protective-equipment-ppe .
• ↵ British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020. https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community/ .
• Pauwels RA ,
• Pedersen S ,
• START Investigators Group
• Bestall JB ,
• Lasserson TJ ,
• Spooner C ,
• Ducharme FM ,
• Bretzlaff JA ,
• Spooner CH ,
• Stockman LJ ,
• Bellamy R ,
• ↵ World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: Interim guidance 13th March 2020. 2020. https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf .
• ↵ Global Initiative for Asthma (GINA). 2020 GINA report, global strategy for asthma management and prevention. 2020. https://ginasthma.org/gina-reports/ .
• McKeever T ,
• Mortimer K ,
• ↵ Office for National Statistics. Analysis of death registrations not involving coronavirus (COVID-19), England and Wales: 28 December 2019 to 1 May 2020. Release date: 5 June 2020. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/analysisofdeathregistrationsnotinvolvingcoronaviruscovid19englandandwales28december2019to1may2020/technicalannex .

• Help & Support
• Lung Health & Diseases
• Lung Disease Lookup
• Learn About Asthma

Asthma Research

Why we need research.

Asthma research helps us understand how the disease is caused, how it develops and how it is best treated. Research can also help us understand who is at high risk for developing asthma, certain triggers, and ways to avoid getting asthma. 

Our Asthma Research Program

The American Lung Association is committed to funding asthma research. Our Awards and Grants Program funds top-notch researchers at important career crossroads to gain long-term commitment to lung health and disease research. Without the life-long dedication of lung researchers, important and much-needed discoveries would not be possible. In addition to the Awards and Grants Program, the Lung Association funds the Airways Clinical Research Centers (ACRC) Network , which implements patient-centered clinical trials, and has helped to change the nature of asthma patient care since its inception in 2000. 

What Research Is Being Done?

Some of the current topics American Lung Association funded researchers are investigating include understanding the immune system’s role in asthma, using mobile technology to reach young African Americans with asthma, and better defining subtypes of asthma. Together, studies like these lead to improved therapy, quality of life, and access to care for all people with asthma.

Thanks to the medical breakthroughs led by Lung Association researchers and their colleagues, we have made significant contributions to improve our understanding of asthma. 

Currently funded Lung Association researchers are:  

• Studying asthma that is resistant to steroid treatments 
• Boosting the immune system to reduce allergic inflammation in airways  
• Understanding which genes are responsible for severe asthma 
• Finding new genetic targets in lung tissue for new asthma therapy and prevention
• Improve our understanding of the challenges in access to asthma medication in schools 
• Evaluating asthma management policy in Chicago schools 
• Providing asthma education to children in the hospital and at home 

Asthma Researchers

Visit our Meet the Researchers section to view our asthma researchers and their studies.

Asthma Clinical Trials

• See our Lung Association  listing of current trials . 
• View ACRC clinical trials that are currently recruiting as well as outcomes from completed studies.

Airways Clinical Research Centers (ACRC) Network

The ACRC is the nation's largest not-for-profit network of clinical research centers dedicated to asthma and chronic obstructive pulmonary disease (COPD) treatment research, attracting some of the best investigators nationwide. The ACRC Network conducts large clinical trials that will directly impact patient care for COPD and asthma. 

Meet our Principal Investigators, see where our centers are located and learn more about some of the important research findings at Lung.org/acrc .

Page last updated: April 19, 2023

A Breath of Fresh Air in Your Inbox

Join over 700,000 people who receive the latest news about lung health, including research, lung disease, air quality, quitting tobacco, inspiring stories and more!

You will now receive email updates from the American Lung Association.

Make a Donation

Your tax-deductible donation funds lung disease and lung cancer research, new treatments, lung health education, and more.

Become a Lung Health Insider

Thank you! You will now receive email updates from the American Lung Association.

Select Your Location

Select your location to view local American Lung Association events and news near you.

Change Language

Lung helpline.

Talk to our lung health experts at the American Lung Association. Our service is free and we are here to help you.

1-800-LUNG-USA

(1-800-586-4872)

• Search by keyword
• Search by citation

Page 1 of 2

Psychological distress and associated factors among asthmatic patients in Southern, Ethiopia, 2021

There is an increased prevalence of psychological distress in adults with asthma. Psychological distress describes unpleasant feelings or emotions that impact the level of functioning. It is a significant exac...

• View Full Text

Retrospective assessment of a collaborative digital asthma program for Medicaid-enrolled children in southwest Detroit: reductions in short-acting beta-agonist (SABA) medication use

Real-world evidence for digitally-supported asthma programs among Medicaid-enrolled children remains limited. Using data from a collaborative quality improvement program, we evaluated the impact of a digital i...

Nonadherence to antiasthmatic medications and its predictors among asthmatic patients in public hospitals of Bahir Dar City, North West Ethiopia: using ASK-12 tool

Globally, adequate asthma control is not yet achieved. The main cause of uncontrollability is nonadherence to prescribed medications.

The hen and the egg question in atopic dermatitis: allergy or eczema comes first

Atopic dermatitis (AD) as a chronic inflammatory systemic condition is far more than skin deep. Co-morbidities such as asthma and allergic rhinitis as well as the psychological impact influence seriously the q...

Medication regimen complexity and its impact on medication adherence and asthma control among patients with asthma in Ethiopian referral hospitals

Various studies have found that medication adherence is generally low among patients with asthma, and that the complexity of the regimen may be a potential factor. However, there is no information on the compl...

Monoclonal antibodies targeting small airways: a new perspective for biological therapies in severe asthma

Small airway dysfunction (SAD) in asthma is characterized by the inflammation and narrowing of airways with less of 2 mm in diameter between generations 8 and 23 of the bronchial tree. It is now widely accepte...

Level of asthma control and its determinants among adults living with asthma attending selected public hospitals in northwestern, Ethiopia: using an ordinal logistic regression model

Asthma is a major public health challenge and is characterized by recurrent attacks of breathlessness and wheezing that vary in severity and frequency from person to person. Asthma control is an important meas...

Static lung volumes and diffusion capacity in adults 30 years after being diagnosed with asthma

Long-term follow-up studies of adults with well-characterized asthma are sparse. We aimed to explore static lung volumes and diffusion capacity after 30 + years with asthma.

Over-prescription of short-acting β 2 -agonists and asthma management in the Gulf region: a multicountry observational study

The overuse of short-acting β 2 -agonists (SABA) is associated with poor asthma control. However, data on SABA use in the Gulf region are limited. Herein, we describe SABA prescription practices and clinical outcom...

A serological biomarker of type I collagen degradation is related to a more severe, high neutrophilic, obese asthma subtype

Asthma is a heterogeneous disease; therefore, biomarkers that can assist in the identification of subtypes and direct therapy are highly desirable. Asthma is a chronic inflammatory disease that leads to change...

Adherence to inhalers and associated factors among adult asthma patients: an outpatient-based study in a tertiary hospital of Rajshahi, Bangladesh

Adherence to inhaler medication is an important contributor to optimum asthma control along with adequate pharmacotherapy. The objective of the present study was to assess self-reported adherence levels and to...

The link between atopic dermatitis and asthma- immunological imbalance and beyond

Atopic diseases are multifactorial chronic disturbances which may evolve one into another and have overlapping pathogenetic mechanisms. Atopic dermatitis is in most cases the first step towards the development...

The effects of nebulized ketamine and intravenous magnesium sulfate on corticosteroid resistant asthma exacerbation; a randomized clinical trial

Asthma exacerbation is defined as an acute attack of shortness of breath with more than 25% decrease in morning peak flow compared to the baseline on 2 consecutive days, which requires immediate standard thera...

Determinants of asthma in Ethiopia: age and sex matched case control study with special reference to household fuel exposure and housing characteristics

Asthma is a chronic inflammatory disorder characterized by airway obstruction and hyper-responsiveness. Studies suggest that household fuel exposure and housing characteristics are associated with air way rela...

Feasibility and acceptability of monitoring personal air pollution exposure with sensors for asthma self-management

Exposure to fine particulate matter (PM 2.5 ) increases the risk of asthma exacerbations, and thus, monitoring personal exposure to PM 2.5 may aid in disease self-management. Low-cost, portable air pollution sensors...

Biological therapy for severe asthma

Around 5–10% of the total asthmatic population suffer from severe or uncontrolled asthma, which is associated with increased mortality and hospitalization, increased health care burden and worse quality of lif...

Treatment outcome clustering patterns correspond to discrete asthma phenotypes in children

Despite widely and regularly used therapy asthma in children is not fully controlled. Recognizing the complexity of asthma phenotypes and endotypes imposed the concept of precision medicine in asthma treatment...

Positive change in asthma control using therapeutic patient education in severe uncontrolled asthma: a one-year prospective study

Severe asthma is difficult to control. Therapeutic patient education enables patients to better understand their disease and cope with treatment, but the effect of therapeutic patient education in severe uncon...

Asthma and COVID-19: a dangerous liaison?

The coronavirus disease 2019 (COVID-19) pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), provoked the most striking international public health crisis of our time. COVI...

Knowledge, attitude, and practice towards COVID-19 among chronic disease patients at Aksum Hospital, Northern Ethiopia, 2020: a cross-sectional study

The Coronavirus disease 2019 outbreak is the first reported case in Wuhan, China in December 2019 and suddenly became a major global health concern. Currently, there is no vaccine and treatment have been repor...

Self-reported vs. objectively assessed adherence to inhaled corticosteroids in asthma

Adherence to inhaled corticosteroids (ICS) in asthma is vital for disease control. However, obtaining reliable and clinically useful measures of adherence remains a major challenge. We investigated the associa...

Association between prevalence of obstructive lung disease and obesity: results from The Vermont Diabetes Information System

The association of obesity with the development of obstructive lung disease, namely asthma and/or chronic obstructive pulmonary disease, has been found to be significant in general population studies, and weig...

Changes in quantifiable breathing pattern components predict asthma control: an observational cross-sectional study

Breathing pattern disorders are frequently reported in uncontrolled asthma. At present, this is primarily assessed by questionnaires, which are subjective. Objective measures of breathing pattern components ma...

The role of leukotriene modifying agent treatment in neuropsychiatric events of elderly asthma patients: a nested case control study

In March 2020, the US Food and Drug Administration decided that the dangers related to neuropsychiatric events (NPEs) of montelukast, one of the leukotriene modifying agents (LTMAs), should be communicated thr...

Asthma and stroke: a narrative review

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation, bronchial reversible obstruction and hyperresponsiveness to direct or indirect stimuli. It is a severe disease causing a...

Comparison of dental caries (DMFT and DMFS indices) between asthmatic patients and control group in Iran: a meta-analysis

The association between caries index, which is diagnosed by Decayed, Missing, and Filled Teeth (DMFT), and asthma has been assessed in several studies, which yielded contradictory results. Meta-analysis is the...

ICS/formoterol in the management of asthma in the clinical practice of pulmonologists: an international survey on GINA strategy

The treatment with short-acting beta-2 agonists (SABA) alone is no longer recommended due to safety issues. Instead, the current Global Initiative for Asthma (GINA) Report recommends the use of the combination...

Sustainability of residential environmental interventions and health outcomes in the elderly

Research has documented that housing conditions can negatively impact the health of residents. Asthma has many known indoor environmental triggers including dust, pests, smoke and mold, as evidenced by the 25 ...

Non-adherence to inhaled medications among adult asthmatic patients in Ethiopia: a systematic review and meta-analysis

Medication non-adherence is one of a common problem in asthma management and it is the main factor for uncontrolled asthma. It can result in poor asthma control, which leads to decreased quality of life, incre...

The outcome of COVID-19 among the geriatric age group in African countries: protocol for a systematic review and meta-analysis

According to the World Health Organization (WHO), the outbreak of coronavirus disease in 2019 (COVID-19) has been declared as a pandemic and public health emergency that infected more than 5 million people wor...

Correction to: A comparison of biologicals in the treatment of adults with severe asthma – real-life experiences

An amendment to this paper has been published and can be accessed via the original article.

The original article was published in Asthma Research and Practice 2020 6 :2

Disease control in patients with asthma and respiratory symptoms (wheezing, cough) during sleep

The Global Initiative for Asthma ( GINA)-defined criteria for asthma control include questions about daytime symptoms, limitation of activity, nocturnal symptoms, need for reliever treatment and patients’ satisfac...

The burden, admission, and outcomes of COVID-19 among asthmatic patients in Africa: protocol for a systematic review and meta-analysis

Coronavirus disease 2019 outbreak is the first reported case in Wuhan, China in December 2019 and suddenly became a major global health concern. According to the European Centre for Disease Prevention and Cont...

The healthcare seeking behaviour of adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe

Although asthma is a serious public health concern in Zimbabwe, there is lack of information regarding the decision to seek for healthcare services among patients. This study aimed to determine the health care...

Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis

Short-acting β2-agonist (SABA) nebulization is commonly prescribed for children hospitalized with severe asthma exacerbation. Either intermittent or continuous delivery has been considered safe and efficient. ...

Patient perceived barriers to exercise and their clinical associations in difficult asthma

Exercise is recommended in guidelines for asthma management and has beneficial effects on symptom control, inflammation and lung function in patients with sub-optimally controlled asthma. Despite this, physica...

Asthma management with breath-triggered inhalers: innovation through design

Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients’ wellbeing and...

A nationwide study of asthma correlates among adolescents in Saudi Arabia

Asthma is a chronic airway inflammation disease that is frequently found in children and adolescents with an increasing prevalence. Several studies are linking its presence to many lifestyle and health correla...

A comparison of biologicals in the treatment of adults with severe asthma – real-life experiences

Anti-IgE (omalizumab) and anti-IL5/IL5R (reslizumab, mepolizumab and benralizumab) treatments are available for severe allergic and eosinophilic asthma. In these patients, studies have shown beneficial effects...

The Correction to this article has been published in Asthma Research and Practice 2020 6 :10

Determinants of Acute Asthma Attack among adult asthmatic patients visiting hospitals of Tigray, Ethiopia, 2019: case control study

Acute asthma attack is one of the most common causes of visits to hospital emergency departments in all age groups of the population and accounts for the greater part of healthcare burden from the disease. Des...

Determinants of non-adherence to inhaled steroids in adult asthmatic patients on follow up in referral hospital, Ethiopia: cross-sectional study

Asthma is one of the major non-communicable diseases worldwide. The prevalence of asthma has continuously increased over the last five decades, resulting in 235 million people suffering from it. One of the mai...

Development of a framework for increasing asthma awareness in Chitungwiza, Zimbabwe

Asthma accounts for significant global morbidity and health-care costs. It is still poorly understood among health professionals and the general population. Consequently, there are significant morbidity and mo...

Epidemiology and utilization of primary health care services in Qatar by asthmatic children 5–12 years old: secondary data analysis 2016–2017

Childhood asthma is a growing clinical problem and a burden on the health care system due to repetitive visits to children’s emergency departments and frequent hospital admissions where it is poorly controlled...

Is asthma in the elderly different? Functional and clinical characteristics of asthma in individuals aged 65 years and older

The prevalence of chronic diseases in the elderly (> 65 years), including asthma, is growing, yet information available on asthma in this population is scarce.

Factors associated with exacerbations among adults with asthma according to electronic health record data

Asthma is a chronic inflammatory lung disease that affects 18.7 million U.S. adults. Electronic health records (EHRs) are a unique source of information that can be leveraged to understand factors associated w...

What is safe enough - asthma in pregnancy - a review of current literature and recommendations

Although asthma is one of the most serious diseases causing complications during pregnancy, half of the women discontinue therapy thus diminishing the control of the disease, mostly due to the inadequate educa...

Biomarkers in asthma: state of the art

Asthma is a heterogenous disease characterized by multiple phenotypes driven by different mechanisms. The implementation of precision medicine in the management of asthma requires the identification of phenoty...

Exhaled biomarkers in childhood asthma: old and new approaches

Asthma is a chronic condition usually characterized by underlying inflammation. The study of asthmatic inflammation is of the utmost importance for both diagnostic and monitoring purposes. The gold standard fo...

Assessment of predictors for acute asthma attack in asthmatic patients visiting an Ethiopian hospital: are the potential factors still a threat?

Recurrent exacerbations in patients with moderate or severe asthma are the major causes of morbidity, mortality and medical expenditure. Identifying predictors of frequent asthma attack might offer the fertile...

Effect of adjusting the combination of budesonide/formoterol on the alleviation of asthma symptoms

The combination of budesonide + formoterol (BFC) offers the advantages of dose adjustment in a single inhaler according to asthma symptoms. We analyzed the relationship between asthma symptoms in terms of peak...

Asthma Research and Practice

ISSN: 2054-7064

• Submission enquiries: Access here and click Contact Us
• General enquiries: [email protected]

• Open access
• Published: 23 June 2023

Global, regional, and national burden of asthma and its attributable risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019

• Zhufeng Wang 1   na1 ,
• Yun Li 1   na1 ,
• Yi Gao 1   na1 ,
• Junfeng Lin 1 ,
• Xuedong Lei 1 ,
• Jinping Zheng 1 &
• Mei Jiang 1  

Respiratory Research volume  24 , Article number:  169 ( 2023 ) Cite this article

11k Accesses

19 Citations

2 Altmetric

Metrics details

The burden of asthma in terms of premature death or reduced quality of life remains a huge issue. It is of great importance to evaluate asthma burden geographically and time trends from 1990 to 2019 and to assess the contributions of age, period, and cohort effects at global level.

Asthma prevalence, deaths, and disability adjusted life years (DALYs) as well as risk-attributable burden were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database and were compared by age and sex. The Smoothing Splines models were used to estimate the relationship between asthma DALYs and the sociodemographic index (SDI). The Age-Period-Cohort model was used to determine effects of ages, periods, and birth cohorts on disease rates.

Between 1990 and 2019, the declines were 24.05% (95% uncertainty interval [UI] − 27.24 to − 20.82) in age-standardized asthma prevalence, 51.3% (− 59.08 to − 43.71) in mortality, and 42.55% (− 48.48 to − 36.61) in DALYs rate. However, the burden of asthma continued to rise, with an estimated 262.41 million prevalent cases globally (95% UI 224.05 to 309.45). Asthma caused greater DALYs in females than in males among people aged 20 years and older. The lowest age-standardized DALYs rate was observed at a SDI of approximately 0.70. The Longitudinal age curves showed an approximate W-shaped pattern for asthma prevalence and a likely J-shaped pattern for asthma mortality. The period effect on prevalence and mortality of asthma decreased from 1990 to 2019. Compared with the 1955–1959 birth cohort, the prevalence relative risk (RR) of asthma was highest in the 1905–1909 birth cohort, whereas the mortality RR continued to decline. At the global level, the percentages of high body-mass index, occupational asthmagens, and smoking contributing to DALYs due to asthma were 16.94%, 8.82%, and 9.87%, respectively.

Conclusions

Although the age-standardized rates of asthma burden declined in the past 30 years, the overall burden of asthma remains severe. High body mass index becomes the most important risk factor for DALYs due to asthma at the global level.

Asthma is a prevalent chronic inflammatory airway disease marked by airflow limitation, airway hyperresponsiveness, and structural changes in the airways [ 1 ]. Despite efforts to address its impact, the Global Initiative for Asthma (GINA) revealed that the burden of asthma in terms of premature death and reduced quality of life remained a significant public health challenge, with economic consequences [ 2 ]. A Canadian study found that the financial burden was associated with productivity losses, and the cost of biologic treatments for uncontrolled asthma was high and even greater for severe uncontrolled asthma [ 3 ].

