Asthma

Asthma is a long-term disease of the airways in which airway inflammation, bronchial hyperresponsiveness and reversible airflow obstruction together make breathing difficult, producing wheeze, chest tightness, cough and shortness of breath. It is among the most common chronic diseases of any age group. It is also a heterogeneous condition rather than a single disorder: the same symptoms can arise from allergic, eosinophilic and other mechanisms, and these subtypes respond differently to treatment. This entry treats asthma as a clinical, biological and social phenomenon, covering its definition, classification, pathophysiology, causes, epidemiology and burden, diagnosis, management, acute attacks, the history of its understanding, its wider economic and public health dimensions, and the questions still under study.

The disease matters because of its scale and its preventability. Estimates of the number of people living with asthma vary by source, from roughly 260 million to about 300 million, and public health agencies describe deaths from it as occurring at a rate of about a thousand per day, most of them in low- and middle-income countries and most of them avoidable. Age-standardized rates have fallen since 1990 in the Global Burden of Disease estimates, yet absolute case numbers continue to grow with population growth and ageing, and the burden falls on health systems, workplaces, schools and families. Understanding asthma therefore requires attention to biology and to the environmental, economic and political conditions in which it develops and is treated.

Definition and Clinical Features

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation that produces recurrent respiratory symptoms and variable airflow limitation. The current Global Initiative for Asthma (GINA) definition rests on two linked features: a history of symptoms such as wheeze, shortness of breath, chest tightness and cough that change over time and in intensity, and expiratory airflow obstruction that varies in the same way. Airway hyperresponsiveness and airway inflammation are usually present, but GINA states that neither is necessary or sufficient for the diagnosis. Airflow limitation may also become persistent in long-standing disease, which is one reason the boundary with chronic obstructive pulmonary disease (COPD) is not always sharp. The usual contrast is that asthma obstruction fluctuates and is at least partly reversible, whereas COPD obstruction is largely fixed. Persistent, partly irreversible obstruction in asthma is generally attributed to airway wall remodelling.

The symptom picture is variable. Patients may report one or several symptoms, and cough can be the only complaint; in such cases airflow may look normal except during bronchial provocation testing. Symptoms are often worse at night or in the early morning, and they are commonly provoked by colds, exercise, allergen exposure, laughter or tobacco smoke. Intensity rises and falls from day to day, and the pattern may also shift with seasons, pollen and viral circulation, and with a patient's life stage over years. Because there is no single symptom that is specific to asthma, the diagnosis depends on the pattern of symptoms across time, supported by objective evidence of variable airflow.

Reversibility is central to the concept. Obstruction is reversible in the sense that it improves with bronchodilator drugs or spontaneously, and clinical guidance describes asthma as variable obstruction that can be reversed with treatment or without it. Clinicians document this in practice through spirometry before and after bronchodilator use, or through serial peak expiratory flow measurements. GINA has stressed that airflow limitation need not be present at the moment of assessment, since lung function in untreated asthma is characteristically variable. A single normal test therefore does not exclude the disease, and a bronchodilator response that is absent on one occasion does not rule it out. Reversibility is thus both a diagnostic test and a conceptual marker of the disease's variability.

Severity and control are assessed as separate questions. Control refers to how far symptoms and exacerbation risk are currently suppressed under treatment, and current GINA guidance asks clinicians to assess control by combining symptom burden with exacerbation risk. Severity describes the level of treatment needed to achieve control, or the degree of difficulty in achieving it, and is often clarified only after adherence, inhaler technique and triggers have been reviewed. Classifications based on clinical phenotypes do not correlate closely with specific pathological processes or treatment responses, so a single label rarely captures the disease in a given patient.

Remission is a more contested idea. Remission is generally understood as a sustained absence of symptoms, exacerbations and lung function decline, with or without ongoing therapy, whereas a cure would imply permanent eradication with no residual airway inflammation. No intervention has been proven to cure asthma, and the term remission does not mean that the disease will never return. The most common working definitions require roughly twelve months without exacerbations, without systemic corticosteroid use, with stable lung function and well-controlled symptoms. Stricter "complete remission" definitions add normal lung function and absence of bronchial hyperresponsiveness. Reported rates vary widely with the criteria used. Spontaneous remission in adults is often estimated at about 2% per year, with earlier onset, less airway obstruction, more marked hyperresponsiveness and smoking cessation associated with a higher chance of remission. In children, clinical remission rates have been reported to be higher than in adults, though definitions remain mostly adult-derived, and a 2024 scoping review found that most paediatric studies defined remission only by the absence of symptoms. With biologic therapies for severe type 2 asthma, the notion of "on-treatment" clinical remission has gained attention, though definitions in that area are still inconsistent and largely based on expert opinion.