The total burden of chronic respiratory diseases was estimated in previous studies by the Chronic Respiratory Disease Collaborators and Li X et al. based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2015 and 2017 [ 4 , 5 , 6 ]. With updated data, the GBD 2019 provides a tool to better quantify health loss and risk-attributable burden. Researchers used the GBD 2019 to investigate chronic respiratory diseases mortality in BRICS (Brazil, Russia, India, China, and South Africa) countries and the burden of chronic respiratory disease and attributable risk factors in North Africa and Middle East, and the burden of childhood asthma [ 7 , 8 , 9 ]. Recently, some studies reported the burden of asthma in China using the GBD 2019 [ 10 , 11 ]. However, there remains a need for more comprehensive comparisons using common indicators such as prevalence, deaths, and disability adjusted life years (DALYs) across countries and regions. Moreover, analyzing the contributions of age, period, and cohort effects at the global level is also necessary.

Asthma management varied in different countries based on their development capacities, with varying priorities. In some African countries, the main challenge was providing effective medicines to asthma patients [ 12 , 13 ]. In certain Asian countries, strengthening the interpretation of asthma guidelines is a priority [ 14 ]. In contrast, in some Latin American countries, improving asthma patients’ self-management education could enhance treatment efficiency [ 15 ].

Asthma affects people of all ages, regardless of the region or country. Referring to the Institute for Health Metrics and Evaluation (IHME) in 2010, global asthma DALYs followed a bimodal distribution, with peak values appearing in age groups 10–14 years and 75–79 years, and a trough value in the age group of 30–34 years. Among individuals younger than 30 years, the burden of DALYs was similar for males and females, but the burden was higher in males with age [ 16 ]. Recent study by the Global Asthma Network Phase one (GAN I) estimated trends in asthma prevalence and severity of symptoms in children aged 6–7 years and adolescents aged 13–14 years [ 17 ]. However, no comprehensive research was conducted to update the global, regional, and national burden of asthma across all ages and stratified by sex in the decade after 2010 [ 16 ]. The changing characteristics of asthma burden and the impact of macro-environmental factors on asthma burden remain unknown.

In addition to accurately estimating the disease burden, it is essential to report the risk-attributable burden of asthma caused by the well-recognized risk factors, such as high body-mass index, smoking, and occupational asthmagens. This information can assist in making policies related to public health [ 18 ]. For instance, the World Health Organization suggested that tobacco control could directly reduce the risk of asthma, and making adjustments to diet or engaging in physical exercise could reduce obesity and thus lower the risk of asthma [ 16 ]. However, the asthma burden attributable to each risk factor is not well defined, particularly in the case of high body-mass index.

This study aimed to provide a comprehensive update on the burden of asthma from multiple angles to provide valuable evidence for future research and policymaking in asthma.

The aim of this study was to provide updated estimates of asthma prevalence, deaths, and DALYs based on data from the GBD 2019 database, to assess trends from 1990 to 2019, and compared estimates across age and sex groups. The relationship between asthma DALYs and the sociodemographic index (SDI) was analyzed. The contributions of age, period, and cohort effects on the trends of asthma prevalence and mortality were reported. The risk-attributable burden of asthma caused by high body-mass index, smoking, and occupational asthmagens was also estimated.

Overview and data source

The GBD database provides a tool to quantify health loss from hundreds of diseases, injuries, and risk factors [ 18 , 19 ]. For this study, the data on asthma prevalence, deaths, and DALYs were derived from the Global Health Data Exchange (GHDx) ( https://vizhub.healthdata.org/gbd-results/ ). In GBD 2019, asthma is a chronic lung disease marked by spasms in the bronchi usually resulting from an allergic reaction or hypersensitivity and causing difficulty in breathing. It is defined asthma as a doctor’s diagnosis and wheezing in the past year. The relevant International Classification of Disease and Injuries (ICD) -10 codes are J45 and J46 (ICD-9 code is 493). Alternative case definitions include self-reported asthma in the past year, self-reported asthma ever, only a doctor’s diagnosis in the past year and only wheezing in the past year. The last full systemic review of the literature on asthma was done for GBD 2016 and data in literature matching the case definitions above were extracted. Some new data from surveys were added. Vital registration and surveillance data from the cause of death (COD) database were used to estimate asthma mortality. The detaied case definition and sources of data for asthma are available in Additional file 1 : Table S1.

The SDI is a composite indicator of development status. It is the geometric mean of 0 to 1 indices of total fertility rate under the age of 25, mean education for those ages 15 and older, and lag distributed income per capita. A location with an SDI of 0 has a theoretical minimum level of development relevant to health, while a location with an SDI of 1 has a theoretical maximum level [ 19 ]. The SDI values are available from GHDx ( https://ghdx.healthdata.org/record/ihme-data/gbd-2019-socio-demographic-index-sdi-1950-2019 ).

The percentage of asthma DALYs attributable to risk factors, including smoking, high body-mass index, and occupational asthmagens was also obtained from the GHDx. The definition of these factors and their relative risk (RR) for asthma are previously reported [ 18 ]. Details are available in Additional file 1 : Table S1.

Statistical analyses

The main modeling tool for asthma is called DisMod-MR version 2.1. Prior settings include a maximum remission of 0.3 (reflecting the upper bound of the highest observed data) and an incidence between the ages of 0 and 0.5 years, as a diagnosis can not be made in young infants. Covariates that are associated with measures of asthma epidemiology in prior studies and for which estimates of those covariates are available for all GBD year-age-sex-location combinations are included in the DisMod model. The standard Cause of Death Ensemble modelling (CODEm) approach was applied to estimate deaths due to asthma. Verbal autopsy data were not included and were instead mapped to an overall chronic respiratory model. The unadjusted death estimates for asthma are combined with those for chronic obstructive pulmonary disease, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases and fit to the distribution of deaths in an overall chronic respiratory disease “parent” model and redistributed to the “child” model proportionately. For all results, the 95% uncertainty (combined from input data, corrections of measurement error, estimates of residual non-sampling error, and so on) intervals were reported.

Results at the global and regional levels were compared by age and sex. The relationship between asthma burden and SDI for the 21 regions and 204 countries and territories was examined using Smoothing Splines models. Age-Period-Cohort analysis ( https://analysistools.cancer.gov/apc ) was used to investigate the influence of age, period, and cohort effects on trends of prevalence and mortality in asthma [ 20 ]. Data were analyzed with R version 4.0.5 ( http://CRAN.R-project.org , R Foundation, Vienna, Austria).

Global level

In 2019, a total of 262.41 (95% UI 224.05 to 309.45) million prevalent cases were estimated, with an age-standardized prevalence of 3415.53 (95% UI 2898.92 to 4066.2) per 100,000, a decrease of 24.05% (20.82 to 27.24%) since 1990. Death cases accounted for asthma were estimated to be 461.07 (95% UI 366.58 to 559.01) thousand, with an age-standardized mortality of 5.8 (95% UI 4.62 to 7.03) per 100,000, a decrease of 51.30% (43.71 to 59.08%) since 1990. The number of DALYs for asthma was 21.55 (95% UI 17.14 to 26.97) million, with an age-standardized DALYs rate of 273.63 (95% UI 216.71 to 343.38) per 100,000, a decrease of 42.55% (36.61 to 48.48%) since 1990 (Table 1 ).

Regional level

The number of prevalent asthma cases increased from 226.9 million in 1990 to 262.41 million in 2019. South Asia (39.87, 95%UI 33.20 to 47.77), High-income North America (35.61, 95%UI 31.84 to 39.98), and Western Europe (27.04, 95%UI 22.87 to 31.92) had the highest number of prevalent cases in 2019 (unit: million). Point deaths from asthma increased from 460.01 thousand in 1990 to 461.07 thousand in 2019, and point DALYs for asthma decreased from 22.32 million in 1990 to 21.55 million in 2019. South Asia, Southeast Asia, and North Africa and Middle East had the highest number of deaths (232.19, 95% UI 160.83 to 316.30; 72.06, 95%UI 61.16 to 81.55; and 32.08, 95%UI 26.20 to 38.35; unit: thousand) and the highest number of DALYs (6.91, 95%UI 5.21 to 8.70; 2.68, 95%UI 2.25 to 3.16; and 1.68, 95%UI 1.32 to 2.12; unit: million) in 2019 (Table 1 ).

High-income North America (9848.14) and Australasia (8393.25) had the highest age-standardized prevalence of more than 7,000 per 100,000 people for asthma, whereas East Asia (2025.52), Central Asia (2277.44), and South Asia (2443.40) had the lowest. A total of seven regions had an age-standardized point mortality of more than ten per 100,000 people for asthma, including Oceania (46.76), four Sub-Saharan African regions [Central Sub-Saharan Africa (20.63), Southern Sub-Saharan Africa (13.78), Western Sub-Saharan Africa (13.13), and Eastern Sub-Saharan Africa (11.29)], and two Asian regions [South Asia (18.95) and Southeast Asia (13.79)]. While six regions had point age-standardized mortality of less than one per 100,000 people for asthma, Western Europe (0.70), Eastern Europe (0.70), and Central Europe (0.81) had the lowest values. The leading point age-standardized DALYs rate for asthma (per 100,000) was observed in Oceania (1102.21), which was almost twice that in the next region, Central Sub-Saharan Africa (572.95). East Asia (106.42), Eastern Europe (124.09), and High-income Asia Pacific (160.29) had the lowest age-standardized DALYs rate for asthma (per 100,000) (Table 1 ). Age-standardized prevalence, mortality, and DALYs rate by sex are shown in Additional file 1 : Figure S1 to Figure S3.

From 1990 to 2019, High-income Asia Pacific (− 48.66%), Eastern Europe (− 42.64%), and Australasia (− 30.56%) experienced the greatest decline in age-standardized prevalence of asthma, and only High-income North America (9.59%) experienced an increase. The decreases in age-standardized deaths from asthma from 1990 to 2019 was observed in all regions, which recorded a decrease from − 31.17 to − 88.21%. High-income Asia Pacific (− 88.21%), Eastern Europe (− 83.43%), and Central Europe (− 82.49%) were the only regions that experienced a decrease greater than 80% during this period. High-income Asia Pacific (− 60.86%), Eastern Europe (− 56.99%), and Andean Latin America (− 51.49%) regions experienced the greatest decline in age-standardized DALYs rates for asthma between 1990 and 2019, while only High-income North America (2.82%) experienced an increase (Table 1 ). The percent change in age-standardized prevalence, mortality, and DALYs rates by sex is shown in Additional file 1 : Figure S4 to Figure S6.

National level

The age-standardized prevalence of asthma for 204 countries and territories ranged from 1072.46 to 10,399.27 per 100,000 in 2019. The United States of America (10,399.27, 95%UI 9140.29 to 11,903.19), the United Kingdom (9166.57, 95%UI 7645.04 to 11,034.51), and Portugal (9106.18, 95%UI 7499.66 to 11,069.60) had the highest age-standardized prevalence of asthma per 100,000, while Nepal (1072.46, 95%UI 932.39 to 1,214.78), Lesotho (1377.07, 95%UI 1185.73 to 1567.73), and Bangladesh (1390.91, 95%UI 1217.24 to 1574.20) had the lowest (Fig.  1 and Additional file 1 : Table S2). Country specific age-standardized mortality for asthma ranged from 0.26 to 80.50 per 100,000 people in 2019. Kiribati (80.50, 95%UI 59.22 to 104.19), Papua New Guinea (55.81, 95%UI 39.05 to 80.31), and Fiji (43.33, 95%UI 34.22 to 54.76) had the highest estimates per 100,000 people. A total of 49 countries had an age-standardized asthma mortality of less than one per 100,000 people in 2019, and Greece (0.26, 95%UI 0.21 to 0.31) had the lowest (Fig.  2 and Additional file 1 : Table S3). The national age-standardized DALYs rate of asthma for more than 1000 per 100,000 people was observed in Kiribati (1795.09, 95%UI 1411.44 to 2242.16) and Papua New Guinea (1250.25, 95%UI 941.24 to 1697.62) in 2019. And Armenia (91.09, 95%UI 59.15 to 136.04) was the only country with asthma DALYs rate below 100 per 100,000 in 2019. (Additional file 1 : Figure S7 & Table S4).

Age-standardized prevalence of asthma per 100,000 population in 2019

Age-standardized death rate of asthma per 100,000 population in 2019

New Zealand (− 55.14%, 95%UI − 59.09 to − 50.36) and Japan (− 52.82%, 95%UI − 57.7 to − 47.85) experienced a decrease in age-standardized prevalence of more than 50% since 1990. While 29 countries showed an increase in age-standardized prevalence since 1990, Oman (31.45%, 95%UI 19.2 to 49.62), followed by Saudi Arabia (26.24%, 95%UI 16.54 to 40.04) and Viet Nam (18.80%, 95%UI 13.14 to 25.63) showed the largest increase (Additional file 1 : Figure S8 & Table S2). Age-standardized mortality decreased in all countries and territories since 1990, with the Republic of Korea (− 90.23%, 95%UI − 92.41 to − 83.76) showing the largest decrease (Additional file 1 : Figure S9 & Table S3). From 1990 to 2019, the Maldives (− 75.61%, 95%UI − 83.03 to − 64.26), Guatemala (− 72.90%, 95%UI − 79.21 to − 63.57), and the Republic of Korea (− 72.35%, 95%UI − 79.18 to − 60.84) experienced the greatest decrease in DALYs for asthma, while an increase was seen only in Montenegro (6.68%, 95%UI − 1.26–15.94), Oman (6.03%, 95%UI − 10.86–24.02), United States of America (4.44%, 95%UI − 3.45–12.86), and Paraguay (3.13%, 95%UI − 7.85–13.73) (Additional file 1 : Figure S10 & Table S4).

Age and sex pattern

More asthma point prevalence cases were observed in children aged five to nine years, with about 19 million in males and 14 million in females, and with a relatively high age-standardized point prevalence of 5717.50 per 100,000 people in males and 4508.27 per 100,000 people in females (Additional file 1 : Figure S11). Males aged 75–79 years and females aged 80–84 years had the highest number of asthma death cases, 28,297.80 cases and 36,492.10 cases, respectively. The highest age-standardized point mortality was observed in people older than 95 years, with 126.14 per 100,000 in males and 118.29 per 100,000 in females (Additional file 1 : Figure S12). The number of asthma DALYs for males and females showed a bimodal distribution. The highest number of asthma DALYs in males was in children aged 5–9 years, which totaled 847,222.3 DALYs, whereas in females it was in adults aged 60–64 years, with a total of 896,868.8 DALYs. The number of asthma DALYs was higher in female adults older than 20–24 years. The peak age-standardized DALYs rate was seen in people aged 80 to 84 years [males: 1060.8, females: 1057.7, unit per 100,000 people] (Fig.  3 ).

Number of DALY cases globally and DALY rate of asthma per 100,000 population, by age and sex in 2019. Boxes indicate DALY cases with 95% uncertainty intervals for men and women. DALY: disability adjusted life year

Association with the sociodemographic index

At the global level, asthma DALYs decreased with the increase in SDI (Fig.  4 ). At the regional level, a non-linear relationship was observed between age-standardized asthma DALYs rate and SDI, and the lowest age-standardized DALYs rate was observed at an SDI of approximately 0.70. Oceania, Southern Sub-Saharan Africa, Southeast Asia, the Caribbean, and Australasia had higher DALYs rates from 1990 to 2019 than expected based on their SDI. At the national level, a L-shaped relationship was observed between asthma DALYs rate and SDI (Additional file 1 : Figure S13). Many countries had higher than expected DALYs rates in 2019 based on their SDI, which was seen in Kiribati, Papua New Guinea, Fiji, and the Central African Republic.

Age-standardized disability adjusted life year (DALY) rates of asthma for the 21 Global Burden of Disease regions by sociodemographic index, 1990–2019. Thirty points are plotted for each region and show the observed age-standardized DALY rates from 1990 to 2019 for that region. Expected values, based on the sociodemographic index and disease rates in all locations, are shown as a solid line. Regions above the solid line represent a higher than expected burden and regions below the line show a lower than expected burden

• Age-period-cohort analysis

Declines were observed in asthma prevalence and mortality (asthma prevalence net drift = − 1.45, unit: %/year; p < 0.05; asthma mortality net drift = − 2.62, unit: %/year; p < 0.05). Comparison between local drifts and net drifts showed statistical significance (p < 0.05), suggesting that the overall annual percentage change (net drift) in asthma prevalence and mortality could not adequately explain the variations in age-specific annual percentage change (local drifts) over time. The longitudinal age curve showed that asthma prevalence had an approximately W-shaped pattern, peaking at age 7.5 years. The results showed that asthma mortality probably had a J-shaped pattern, with a higher rate in children younger than 7.5 years (rate = 7.68 in children aged 2.5 years), and it was lowest at age 12.5 years (rate = 1.13) and then increased with age.

Period RR results showed higher relative risks for asthma prevalence and mortality before 2002 (asthma prevalence: RR = 1.26 in 1992, RR = 1.13 in 1997; asthma mortality: RR = 1.29 in 1992, RR = 1.16 in 1997). Cohort RR results showed higher relative risks in asthma prevalence and mortality before the 1955 birth cohort (both asthma prevalence and mortality: RR = 1.00 in 1955) and lower relative risks in subsequent birth cohorts (Additional file 1 : Figure S14).

• Risk factors

Factors such as high body mass index, occupational asthmagens, and smoking had some influence on asthma DALYs at the global level, accounting for 16.94%, 8.82%, and 9.87%, respectively. At the regional level, 10.03 to 30.48% of asthma DALYs were due to high body mass index, 4.82–10.85% of asthma DALYs were due to occupational asthmagens, and 1.2–17.31% of asthma DALYs were due to smoking (Fig.  5 ). The leading risk factor in terms of risk-attributable DALYs globally in 2019 was high body-mass index in females (risk-attributable DALYs = 19.06%) (Additional file 1 : Figure S15) and smoking in males (risk-attributable DALYs = 15.38%) (Additional file 1 : Figure S16).

Percentage of disability adjusted life years (DALYs) due to asthma attributable to each risk factor for the 21 Global Burden of Disease regions in 2019

At the global level, asthma DALYs attributed to high body mass index showed a W-shaped distribution, in which it increased rapidly in adults aged 20–24 years (15.05%) and peaked at age of 45–49 years (23.64%), decreased to a low level at age of 80–84 years (14.47%), and then increased again. Asthma DALYs attributed to occupational asthmagens showed an inverted U-shaped distribution in individuals aged 15–84 years and peaked at age of 35–39 years (16.25%). Asthma DALYs attributed to smoking showed an inverted U-shaped distribution in people aged 30–95 years and peaked at age of 60–64 years (16.31%) (Additional file 1 : Figure S17). Notably, in every age group between 25 and 74 years, more than 20% of asthma DALYs in females were attributed to high body mass index (Additional file 1 : Figure S18). And asthma DALYs attributed to smoking in males showed a U-shaped distribution in individuals older than 35 years, with a peak of 25.87% at age of 60–64 years (Additional file 1 : Figure S19).

In this study, the burden of asthma was analyzed based on the GBD database. We found that age-standardized asthma prevalence, mortality, and DALYs had marked declines in the past 30 years, but the number of prevalent and death cases of asthma increased. Many countries had higher DALYs rates in 2019 than expected based on their SDI. The Age-Period-Cohort effects of asthma prevalence and mortality were determined. In terms of the percentage of asthma-related DALYs attributable to each risk factor, high body mass-index had the largest effect, while occupational asthmagens and smoking had a similar effect at the global level.