Classification and Phenotypes

Asthma is heterogeneous, and clinicians and researchers have long tried to sort patients into groups that share causes, clinical course or treatment response. The earliest schemes were organised around allergy, dividing asthma into forms with and without evident allergen sensitization. Later systems added clinical features, patterns of airway inflammation and statistical cluster analysis. In practice the categories overlap: eosinophilic inflammation appears in both allergic and non-allergic patients, and many people have features of several groups at once.

Allergic and non-allergic asthma

Allergic (atopic) asthma is linked to sensitization to inhaled allergens such as house dust mite, pollens and moulds. Sensitization is usually shown by allergen-specific IgE in the blood or by skin tests, and this form often begins in childhood. Non-allergic (intrinsic) asthma lacks this sensitization and is more frequently adult-onset. Cluster studies in adults commonly describe early-onset allergic disease, which can be mild or severe, alongside late-onset non-allergic disease. The late-onset group is often eosinophilic but sometimes neutrophilic.

Inflammatory subtypes

Sputum cell counts are the most widely used way to sort airway inflammation. Sputum cytometry divides patients into four groups: eosinophilic, neutrophilic, mixed granulocytic and pauci-granulocytic. Eosinophilic asthma is the Th2-high type, driven by T helper 2 cells and type 2 cytokines, and it responds best to corticosteroids and biologic therapies. It accounts for most severe cases. Eosinophilic disease can be further split into atopic forms, arising from specific allergic reactivity, and nonatopic forms, in which innate mechanisms play a larger part.

Neutrophilic asthma is less common, with prevalence commonly estimated at 5–10% of patients with asthma. It is Th2-low and tends to respond poorly to inhaled corticosteroids. Proposed biomarkers include sputum and blood neutrophils, and the pathway involves TSLP and Th17 signalling, bacterial colonization and inflammation of the airway. Obesity, gastro-oesophageal reflux and smoking have been associated with it. Its status as a distinct endotype is contested: a 2025 review argued that the Th2-low definition may be imprecise, since many patients labelled this way show eosinophilia below about 2% of sputum cells. Mixed granulocytic asthma combines high eosinophil and neutrophil counts, while pauci-granulocytic asthma shows little of either.

Trigger- and context-defined forms

• Occupational asthma is caused by exposure to sensitizing agents at work, such as flour, laboratory animal proteins and isocyanates. Symptoms may improve away from the workplace. It is one of the best-recognised trigger-defined forms, and it is linked to earlier exposure history rather than to a single gene. See occupational asthma.
• Exercise-induced bronchoconstriction involves airway narrowing during or after exertion, often worsened by cold or dry air. It can occur in people with otherwise mild disease and in elite athletes.
• Aspirin-exacerbated respiratory disease (AERD) combines asthma, chronic rhinosinusitis with nasal polyps and respiratory reactions to aspirin and other drugs that inhibit COX-1. The syndrome was first described in 1922 and its triad was formalised in 1968. Reactions are not IgE-mediated. They are linked to overproduction of cysteinyl leukotrienes and mast cell activation. Onset is usually in adulthood, and AERD is estimated to affect about 7% of people with mild to moderate asthma and around 14% of those with severe asthma. Patients tend to have more severe disease.
• Thunderstorm asthma describes sudden epidemics of severe asthma during storms in pollen seasons. The leading hypothesis is that moisture rupture of grass pollen, especially ryegrass, releases small particles that reach the lower airways. Risk is highest in people who are sensitized to grass pollen, have allergic rhinitis and are exposed outdoors during the event, and in those with poorly controlled asthma. The exact mechanism is still unclear, and such epidemics remain uncommon.

Severe asthma, asthma–COPD overlap and classification frameworks

Severe asthma requires high-dose inhaled treatment or regular systemic corticosteroids to control, or remains uncontrolled despite them. Several studies have identified three to five severe-asthma clusters, but the groups differ between studies. In 2012, Wenzel proposed six categories linking biology to clinical patterns: early-onset allergic Th2, late-onset eosinophilic, exercise-induced, obesity-related, neutrophilic and paucigranulocytic asthma. Asthma–COPD overlap describes patients who share features of both diseases, such as persistent airflow limitation, often in older people with a history of smoking.

The distinction between phenotype and endotype is central to these frameworks. A phenotype is a recognisable cluster of demographic, clinical or physiological features. An endotype is a subtype defined by an underlying mechanism or by treatment response. A 2011 consensus report recommended endotypes as the basis for precision therapy. Multi-omics analyses of sputum and computational clustering now aim to refine endotypes, but the same clinical phenotype may contain several endotypes, and one endotype may appear across several phenotypes.