From 1990 to 2019, age-standardized asthma prevalence and DALYs decreased globally, but increased in some countries such as Oman, Saudi Arabia and Viet Nam, and so on. Previous epidemiological studies of asthma in Oman, Saudi Arabia, and Viet Nam mentioned some reasons for the high disease burden of asthma, such as inadequate use of preventive asthma medications and inadequate use of pulmonary function tests to diagnose or monitor asthma progression [ 21 , 22 ]. For some countries, it could also be important to improve awareness of asthma in the population [ 23 ]. A study in Portugal also concluded that physicians needed to improve their knowledge of asthma diagnosis and treatment [ 24 ].

On the other hand, our results showed that countries could have a high age-standardized asthma prevalence but a low age-standardized asthma death rate, which was mainly observed in high-income countries. The main reason for this phenomenon might be that most high-income countries did a good job in managing medicines and standard care for asthma patients. Thus, although some unavoidable risk factors such as urbanization led to high asthma prevalence, the asthma mortality was maintained at a low level. In contrast, some low- and middle-income countries (LMICs) had low age-standardized asthma prevalence but high age-standardized asthma death rates. Effective, accessible, and affordable medicines were a major challenge for LMICs [ 25 , 26 ]. For example, in some countries, long-term standards for medical care were not established and there were few outstanding physicians and organizations, so medical care for asthma patients was generally poor. Therefore, there are still many unnecessary deaths from asthma in these LMICs. The location of these LMICs, such as Kiribati, Papua New Guinea, and Fiji, is near the ocean, and the ocean climate may influence the prevalence of asthma. However, the relationship between ocean climate and the prevalence of asthma was not well-determined [ 27 ].

Stratified by sex and age, we found that the distribution of asthma DALYs had some changes over the past 10 years. Results from IHME’s analysis in 2010 showed that peak asthma DALYs occurred at age of 10–14 years and at age of 75–79 years, and the trough value was at age of 30–34 years [ 16 ]. However, in our study, the global asthma DALYs in 2019 found that both the peak and trough DALYs occurred at an earlier age. Additionally, the results of the IHME study showed that the distribution of asthma DALYs was similar in males and females before the age of 30–34 years, and the burden of asthma was higher in males than that in females with age. However, our results showed that asthma DALYs in females was higher than that in males in people older than 20 years, which was consistent with the Centers for Disease Control and Prevention (US) reports indicating that women had a higher prevalence than men in adults, based on the current surveillance summaries [ 28 ]. But trends of asthma burden would not be the same in every country or region. A survey derived from seven cities in China showed that men had higher asthma prevalence among people older than 15 years in six cities [ 29 ]. The distribution patterns of asthma prevalence and DALYs by age and sex, which were influenced by various risk factors, were not well explained. For instance, the phenomenon that females showed higher asthma prevalence after puberty might be related to the pathogenic effect of sex hormones [ 30 ].

In terms of Age-Period-Cohort analysis, longitudinal age curves showed that asthma was most prevalent in children, while the elderly had the highest asthma mortality. Childhood asthma is influenced by a multitude of factors that contribute to its increased prevalence. These factors include viral infections, air pollution, genetic susceptibility, obesity, and abnormal immune maturation during early life [ 31 , 32 , 33 , 34 ]. While the factors causing asthma in the elderly could be mainly attributed to social factors or in conjunction with comorbidities. However, the relationship between these factors and the pathogenesis of asthma is complex, and further studies on the biological mechanism are needed [ 35 , 36 ]. The period effect on prevalence and mortality of asthma decreased from 1990 to 2019, which could be related to the improvement in the management of asthma [ 2 , 37 , 39 ]. When inhaled corticosteroids (ICS) or combination therapy of ICS with long-acting beta2 agonists (LABA) or long-acting muscarinic antagonists (LAMA) were introduced for asthma, great improvements in symptom control were observed, and exacerbations and asthma-related mortality also decreased [ 2 ]. Methylxanthines such as theophylline and aminophylline were also used for many years to treat patients with asthma [ 40 ]. Among biologic agents, omalizumab helps reduce the frequency and severity of asthma attacks by binding to immunoglobulin E (IgE), while mepolizumab and reslizumab are monoclonal antibodies that target interleukin-5 (IL-5) and are used to treat severe eosinophilic asthma [ 2 ]. However, based on GBD 2019, the drug-related reduction in asthma mortality could not be estimated due to lack of data on the different drugs, and further studies are needed to assess the related burden. Additionally, previous studies found that changes in policy and social economics could influence air quality, tobacco use, and awareness of early screening or diagnosis of asthma, which could also affect disease rates [ 41 , 42 ].

Regarding risk factors, our results showed that high body mass index was most critical for DALYs due to asthma at the global level, which was consistent with the findings of previous studies [ 6 , 43 , 44 , 45 ]. Li et al. found that the age-standardized mortality of asthma attributed to smoking decreased shapely from 1990 to 2017, while in 2017, the age-standardized mortality of asthma attributed to high body mass index had a larger effect than that of smoking [ 6 ]. However, smoking was still thought to be one of the main risk factors for asthma [ 46 , 47 ]. The results of the International Study of Asthma and Allergies in Childhood (ISAAC) showed that open-fire cooking and maternal tobacco use could be the risk factors for asthma symptoms in children aged 6–7 years and 13–14 years [ 48 ]. When analyzing the percentage of DALYs due to asthma attributable to smoking, our results also indicated that smoking had a large impact on asthma DALYs, which was 9.87% at the global level. In Central Europe, Western Europe, and Eastern Europe, smoking had a greater impact on asthma DALYs, accounting for 17.31%, 15.89%, and 14.37%, respectively. As a result, we considered it essential for governments to continue the decisions on tobacco control and dietary adjustments, and to improve measures to prevent occupational asthmagens, because occupational asthmagens also had a large impact on DALYs [ 49 ]. And more high-quality epidemiological studies are needed to identify the potential risk factors for asthma, to identify the cause, and to reduce exposure to these factors.

Our study updated asthma burden data and analyzed changes over the past three decades, which could provide clues for future studies and useful information for policy makers. However, our study had some limitations. First, our study might provide little interesting information about the burden of asthma in a clinical context because of a lack of data on emergency department visits, hospital admissions, and use of key asthma medications. Second, our study considered only the best-known risk factors for asthma and not some potential factors such as household air pollution from solid fuels and particulate matter in the workplace. Due to the lack of data on the risk burden of obesity, future epidemiologic studies are needed to determine the impact of other potential factors. Third, many countries did not have registration systems to record deaths, so estimates had to be obtained from autopsy studies. However, in these studies, estimates of asthma-related deaths did not distinguish between the different types of chronic respiratory diseases that should not be recorded, resulting in underestimation. Fourth, although multiple calculation methods, correction of disease miscoding, and redistribution of waste codes were used in the GBD study, the potential inaccuracy of the data also had to be considered.

The age-standardized disease burden rate of asthma declined by some extent over the past 30 years. However, the number of prevalent cases and deaths of asthma continues to increase and the burden remains severe, especially in countries with a low SDI. Age-Period-Cohort effects of asthma prevalence and mortality were determined. High body mass index becomes the most important risk factor for DALYs due to asthma at the global level.

Abbreviations

Brazil, Russia, India, China, and South Africa

Cause of Death

Cause of Death Ensemble modelling

Disability adjusted life years

Global Asthma Network Phase one

Global Burden of Disease

Global Health Data Exchange

Global Initiative for Asthma

International Classification of Disease and Injuries

Inhaled corticosteroids

Immunoglobulin E

Interleukin-5

Institute for Health Metrics and Evaluation

International Study of Asthma and Allergies in Childhood

Long-acting beta2 agonists

Long-acting muscarinic antagonists

Low- and middle-income countries

Relative risk

Sociodemographic index

95% Uncertainty interval

Oh CK, Leigh R, McLaurin KK, et al. A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir Res. 2013;14(1):93. https://doi.org/10.1186/1465-9921-14-93 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2023. Available from: www.ginasthma.org .

Sadatsafavi M, Rousseau R, Chen W, et al. The preventable burden of productivity loss due to suboptimal asthma control: a population-based study. Chest. 2014;145(4):787–93. https://doi.org/10.1378/chest.13-1619 .

Article   PubMed   Google Scholar  

Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5(9):691–706. https://doi.org/10.1016/s2213-2600(17)30293-x .

Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2020;8(6):585–96. https://doi.org/10.1016/s2213-2600(20)30105-3 .

Trends and risk factors of mortality and disability adjusted life years for chronic respiratory diseases from 1990 to 2017: systematic analysis for the Global Burden of Disease Study 2017. BMJ (Clinical research ed) 2020;370:m3150. https://doi.org/10.1136/bmj.m3150 .

Bai J, Zhao Y, Yang D, et al. Secular trends in chronic respiratory diseases mortality in Brazil, Russia, China, and South Africa: a comparative study across main BRICS countries from 1990 to 2019. BMC Public Health. 2022;22(1):91. https://doi.org/10.1186/s12889-021-12484-z .

Article   PubMed   PubMed Central   Google Scholar  

Fallahzadeh A, Sharifnejad Tehrani Y, Sheikhy A, et al. The burden of chronic respiratory disease and attributable risk factors in North Africa and Middle East: findings from global burden of disease study (GBD) 2019. Respir Res. 2022;23(1):268. https://doi.org/10.1186/s12931-022-02187-3 .

Zhang D, Zheng J. The Burden of Childhood Asthma by age group, 1990–2019: a systematic analysis of global burden of disease 2019 data. Front Pediatr. 2022;10:823399. https://doi.org/10.3389/fped.2022.823399 .

Liu M, Gan H, Lin Y, et al. Prevalence and disability-adjusted life year rates of asthma in China: findings from the GBD Study 2019 of the G20. Int J Environ Res Public Health. 2022;19(22):14663. https://doi.org/10.3390/ijerph192214663 .

Luo Y, Wang M, Tian Y. Trends and age-period-cohort effects on incidence and mortality of asthma in Sichuan Province, China, 1990–2019. BMC Pulm Med. 2022;22(1):298. https://doi.org/10.1186/s12890-022-02059-y .

Bissell K, Perrin C, Beran D. Access to essential medicines to treat chronic respiratory disease in low-income countries. Int J Tuberc Lung Dis. 2016;20(6):717–28. https://doi.org/10.5588/ijtld.15.0734 .

Article   CAS   PubMed   Google Scholar  

Asher I, Bissell K, Ellwood P, et al. Global asthma network identifies gaps in essential asthma medicines. 53 Allergy and Immunology, 2016.

Singh S, Sharma BB, Sharma SK, et al. Prevalence and severity of asthma among Indian school children aged between 6 and 14 years: associations with parental smoking and traffic pollution. J Asthma. 2016;53(3):238–44. https://doi.org/10.3109/02770903.2015.1087558 .

Arias SJ, Neffen H, Bossio JC, et al. Prevalence and features of asthma in young adults in Urban Areas of Argentina. Arch Bronconeumol (Engl Ed). 2018;54(3):134–9. https://doi.org/10.1016/j.arbres.2017.08.021 .

The Global Asthma Report 2018. Auckland, New Zealand: Global Asthma Network, 2018.

Asher MI, Rutter CE, Bissell K, et al. Worldwide trends in the burden of asthma symptoms in school-aged children: global Asthma Network Phase I cross-sectional study. Lancet. 2021;398(10311):1569–80. https://doi.org/10.1016/S0140-6736(21)01450-1 .

Collaborators GBDRF. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396(10258):1223–49. https://doi.org/10.1016/S0140-6736(20)30752-2 .

GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222. https://doi.org/10.1016/S0140-6736(20)30925-9 .

Rosenberg PS, Check DP, Anderson WF. A web tool for age-period-cohort analysis of cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prevent. 2014;23(11):2296–302. https://doi.org/10.1158/1055-9965.Epi-14-0300 .

Article   Google Scholar  

Al-Busaidi N, Habibulla Z, Bhatnagar M, et al. The Burden of Asthma in Oman. Sultan Qaboos Univ Med J. 2015;15(2):e184–90.

PubMed   PubMed Central   Google Scholar  

Mohamed Hussain S, Ayesha Farhana S, Mohammed AS. Time trends and regional variation in prevalence of asthma and associated factors in Saudi Arabia: a systematic review and meta-analysis. Biomed Res Int. 2018;2018:8102527. https://doi.org/10.1155/2018/8102527 .

Nguyen VN, Huynh TTH, Chavannes NH. Knowledge on self-management and levels of asthma control among adult patients in Ho Chi Minh City, Vietnam. Int J Gen Med. 2018;11:81–9. https://doi.org/10.2147/ijgm.S157050 .

Joao C, Jacome C, Brito D, et al. Prevalence and characterisation of patients with asthma according to disease severity in Portugal: findings from the EPI-ASTHMA pilot study. J Asthma Allergy. 2022;15:1441–53. https://doi.org/10.2147/JAA.S381716 .

Babar ZU, Lessing C, Mace C, et al. The availability, pricing and affordability of three essential asthma medicines in 52 low- and middle-income countries. Pharmacoeconomics. 2013;31(11):1063–82. https://doi.org/10.1007/s40273-013-0095-9 .

Chiang CY, Ait-Khaled N, Bissell K, et al. Management of asthma in resource-limited settings: role of low-cost corticosteroid/beta-agonist combination inhaler. Int J Tuberc Lung Dis. 2015;19(2):129–36. https://doi.org/10.5588/ijtld.14.0363 .

Bonomo S, Ferrante G, Palazzi E, et al. Evidence for a link between the Atlantic Multidecadal Oscillation and annual asthma mortality rates in the US. Sci Rep. 2019;9(1):11683. https://doi.org/10.1038/s41598-019-48178-1 .

Pate CA, Zahran HS, Qin X, et al. Asthma Surveillance—United States, 2006–2018. MMWR Surveill Summ. 2021;70(No. SS-5):1–32. https://doi.org/10.15585/mmwr.ss7005a1 .

Fu QL, Du Y, Xu G, et al. Prevalence and occupational and environmental risk factors of self-reported asthma: evidence from a cross-sectional survey in seven chinese cities. Int J Environ Res Public Health. 2016. https://doi.org/10.3390/ijerph13111084 .

Minelli C, van der Plaat DA, Leynaert B, et al. Age at puberty and risk of asthma: a Mendelian randomisation study. PLoS Med. 2018;15(8):e1002634. https://doi.org/10.1371/journal.pmed.1002634 .

Zhang Z, Lai HJ, Roberg KA, et al. Early childhood weight status in relation to asthma development in high-risk children. J Allergy Clin Immunol. 2010;126(6):1157–62. https://doi.org/10.1016/j.jaci.2010.09.011 .

Ho WC, Lin YS, Caffrey JL, et al. Higher body mass index may induce asthma among adolescents with pre-asthmatic symptoms: a prospective cohort study. BMC Public Health. 2011;11:542. https://doi.org/10.1186/1471-2458-11-542 .

Weinmayr G, Forastiere F, Büchele G, et al. Overweight/obesity and respiratory and allergic disease in children: international study of asthma and allergies in childhood (ISAAC) phase two. PLoS ONE. 2014;9(12):e113996. https://doi.org/10.1371/journal.pone.0113996 .

von Mutius E, Smits HH. Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention. Lancet. 2020;396(10254):854–66. https://doi.org/10.1016/S0140-6736(20)31861-4 .

Hasegawa K, Gibo K, Tsugawa Y, et al. Age-related differences in the rate, timing, and diagnosis of 30-day readmissions in hospitalized adults with asthma exacerbation. Chest. 2016;149(4):1021–9. https://doi.org/10.1016/j.chest.2015.12.039 .

Arismendi E, Bantula M, Perpina M, et al. Effects of obesity and asthma on lung function and airway dysanapsis in adults and children. J Clin Med. 2020. https://doi.org/10.3390/jcm9113762 .

Salama AA, Mohammed AA, Okda El SE, et al. Quality of care of Egyptian asthmatic children: clinicians adherence to asthma guidelines. Ital J Pediatr. 2010;36:33. https://doi.org/10.1186/1824-7288-36-33 .

Lehmann S, Sprünken A, Wagner N, et al. Clinical relevance of IgE-mediated sensitization against the mould Alternaria alternata in children with asthma. Ther Adv Respir Dis. 2017;11(1):30–9. https://doi.org/10.1177/1753465816680786 .

Vichyanond P, Pensrichon R, Kurasirikul S. Progress in the management of childhood asthma. Asia Pac Allergy. 2012;2(1):15–25. https://doi.org/10.5415/apallergy.2012.2.1.15 .

Craig SS, Dalziel SR, Powell CVE, et al. Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane reviews. Paediatr Respir Rev. 2021;38:63–5. https://doi.org/10.1016/j.prrv.2020.08.006 .

Okui T. Age-period-cohort analysis of asthma, allergic rhinitis, and atopic dermatitis prevalence in Japan. Environ Anal Health Toxicol. 2020;35(3):e2020012. https://doi.org/10.5620/eaht.2020012 .

Ryan-Ibarra S, Milet M, Lutzker L, et al. Age, period, and cohort effects in adult lifetime asthma prevalence in California: an application of hierarchical age-period-cohort analysis. Ann Epidemiol. 2016;26(2):87–92. https://doi.org/10.1016/j.annepidem.2015.12.002 .

Granell R, Henderson AJ, Evans DM, et al. Effects of BMI, fat mass, and lean mass on asthma in childhood: a Mendelian randomization study. PLoS Med. 2014;11(7):e1001669. https://doi.org/10.1371/journal.pmed.1001669 .

Sikorska-Szaflik H, Połomska J, Sozańska B. The impact of dietary intervention in obese children on asthma prevention and control. Nutrients. 2022. https://doi.org/10.3390/nu14204322 .

Sharma V, Cowan DC. Obesity, inflammation, and severe asthma: an update. Curr Allergy Asthma Rep. 2021;21(12):46. https://doi.org/10.1007/s11882-021-01024-9 .

Kim SY, Sim S, Choi HG. Active and passive smoking impacts on asthma with quantitative and temporal relations: a Korean Community Health Survey. Sci Rep. 2018;8(1):8614. https://doi.org/10.1038/s41598-018-26895-3 .

Beasley R, Semprini A, Mitchell EA. Risk factors for asthma: is prevention possible? Lancet. 2015;386(9998):1075–85. https://doi.org/10.1016/S0140-6736(15)00156-7 .

Silverwood RJ, Rutter CE, Mitchell EA, et al. Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation? Clin Exp Allergy. 2019;49(4):430–41. https://doi.org/10.1111/cea.13325 .

Mao S, Wu L, Shi W. Prevalence and distribution patterns of allergens among children with asthma and asthma-like symptoms in Shanghai, China. Respir Res. 2020;21(1):57. https://doi.org/10.1186/s12931-020-1318-1 .

Download references

Acknowledgements

We would like to thank the staff of the Institute for Health Metrics and Evaluation and its collaborators who prepared these publicly available data.

This study was funded by National Key R&D Program of China (2018YFC1311900 and 2016YFC1304603), National Key Technology R&D Program (2015BAI12B10). The study funders had no role in the conceptualisation, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Author information

Zhufeng Wang, Yun Li and Yi Gao contributed equally as co-first authors.

Authors and Affiliations

National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510120, Guangdong, China

Zhufeng Wang, Yun Li, Yi Gao, Junfeng Lin, Xuedong Lei, Jinping Zheng & Mei Jiang

Department of Allergy and Clinical Immunology, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

You can also search for this author in PubMed   Google Scholar

Contributions

Conception and design: MJ and JPZ. Administrative support: MJ and JPZ. Provision of study materials or patients: Not applicable. Collection and assembly of data: ZFW, YL and YG. Data analysis and interpretation: Z.F.W, Y.L and Y.G. Manuscript writing: All authors. Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Jinping Zheng or Mei Jiang .

Ethics declarations

Ethics approval and consent to participate.

Not applicable. This study was carried out without direct patient and public involvement as this was a systematic review. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: table s1..

Definition and data sources. Table S2. Prevalence of asthma in 1990 and 2019 and the percentage change in the age-standardized ratesper 100,000, by location. Table S3. Deaths of asthma in 1990 and 2019 and the percentage change in the age-standardized ratesper 100,000, by location. Table S4. Disability adjusted life yearsof asthma in 1990 and 2019 and the percentage change in the age-standardized ratesper 100,000, by location. Figure S1 . The age-standardized prevalence of asthma in 2019 for the 21 Global Burden of Disease regions, by sex. Figure S2 . The age-standardized deaths rate of asthma in 2019 for the 21 Global Burden of Disease regions, by sex. Figure S3 . The age-standardized DALY rate of asthma in 2019 for the 21 Global Burden of Disease regions, by sex. DALY: disability adjusted life year. Figure S4 . The percentage change in the age-standardized prevalence of asthma from 1990 to 2019 for the 21 Global Burden of Disease regions, by sex. Figure S5 . The percentage change in the age-standardized death rate of asthma from 1990 to 2019 for the 21 Global Burden of Disease regions, by sex. Figure S6 . The percentage change in the age-standardized DALY rate of asthma from 1990 to 2019 for the 21 Global Burden of Disease regions, by sex. DALY: disability adjusted life year. Figure S7 . Age-standardized disability adjusted life yearsrate of asthma per 100 000 population in 2019. Figure S8 . The percentage change in the age-standardized prevalence of asthma from 1990 to 2019 for the 204 Global Burden of Disease countries and territories. Figure S9 . The percentage change in the age-standardized death rate of asthma from 1990 to 2019 for the 204 Global Burden of Disease countries and territories. Figure S10 . The percentage change in the age-standardized DALY rate of asthma from 1990 to 2019 for the 204 Global Burden of Disease countries and territories. Figure S11 . Number of prevalent cases globally and prevalence of asthma per 100 000 population, by age and sex in 2019. Boxes indicate prevalent cases with 95% uncertainty intervals for men and women. Figure S12 . Number of death cases globally and death rate of asthma per 100 000 population, by age and sex in 2019. Boxes indicate death cases with 95% uncertainty intervals for men and women. Figure S13. Age-standardized disability adjusted life yearrates of asthma for the 204 Global Burden of Disease countries and territories by sociodemographic index, in 2019. Points are plotted for each country and territory and show the observed age-standardized DALY rates in 2019 for that country or territory. Expected values, based on the sociodemographic index and disease rates in all locations, are shown as a solid line. Countries and territories above the solid line represent a higher than expected burden and countries and territories below the line show a lower than expected burden. Figure S14. The Age-Period-Cohort analysis in prevalence and death rate of asthma; A: The age effect in the prevalence of asthma; B: The age effect in the death rate of asthma; C: The period effect in the prevalence of asthma; D: The period effect in the death rate of asthma; E: The cohort effect in the prevalence of asthma; F: The cohort effect in the death rate of asthma. Figure S15. Percentage of DALYs due to asthma attributable to risk factors among females for 21 GBD regions in 2019. DALY = disability adjusted life years. Figure S16. Percentage of DALYs due to asthma attributable to risk factors among males for 21 GBD regions in 2019. DALY = disability adjusted life years. Figure S17. Percentage of DALYs due to asthma attributable to each risk factor, by age, in 2019. DALY = disability adjusted life years. Figure S18. Percentage of DALYs due to asthma attributable to each risk factor among females, by age, in 2019. DALY = disability adjusted life years. Figure S19. Percentage of DALYs due to asthma attributable to each risk factor among males, by age, in 2019. DALY = disability adjusted life years.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Wang, Z., Li, Y., Gao, Y. et al. Global, regional, and national burden of asthma and its attributable risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019. Respir Res 24 , 169 (2023). https://doi.org/10.1186/s12931-023-02475-6

Download citation

Received : 19 January 2023

Accepted : 10 June 2023

Published : 23 June 2023

DOI : https://doi.org/10.1186/s12931-023-02475-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Respiratory Research

ISSN: 1465-993X

• General enquiries: [email protected]

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Environmental Factor

Your online source for niehs news, niehs-supported research can help people with asthma breathe better.

Recent scientific advances help to identify root causes of and new treatment approaches for asthma, a chronic respiratory disease.

By Janelle Weaver and Caroline Stetler

In recognition of Asthma Awareness Month, Environmental Factor shares the latest discoveries made by NIEHS scientists and grant recipients related to the chronic respiratory disease.

Asthma, which is characterized by coughing, wheezing, chest tightness, and shortness of breath, affects about 25 million people in the United States, including 4.7 million children and adolescents. In 2021, more than 3,500 people across the country died from asthma-related causes.

The following examples of recently published research aim to improve the diagnosis, treatment, and prevention of asthma by better understanding the environment’s role in the disease.

Majority of clinicians do not frequently assess environmental asthma triggers

Environmental assessment and recommendations to patients vary considerably among asthma care providers, according to NIEHS researchers and their collaborators. A higher percentage of specialists assessed asthma triggers at home, school, or work than primary care or advanced practice providers. However, 46%-76% of clinicians, depending on clinician type, reported not assessing triggers almost always during asthma visits. Read the full summary .

Citation : Salo PM, Akinbami LJ, Cloutier MM, Wilkerson JC, Elward KS, Mazurek JM, Diette GB, Mitchell TA, Williams S, Zeldin DC. 2023. Environmental management of asthma in clinical practice: results from the 2012 National Ambulatory Medical Care Survey . J Allergy Clin Immunol Glob 3(1):100192.

Plasma proteomic signatures of adult asthma

A large-scale proteomics study identified more than 100 plasma proteins associated with asthma in adults, according to NIEHS researchers and their collaborators. In addition to validating previous associations, the researchers identified many novel proteins that could inform the development of diagnostic biomarkers and therapeutic targets in asthma management. Read the full summary .

Citation : Smilnak GJ, Lee Y, Chattopadhyay A, Wyss AB, White JD, Sikdar S, Jin J, Grant AJ, Motsinger-Reif AA, Li JL, Lee M, Yu B, London SJ. 2024. Plasma protein signatures of adult asthma . Allergy 79(3):643-655.

Targeting the root cause of asthma

Housing policy may be a tool to reduce childhood asthma disparities, according to recent findings from the NIEHS-funded Mobility Asthma Project . As reported in the Journal of the American Medical Association, children who move to neighborhoods with lower rates of poverty experience significant improvements in asthma symptoms, in part by reducing stress. Read the full article .

Citation : Pollack CE, Roberts LC, Peng RD, Cimbolic P, Judy D, Balcer-Whaley S, Grant T, Rule A, Deluca S, Davis MF, Wright RJ, Keet CA, Matsui EC. 2023. Association of a housing mobility program with childhood asthma symptoms and exacerbations . JAMA 329(19):1671-1681.

Why anti-thromboxane therapies have failed in asthma clinical trials

Thromboxane A2 (TXA2) can dampen the immune response in the allergic lung, which may have important therapeutic consequences, according to NIEHS researchers and their collaborators. In contrast to its acute, pro-inflammatory, and bronchoconstrictive effects, TXA2 also has longer-lasting immunosuppressive effects that attenuate Th2 and Th9 cell differentiation that drives asthma progression. These results help explain the failure of anti-thromboxane therapies and suggest that targeting the TXA2/TP receptor signaling pathway may lead to the development of novel asthma treatments. Read the full summary .

Citation : Li H, Bradbury JA, Edin ML, Gruzdev A, Li H, Graves JP, DeGraff LM, Lih FB, Feng C, Wolf ER, Bortner CD, London SJ, Sparks MA, Coffman TM, Zeldin DC. 2024. TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9 and Treg differentiation . J Clin Invest e165689 [Online 14 Mar 2024].

Community-level characteristics modify childhood asthma risk

Early-life air pollution exposure is associated with increased childhood asthma incidence, with higher risk among minoritized families living in densely populated communities, according to NIEHS-funded researchers. Their results suggest that exposure to fine particulate matter (PM) smaller than 2.5 microns in diameter (PM2.5) and nitrogen dioxide (NO2) may play a role in the development of asthma by early and middle childhood in communities characterized by fewer opportunities and resources and multiple environmental exposures. Read the full article .

Citation : Zanobetti A, Ryan PH, Coull BA, Luttmann-Gibson H, Datta S, Blossom J, Brokamp C, Lothrop N, Miller RL, Beamer PI, Visness CM, Andrews H, Bacharier LB, Hartert T, Johnson CC, Ownby DR, Khurana Hershey GK, Joseph CLM, Mendonça EA, Jackson DJ, Zoratti EM, Wright AL, Martinez FD, Seroogy CM, Ramratnam SK, Calatroni A, Gern JE, Gold DR; ECHO Children’s Respiratory and Environmental Workgroup. 2024. Early-Life exposure to air pollution and childhood asthma cumulative incidence in the ECHO CREW Consortium . JAMA Netw Open 7(2):e240535.

Additional resources to explore

• For resources on the prevention, treatment, and management of asthma, check out the NIH Learn More Breathe Better® program .
• Lower allergen levels in your home by reviewing these tips on the NIEHS asthma webpage .
• Join an asthma study to help scientists understand how bacteria and other factors in the environment affect people who have moderate to severe asthma.
• Learn about new research exploring the asthma-air pollution connection .
• Check out the asthma research portal from the National Institute of Allergy and Infectious Diseases.

(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison. Caroline Stetler is Editor-in-Chief of the Environmental Factor, produced monthly by the NIEHS Office of Communications and Public Liaison.)

Related Articles

Lisa Rider inducted into Association of American Physicians

Ask the Expert: How does NIEHS research on PFAS affect me?

NIEHS Women’s Health Awareness event celebrates 10th anniversary

Community engagement critical to addressing women’s health concerns

Monica Bertagnolli starts as new NIH director

• History, Facts & Figures
• YSM Dean & Deputy Deans
• YSM Administration
• Department Chairs
• YSM Executive Group
• YSM Board of Permanent Officers
• FAC Documents
• Current FAC Members
• Appointments & Promotions Committees
• Ad Hoc Committees and Working Groups
• Chair Searches
• Leadership Searches
• Organization Charts
• Faculty Demographic Data
• Professionalism Reporting Data
• 2022 Diversity Engagement Survey
• State of the School Archive
• Faculty Climate Survey: YSM Results
• Strategic Planning
• Mission Statement & Process
• Beyond Sterling Hall
• COVID-19 Series Workshops
• Previous Workshops
• Departments & Centers
• Find People
• Biomedical Data Science
• Health Equity
• Inflammation
• Neuroscience
• Global Health
• Diabetes and Metabolism
• Policies & Procedures
• Media Relations
• A to Z YSM Lab Websites
• A-Z Faculty List
• A-Z Staff List
• A to Z Abbreviations
• Dept. Diversity Vice Chairs & Champions
• Dean’s Advisory Council on Lesbian, Gay, Bisexual, Transgender, Queer and Intersex Affairs Website
• Minority Organization for Retention and Expansion Website
• Office for Women in Medicine and Science
• Committee on the Status of Women in Medicine Website
• Director of Scientist Diversity and Inclusion
• Diversity Supplements
• Frequently Asked Questions
• Recruitment
• By Department & Program
• News & Events
• Executive Committee
• Aperture: Women in Medicine
• Self-Reflection
• Portraits of Strength
• Mindful: Mental Health Through Art
• Event Photo Galleries
• Additional Support
• MD-PhD Program
• PA Online Program
• Joint MD Programs
• How to Apply
• Advanced Health Sciences Research
• Clinical Informatics & Data Science
• Clinical Investigation
• Medical Education
• Visiting Student Programs
• Special Programs & Student Opportunities
• Residency & Fellowship Programs
• Center for Med Ed
• Organizational Chart
• Leadership & Staff
• Committee Procedural Info (Login Required)
• Faculty Affairs Department Teams
• Recent Appointments & Promotions
• Academic Clinician Track
• Clinician Educator-Scholar Track
• Clinican-Scientist Track
• Investigator Track
• Traditional Track
• Research Ranks
• Instructor/Lecturer
• Social Work Ranks
• Voluntary Ranks
• Adjunct Ranks
• Other Appt Types
• Appointments
• Reappointments
• Transfer of Track
• Term Extensions
• Timeline for A&P Processes
• Interfolio Faculty Search
• Interfolio A&P Processes
• Yale CV Part 1 (CV1)
• Yale CV Part 2 (CV2)
• Samples of Scholarship
• Teaching Evaluations
• Letters of Evaluation
• Dept A&P Narrative
• A&P Voting
• Faculty Affairs Staff Pages
• OAPD Faculty Workshops
• Leadership & Development Seminars
• List of Faculty Mentors
• Incoming Faculty Orientation
• Faculty Onboarding
• Past YSM Award Recipients
• Past PA Award Recipients
• Past YM Award Recipients
• International Award Recipients
• Nominations Calendar
• OAPD Newsletter
• Fostering a Shared Vision of Professionalism
• Academic Integrity
• Addressing Professionalism Concerns
• Consultation Support for Chairs & Section Chiefs
• Policies & Codes of Conduct
• First Fridays
• Fund for Physician-Scientist Mentorship
• Grant Library
• Grant Writing Course
• Mock Study Section
• Research Paper Writing
• Establishing a Thriving Research Program
• Funding Opportunities
• Join Our Voluntary Faculty
• Child Mental Health: Fostering Wellness in Children
• Faculty Resources
• Research by Keyword
• Research by Department
• Research by Global Location
• Translational Research
• Research Cores & Services
• Program for the Promotion of Interdisciplinary Team Science (POINTS)
• CEnR Steering Committee
• Experiential Learning Subcommittee
• Goals & Objectives
• Issues List
• Print Magazine PDFs
• Print Newsletter PDFs
• YSM Events Newsletter
• Social Media
• Patient Care

INFORMATION FOR

• Residents & Fellows
• Researchers

Finding the Right Approach to Treating Asthma

A q&a with sandra zaeh, sandra zaeh, md.

Sandra Zaeh, MD , is interested in improving clinical outcomes for patients with asthma. In recent research, she found that current guideline-based asthma treatment is implemented less than 15 percent of the time for moderate to severe asthma due to various factors, including a lack of knowledge about the proper treatment approach.

In the next few months, as a newly promoted assistant professor of medicine in the Yale Department of Internal Medicine Section of Pulmonary, Critical Care, and Sleep Medicine, Zaeh will lead the recruitment of subjects from the Yale Center for Asthma and Airways Disease for a study in collaboration with Brigham and Women’s Hospital. Funded by the Patient-Centered Outcomes Research Institute, the study aims to improve the quality of care for patients at risk of asthma attacks.

In an interview, Zaeh discusses the basics of asthma, different approaches to treating the inflammatory condition, and why controlling asthma is of the utmost importance to asthma physicians and pulmonologists.

What is asthma?

Asthma is a chronic lung disease in which the bronchial airways in the lungs get narrowed and swollen, making it difficult to breathe. People with asthma can feel fine for some time, and then a trigger can cause an asthma attack, which can lead to significant health repercussions. Asthma disproportionately affects Black and Latinx people, low-income populations, and other groups.

How does asthma affect quality of life?

Uncontrolled asthma with frequent exacerbations can cause adults to miss days of work and children to miss school. Asthma can impact your ability to breathe on a day-to-day basis. It can lead to hospitalizations, emergency room visits, and, in some cases, fatality.

How is asthma treated?

For the past several decades, the treatment paradigm for asthma has involved control and relief medications. Controller therapy usually includes an inhaled corticosteroid that you take one to two times a day to control your symptoms. You take a reliever therapy between controller doses to minimize asthma symptoms such as cough, shortness of breath, and wheezing. The traditional reliever therapy has been albuterol, a short-acting bronchodilator that quickly opens the airways.

Interestingly, the data now supports a slightly different management strategy. The big update in asthma management is the introduction of anti-inflammatory reliever therapy for asthma. Current guidelines promote the use of the same inhaler for both control and relief for moderate to severe asthma, with a combination of an inhaled steroid and a quick-acting, long-acting beta agonist called formoterol. This approach is called SMART, or Single Maintenance and Reliever Therapy, because one inhaler does the job that two inhalers used to do.

Tell us about your study involving patients at risk of asthma attacks.

Even though SMART is currently guideline-based care, we’re having difficulty implementing this approach in clinical practice. There are similar, alternative approaches that may be better for certain patients. One of those approaches, which will be tested in this study, is PARTICS, or Patient Activated Reliever-Triggered Inhaled CorticoSteroids. Every time PARTICS patients use their albuterol inhaler, they’re asked to use one puff of inhaled steroid. When they use their albuterol nebulizer as a reliever, they're asked to use five puffs of inhaled steroid. It’s different than SMART because the approach uses more than one inhaler and incorporates the use of nebulizers as relievers.

Many people in the U.S. use an albuterol nebulizer as a reliever because they feel it works more effectively. The PARTICS approach incorporates those individuals.

Studied in Black and Latinx patients with moderate to severe asthma a few years ago, PARTICS was shown to reduce severe asthma exacerbations and improve asthma control and quality of life. Our study compares PARTICS to SMART, the current standard of care. The idea of the study is to test to see if the two approaches are equally effective or if one is more effective than the other.

What do you hope to accomplish through this research?

It’s important to have different asthma management approaches that can be used and tailored for each patient based on needs and preferences. For example, PARTICS is perhaps more appropriate than SMART for people who use nebulizers as their reliever. PARTICS may be more effective or better covered by insurance for some people.

Whether PARTICS or SMART, these approaches are the future of asthma management. By studying these different anti-inflammatory reliever approaches, we can improve implementation and use these therapies more efficaciously.

The more options we have to treat asthma, the better.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within Yale School of Medicine’s Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSM's website , or follow them on Facebook and Twitter .

• Internal Medicine
• Pulmonary, Critical Care and Sleep Medicine

Featured in this article

• Sandra Zaeh, MD, MS Instructor

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Open access
• Published: 26 April 2024

How to make Asthma Right Care ‘easy’ in primary care: learnings from the 2023 Asthma Right Care Summit

• Siân Williams 1 ,
• Jaime Correia de Sousa   ORCID: orcid.org/0000-0001-6459-7908 1 , 2 ,
• Ee Ming Khoo   ORCID: orcid.org/0000-0003-3191-1264 1 , 3 ,
• Habib Ghedira 4 , 5 ,
• Vincent Mak 1 , 6 ,
• Mar Martínez Vázquez 7 , 8 ,
• Cláudia Vicente 9 , 10 &
• Darush Attar-Zadeh 1 , 11  

npj Primary Care Respiratory Medicine volume  34 , Article number:  4 ( 2024 ) Cite this article

457 Accesses

2 Altmetric

Metrics details

• Health policy
• Health services
• Patient education
• Respiratory signs and symptoms

Introduction

Asthma affects approximately 262 million people worldwide with an estimated 1000 people dying from asthma attacks each day 1 , 2 . The majority of asthma attacks are preventable and the substantial mortality, morbidity, healthcare utilisation, environmental and economic burden asthma causes are all largely avoidable. Owing to its impact on the individual and society, asthma warrants a biopsychosocial, holistic approach best provided by primary care. However, the lack of universal health coverage and investment in primary care creates preventable harm, inequalities and inequity within and between countries 3 , 4 .