Pathophysiology and Mechanisms

Type 2 inflammation

Most asthma is organized around a type 2 immune program. T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s) are the main producers of IL-4, IL-5 and IL-13, which are often treated as the signature cytokines of the disease. Their roles differ but overlap: IL-4 and IL-13 drive B cells to switch to IgE production, IL-13 induces goblet-cell hyperplasia and mucus output, and IL-5 promotes eosinophil maturation in the bone marrow, while IL-4 and IL-13 help draw eosinophils into the airway. IgE binds to mast cells, which release histamine and other mediators when they meet an allergen, linking sensitization to acute symptoms. Eosinophils add to tissue injury through their own granule proteins and mediators. Because these pathways leave measurable traces, fractional exhaled nitric oxide, serum IgE, periostin and blood or sputum eosinophil counts serve as type 2 markers, although none captures the whole process. Type 2 disease is not universal: IL-17 and IL-22 from Th17 cells are linked to neutrophilic, non-type 2 asthma.

Acute bronchoconstriction

The rapid narrowing of the airway during an attack is driven mainly by contraction of airway smooth muscle, which mast cell mediators such as histamine and prostaglandin D2 can provoke. In isolated human bronchi, prolonged exposure to TSLP, IL-33 and IL-25 enhanced IgE-triggered contraction and mediator release, suggesting that epithelial signals make mast cells more reactive. Goblet cells and submucosal glands produce excess mucus, and leakage of plasma into the airway wall causes mucosal oedema; both reduce the airway lumen further. Neural and hormonal regulation adds another layer. Cholinergic reflexes driven by vagal sensory input promote constriction and secretion, whereas beta-2 adrenergic stimulation relaxes smooth muscle, so reduced adrenergic responsiveness can increase narrowing. These acute changes are largely reversible, which distinguishes them from the structural alterations described below.

Epithelial alarmins

The airway epithelium is the first barrier against inhaled allergens, viruses, pollutants and microbes. When its tight junctions are cleaved or its cells undergo necroptosis, it releases the alarmins thymic stromal lymphopoietin (TSLP), IL-33 and IL-25. Allergen-derived proteases can activate PAR-2 receptors on epithelial cells and also act on IL-33, generating a shorter isoform with far greater biological activity. TSLP activates dendritic cells, which prime naive T helper cells toward a Th2 profile, and IL-33 reinforces this TSLP–dendritic cell axis while also activating ILC2s. IL-33 is stored in the nucleus of epithelial cells and functions as a damage signal when those cells are injured. IL-25 acts more narrowly on type 2 responses, promoting eosinophil activation and survival and enhancing Th2 activation. Because these alarmins sit upstream of many effector pathways, they have become therapeutic targets, as discussed in the management section.

Airway remodelling

Remodelling refers to the structural component of asthma, and it involves both the epithelium and the tissue beneath it. Repeated injury and epithelial cell apoptosis, together with fibroblast activation and changes in the extracellular matrix, lead to subepithelial fibrosis and thickening of the reticular basement membrane. Airway smooth muscle becomes hypertrophic and hyperplastic, goblet cells multiply through metaplasia, and sensory nerve endings and blood vessels increase in number. IL-13 is a major driver of these changes, and IL-4 and IL-13 also contribute to airway hyperresponsiveness. Because the structural changes are persistent, they limit airflow even when acute inflammation has settled, and they are generally considered only partly reversible. Remodelling tends to be more pronounced in severe asthma, where it has been linked to reduced corticosteroid responsiveness. In an experimental chronic allergen model, corticosteroids did not fully reduce airway smooth muscle mass or hyperresponsiveness, illustrating how structural change can outlast the inflammation that produced it.

Causes and Risk Factors

Genetic susceptibility

Asthma clusters in families, and twin designs have long been used to estimate how much of its risk is inherited. Across the published estimates, figures have ranged from 35% to 95%, with those derived from twin studies generally sitting at the lower end. Estimates are higher in children: one twin analysis of childhood asthma put the heritability of any childhood asthma at 0.82, with a 95% confidence interval of 0.79 to 0.85.

Genome-wide association studies (GWAS) have greatly expanded the list of implicated sites. More than 140 susceptibility loci have been identified so far. The field's first GWAS, published by Moffatt and colleagues in 2007, linked a region of chromosome 17q12–21 to childhood asthma, and asthma-associated SNPs in this locus were related to mRNA expression levels of ORMDL3. Most of these loci, however, have modest individual effects. Common variants explain only part of the picture: they account for about 25.6% of heritability in childhood-onset asthma but only 10.6% in adult-onset asthma. The missing heritability is an open problem, and the genes that are implicated point toward immune signalling, including pathways that carry airway epithelial damage to the adaptive immune system.

Gene–environment interaction

Genetic susceptibility is often expressed only under particular exposures, a process studied as gene–environment interaction. The best-known example is the "farm effect": many children growing up in farm-like environments are protected from later asthma. This is thought to reflect microbial exposure acting on immune genes during early development. Endotoxin, a bacterial cell-wall component, is one such exposure, and host molecules that bind endotoxin, such as CD14 and TLR4, are candidate mediators. In one farm study, being raised on a farm in childhood was protective against childhood-onset asthma among carriers of a particular TLR2 variant. A proposed "endotoxin switch" model suggests that the C allele of CD14 confers risk at low endotoxin exposure, whereas the T allele confers risk at high exposure, which could explain some contradictory findings between studies.