Despite knowledge about how to manage it effectively, asthma is often overlooked as a clinical, health and research priority. Currently, a key problem in asthma management is the over-reliance on episodic care defined as a system-wide over-reliance on symptom relief and rescue. This includes inhaled short-acting β 2 -receptor agonists (SABAs), systemic steroids and the overuse of emergency services and hospitalisation, which may partly be caused by lack of adherence to the appropriate medication and disregard of symptoms by patients.

Since 2019, the Global Initiative for Asthma (GINA) no longer recommends treatment of asthma with SABA monotherapy in adults, adolescents and children over 6 years. For the best outcomes, inhaled corticosteroids (ICS)-containing treatment should be initiated when (or as soon as possible after) asthma is diagnosed. All patients should also be provided with a reliever inhaler for quick symptom relief, preferably an anti-inflammatory reliever (AIR), including ICS-formoterol and ICS-SABA 5 .

In 2017, the International Primary Care Respiratory Group (IPCRG) initiated a social movement, Asthma Right Care, to mobilise stakeholders firstly to acknowledge that problems exist, particularly over-reliance on SABA, and secondly to take responsibility for remedying them 3 . This movement aims to disrupt the current system by demonstrating the scale of the problem, and then build on adult-learning principles, offering problem-based education about right care 6 , 7 , guided by national guidelines and/or GINA.

Making Asthma Right Care ‘easy’ in primary care

To obtain a greater understanding of current asthma management worldwide, a survey (see Supplementary Information) based on the IPCRG’s situational analyses for its Teach the Teacher ® programmes and structured according to IPCRG’s eight person-centred statements ( https://www.ipcrg.org/asthmarightcare/what-does-good-quality-asthma-care-look-like , see Supplementary Information) was sent out as an online form to representatives from 47 countries where IPCRG had active contacts with practising clinicians. There was representation from low-, middle- and high-income countries and, in some cases, there was more than one response from a country where different disciplines were represented, including family medicine, community pharmacy and pulmonology (seeing primary care patients). We received 57 responses from 33 countries: 40/57 from respiratory-interested clinicians working in primary care and 17/57 from respiratory specialists. Following the analysis of responses, on the 9 September 2023, an international summit facilitated by a multinational IPCRG faculty took place in Milan, Italy, called ‘Making Asthma Right Care “easy” in primary care’. IPCRG primary care colleagues familiar with Asthma Right Care were joined by 19 delegates from 13 countries from Asia, Latin America and Africa who had expressed interest in engaging in the movement. Figure 1 highlights the objectives of the summit.

Objectives from the ‘Making Asthma Right Care “easy” in primary care’ summit.

Current asthma management worldwide

The survey responses reported a variation in asthma care, diagnosis and management worldwide—the responses to all questions and representativity from countries are available in the Supplementary Information.

Overall, 47/57 (82%) respondents reported the existence of local or national guidelines for asthma management (Fig. 2 ) and about one third of them considered that these were frequently implemented in practice. Approximately three quarters of the respondents felt that there were no national policies to support the implementation of local/national guidelines.

N =57 respondents from 33 countries, unless otherwise stated. The responses include representation from low- (1/33), lower-middle- (7/33), upper-middle- (12/33) and high- (13/33) income countries, according to the World Bank classification 17 . GINA Global Initiative for Asthma.

Key elements of right care were reported missing in many of the countries (Fig. 3 ). Only approximately a third of respondents noted that asthma inhaler technique training is given always or frequently in their country when a device is prescribed.

N =57 respondents from 33 countries, unless otherwise stated. The responses include representation from low- (1/33), lower-middle- (7/33), upper-middle- (12/33) and high- (13/33) income countries, according to the World Bank classification 17 .

Identifying the key barriers to the delivery of right care

Given time constraints, the meeting mainly focused on asthma management, but diagnostic challenges were also acknowledged as significant. During small-group discussions, delegates considered the drivers and barriers for implementation of right care in their countries. These can be characterised as lack of: (1) education and awareness; (2) capacity and investment in publicly funded healthcare; (3) access to and affordability of medicines; and (4) optimised systems.

There was a strong consensus that improved context-specific asthma education is essential. Some primary care physicians do not consider asthma an important condition that warrants their time to learn about or manage. There is a lack of incentive and of confidence to diagnose asthma in some regions and, in general, confidence and capability in asthma management is too variable to ensure right care for all patients. Family physicians, nurses, pharmacists and patients need to receive better education to recognise when asthma is poorly controlled, to understand the need to treat the underlying inflammation and the risks of over-reliance on SABA monotherapy. Overcoming a lack of disease awareness through education is particularly important in countries where the term ‘asthma’ is not used owing to cultural stigma; alternative incorrect terms such as ‘allergic bronchitis’ contribute to misunderstanding and incorrect treatment. Moreover, appropriate education could facilitate the involvement of people with asthma in their treatment decisions. There is an additional wider need to educate the public and those with the power to influence the public (e.g. journalists, who frequently use wrong inhaler images—for a selection of appropriate images visit: https://www.ipcrg.org/gallery ). Educational interventions should be tailored to different levels of asthma awareness and literacy, and the messages should be framed appropriately; for example, emphasis on patient safety is a key element in clinician education, discussions with health administrators and managers, or when speaking with patient organisations. Teachers with the capability to teach primary care and with the knowledge about right care are needed to lead the improvement.

The lack of capacity, resources and time remain universal issues in primary care. Family physicians and nurses often manage many different health conditions, so chronic respiratory diseases are not always a priority. An insufficient number of skilled professionals (i.e. physicians, nurses, pharmacists) able to diagnose asthma is a major barrier in most countries. This can also lead to pulmonologists feeling overburdened.

Ideally, investment in publicly funded healthcare should be a focus to ensure equal access to diagnostic skills, tools and treatments across sectors. Economic constraints and affordability of asthma treatments are major barriers; many countries lack reimbursement schemes and/or apply prescription charges for treatments. The goal should be for universal health coverage to include evidence-based treatment options for asthma.

Continuity of care is key for successful management of asthma. Where primary care is empowered to deliver asthma care, electronic patient records and systems to invite patients at highest risk for follow-up appointments are essential but are not always available. Effective referral systems and compatible electronic patient records are also vital to achieving optimal patient-centred communication between primary, secondary and tertiary care. Depending on the region, access to secondary care may be restricted or permission from respiratory specialists to initiate or change treatment in primary care may be required, which can delay care and compromise safety. Since SABA is available over the counter or can easily be bought online without a prescription in many countries, patients may bypass medical care and self-manage. Optimising systems could facilitate the implementation of guidelines in clinical practice and ensure the delivery of right care.

Tools to improve asthma care

Social movements mobilise followers by prompting conversations that raise awareness of the problem and seek solutions 8 . In small groups divided by region and language and facilitated by IPCRG, the delegates reviewed three Asthma Right Care tools that the IPCRG has developed to facilitate these conversations (Fig. 4 ). All three tools can be used in clinical practice and also clinical education settings to start conversations that begin to shift perceptions about either a problem or the potential solutions 9 .

a Asthma SABA slide rule; b ‘Question and challenge’ cards; c Reliever Reliance Test. IPCRG. Asthma Right Care Key Resources. Available at: https://www.ipcrg.org/asthmarightcare/asthma-right-care-key-resources (Accessed February 2024). IPCRG International Primary Care Respiratory Group, SABA short-acting β 2 -receptor agonist.

(a) Asthma SABA slide rule : invites the user to explore how many puffs (as opposed to doses) of SABA inhaler are being used compared with the international guideline advice. Inspired by the Readiness Ruler, on the reverse are a visual analogue scale and Motivational Interviewing questions exploring the importance of requesting a review and confidence to have conversations with healthcare professionals 3 .

(b) ‘Question and challenge’ cards : useful cards for icebreakers, discussion fora and social media, inspired by the ‘Whose Shoes’ game 3 ( http://nutshellcomms.co.uk/ ).

(c) Reliever Reliance Test : a self-administered test based on the Beliefs About Medicines Questionnaire 10 and SABA Reliance Questionnaire, co-developed with behavioural scientists, which aims to identify patients at risk of over-reliance on SABA medication and elicit their beliefs 11 .

Since 2017, IPCRG Asthma Right Care country programmes have tested these tools in multiple settings, adapting them in context. More recently, additional tools have also been co-developed and can be shared to help drive change 12 .

Initiatives to improve asthma care

In addition to reviewing the tools, summit delegates considered the feasibility of adapting several success stories in their countries.

Three-step AIR Treatment Guideline in New Zealand 13

In 2020, New Zealand national asthma guidelines, which had strong primary care involvement, recommended AIR therapy as the preferred management approach (Fig. 5 ). The guidelines were launched with a structured communication plan for wide distribution and encouragement for implementation in practice. A recently published evaluation of the impact of these guidelines identified a significant increase in the dispensing of ICS–formoterol and a reduction in the dispensing of SABA inhalers since the release of the recommendations 14 . This evidence suggests that widespread transition to AIR therapy regimens as recommended by GINA could be achieved if recommended in national asthma guidelines, jointly developed and endorsed as the preferred therapeutic approach by primary and secondary care, and supported by optimised systems for access to medicines and appropriate clinician reimbursement. It is also important to consider the patients’ preference as it will likely impact their adherence to the medication.

Reproduced with permission from: Asthma and Respiratory Foundation NZ, New Zealand Adolescent and Adult Asthma Guidelines 2020 13 . AIR anti-inflammatory reliever.

Taking advantage of teachable moments in Spain

In Spain, community pharmacist capability and confidence have been improved through a Teach the Teacher ® 15 programme led by IPCRG-taught pharmacists and family physician teachers. This recognises the opportunity for community pharmacists when a SABA inhaler is requested over the counter to take advantage of the teachable moment that it might offer. Strong relationships among patients, family physicians and community pharmacists have been developed to change the asthma pathway, moving away from providing SABA canisters on demand over the counter in pharmacies to using Asthma Right Care tools with individuals, offering advice about right care and prompting those with poorly controlled asthma to visit their family physician for review 16 . This approach resulted in 500,000 fewer SABA canisters sold in 2020 compared with 2018.

Patient and public engagement in Portugal

In Portugal, creative bottom-up approaches to patient and public engagement have been used. To date, more than 50 organised walks and talks (‘Caminhasma’, meaning ‘walk with asthma’) planned by primary care physicians, nurses and community pharmacists involving almost 4000 people within their communities, have taken place to improve asthma literacy and awareness. Subsequently, the initiative has been replicated in Brazil. Also, the Asthma Right Care (known as ‘CAPA’) team has co-created a teaching film and delivered a series of television interviews for a health channel, as well as clinical webinars. A new campaign aimed at adolescents with a video promoting a game between the viewers to teach about asthma is being developed in partnership with the Ministry of Education of Portugal.

Draft national asthma law in Argentina

In Argentina, respiratory-interested clinicians have advocated to the national senate for an asthma law to allow equal access to care for every person with asthma. They have separately worked with colleagues in other specialities to raise awareness about specific at-risk groups such as pregnant women who, according to an unpublished national survey, often stop taking their asthma prescription during pregnancy.

Asthma lexicon in Tunisia

In Tunisia, a multidisciplinary Asthma Right Care steering group prioritised a SABA overuse awareness programme in community pharmacies supported by the Pharmacists Union and the Private Physicians Union. The programme was presented to the Minister of Health who encouraged the initiative. IPCRG’s tools, such as the Reliever Reliance Test and Asthma Slide Rule, were translated to Tunisian dialect to support the nationwide programme. The group also developed a lexicon of Tunisian dialect’s usual asthma and allergy words with their translation in French and English. This lexicon ensures that the terminology used in communication becomes more consistent across the healthcare system.

Many other success stories are emerging, demonstrating the value of bottom-up approaches that engage primary care and patients in highlighting the problem of episodic care and then taking responsibility to address it through education and advocacy for system change.

Nine statements to improve respiratory care

The delegates were shown and supported nine key actions to improve respiratory care that IPCRG and the World Organization of Family Doctors (WONCA) Europe agreed at the 2023 WONCA Council meeting (see Fig. 6 ).

IPCRG International Primary Care Respiratory Group, WONCA World Organization of Family Doctors.

Conclusions

Currently, no universal approach exists to tackle the obstacles to right care in asthma, but the Asthma Right Care movement has demonstrated that change is possible with leadership, teamwork, community involvement and commitment. There are a number of tools available that can be used and adapted considering local contexts. To achieve large-scale improvements, context-specific strategies that engage as many parts of the healthcare system in as many geographic areas as possible, are needed; the aim is for improved awareness and behaviour change. At the end of the summit, it was agreed that to generate and sustain change every country needs ‘Asthma Right Care champions’ passionate about engaging all stakeholders using Asthma Right Care tools. The IPCRG commits to building these champions’ capacity to advocate for and lead change, and to teach their peers through IPCRG Teach the Teacher © cascade models 15 .

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability

All data supporting the findings presented in this manuscript are available within the paper and its Supplementary Information.

World Health Organization. Asthma. WHO newsroom. Fact sheets. https://www.who.int/news-room/fact-sheets/detail/asthma (2023).

Global Asthma Network. Global Asthma Report 2022. http://globalasthmanetwork.org/Global_Asthma_Report_2022.pdf (2022).

Williams, S. Asthma Right Care: what will you commit to? J. Gen. Pract. Nurs. 7 , 12 (2021).

Google Scholar  

Williams, S. et al. Respiratory research funding is inadequate, inequitable, and a missed opportunity. Lancet Respir. Med. 8 , e67 (2020).

Article   CAS   PubMed   PubMed Central   Google Scholar  

GINA. Global strategy for asthma management and prevention; updated 2023. https://www.ginasthma.org (2023).

Saini, V. Right Care Series: The Lancet. https://www.thelancet.com/series/right-care (2017).

Tsiligianni, I., Christodoulakis, A. & Williams, S. Improving primary healthcare education through lessons from a flock of birds. NPJ Prim. Care Respir. Med. 33 , 22 (2023).

Article   Google Scholar  

Nesta. We change the world report. https://media.nesta.org.uk/documents/we_change_the_world_report.pdf (2023).

Boghossian, P. & Lindsay, J. How to have impossible conversations: a very practical guide. First. Life long; 2019. Conversational leadership. https://conversational-leadership.net/ (2019).

Horne, R., Weinman, J. & Hankins, M. The Beliefs about Medicines Questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychol. Health 14 , 1 (1999).

Chan, A. H. Y. et al. SABA Reliance Questionnaire (SRQ): identifying patient beliefs underpinning reliever overreliance in asthma. J. Allergy Clin. Immunol. Pract. 8 , 3482.e1–3489.e1 (2020).

The International Primary Care Respiratory Group. Asthma Right Care key resources. https://www.ipcrg.org/asthmarightcare/asthma-right-care-key-resources (2023).

Beasley, R. et al. Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines 2020: a quick reference guide. NZ Med. J. 133 , 73 (2020).

Hatter, L. et al. Patterns of asthma medication use in New Zealand after publication of National Asthma Guidelines. J. Allergy Clin. Immunol. Pract. 11 , 2757.e5–2764.e5 (2023).

The International Primary Care Respiratory Group. Teach the teacher. https://www.ipcrg.org/projects/education/teach-the-teacher (2023).

Grupo de Respiratorio en Atención primaria (GRAP), Sociedad Española de Farmacia Clinica, Familiar y Comunitaria (SEFAC), International Primary Care Respiratory Group (IPCRG) & Local Spanish Colleges of Pharmacists. How Spanish pharmacists have improved their role in asthma management from supplying SABA without restriction to prescription-only dispensing. https://www.ipcrg.org/resources/search-resources/how-spanish-pharmacists-have-improved-their-role-in-asthma-management (2021).

World Bank. World Bank country and lending groups. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups (2024).

Download references

Acknowledgements

The authors acknowledge 3 Stories High, UK, for medical writing support, which was funded by AstraZeneca. IPCRG received funding from AstraZeneca to develop the Asthma Right Care initiative. IPCRG would like to thank all the IPCRG member countries who participated in the survey. For further information on the survey and participants, please see Supplementary Information.

Author information

Authors and affiliations.

International Primary Care Respiratory Group, London, UK

Siân Williams, Jaime Correia de Sousa, Ee Ming Khoo, Vincent Mak & Darush Attar-Zadeh

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

Jaime Correia de Sousa

Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

Ee Ming Khoo

Pulmonologist, Lac II, Tunis, Tunisia

Habib Ghedira

International Primary Care Respiratory Group, Tunis, Tunisia

Imperial College Healthcare National Health Service Trust, London, UK

Vincent Mak

Zorroza Primary Care Unit, Bilbao, Spain

Mar Martínez Vázquez

International Primary Care Respiratory Group, Bilbao, Spain

Araceti Family Health Unit, Coimbra, Portugal

Cláudia Vicente

International Primary Care Respiratory Group, Coimbra, Portugal

National Health Service North West London Integrated Care Board, London, UK

Darush Attar-Zadeh

You can also search for this author in PubMed   Google Scholar

Contributions

S.W. was responsible for conceptualisation, methodology, supervision, validation and writing of the original draft. S.W. and E.M.K. drafted the questionnaire. S.W., J.C.S., E.M.K., H.G., V.M., M.M.V., C.V. and D.A.-Z. contributed equally to the design of the workshop, writing and reviewing of the final manuscript.

Corresponding author

Correspondence to Siân Williams .

Ethics declarations

Competing interests.

S.W. is the CEO of IPCRG. IPCRG reports educational grants from GSK, AstraZeneca, Boehringer Ingelheim and membership subscription from Vitalograph, as well as current research grants from RESPIRE and UK Research and Innovation (FRESHAIR4Life). J.C.d.S. reports grant funding to his institution from AstraZeneca and GSK, and advisory board and consulting fees paid to him from Boehringer Ingelheim, GSK, AstraZeneca, Bial and Medinfar. He also received payment for lectures from GSK, AstraZeneca and Sanofi Pasteur; support for attending meetings from Mundipharma and Mylan; and has a leadership role at IPCRG. E.M.K. reports grants from the National Institute for Health and Care Research Global Health Research Unit on Respiratory Health (RESPIRE); personal fees from AstraZeneca; and is the President of the IPCRG and the Primary Care Respiratory Group Malaysia. H.G. reports advisory board and lecture honoraria from AstraZeneca, Sanofi, Boehringer Ingelheim and travel bursary from Recordati. V.M. reports lecture/advisory board honoraria and travel bursaries from Chiesi and AstraZeneca. M.M.V. reports advisory board honoraria, lecture honoraria and travel bursary from AstraZeneca, Gebro and Menarini. C.V. is the GRESP coordinator in Portugal, the secretary in group 01.03 of ERS and has a leadership role at IPCRG. C.V. reports advisory board honoraria and lecture honoraria from AstraZeneca, GSK, Pfizer, Viatris and Medinfar. D.A.-Z. reports advisory board honoraria/lecture honoraria/travel bursary from AstraZeneca, Boehringer Ingelheim, Chiesi, Clement Clarke International, GSK, Janssen-Cilag, Orion, Pfizer and Trudell Medical.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information, reporting summary, rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Williams, S., Correia de Sousa, J., Khoo, E.M. et al. How to make Asthma Right Care ‘easy’ in primary care: learnings from the 2023 Asthma Right Care Summit. npj Prim. Care Respir. Med. 34 , 4 (2024). https://doi.org/10.1038/s41533-024-00366-x

Download citation

Received : 18 December 2023

Accepted : 10 April 2024

Published : 26 April 2024

DOI : https://doi.org/10.1038/s41533-024-00366-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

May 10, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

reputable news agency

Could better inhalers help patients, and the planet?

by Martha Bebinger, WBUR, KFF Health News

Miguel Divo, a lung specialist at Brigham and Women's Hospital in Boston, sits in an exam room across from Joel Rubinstein, who has asthma. Rubinstein, a retired psychiatrist, is about to get a checkup and hear a surprising pitch—for the planet, as well as his health.