Other interactions are equally context-dependent. In the Isle of Wight birth cohort, maternal smoking during pregnancy was associated with early-onset persistent wheeze, and the effect was stronger in children carrying a common IL-13 haplotype. A Taiwanese case-control study also found that a GSTP1 genotype was linked to markedly higher asthma odds in areas with higher nitrogen oxide and sulphur dioxide levels. Replication has been uneven: differences in statistical power, study populations, study design and the characterization of exposures and phenotypes all make it hard to confirm interactions across studies.

Early-life exposures

The hygiene hypothesis was introduced by Strachan in 1989, and growing up with less microbial exposure may render the immune system susceptible to a Th2-predominant allergic response. The idea has since broadened: later frameworks propose that early-life contact with diverse microbial communities lowers the risk of allergic diseases and asthma. Infant antibiotic use is among the most studied factors. Pooled analyses find that infant antibiotic courses are linked to a higher later chance of asthma, although results differ considerably between studies. Proposed mechanisms include disruption of gut flora, which may weaken the establishment of oral tolerance and regulatory T-cell responses, which links the antibiotic question to the microbiome debate. Accumulating observational and experimental data tie early-life gut dysbiosis to later asthma. The evidence remains contested, and the hygiene hypothesis may not be the only explanation for the speed of the rise in allergic disease.

Environmental and host factors

Several other exposures act on airways that may already be primed by genetic or early-life factors. Outdoor and indoor air pollution, including emissions from combustion, tobacco smoke, occupational sensitisers, and damp housing with mould are all recognised contributors. Higher body mass index also appears as a risk factor in global burden analyses. Their relative weight differs across populations and across the life course, and they are discussed in more detail in the sections on epidemiology and public health.

Epidemiology and Global Burden

The most comprehensive recent estimates come from the Global Burden of Disease (GBD) 2021 study. In 2021, there were an estimated 260 million (95% UI 227–298) individuals with asthma and 129 million (124–134) individuals with atopic dermatitis worldwide. Absolute counts have moved in a less straightforward way: asthma cases declined from 287 million (250–331) in 1990 to 238 million (209–272) in 2005 but increased to 260 million in 2021. Population growth and ageing account for much of the rise in counts, while rates tell a different story. Age-standardised prevalence rates decreased by 40·0% (from 5568·3 per 100 000 to 3340·1 per 100 000) for asthma, and the age-standardised incidence rate fell from 736 per 100,000 population in 1990 to 516 per 100,000 in 2021. The decline appears to have slowed during the COVID-19 pandemic, when the downward trend in prevalence had stagnated.

Mortality and disability are concentrated where resources are scarcest. In 2021, the number of DALYs attributed to asthma was 21.42 million (95 % UI: 16.96 million to 26.89 million), with an ASDR of 264.62 per 100,000, and the number of deaths due to asthma was 436,192.95. GBD analyses find that asthma deaths and DALYs rates were concentrated in lower SDI regions. The Socio-demographic Index (SDI) shows an opposing pattern for prevalence: asthma incidence decreased with raising socio-demographic index (SDI), but asthma prevalence increased with increasing SDI. Age follows a similar split. People aged < 5 years exhibited the highest asthma incidence, and those aged ≥ 70 years old had the highest prevalence, death, and DALYs rates of asthma.

Sex and age patterns shift across the life course. In childhood, boys predominate: in most studies approximately 2/3 of the subjects with asthma or wheezing are males and 1/3 are females. Pediatric analyses place the peak in the peak in children aged 5–9 years, and the preschool group recorded a 34.17% decrease since 1990, the largest reduction among the pediatric age groups. The balance reverses in adolescence, when higher incidence and prevalence of asthma have been previously reported in males in childhood and in females in adolescence and adulthood. The timing of this switch is still debated, since conflicting research exists on whether puberty itself drives it. In adulthood, asthma predominantly affected females, and one GBD-based summary notes that the decrease in asthma burden occurred predominantly in men rather than women.

Projections suggest that case numbers will keep rising while age-standardised rates level off. GBD forecasts 275 million (224–330) asthma cases in 2050, with population growth driving this increase. Rates, however, are expected to remain stable (–23·2% [–44·4 to 5·3] for asthma and –1·4% [–9·1 to 7·0] for atopic dermatitis) from 2021 to 2050. The wide interval means that the future rate could still fall substantially or stay roughly where it is.

Geographic contrasts are substantial, and they depend on how burden is measured. Prevalence in some wealthy countries has levelled off, whereas the incidence continues to show a marked upward trend in many low-and middle-income countries. Childhood prevalence has historically been higher in developed countries than in developing countries, yet mortality is highest in poorer settings, so the same disease looks different depending on whether diagnosis or death is the outcome. These comparisons are hard to make directly. GBD estimates are model-based: they are produced using CODEm and DisMod-MR to estimate age-, sex-, and region-specific disease indicators, drawing on data from 389 sources for asthma. Survey and clinical estimates can diverge sharply, and one review reports that the prevalence of physician-diagnosed asthma reported was 4.3 %, which covered up to 21-fold across 70 countries. Differences in questionnaire wording, diagnostic criteria and data availability therefore affect how far such figures can be compared across countries and periods.

Diagnosis and Assessment

Clinical history and differential diagnosis

No single test confirms asthma. Diagnosis rests first on the history: episodic wheeze, chest tightness, cough and breathlessness that vary over time, worsen at night or on exposure to particular triggers, and often coexist with allergic disease or a family history of atopy. Examination is frequently normal between episodes, so the history carries much of the diagnostic weight. Clinicians must separate asthma from chronic obstructive pulmonary disease (COPD), which typically occurs in older adults with a smoking or other inhaled-exposure history and shows little lasting response to treatment. Other conditions that can mimic episodic breathlessness include vocal cord dysfunction, which produces inspiratory noise and throat-level obstruction rather than lower-airway wheeze; heart failure, which is suggested by orthopnoea, crackles and oedema; and foreign-body aspiration, which tends to have a sudden onset and may be unilateral.

Spirometry and reversibility

Spirometry is usually the first objective test. A reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) indicates airflow obstruction, but the cut-off varies between guidelines: GOLD uses a fixed value of 0.7 for COPD, whereas the Global Initiative for Asthma uses a somewhat looser threshold for adults and a higher one for children. In adults, an increase of at least 12% and 0.2 L in FEV1 or FVC after a short-acting bronchodilator is conventionally regarded as significant reversibility; in children aged five to 18 the threshold is 12% alone. Patients are asked to withhold short-acting bronchodilators for several hours beforehand, and a response is typically judged after a dose of around 400 µg salbutamol. Full reversibility is typical of asthma, whereas COPD usually responds only partly.

Reversibility is not a perfect discriminator. Large responses can occur in COPD, and many people with long-standing asthma show very little change after a bronchodilator. Some recent analyses argue that the 12%/200 mL rule has limited sensitivity and reproducibility, which has led to proposals for alternative criteria. Serial peak expiratory flow monitoring is therefore used alongside spirometry; a diurnal variation of more than 20% recorded at home over about two weeks favours asthma. In young children, studies have found spirometric indices to be more sensitive for detecting a bronchodilator response than for detecting obstruction itself, and the response magnitude observed is often smaller than the adult threshold.

Bronchial provocation tests

When spirometry is normal but clinical suspicion remains, bronchial provocation testing measures airway hyperresponsiveness, a central feature of asthma. The methacholine challenge is the most widely used: the patient inhales progressively higher doses of a cholinergic agonist, and the test is positive when FEV1 falls by 20% or more, a threshold expressed as the provocative concentration PC20. Methacholine is highly sensitive, so a negative result is often used to exclude asthma, but it is less specific. Histamine can be used in a similar way, though it lacks regulatory approval in the United States and Canada, where methacholine is licensed. Indirect challenges such as exercise and inhaled mannitol act through endogenous mediators released from mast cells, and they tend to have higher specificity, making a positive result more persuasive. Studies comparing methacholine and mannitol have reported different diagnostic properties, and a single test does not settle every case.

Type 2 biomarkers

Blood and airway markers of type 2 inflammation are increasingly used to support diagnosis and to predict treatment response, but none is decisive alone. Fractional exhaled nitric oxide (FeNO) is non-invasive and easy to perform, and in adults a level above about 25 ppb is commonly taken to indicate eosinophilic airway inflammation and a likelihood of corticosteroid response. However, the values seen in healthy people overlap substantially with those used to define elevated FeNO, and different guidelines use different cut-offs, such as 50 ppb in several international recommendations. Peripheral blood eosinophil counts are also informative, particularly for predicting exacerbations, but they are influenced by systemic factors. FeNO largely reflects IL-4 and IL-13 activity, whereas blood eosinophils mainly reflect IL-5, so the two markers may disagree. Combined thresholds have been proposed as a way to rule asthma in or out without further testing in some settings, although a retrospective study from China concluded that neither marker alone is sufficient for an accurate diagnosis. Serum IgE is not currently recommended as a stand-alone marker for eosinophilic asthma. Induced sputum cytology provides direct evidence of airway eosinophilia but is laborious and often unobtainable outside specialist centres.

Preschool wheeze

Diagnosis is especially difficult in preschool children. Many young children wheeze during viral infections, and wheezing in this age group is heterogeneous: many will not have asthma in later childhood, while others will. Lung function tests are hard to perform reliably at this age, and the bronchodilator and provocation criteria used in adults are not directly transferable. Clinicians therefore combine symptom patterns, atopic features, family history and treatment response, and the choice of whether to label a child as having asthma remains a practical and contested decision.