Divo explains that boot-shaped inhalers, which represent nearly 90% of the U.S. market for asthma medication , save lives but also contribute to climate change . Each puff from an inhaler releases a hydrofluorocarbon gas that is 1,430 to 3,000 times as powerful as the most commonly known greenhouse gas, carbon dioxide.

"That absolutely never occurred to me," said Rubinstein. "Especially, I mean, these are little, teeny things."

So Divo has begun offering a more eco-friendly option to some patients with asthma and other lung diseases: a plastic, gray cylinder about the size and shape of a hockey puck that contains powdered medicine. Patients suck the powder into their lungs—no puff of gas required and no greenhouse gas emissions.

"You have the same medications, two different delivery systems," Divo said.

Patients in the United States are prescribed roughly 144 million of what doctors call metered-dose inhalers each year, according to the most recently available data published in 2020. The cumulative amount of gas released is the equivalent of driving half a million gas-powered cars for a year. So, the benefits of moving to dry powder inhalers from gas inhalers could add up.

Hydrofluorocarbon gas contributes to climate change, which is creating more wildfire smoke, other types of air pollution, and longer allergy seasons. These conditions can make breathing more difficult—especially for people with asthma and chronic obstructive pulmonary disease , or COPD—and increase the use of inhalers.

Divo is one of a small but growing number of U.S. physicians determined to reverse what they see as an unhealthy cycle.

"There is only one planet and one human race," Divo said. "We are creating our own problems and we need to do something."

So Divo is working with patients like Rubinstein who may be willing to switch to dry powder inhalers. Rubinstein said no to the idea at first because the powder inhaler would have been more expensive. Then his insurer increased the copay on the metered-dose inhaler so Rubinstein decided to try the dry powder.

"For me, price is a big thing," said Rubinstein, who has tracked health care and pharmaceutical spending in his professional roles for years. Inhaling the medicine using more of his own lung power was an adjustment. "The powder is a very strange thing, to blow powder into your mouth and lungs."

But for Rubinstein, the new inhaler works and his asthma is under control. A recent study found that some patients in the United Kingdom who use dry powder inhalers have better asthma control while reducing greenhouse gas emissions. In Sweden, where the vast majority of patients use dry powder inhalers, rates of severe asthma are lower than in the United States.

Rubinstein is one of a small number of U.S. patients who have made the transition. Divo said that, for a variety of reasons, only about a quarter of his patients even consider switching. Dry powder inhalers are often more expensive than gas propellant inhalers. For some, dry powder isn't a good option because not all asthma or COPD sufferers can get their medications in this form. And dry powder inhalers aren't recommended for young children or elderly patients with diminished lung strength.

Also, some patients using dry powder inhalers worry that without the noise from the spray, they may not be receiving the proper dose. Other patients don't like the taste powder inhalers can leave in their mouths.

Divo said his priority is making sure patients have an inhaler they are comfortable using and that they can afford. But, when appropriate, he'll keep offering the dry powder option.

Advocacy groups for asthma and COPD patients support more conversations about the connection between inhalers and climate change.

"The climate crisis makes these individuals have a higher risk of exacerbation and worsening disease," said Albert Rizzo, chief medical officer of the American Lung Association. "We don't want medications to contribute to that."

Rizzo said there is work being done to make metered-dose inhalers more climate-friendly. The United States and many other countries are phasing down the use of hydrofluorocarbons, which are also used in refrigerators and air conditioners. It's part of the global attempt to avoid the worst possible impacts of climate change. But inhaler manufacturers are largely exempt from those requirements and can continue to use the gases while they explore new options.

Some leading inhaler manufacturers have pledged to produce canisters with less potent greenhouse gases and to submit them for regulatory review by next year. It's not clear when these inhalers might be available in pharmacies. Separately, the FDA is spending about $6 million on a study about the challenges of developing inhalers with a smaller carbon footprint.

Rizzo and other lung specialists worry these changes will translate into higher prices. That's what happened in the early to mid-2000s when ozone-depleting chlorofluorocarbons (CFCs) were phased out of inhalers. Manufacturers changed the gas in metered-dose inhalers and the cost to patients nearly doubled. Today, many of those re-engineered inhalers remain expensive.

William Feldman, a pulmonologist and health policy researcher at Brigham and Women's Hospital, said these dramatic price increases occur because manufacturers register updated inhalers as new products, even though they deliver medications already on the market. The manufacturers are then awarded patents, which prevent the production of competing generic medications for decades. The Federal Trade Commission says it is cracking down on this practice.

After the CFC ban, "manufacturers earned billions of dollars from the inhalers," Feldman said of the re-engineered inhalers.

When inhaler costs went up, physicians say, patients cut back on puffs and suffered more asthma attacks. Gregg Furie, medical director for climate and sustainability at Brigham and Women's Hospital, is worried that's about to happen again.

"While these new propellants are potentially a real positive development, there's also a significant risk that we're going to see patients and payers face significant cost hikes," Furie said.

Some of the largest inhaler manufacturers, including GSK, are already under scrutiny for allegedly inflating prices in the United States. Sydney Dodson-Nease told NPR and KFF Health News that the company has a strong record for keeping medicines accessible to patients but that it's too early to comment on the price of the more environmentally sensitive inhalers the company is developing.

Developing affordable, effective, and climate-friendly inhalers will be important for hospitals as well as patients. The Agency for Healthcare Research and Quality recommends that hospitals looking to shrink their carbon footprint reduce inhaler emissions. Some hospital administrators see switching inhalers as low-hanging fruit on the list of climate-change improvements a hospital might make.

But Brian Chesebro, medical director of environmental stewardship at Providence, a hospital network in Oregon, said, "It's not as easy as swapping inhalers."

Chesebro said that even among metered-dose inhalers, the climate impact varies. So pharmacists should suggest the inhalers with the fewest greenhouse gas emissions. Insurers should also adjust reimbursements to favor climate-friendly alternatives, he said, and regulators could consider emissions when reviewing hospital performance.

Samantha Green, a family physician in Toronto, said clinicians can make a big difference with inhaler emissions by starting with the question: Does the patient in front of me really need one?

Green, who works on a project to make inhalers more environmentally sustainable, said that research shows a third of adults diagnosed with asthma may not have the disease.

"So that's an easy place to start," Green said. "Make sure the patient prescribed an inhaler is actually benefiting from it."

Green said educating patients has a measurable effect. In her experience, patients are moved to learn that emissions from the approximately 200 puffs in one inhaler are equivalent to driving about 100 miles in a gas-powered car. Some researchers say switching to dry powder inhalers may be as beneficial for the climate as a patient adopting a vegetarian diet.

One of the hospitals in Green's health care network, St. Joseph's Health Center, found that talking to patients about inhalers led to a significant decrease in the use of metered-dose devices. Over six months, the hospital went from 70% of patients using the puffers, to 30%.

Green said patients who switched to dry powder inhalers have largely stuck with them and appreciate using a device that is less likely to exacerbate environmental conditions that inflame asthma.

2024 Kaiser Health News. Distributed by Tribune Content Agency, LLC.

Explore further

Feedback to editors

Study traces an infectious language epidemic

5 hours ago

Visual experiences unique to early infancy provide building blocks of human vision, study finds

15 hours ago

Study points to personalized treatment opportunities for glioblastoma

Research team introduces new tool to boost battle against childhood undernutrition

16 hours ago

How herpes hijacks a ride into cells

17 hours ago

How the brain is flexible enough for a complex world, without being thrown into chaos

Researchers create AI model to understand how brain activity relates to illness

Study reveals need to review temperature control measures in hospitals to manage Legionella

'What was that?' How brains convert sounds to actions

18 hours ago

ERR-gamma 'trains' stomach stem cells to become acid-producing cells

Related stories.

Mayo Clinic Minute: How to use an asthma inhaler

Jun 27, 2023

Switch to dry powder inhaler more than halves carbon footprint of asthma treatment

Feb 4, 2022

Switching to 'green' inhalers could reduce carbon emissions and cut costs

Oct 29, 2019

Asthma meds have become shockingly unaffordable—but relief may be on the way

Mar 8, 2024

Regulatory, patent reform needed for inhalers for asthma, COPD

May 21, 2022

Another coronavirus health threat: Too few asthma inhalers

Mar 31, 2020

Recommended for you

Using MRI, engineers have found a way to detect light deep in the brain

19 hours ago

Unobtrusive, implantable device could deepen our understanding of behavioral responses

Flicker stimulation shines in clinical trial for epilepsy

20 hours ago

Scientists make progress on new charged particle therapy for cancer

'Smart' contact lenses could someday enable wireless glaucoma detection

May 9, 2024

New treatment could reverse hair loss caused by autoimmune skin disease alopecia areata

Let us know if there is a problem with our content.

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

ORIGINAL RESEARCH article

Functional connectivity alterations in the thalamus among patients with bronchial asthma.

• 1 Jiangxi Medical College, Nanchang University, Nanchang, China
• 2 Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
• 3 Department of Ophthalmology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China

Objective: Bronchial Asthma (BA) is a common chronic respiratory disease worldwide. Earlier research has demonstrated abnormal functional connectivity (FC) in multiple cognition-related cortices in asthma patients. The thalamus (Thal) serves as a relay center for transmitting sensory signals, yet the modifications in the thalamic FC among individuals with asthma remain uncertain. This research employed the resting-state functional connectivity (rsFC) approach to explore alterations in thalamic functional connectivity among individuals with BA.

Patients and methods: After excluding participants who did not meet the criteria, this study finally included 31 patients with BA, with a gender distribution of 16 males and 15 females. Subsequently, we recruited 31 healthy control participants (HC) matched for age, gender, and educational background. All participants underwent the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale (HAMD) assessment. Following this, both groups underwent head magnetic resonance imaging scans, and resting-state functional magnetic resonance imaging (rs-fMRI) data was collected. Based on the AAL (Automated Anatomical Labeling) template, the bilateral thalamic regions were used as seed points (ROI) for subsequent rsFC research. Pearson correlation analysis was used to explore the relationship between thalamic functional connectivity and neuropsychological scales in both groups. After controlling for potential confounding factors such as age, gender, intelligence, and emotional level, a two-sample t-test was further used to explore differences in thalamic functional connectivity between the two groups of participants.

Result: Compared to the HC group, the BA group demonstrated heightened functional connectivity (FC) between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Concurrently, there was a decrease in FC with both the Lentiform Nucleus (LN) and the left corpus callosum (CC). Performing FC analysis with the right thalamus as the Region of Interest (ROI) revealed an increase in FC between the right thalamus and the right SFG as well as the left CPL. Conversely, a decrease in FC was observed between the right thalamus and the right LN as well as the left CC.

Conclusion: In our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit aberrant alterations in FC between the thalamus and various brain areas connected to vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the advancement of BA.

Introduction

Asthma is a condition marked by recurrent wheezing, breathlessness, and coughing. Over 400 million individuals across the globe are affected by asthma. Currently, asthma affects 6.3% of the youth population in China ( 1 ). Previous research on the pathological mechanisms of asthma has primarily focused on airway inflammation and airway remodeling ( 2 ). However, peripheral inflammatory substances can also impact the central nervous system via various pathways ( 3 ). In a prior study, brain MRI scans revealed abnormal changes in the brains of asthma patients ( 4 ). Furthermore, markers associated with central nervous degeneration and neuroinflammation have been detected in the blood of asthma patients, suggesting potential consequences of asthma on the central nervous system ( 5 ).

The mechanisms through which asthma affects the central nervous system are not yet fully understood. However, it is currently believed that the long-term chronic hypoxia induced by asthma may initiate and exacerbate certain pathophysiological processes, such as reduced perfusion, endothelial dysfunction, and neuroinflammation. In addition to these factors, chemotactic factors produced by airway inflammation can directly traverse the blood–brain barrier, leading to increased release of reactive oxygen species by microglial cells, inducing neuronal apoptosis ( 6 ). A recent study found that allergens can reduce communication activity between the amygdala and the respiratory control cortex, exacerbating respiratory difficulties ( 7 ). Furthermore, asthma exhibits an overall suppression of the HPA axis, and long-term corticosteroid use also inhibits the HPA axis. This alteration is associated with a reduction in hippocampal volume, thereby impacting working memory ( 8 ). Additionally, asthma-related nocturnal sleep disturbances are associated with poorer cognitive function ( 9 ). Inherent difficulties in respiratory regulation, cognitive deficits, and emotional control disturbances all contribute to the duration and severity of asthma attacks.

When neuronal metabolic activity is ongoing, local changes in cerebral oxygen content and blood supply occur. fMRI is capable of detecting magnetic field fluctuations resulting from the mismatch between local oxygen consumption and cerebral blood flow in various brain areas, thereby reflecting the metabolic activity of brain areas. Rs-fMRI has increasingly been employed to investigate brain activity alterations in BA patients. Li et al. ( 10 ) found abnormal activity in the angular gyrus, prefrontal cortex, temporal gyrus, superior frontal gyrus, and occipital lobe when using fMRI to analyze brain region activity and neural networks in asthma patients. Ritz et al. ( 11 ) conducted an fMRI study on individuals with poorly controlled asthma and found increased activation in their dorsal anterior cingulate cortex (dACC). A study revealed abnormalities in these metrics in the frontal and superior lobes of the brains of asthmatic children, closely associated with attention deficits ( 12 ). Most of these studies focus on regional activity in the asthmatic brain cortex or changes in connectivity at the network level. In previous research, we found a substantial reduction in bilateral thalamic connectivity in asthma individuals ( 13 ). On the other hand, recent research has revealed an inverse relationship between the length of time an individual has had asthma, the level of asthma management, and the frequency of asthma attacks and the volume of the thalamus ( 14 ).

The thalamus is often described as an intermediary station for sensory information, playing a pivotal role in not only transmitting sensory input but also participating in cognitive processes. Additionally, it exerts significant control over visceral functions, motor coordination, and the maintenance of cerebral arousal ( 15 ). The thalamus acts as a gatekeeper for information directed to the cerebral cortex, selectively enhancing or inhibiting the activation of specific information pathways based on the behavioral state ( 16 ). With extensive and global connections to numerous brain regions, the thalamus and its constituent nuclei are likely major hubs within multiple brain networks ( 17 ). Consequently, conducting a comprehensive investigation into the functional connections between the thalamus and various other cerebral areas is deemed essential. The rs-FC primarily assesses the statistical associations among signals throughout the entire brain and particular brain areas, demonstrating the potential for exploring how different brain regions coordinate their operations. In this study, we will be the first to employ rs-FC to uncover evidence of abnormal functional connections within the thalamus in asthma patients. We hypothesize that thalamic FC differs from that of the healthy population, and this difference may be implicated in potential neurobiological mechanisms underlying cognitive impairments and emotional dysregulation in asthma patients.

Materials and methods

Clinical data.

The criteria for selecting asthma subjects are as follows: (1) Adults under the age of 60; (2) presence of recurrent wheezing, with the forced expiratory volume in 1 s (FEV1) falling between 45 and 80% of the predicted normal value; (3) a positive bronchodilator test (FEV1 reversibility of at least 12% and 200 mL after the administration of 200 to 400 μg of salbutamol sulfate); and (4) individuals in a non-acute phase of asthma.

The criteria that are not suitable for the research object are as follows: (1) The presence of other respiratory system diseases; (2) Psychiatric disorders or other chronic diseases that may affect brain structure and function; (3) Drug dependence or adverse habits; (4) Lack of necessary MRI data or clinical assessment information; (5) Maximum head displacement exceeding 2.5 mm in the x, y, and/or z directions, or angle rotation exceeding 2.5 degrees around any axis; (6) Contraindications related to MRI examinations; (7) Absence of claustrophobia and the ability to tolerate MRI examinations. In the end, a total of 31 patients diagnosed with BA participated, comprising 16 males and 15 females. Simultaneously, We selected 31 HCs (16males and 15 females) with basic information matching.

The situations in HCs that are inappropriate for participation are as follows: (1) Presence of asthma or other diseases; (2) Brain or psychological disorders; (3) Completing an MRI examination carries risks; (4) Maximum head displacement exceeding 2.5 mm in the x, y, and/or z directions, or angle rotation exceeding 2.5 degrees around any axis; (5) Incomplete relevant data.

Neuropsychological assessment

To ensure the reliability of the measured results, we employed the Montreal Cognitive Assessment (MoCA) scale as a cognitive function measurement tool. The maximum score on the scale is 30 points, with an additional point given if the participant has an education level of ≤12 years. Scores between 18 and 26 indicate mild cognitive impairment (MCI) ( 18 ). Furthermore, we utilized the 17-item Hamilton Depression Rating Scale (HAMD-17) to evaluate the emotional status of the two groups of participants ( 19 ). The test results from this scale will provide a basis for analyzing cognitive and emotional differences among the subjects.

fMRI data acquisition

Utilizing an 8-channel phased-array head coil, we acquired MRI data employing the Trio 3-Tesla MR scanner from Siemens, Germany. Participants were instructed to remain awake but refrain from engaging in any cognitive activities. Head motion was minimized using a foam cushion, and noise interference was mitigated through the use of earplugs. The parameters for obtaining fMRI images are shown in Table 1 .

Table 1 . Magnetic resonance imaging acquisition parameters.

Data preprocessing

To begin, we validated the quality of the MRI data using the MRIcro software package (Montreal Neurological Institute, Canada) and excluded those with poor quality. Subsequently, we employed the DPABI V5.0 toolbox for brain imaging data processing and analysis to preprocess the fMRI data. This toolbox operates on the MatLab 2018b platform (Mathworks, Natick, MA, United States). We perform data preprocessing, including the following steps: (1) Converted the DICOM (Digital Imaging and Communications in Medicine) format to the NIFTI (Neuroimaging Informatics Technology Initiative) format (2) Discarding the first 10 time records (3) Correction of temporal differences between slices (4) Correction of head motion exceeding 2 millimeters or 2 degrees (5) Alignment and division of functional and structural images, normalized to the standard space, with Resampling to 3 mm x 3 mm x 3 mm Voxel Units (6) An isotropic Gaussian kernel with a Full-Width at Half-Maximum (FWHM) value of 6 mm was applied for spatial smoothing. Temporal filtering in the frequency range of 0.01–0.08 Hz was used to address linear drift (7) The regression covariates included the Friston-24 head motion parameters, as well as white matter, cerebrospinal fluid, and scale scores.