Treatment and Disease Management

Controller therapy and the anti-inflammatory reliever

Inhaled corticosteroids (ICS) form the base of long-term control. The Global Initiative for Asthma (GINA) recommends that almost everyone with asthma receive an ICS-containing regimen, either taken every day or, for adults and adolescents with mild disease, as a combination inhaler used only when needed. The 2025 GINA strategy divides medicines into controllers, relievers and add-on therapies. Its preferred approach, Track 1, uses low-dose ICS combined with formoterol, a fast-acting, long-acting β₂-agonist, as both the daily controller and the as-needed reliever. This is known as anti-inflammatory reliever therapy. In adults and adolescents, as-needed ICS-formoterol reduced severe exacerbations by roughly 60–65% compared with a short-acting β₂-agonist (SABA) reliever alone.

Track 2, which pairs a SABA reliever with a separate daily ICS, remains an alternative where Track 1 is not feasible. It depends heavily on daily ICS adherence, and GINA considers SABA-only treatment no longer acceptable at any step. For moderate or severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART), in which the same ICS-formoterol inhaler is used daily and as needed. Access remains a serious constraint: GINA has kept the two-track figure because combination inhalers are scarce in most low- and middle-income countries, where budesonide-formoterol has been added to the WHO essential medicines list as a possible low-cost option.

Stepwise escalation and de-escalation

Treatment is organised as a ladder. Steps 1 and 2 use as-needed low-dose ICS-formoterol, step 3 introduces daily low-dose MART, and step 4 uses medium-dose MART. Escalation is considered when control is poor despite correct inhaler technique and good adherence, and it typically moves within a track before any change in agent. At step 5, patients are referred to specialist services for phenotyping and add-on treatment, such as a long-acting muscarinic antagonist (LAMA), a leukotriene receptor antagonist (LTRA), low-dose azithromycin or a biologic. Patients with good symptom control can still have severe exacerbations or asthma-related death, so control is judged on risk as well as symptoms. When control is sustained, treatment is stepped down gradually, with review after each change, to the lowest level that keeps the disease controlled.

Biologic therapies for severe type 2 asthma

Biologics are reserved for severe asthma with type 2 inflammation, which is driven by cytokines such as IL-4, IL-5 and IL-13 and by IgE. Six biologics are approved for this purpose across four targeting strategies:

• Anti-IgE (omalizumab) is used when serum IgE falls within a defined range and there is sensitization to perennial aeroallergens.
• Anti-IL-5 and anti-IL-5 receptor agents (mepolizumab, reslizumab, benralizumab) are selected on blood eosinophil counts, typically at least 0.15 × 10⁹ cells/L at screening or 0.3 × 10⁹/L within the past year. Benralizumab is given monthly for three doses and then every eight weeks, and mepolizumab every four weeks.
• Anti-IL-4 receptor α (dupilumab) blocks signalling by both IL-4 and IL-13. It is considered when blood eosinophils or fractional exhaled nitric oxide (FeNO) are raised, and it can cause transient eosinophilia.
• Anti-TSLP (tezepelumab) acts on an upstream epithelial alarmin and is licensed without a biomarker requirement. It is effective in both type 2-high and type 2-low disease, although its benefit is attenuated in patients with the lowest biomarker levels.

Selection also depends on comorbidities and individual circumstances. Nasal polyposis, atopic dermatitis and food allergy favour some agents, while a history of high blood eosinophil counts raises concern for hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis, which favours anti-IL-5 therapy over dupilumab. Pregnancy plans are often decisive, as omalizumab is generally regarded as the safest option when pregnancy is possible in the near term. Switching to a different biologic after a suboptimal response is reported to succeed in some patients. Biologics are normally added only after modifiable factors, including adherence, inhaler technique, triggers and comorbidities, have been addressed.

Non-drug management and adherence

Non-pharmacological care is as important as medication. Clinicians check inhaler technique and adherence at each visit, and device choice matters: a single inhaler that serves as both controller and reliever reduces technique errors and the risk of inadvertent non-adherence compared with separate inhalers. Patients are taught to use a reliever only as needed rather than regularly, so that an increasing need for reliever use can be recognised as a sign of worsening control.

A written asthma action plan sets out how to recognise early deterioration, using symptoms or peak expiratory flow, and what to do at each stage, including when to increase treatment and when to seek urgent help. Self-monitoring, trigger reduction and smoking cessation are routine parts of care. Systematic reviews find that many patients have inadequate knowledge of their disease and of inhaler technique, and that a written plan, provider partnership, social support and reliable medication access all improve self-management.

Adherence is the central practical problem. It tends to decline over time, and poor adherence to preventer inhalers is associated with frequent exacerbations, heavy salbutamol use and, in some cases, pressure to escalate doses unnecessarily. Strategies to improve it include motivational discussion of barriers, correction of technique errors and simplified regimens.

Acute Exacerbations and Severe Attacks

Triggers and onset

An acute exacerbation is a period of worsening symptoms and lung function. The most common triggers are viral infections and environmental allergens, and workplace exposures to sensitizers or irritants can also provoke attacks. Infections were the main trigger of exacerbations in both groups in one 2016 review of children admitted to a paediatric emergency department, and allergy was the second most important trigger in school-aged children. The same study found that exacerbations peaked in autumn and winter among preschoolers, and in spring and early autumn among school-aged children. Cold air, exercise, air pollution and thunderstorms are also recognised triggers, although the response to each varies from person to person. Attacks usually develop over several hours, which leaves a window for early recognition and treatment even in severe cases.

Emergency treatment and admission

Clinicians grade exacerbations as mild, moderate, severe or life-threatening, using symptoms, physical examination, lung function and blood oxygen saturation. The immediate aims are to correct hypoxaemia and rapidly reverse airway narrowing. Both are best achieved by oxygen administration and repeated doses of short-acting beta2 agonists, which are usually combined early with the anticholinergic ipratropium bromide. Systemic corticosteroids, given orally or intravenously, are started early because they reduce the risk of relapse. For severe attacks, intravenous magnesium sulfate may be considered. Oxygen is generally targeted to keep saturations above about 92%, and is usually unnecessary in mild or moderate attacks. Patients whose symptoms worsen despite initial treatment, or who have severe or life-threatening features, are transferred to an acute-care facility, with severe cases treated as a medical emergency.

Life-threatening asthma and status asthmaticus

Status asthmaticus is a life-threatening condition characterized by progressive respiratory failure due to asthma that is unresponsive to standard therapeutic measures. Any patient who does not respond to initial nebulised bronchodilators should be regarded as potentially in this state. Warning signs include exhaustion, drowsiness and confusion, which may signal that the patient is tiring. Hypercapnia alone is not an indication for ventilation, whereas coma, cardiac or respiratory arrest and refractory hypoxaemia are absolute indications. Intubation itself is a hazardous moment: half of the life-threatening complications occur at or around the time of intubation, and hypotension is common when positive-pressure ventilation begins.

Non-invasive ventilation can reduce the work of breathing and help correct hypoxaemia and hypercapnia, but intubation should not be delayed if the patient does not improve on conservative therapy. Invasive ventilation carries specific risks. Air trapping causes dynamic hyperinflation, which can produce hypotension, barotrauma and pneumothorax. Practice therefore favours a protective strategy with low tidal volumes, lengthened expiratory time and tolerance of permissive hypercapnia, together with sedation and continued bronchodilator therapy. Reported mortality for status asthmaticus ranges from about 1% to 10%, and the risk is greater when severity is underestimated or treatment is inadequate.

Follow-up after an attack

Discharge planning is an important part of care. Patients are generally sent home with a reliever inhaler and a controller inhaler, a short course of oral corticosteroids, education and a follow-up appointment within a few days. Review should cover inhaler technique, adherence, written action plans and modifiable risks such as allergen exposure and smoking.

A key modifiable risk is excessive use of short-acting β2-agonist relievers. In a Swedish national cohort, one-third of asthma patients collected three or more SABA canisters annually, and mortality rose with the number of canisters collected, with a hazard ratio of 2.35 for those collecting eleven or more compared with two or fewer. A UK national review identified high SABA prescribing as a key factor in more than 40% of asthma deaths. These are observational associations, and overuse may partly mark poor underlying control, but they support reviewing reliever use after every attack and ensuring that controller therapy is in place. Clinicians' definitions of acceptable use have also been found to vary widely, which is one reason follow-up visits are emphasised in guidance.

History of Understanding and Treatment

The word itself is a Greek inheritance. The English term derives from the Greek word "asthmaino," which indicates "panting or gasping". Hippocrates is usually credited with its first medical use, though scholars still debate whether he meant a distinct disease or a symptom of illness, and he linked the condition to certain occupations such as fishermen, tailors and metalworkers. Later Greek writers built on this. Aretaeus of Cappadocia, writing in the first century CE, gave the first full clinical description of the condition. Galen, a few generations later, is considered the first to describe asthma as an obstruction of the air passages, and he dissected animals to study respiratory disorders. In the medieval Arabic tradition the condition was called al-Rabw, and Avicenna explained the attack as a narrowing of the breathing passages produced by phlegm gathering in the windpipe.

From the Renaissance until the nineteenth century, asthma was often treated as a disorder of nerves or muscle, and many physicians regarded its attacks chiefly as a spasm of the bronchial muscles. Understanding changed slowly through the twentieth century. In 1946, Curry first quantified bronchial or airway hyperresponsiveness as a major pathophysiological feature of asthma by giving subjects increasing doses of inhaled histamine, and this test later became one of the most reliable diagnostic tools. The same period saw inhaled adrenaline-type drugs, then more selective bronchodilators, become the main means of relieving attacks, while inhaled corticosteroids, introduced in the 1970s, began to be used to suppress the underlying inflammation. Together these developments shifted the field from viewing asthma as a spasm toward treating it as a chronic inflammatory disease, a shift that has shaped treatment ever since.