Functional connectivity analysis based on seed regions

To begin, we adopted a cubic size of 6 × 6 × 6 mm for the bilateral thalamus, designated as our region of interest (ROI). This choice ensured thorough coverage of critical thalamic regions while mitigating biases associated with oversized or undersized ROIs. Next, we established the thalamic ROI in the standardized MNI (Montreal Neurological Institute) space using the AAL (Automated Anatomical Labeling) template. This template, offering detailed anatomical partitioning of the brain, facilitated the creation of a uniform reference framework for consistent cross-individual comparisons. Subsequently, we employed affine transformation and non-linear transformation via SPM (Statistical Parametric Mapping) software to accurately map the ROI to individual subject space. This step was essential for accommodating anatomical variability across individuals and ensuring the precision of functional connectivity analyses. Once the thalamic ROI was accurately defined and mapped, we computed Pearson correlation coefficients between the bilateral thalamus and every voxel in the entire brain. These correlation coefficients underwent Fisher’s Z transformation to approximate a normal distribution. The resulting Z values represented the strength of functional connectivity, offering a quantitative assessment of the functional interactions between the thalamus and the broader brain network.

Statistical analysis

We conducted statistical analyses using SPSS 27 software, and continuous data were presented as means ± standard deviations. Group comparisons for age, level of education, and BMI were performed using independent sample t-tests. Additionally, a one-way ANOVA was conducted to compare the scores of psychological assessments and cognitive functions, adjusting for the effects of age, gender, and educational level. After controlling for potential confounders such as age, gender, intelligence, and emotional level, a two-sample t-test was further employed to explore the differences in thalamic functional connectivity between the two groups of participants. Subsequently, the DPABI software was employed to analyze intergroup differences while considering age, education level, and head motion as covariates. Utilizing AlphaSim for correction, p < 0.05. Finally, the xjView software was utilized to report the locations of brain regions with significant functional connectivity.

Demographic statistics and clinical scales

In our investigation, there were no notable disparities in terms of age, gender, body weight, or BMI between the BA patients and HCs ( p > 0.05). The findings are displayed as the mean value with its corresponding standard deviation (SD). The duration of asthma in our study was observed to be 24.12 years, with a standard deviation of 4.61 years. The HAMD scores for the BA group and the HC group are 8.13 ± 2.39 and 4.74 ± 1.77, respectively, while the MoCA scores for the BA group and the HC group are 25.52 ± 1.93 and 27.55 ± 1.34, respectively. The BA group shows mild cognitive impairment and emotional changes. Please refer to Table 2 for detailed results.

Table 2 . Demographics and clinical measurements by group.

Differences in resting-state functional connectivity between the two groups

The results of inter-group rs-FC comparisons based on bilateral thalamic seed regions and voxels from other brain areas are presented in Table 3 . In comparison to the HC group, the BA group exhibited increased FC between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Simultaneously, it demonstrated decreased FC with both the lentiform nucleus (LN) and the left corpus callosum (CC). The right thalamus showed increased FC with the right SFG and the left CPL, while FC with the right LN and the left CC decreased. The anatomical locations, voxel sizes, and corresponding MNI peak coordinates of differential brain regions between the two groups are detailed in Table 3 . Figures 1 , 2 depict the brain regions where notable alterations in bilateral thalamic rs-FC were observed in both groups.

Table 3 . Differences in FC with the thalamus were observed in brain regions between two groups.

Figure 1 . Spatial distribution maps of functional connectivity (FC) in the brain regions of the bronchial asthma group (A) and the healthy control group (B) , based on the seed point of the left thalamus. (C, D) The brain regions where there are significant differences in FC between the two groups (with a voxel-level p -value less than 0.05, corrected using AlphaSim). Color bars indicate t-scores; cool colors indicate regions in BA with lower FC values compared to HC, while warm colors indicate the opposite.

Figure 2 . Spatial distribution maps of functional connectivity (FC) in the brain regions of the bronchial asthma group (A) and the healthy control group (B) , based on the seed point of the right thalamus. (C, D) The brain regions where there are significant differences in FC between the two groups (with a voxel-level p -value less than 0.05, corrected using AlphaSim). Color bars indicate t-scores; cool colors indicate areas in BA with lower FC values compared to HC, while warm colors indicate the opposite.

Correlation analysis

Partial correlation analysis revealed a negative correlation between the FC values of the left thalamus (L-Thal) and right superior frontal gyrus (R-SFG) in the BA group and MoCA scores (r = −0.7437, p < 0.0001, Figure 3A ), as well as a positive correlation with HAMD scores (r = 0.7232, p < 0.0001, Figure 3C ). Furthermore, the FC values of L-Thal and left cerebellar posterior lobe (L-CPL) showed a negative correlation with MoCA scores (r = −0.6701, p < 0.0001, Figure 3B ) and a positive correlation with HAMD scores (r = 0.7449, p < 0.0001, Figure 3D ). The FC values between the bilateral thalamus and other differential brain regions did not show significant correlations with neuro-psychological measurement assessments.

Figure 3 . Correlation between inter-group differential brain regions based on thalamus functional connectivity analysis and scores on neuro-psychological assessment scales. The vertical axis represents the functional connectivity (FC) values, while the horizontal axis corresponds to the scores on the neuro-psychological assessment scales. MoCA, Montreal Cognitive Assessment; HAMD, Hamilton Depression; Thal, thalamus; SFG, superior frontal gyrus; CPL, cerebellar posterior lobe; L for Left; R for Right.

Previous research has found a significant decrease in voxel-mirrored homotopic connectivity (VMHC) between the bilateral thalamus in asthma patients, reflecting specific changes in internal information exchange, integration, and coordination within the thalamus ( 13 ). However, unlike discussions on functional changes between homologous regions of the bilateral thalamus with VMHC, functional connectivity (FC) analysis focuses more on alterations in the interaction between the thalamus as a key relay station and different brain regions ( 20 , 21 ). This study is the first to look into rs-FC in BA patients between the thalamus and other brain areas. The principal discoveries of this study demonstrate that individuals with asthma show extensive FC deficiencies in multiple brain regions associated with emotion regulation, cognitive control, somatic sensation, arousal, visual processing, and auditory processing. These findings align with our initial hypothesis. Despite statistical analyses revealing only mild cognitive impairment and emotional abnormalities in the BA group based on the scores from the two assessment scales, subsequent correlation analyses unveiled potential neurobiological indicators reflecting cognition and emotion. Specifically, the functional connectivity strength between the left thalamus (L-Thal) and the right superior frontal gyrus (R-SFG), as well as the left cerebellar posterior lobe (L-CPL), was identified.

The cerebellum posterior lobe (CPL) constitutes a significant portion of the human cerebellum ( 22 ). The thalamus conveys signals originating from the dentate nucleus of the CPL and subsequently projects them to the cerebral cortex, providing processed information back to the cerebellum ( 23 ). This neural circuit is typically associated with precision task execution, visual processing, speech expression, and emotional responses ( 24 , 25 ). Similarly, we observed a significant correlation between increased functional connectivity (FC) between the thalamus and cerebellar posterior lobe (CPL) and the presence of cognitive impairment and emotional abnormalities. Aberrant FC results in a decline in functional interaction capacity between brain regions, thereby weakening the efficiency of information transmission. In research examining primary nocturnal enuresis in children, disturbances in arousal were linked to diminished functional connectivity between the thalamus and CPL ( 26 ). In the study conducted by Liu and colleagues ( 27 ), it was also observed that individuals suffering from sleep disorders exhibited elevated metabolic activity in both the thalamus and the CPL. Xie et al. ( 28 ) investigated the spontaneous brain activity in patients with obstructive sleep apnea (OSA) using the percentage of amplitude fluctuation (PerAF). Their findings revealed an increased PerAF in the CPL, which correlates with the presence of sleep disturbances. Another study also indicates enhanced regional activity in the left CPL in BA patients ( 29 ). In our study, we observed enhanced FC between the Thal and CPL. This may potentially amplify projections to the cortical areas of CPL, resulting in cortical excitation. This could possibly explain the higher prevalence of nocturnal awakenings and sleep disturbances in asthma patients. Prolonged insufficient sleep can lead to decreased vigilance, resulting in reduced responsiveness of individuals with asthma to external threats ( 30 , 31 ). This may contribute to an increased risk of triggering asthma-related behaviors. Research indicates that, compared to non-depressed individuals with asthma, those with depression exhibit significantly increased cerebral blood flow in the CPL ( 32 – 34 ). The inclination toward depression is also related to CPL metabolism ( 35 ). Furthermore, as a region with a “proofreading” function for information, the increased signal strength in the cerebellum reflects abnormal control of respiratory muscles, and this change in asthmatic individuals may be associated with alterations in their respiratory rate ( 36 , 37 ). It is worth noting that in the cerebellum-thalamus-cerebral cortex (CTC) ascending loop, we have only identified FC changes between the cerebellum and thalamus in BA patients. In the future, probabilistic fiber tractography can be used to determine the regions with strong fiber bundle connections between the thalamus and the cerebellum, serving as ROIs for the projection of the cerebellum onto the thalamus. This approach can be employed to construct the FC between the thalamus and the cortex within this circuit, thereby elucidating the specific changes within the CTC in individuals with asthma.

LN, including the pallidum and the putamen nucleus, is a critical part of the basal ganglia, projecting to the ventrolateral nucleus of the thalamus and the lateral geniculate body ( 38 ). The basal ganglia-thalamus-cortical loop (BTC) is involved in arousal and attention functions ( 39 ). It also mediates regulatory control over a wide range of cortical areas, playing a pivotal role in emotional processing, motor control, cognitive processing, and motivational behavior ( 40 ). In our study, we observed a reduction in FC between the left thalamus and bilateral LN, while the right thalamus exhibited decreased FC, specifically with the right LN. The altered FC patterns may contribute to an overall decrease in information transmission efficiency between the thalamus and the cerebral cortex. Previous fMRI studies have indicated that the pallidum and the putamen nucleus often exhibit abnormal spontaneous activity when individuals are experiencing emotions such as fear, anxiety, and sadness ( 41 ). Individuals with asthma are more likely to trigger anxious thoughts about the dire consequences of an asthma attack. Additionally, it is widely hypothesized that the aberrant neural activity in this circuit serves as a fundamental neural mechanism in individuals with obsessive-compulsive disorder ( 42 ). Decreased thalamic gating efficiency can lead to a greater projection of intrusive, distressing thoughts into the cortex ( 16 ). Under the influence of obsessive thoughts and anxious emotions, this can result in more frequent oral corticosteroid and bronchodilator use. Prolonged corticosteroid treatment is linked to a decrease in LN volume, which in turn leads to more severe anxiety occurrences ( 14 , 43 ). Furthermore, damage to dopaminergic neurons in LN is closely associated with cognitive impairments in schizophrenia, including deficits in attention, working memory, reward processing, and executive functions ( 44 ). The LN is involved in the reward processing system and is responsible for linking different sensory cues with rewarding outcomes. In individuals suffering from severe depression, LN becomes abnormally activated during the occurrence of negative emotions, thereby intensifying the avoidance motivation to alleviate the experience of negative emotions ( 45 , 46 ). Impairments in reward and executive functions in BA patients may lead to reduced proactiveness in seeking medication and a higher likelihood of experiencing negative emotions. In the future, it is also possible to integrate multimodal data from DTI and fMRI to segmentally construct a detailed profile of BTC changes in BA patients.

The SFG is situated in the anterior medial prefrontal cortex, a key region within the default mode network (DMN), and is primarily involved in functions such as attention selection, inhibitory control, stress perception, and working memory ( 47 , 48 ). The DMN consumes a substantial amount of energy during rest, making it particularly susceptible to oxidative stress damage and the influence of diseases ( 49 ). Previous research has shown reduced activity in other brain regions of the DMN in individuals with asthma, such as the angular gyrus and the precuneus, confirming regional functional and network-level intrinsic activity abnormalities in the brains of BA patients ( 10 ). Hwang et al. ( 17 ) discovered robust functional connections between the DMN and various thalamic nuclei. Therefore, we hypothesize that, to compensate for the reduction in internal network activity, the thalamus and SFG’s FC will increase adaptively. The thalamus mediates top-down regulation and the filtering and integration of sensory information, as well as serving as a crucial hub for selective inhibition of external stimuli and focused attention ( 50 ). Meanwhile, the prefrontal cortex plays a central role in processing higher-level emotional and cognitive information. The enhanced functional connection between SFG and the thalamus is considered a neurofunctional characteristic of schizophrenia, often characterized by excessive attention to external stimuli and abnormal emotional reactions to these stimuli ( 51 ). Furthermore, these changes in BA patients may lead to a reduction in the use of adaptive strategy, potentially resulting in emotional regulation disorders ( 52 , 53 ). Research indicates a positive correlation between spontaneous activity in SFG and perceived stress, with excessive perceived stress typically stemming from negative emotions such as anxiety and depression ( 54 ). The thalamus also plays a role in mediating noxious input to the cortex, and the functional reorganization of the SFG is crucial in top-down modulation of pain experiences, with strong FC between them potentially contributing to the sustained perception of pain ( 55 ). The thalamus and SFG’s FC serve as a shared pathway in the experiences of breathlessness and pain perception ( 56 , 57 ). We hypothesize that asthma patients, in the long-term management of their breathing difficulties, gradually adapt to the stress associated with pain, transforming their adaptation to breathlessness into a tolerance for pain. This adaptation is manifested through increased spontaneous activity in the superior frontal gyrus (SFG). Therefore, the heightened functional connectivity (FC) between the thalamus and SFG in BA patients may be linked to emotional regulation disorders, perceived stress, and experiences related to pain and breathlessness.

PCG is a crucial region within the sensorimotor network responsible for processing various types of sensory perceptions. Sensory stimuli are conveyed through C-fibers to the spinal thalamic tract and are then relayed to the PCG via the thalamic ventral posterior nucleus ( 58 ). In their analysis of gender differences in chronic cough, Morice et al. ( 59 ) found that females exhibited higher sensitivity in their cough reflex, which was associated with increased activation in the PCG. Our research has revealed that, in comparison to HCs, asthma patients exhibit increased FC between the thalamus and PCG. This finding aligns with the tendency for asthma patients to experience coughing more frequently. Furthermore, damage to the PCG cortex could potentially affect respiratory motor control. Zhang et al. ( 60 ), in their fMRI analysis of COPD patients, observed enhanced low-frequency amplitude of fluctuations (ALFF) in the PCG, which was closely related to over-breathing. As the condition worsens, patients with asthma may gradually experience decreased sensitivity in perceiving asthma symptoms within the somatosensory cortex. This decline in perception sensitivity may hinder their ability to promptly address their condition due to reduced perception strength ( 61 ). Previous research has yielded varying results, showing reduced functional connectivity (FC) between the insular cortex and the PCG in BA patients ( 42 ). This reduction may be attributed to pathological activation in the PCG, which subsequently diminishes the FC between the insular cortex and PCG. Furthermore, early cognitive development often relies on essential sensory experiences, and excessive input from the thalamus can lead to aberrant sensory experiences, ultimately impacting cognitive function ( 58 ). Hence, the PCG is involved in the occurrence of bronchial hyperreactivity and respiratory overdrive in asthma, and it can serve as a potential biomarker for the severity of asthma symptoms.

Lastly, we have observed a decrease in FC between the CC and the thalamus, even though there is no apparent anatomical correlation between them. But functionally, they are interconnected, such as in the context of visual short-term memory capacity ( 62 ), visual processing ( 63 ), and speech formation ( 64 ). In fact, the input from the thalamus plays a highly instructive role in the maturation trend of the CC area, achieved through the regulation of neuronal projection, development, signal transduction, and activity-dependent plasticity ( 65 , 66 ). The CC serves as an intermediary for interhemispheric communication ( 67 ) and indirectly contributes to cognitive functions like language, attention, working memory, and visual spatial memory ( 68 – 70 ). Previous studies have suggested that CC atrophy in BA patients might be mediated by allergens ( 71 ) and affect the cortical metabolism associated with cognitive functions ( 72 ). In BA patients, there is a reduction in the FC between the CC and the thalamus, which we hypothesize is associated with a decline in the coordinated processing of sensory stimuli across both brain hemispheres. This decline includes the ability to recognize odors from olfactory stimuli ( 73 , 74 ). This might explain why asthma patients have difficulty identifying harmful gases, which can trigger asthma symptoms. In an fMRI study, Wang et al. ( 75 ) found that damage to the white matter integrity of the CC is related to the severity of anxiety. Changes in FC between the thalamus and these brain structures contribute to understanding the pathophysiological mechanisms underlying cognitive impairments, emotional dysregulation, and motor control failures in BA patients. In the future, inducing positive plastic changes may be considered in the treatment of BA to promote brain function recovery.

Limitations

Nonetheless, there are certain constraints associated with this study. In the first place, the sample size was rather limited owing to rigorous inclusion criteria. Furthermore, during the administration of the neuro-psychological assessment scales, it is noteworthy that the subjects may not have fully adhered to a conservative representation of their condition, introducing a potential bias to the test results. Thirdly, this study did not investigate how these FC differences change over time. Future research could employ dynamic FC analysis to elucidate this aspect. Hence, it is imperative to conduct longitudinal studies using a variety of analytical approaches for fMRI. This will enable us to investigate the evolving patterns in FC as time progresses. Fourthly, our study only identified brain regions where there were differences in FC between the BA group and the HCs concerning the thalamus and other cortical regions. In the future, machine learning methods such as support vector machine (SVM) classifiers can be employed to determine whether these brain regions can serve as discriminative features for distinguishing these groups.

In our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit abnormal changes in functional connectivity between the thalamus and various brain regions associated with vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the progression of BA.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving humans were approved by Ethics Committee of Jiangxi Provincial People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent in this study.

Author contributions

TW: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Writing – original draft. JW: Funding acquisition, Supervision, Writing – review & editing. XH: Methodology, Resources, Software, Writing – review & editing. L-xD: Investigation, Methodology, Writing – review & editing. K-mZ: Investigation, Methodology, Writing – review & editing.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Jiangxi Provincial Natural Science Foundation General Project (20202BAB206003).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

1. Wong, QYA, Lim, JJ, Ng, JY, Malipeddi, P, Lim, YYE, Sio, YY, et al. An updated prevalence of asthma, its phenotypes, and the identification of the potential asthma risk factors among young Chinese adults recruited in Singapore. World Allergy Organ J . (2023) 16:100757. doi: 10.1016/j.waojou.2023.100757

PubMed Abstract | Crossref Full Text | Google Scholar

2. Habib, N, Pasha, MA, and Tang, DD. Current understanding of asthma pathogenesis and biomarkers. Cells . (2022) 11:764. doi: 10.3390/cells11172764

3. Quan, N, and Banks, WA. Brain-immune communication pathways. Brain Behav Immun . (2007) 21:727–35. doi: 10.1016/j.bbi.2007.05.005

4. Parker, J, Wolansky, LJ, Khatry, D, Geba, GP, and Molfino, NA. Brain magnetic resonance imaging in adults with asthma. Contemp Clin Trials . (2011) 32:86–9. doi: 10.1016/j.cct.2010.09.006

Crossref Full Text | Google Scholar

5. Rosenkranz, MA, Dean, DC III, Bendlin, BB, Jarjour, NN, Esnault, S, Zetterberg, H, et al. Neuroimaging and biomarker evidence of neurodegeneration in asthma. J Allergy Clin Immunol . (2022) 149:589–598.e6. doi: 10.1016/j.jaci.2021.09.010

6. Parajuli, B, Horiuchi, H, Mizuno, T, Takeuchi, H, and Suzumura, A. CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia. Glia . (2015) 63:2274–84. doi: 10.1002/glia.22892

7. Dehdar, K, Salimi, M, and Raoufy, MR. Allergen disrupts amygdala-respiration coupling. Respir Physiol Neurobiol . (2022) 297:103835. doi: 10.1016/j.resp.2021.103835

8. Kroll, JL, and Ritz, T. Asthma, the central nervous system, and neurocognition: current findings, potential mechanisms, and treatment implications. Neurosci Biobehav Rev . (2023) 146:105063. doi: 10.1016/j.neubiorev.2023.105063

9. Lavielle, P, Talavera, JO, Reynoso, N, González, M, Gómez-Díaz, RA, Cruz, M, et al. Prevalence of cognitive impairment in recently diagnosed type 2 diabetes patients: are chronic inflammatory diseases responsible for cognitive decline? PLoS One . (2015) 10:e0141325. doi: 10.1371/journal.pone.0141325

10. Li, S, Lv, P, He, M, Zhang, W, Liu, J, Gong, Y, et al. Cerebral regional and network characteristics in asthma patients: a resting-state fMRI study. Front Med . (2020) 14:792–801. doi: 10.1007/s11684-020-0745-1

11. Ritz, T, Kroll, JL, Patel, SV, Chen, JR, Yezhuvath, US, Aslan, S, et al. Central nervous system signatures of affect in asthma: associations with emotion-induced bronchoconstriction, airway inflammation, and asthma control. J Appl Physiol . (1985) 126:1725–36. doi: 10.1152/japplphysiol.01018.2018

12. Zhu, L, Zhao, J, Yang, Y, Shangguan, Q, Chen, Y, He, Y, et al. Brain network study of attentional cognitive impairment in children with bronchial asthma. Int J Dev Neurosci . (2023) 83:224–31. doi: 10.1002/jdn.10250

13. Wu, YJ, Rao, J, Huang, X, Wu, N, Shi, L, Huang, H, et al. Impaired interhemispheric synchrony in bronchial asthma. Int J Gen Med . (2021) 14:10315–25. doi: 10.2147/IJGM.S343269

14. Ritz, T, Kroll, JL, Aslan, S, Janssens, T, Khan, DA, Pinkham, AE, et al. Subcortical gray matter volumes in asthma: associations with asthma duration, control, and anxiety. Brain Imaging Behav . (2020) 14:2341–50. doi: 10.1007/s11682-019-00188-3

15. Roy, DS, Zhang, Y, Halassa, MM, and Feng, G. Thalamic subnetworks as units of function. Nat Neurosci . (2022) 25:140–53. doi: 10.1038/s41593-021-00996-1

16. Niu, Q, Yang, L, Song, X, Chu, C, Liu, H, Zhang, L, et al. Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder. Neuropsychiatr Dis Treat . (2017) 13:507–13. doi: 10.2147/NDT.S117510

17. Hwang, K, Bertolero, MA, Liu, WB, and D'Esposito, M. The human thalamus is an integrative hub for functional brain networks. J Neurosci . (2017) 37:5594–607. doi: 10.1523/JNEUROSCI.0067-17.2017

18. Bourgeois, JA, John, M, Zepf, R, Greene, M, Frankel, S, and Hessol, NA. Functional deficits and other psychiatric associations with abnormal scores on the Montreal cognitive assessment (MoCA) in older HIV-infected patients. Int Psychogeriatr . (2020) 32:105–18. doi: 10.1017/S1041610219000413

19. Ren, S, Chang, M, Yin, Z, Feng, R, Wei, Y, Duan, J, et al. Age-related alterations of white matter integrity in adolescents and young adults with bipolar disorder. Front Psych . (2019) 10:1010. doi: 10.3389/fpsyt.2019.01010

20. Kocar, TD, Müller, HP, and Kassubek, J. Differential functional connectivity in thalamic and dopaminergic pathways in restless legs syndrome: a meta-analysis. Ther Adv Neurol Disord . (2020) 13:1756286420941670. doi: 10.1177/1756286420941670

21. Donahue, EK, Venkadesh, S, Bui, V, Tuazon, AC, Wang, RK, Haase, D, et al. Physical activity intensity is associated with cognition and functional connectivity in Parkinson's disease. Parkinsonism Relat Disord . (2022) 104:7–14. doi: 10.1016/j.parkreldis.2022.09.005

22. Liu, WF, Shu, YQ, Zhu, PW, Li, B, Shi, WQ, Lin, Q, et al. The cerebellum posterior lobe associates with the exophthalmos of primary hyperthyroidism: a resting-state fMRI study. Int J Endocrinol . (2019) 2019:8135671. doi: 10.1155/2019/8135671

23. Qiao, J, Wu, ZM, Ye, QP, Dai, M, Dai, Y, He, ZT, et al. Characteristics of dysphagia among different lesion sites of stroke: a retrospective study. Front Neurosci . (2022) 16:944688. doi: 10.3389/fnins.2022.944688

24. Zhu, B, Wang, Y, Zhang, G, Ouyang, H, Zhang, J, Zheng, Y, et al. Acupuncture at KI3 in healthy volunteers induces specific cortical functional activity: an fMRI study. BMC Complement Altern Med . (2015) 15:361. doi: 10.1186/s12906-015-0881-3

25. Schmahmann, JD . The cerebellum and cognition. Neurosci Lett . (2019) 688:62–75. doi: 10.1016/j.neulet.2018.07.005

26. Zhang, A, Zhang, L, Wang, M, Zhang, Y, Jiang, F, Jin, X, et al. Functional connectivity of thalamus in children with primary nocturnal enuresis: results from a resting-state fMRI study. Brain Imaging Behav . (2021) 15:355–63. doi: 10.1007/s11682-020-00262-1

27. Liu, X, Yu, T, Zhao, X, Yu, P, Lv, R, Wang, C, et al. Risk factors and brain metabolic mechanism of sleep disorders in autoimmune encephalitis. Front Immunol . (2021) 12:738097. doi: 10.3389/fimmu.2021.738097

28. Xie, W, Shu, Y, Liu, X, Li, K, Li, P, Kong, L, et al. Abnormal spontaneous brain activity and cognitive impairment in obstructive sleep apnea. Nat Sci Sleep . (2022) 14:1575–87. doi: 10.2147/NSS.S376638

29. Huang, H, Li, SY, Shi, L, Huang, X, and Wang, J. Altered spontaneous brain activity in patients with asthma: a resting-state functional MRI study using regional homogeneity analysis. NeuroReport . (2021) 32:1403–7. doi: 10.1097/WNR.0000000000001736

30. Liu, X, Yan, Z, Wang, T, Yang, X, Feng, F, Fan, L, et al. Connectivity pattern differences bilaterally in the cerebellum posterior lobe in healthy subjects after normal sleep and sleep deprivation: a resting-state functional MRI study. Neuropsychiatr Dis Treat . (2015) 11:1279–89. doi: 10.2147/NDT.S84204

31. Albakri, U, Drotos, E, and Meertens, R. Sleep health promotion interventions and their effectiveness: an umbrella review. Int J Environ Res Public Health . (2021) 18:5533. doi: 10.3390/ijerph18115533

32. Zhang, Y, Yang, Y, Wang, Z, Bian, R, Jiang, W, Yin, Y, et al. Altered regional cerebral blood flow of right cerebellum posterior lobe in asthmatic patients with or without depressive symptoms. Front Psych . (2018) 9:225. doi: 10.3389/fpsyt.2018.00225

33. Wildgruber, D, Riecker, A, Hertrich, I, Erb, M, Grodd, W, Ethofer, T, et al. Identification of emotional intonation evaluated by fMRI. NeuroImage . (2005) 24:1233–41. doi: 10.1016/j.neuroimage.2004.10.034

34. Fu, X, Zhang, F, Liu, F, Yan, C, and Guo, W. Editorial: brain and somatization symptoms in psychiatric disorders. Front Psych . (2019) 10:146. doi: 10.3389/fpsyt.2019.00146

35. Cheng, B, Roberts, N, Zhou, Y, Wang, X, Li, Y, Chen, Y, et al. Social support mediates the influence of cerebellum functional connectivity strength on postpartum depression and postpartum depression with anxiety. Transl Psychiatry . (2022) 12:54. doi: 10.1038/s41398-022-01781-9

36. Harper, RM, Macey, PM, Henderson, LA, Woo, MA, Macey, KE, Frysinger, RC, et al. fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. J Appl Physiol . (1985) 94:1583–95. doi: 10.1152/japplphysiol.00881.2002

37. Pollok, B, Jurkiewicz, M, and Krause, V. Anodal transcranial direct current stimulation (atDCS) of the primary motor cortex (M1) facilitates nonconscious error correction of negative phase shifts. Neural Plast . (2022) 2022:9419154. doi: 10.1155/2022/9419154

38. Tang, S, Liu, X, Nie, L, Qian, F, Chen, W, and He, L. Three-dimensional pseudocontinuous arterial spin labeling perfusion imaging shows cerebral blood flow perfusion decline in attention-deficit/hyperactivity disorder children. Front Psych . (2023) 14:1064647. doi: 10.3389/fpsyt.2023.1064647

39. Zhang, J, Zhang, H, Yan, F, Zhang, H, Zhang, E, Wang, X, et al. Investigating the mechanism and prognosis of patients with disorders of consciousness on the basis of brain networks between the thalamus and whole-brain. Front Neurol . (2022) 13:990686. doi: 10.3389/fneur.2022.990686

40. Aravamuthan, BR, and Waugh, JL. Localization of basal ganglia and thalamic damage in Dyskinetic cerebral palsy. Pediatr Neurol . (2016) 54:11–21. doi: 10.1016/j.pediatrneurol.2015.10.005

41. Ashworth, E, Brooks, SJ, and Schiöth, HB. Neural activation of anxiety and depression in children and young people: a systematic meta-analysis of fMRI studies. Psychiatry Res Neuroimaging . (2021) 311:111272. doi: 10.1016/j.pscychresns.2021.111272

42. Zhang, Y, Yang, Y, Bian, R, Yin, Y, Hou, Z, Yue, Y, et al. Group cognitive behavior therapy reversed insula subregions functional connectivity in asthmatic patients. Front Aging Neurosci . (2017) 9:105. doi: 10.3389/fnagi.2017.00105

43. Liang, J, Yu, Q, Liu, Y, Qiu, Y, Tang, R, Yan, L, et al. Gray matter abnormalities in patients with major depressive disorder and social anxiety disorder: a voxel-based meta-analysis. Brain Imaging Behav . (2023) 17:749–63. doi: 10.1007/s11682-023-00797-z

44. Li, P, Zhao, SW, Wu, XS, Zhang, YJ, Song, L, Wu, L, et al. The association between Lentiform nucleus function and cognitive impairments in schizophrenia. Front Hum Neurosci . (2021) 15:777043. doi: 10.3389/fnhum.2021.777043

45. Wang, X, Zhou, X, Dai, Q, Ji, B, and Feng, Z. The role of motivation in cognitive reappraisal for depressed patients. Front Hum Neurosci . (2017) 11:516. doi: 10.3389/fnhum.2017.00516

46. Zhang, L, Li, Q, du, Y, Gao, Y, Bai, T, Ji, GJ, et al. Effect of high-definition transcranial direct current stimulation on improving depression and modulating functional activity in emotion-related cortical-subcortical regions in bipolar depression. J Affect Disord . (2023) 323:570–80. doi: 10.1016/j.jad.2022.12.007

47. Greicius, MD, Krasnow, B, Reiss, AL, and Menon, V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA . (2003) 100:253–8. doi: 10.1073/pnas.0135058100

48. Briggs, RG, Khan, AB, Chakraborty, AR, Abraham, CJ, Anderson, CD, Karas, PJ, et al. Anatomy and white matter connections of the superior frontal gyrus. Clin Anat . (2020) 33:823–32. doi: 10.1002/ca.23523

49. Wang, Y, Chen, L, Cai, F, Gao, J, Ouyang, F, Chen, Y, et al. Altered functional connectivity of the thalamus in primary angle-closure glaucoma patients: a resting-state fMRI study. Front Neurol . (2022) 13:1015758. doi: 10.3389/fneur.2022.1015758

50. Yuan, HL, Lai, CYY, Wong, MNK, Kwong, TC, Choy, YS, Mung, SWY, et al. Interventions for sensory over-responsivity in individuals with autism Spectrum disorder: a narrative review. Children . (2022) 9:1584. doi: 10.3390/children9101584

51. Widmayer, S, Borgwardt, S, Lang, UE, Stieglitz, RD, and Huber, CG. Functional neuroimaging correlates of aggression in psychosis: a systematic review with recommendations for future research. Front Psych . (2018) 9:777. doi: 10.3389/fpsyt.2018.00777

52. Shi, J, Yao, Y, Zhan, C, Mao, Z, Yin, F, and Zhao, X. The relationship between big five personality traits and psychotic experience in a large non-clinical youth sample: the mediating role of emotion regulation. Front Psych . (2018) 9:648. doi: 10.3389/fpsyt.2018.00648

53. Guo, WB, Liu, F, Xue, ZM, Xu, XJ, Wu, RR, Ma, CQ, et al. Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: a resting-state fMRI study. Prog Neuro-Psychopharmacol Biol Psychiatry . (2012) 37:153–60. doi: 10.1016/j.pnpbp.2012.01.011

54. Wang, S, Zhao, Y, Zhang, L, Wang, X, Wang, X, Cheng, B, et al. Stress and the brain: perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence. Hum Brain Mapp . (2019) 40:4982–93. doi: 10.1002/hbm.24752

55. Lee, JJ, Lee, S, Lee, DH, and Woo, CW. Functional brain reconfiguration during sustained pain. eLife . (2022) 11:463. doi: 10.7554/eLife.74463

56. von Leupoldt, A, Sommer, T, Kegat, S, Baumann, HJ, Klose, H, Dahme, B, et al. Dyspnea and pain share emotion-related brain network. NeuroImage . (2009) 48:200–6. doi: 10.1016/j.neuroimage.2009.06.015

57. Herigstad, M, Hayen, A, Evans, E, Hardinge, FM, Davies, RJ, Wiech, K, et al. Dyspnea-related cues engage the prefrontal cortex: evidence from functional brain imaging in COPD. Chest . (2015) 148:953–61. doi: 10.1378/chest.15-0416

58. Zhu, W, Tang, W, Liang, Y, Jiang, X, Li, Y, Chen, Z, et al. Aberrant functional connectivity of sensorimotor network and its relationship with executive dysfunction in bipolar disorder type I. Front Neurosci . (2021) 15:823550. doi: 10.3389/fnins.2021.823550

59. Morice, AH, Jakes, AD, Faruqi, S, Birring, SS, McGarvey, L, Canning, B, et al. A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J . (2014) 44:1149–55. doi: 10.1183/09031936.00217813

60. Zhang, J, Chen, J, Yu, Q, Fan, C, Zhang, R, Lin, J, et al. Alteration of spontaneous brain activity in COPD patients. Int J Chron Obstruct Pulmon Dis . (2016) 11:1713–9. doi: 10.2147/COPD.S110089

61. Davenport, P W, Cruz, M, Stecenko, A A, and Kifle, Y. Respiratory-related evoked potentials in children with life-threatening asthma. Am J Respir Crit Care Med . (2000) 161:1830–5. doi: 10.1164/ajrccm.161.6.9903077

62. Menegaux, A, Meng, C, Neitzel, J, Bäuml, JG, Müller, HJ, Bartmann, P, et al. Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults. NeuroImage . (2017) 150:68–76. doi: 10.1016/j.neuroimage.2017.02.017

63. Zarkali, A, McColgan, P, Leyland, LA, Lees, AJ, Rees, G, and Weil, RS. Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction. Neurology . (2020) 94:e1525–38. doi: 10.1212/WNL.0000000000009014

64. Schaltenbrand, G . The effects on speech and language of stereotactical stimulation in thalamus and corpus callosum. Brain Lang . (1975) 2:70–7. doi: 10.1016/S0093-934X(75)80055-1

65. Wilson, S, Pietsch, M, Cordero-Grande, L, Price, AN, Hutter, J, Xiao, J, et al. Development of human white matter pathways in utero over the second and third trimester. Proc Natl Acad Sci USA . (2021) 118:e2023598118. doi: 10.1073/pnas.2023598118

66. De León Reyes, NS, Bragg-Gonzalo, L, and Nieto, M. Development and plasticity of the corpus callosum. Development . (2020) 147:dev189738. doi: 10.1242/dev.189738

67. Mizutani, R, Saiga, R, Ohtsuka, M, Miura, H, Hoshino, M, Takeuchi, A, et al. Three-dimensional X-ray visualization of axonal tracts in mouse brain hemisphere. Sci Rep . (2016) 6:35061. doi: 10.1038/srep35061

68. Koo, DL, Cabeen, RP, Yook, SH, Cen, SY, Joo, EY, and Kim, H. More extensive white matter disruptions present in untreated obstructive sleep apnea than we thought: a large sample diffusion imaging study. Hum Brain Mapp . (2023) 44:3045–56. doi: 10.1002/hbm.26261

69. Roy, B, Sahib, AK, Kang, D, Aysola, RS, and Kumar, R. Brain tissue integrity mapping in adults with obstructive sleep apnea using T1-weighted and T2-weighted images. Ther Adv Neurol Disord . (2022) 15:17562864221137505. doi: 10.1177/17562864221137505

70. Kheirandish-Gozal, L, Sahib, AK, Macey, PM, Philby, MF, Gozal, D, and Kumar, R. Regional brain tissue integrity in pediatric obstructive sleep apnea. Neurosci Lett . (2018) 682:118–23. doi: 10.1016/j.neulet.2018.06.002

71. Dehdar, K, and Raoufy, MR. Effects of inhaled corticosteroids on brain volumetry, depression and anxiety-like behaviors in a rat model of asthma. Respir Physiol Neurobiol . (2023) 315:104121. doi: 10.1016/j.resp.2023.104121

72. Yamauchi, H, Fukuyama, H, Nagahama, Y, Katsumi, Y, Dong, Y, Konishi, J, et al. Atrophy of the corpus callosum associated with cognitive impairment and widespread cortical hypometabolism in carotid artery occlusive disease. Arch Neurol . (1996) 53:1103–9. doi: 10.1001/archneur.1996.00550110039011

73. Martinez-Nunez, AE, Soltanian-Zadeh, H, Latack, K, Ghazi, N, and Mahajan, A. Hyposmia and apathy in early, de novo Parkinson's disease: lessons from structural brain connectivity. J Neurol Sci . (2023) 452:120767. doi: 10.1016/j.jns.2023.120767

74. Eslinger, PJ, Damasio, AR, and Van Hoesen, GW. Olfactory dysfunction in man: anatomical and behavioral aspects. Brain Cogn . (1982) 1:259–85. doi: 10.1016/0278-2626(82)90028-8

75. Wang, W, Peng, Z, Wang, X, Wang, P, Li, Q, Wang, G, et al. Disrupted interhemispheric resting-state functional connectivity and structural connectivity in first-episode, treatment-naïve generalized anxiety disorder. J Affect Disord . (2019) 251:280–6. doi: 10.1016/j.jad.2019.03.082

Keywords: asthma, thalamus, fMRI, functional connectivity, cognitive impairment

Citation: Wang T, Huang X, Dai L-x, Zhan K-m and Wang J (2024) Functional connectivity alterations in the thalamus among patients with bronchial asthma. Front. Neurol . 15:1378362. doi: 10.3389/fneur.2024.1378362

Received: 30 January 2024; Accepted: 15 April 2024; Published: 10 May 2024.

Reviewed by:

Copyright © 2024 Wang, Huang, Dai, Zhan and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jun Wang, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.