The Global Initiative for Asthma (GINA) was a product of the later stage of this change. It was established by the World Health Organization and the National Heart, Lung and Blood Institute in 1993 to develop a global strategy for managing and preventing asthma. Its first report, published in 1995, A Global Strategy for Asthma Management and Prevention, has been translated into several languages, widely adopted and provided the foundation for several asthma guidelines worldwide. Its approach moved from expert opinion toward evidence: the late 1990s saw a change from an opinion-based to an evidence-based approach to managing asthma severity. The reports are prepared by international experts from primary, secondary and tertiary care, and are annually updated following a review of evidence. GINA itself describes its output as a strategy rather than a binding guideline, which national bodies can adapt to local conditions, and that flexibility has helped standardize diagnosis and stepwise treatment across very different health systems.

The move away from chlorofluorocarbon (CFC) propellants illustrates how environmental policy reached respiratory medicine. All metered-dose inhalers marketed before 1995 contained CFCs as a propellant. Because these compounds deplete the stratospheric ozone layer, their production was banned from 1996 under the terms of the Montreal Protocol, except for specific exemptions. Replacement was costly and slow. Development costs for switching inhalers to hydrofluoroalkane propellants have been estimated well in excess of US$2 billion, and the transition has taken over 20 years to complete. In the United States, the FDA did not end the essential-use status of CFC albuterol inhalers until an April 2005 rule. Afterwards, out-of-pocket costs rose: one analysis found that the average out-of-pocket cost for a 30-day supply of albuterol was around $14 between 2004 and 2006, and ranged between $18 and $25 between 2007 and 2010. Because the newer propellants are potent greenhouse gases, the transition is also linked to climate policy; one analysis expects that a global inhaler transition will probably take at least another decade and could lead to significantly increased cost to the 650 million patients with asthma or COPD.

Social, Economic and Public Health Dimensions

Asthma imposes costs that extend well beyond the clinic. In the United States, a national analysis of 2008–2013 data estimated that asthma was responsible for $3 billion in losses due to missed work and school days, $29 billion due to asthma-related mortality, and $50.3 billion in medical costs. The authors' own caveat is that these totals are conservative: their models excluded people whose asthma went untreated, and they left out transport costs, time spent waiting for appointments, and reduced productivity while people were working or studying with symptoms (the study likely underestimated the total cost, because it did not include people whose asthma went untreated, and it also omitted nonmedical costs such as transportation expenses, time lost waiting for appointments and diminished productivity). Absenteeism is closely tied to severity. In a separate analysis of Medical Expenditure Panel Survey records from 2010–2017, patients with mild, moderate and severe asthma missed on average 0.76, 2.31 and 7.19 work or school days a year, which corresponded to indirect costs of about $106, $321 and $1,000 per person (patients with mild, moderate, and severe asthma reported 0.76, 2.31, and 7.19 missed work or school days, resulting in $106, $321, and $1000 indirect costs per person per year, respectively). The burden also reaches families. Caregivers of children with poorly controlled asthma report more days off work and heavier financial strain than caregivers of children whose asthma is better controlled (caregivers of children with poorly controlled asthma report more days off work and more significant financial burden than those with better controlled asthma).

The size of these costs varies with how health care is financed. At the state level in the US, per-capita medical costs of asthma ranged from roughly $1,860 to $2,514 (per capita medical costs of asthma ranged from $1,860 (Mississippi) to $2,514 (Michigan)). Uninsured people also show markedly lower recorded spending on asthma than insured people. That pattern more likely reflects unmet need, such as forgone prescriptions and visits, than milder disease, though the data alone cannot separate these explanations.

Access to treatment and to a healthy environment is unevenly distributed. Low income is linked to higher asthma prevalence, more exacerbations, hospitalizations and intensive care admissions (low income is linked to asthma prevalence, exacerbations, hospitalizations, and intensive care unit admission). Housing conditions are a major pathway. Poor housing quality has been associated with childhood asthma and worse morbidity, and children in low-income communities are disproportionately exposed to cockroach and mouse allergens (children with asthma living in low-income communities are disproportionately exposed to pest allergens such as mouse and cockroach). Exposure to outdoor air pollution follows similar lines, with people living in poverty and those with less education more likely to breathe higher levels of it. Racial disparities in the US are large: non-Hispanic Black children are twice as likely to have an asthma diagnosis and five times likelier to be hospitalized for asthma than their non-Hispanic White peers. An analysis of the NHLBI Severe Asthma Research Program found that persistent racial disparities in asthma can largely be explained by socioeconomic and environmental factors, such as access to healthcare and housing conditions. Barriers to care compound these inequities, including inadequate insurance, overstretched clinics, too few culturally and linguistically competent providers, and low health literacy (major barriers to health care access in poor communities include lack of adequate health insurance coverage, overwhelmed clinics, shortages of culturally and linguistically competent providers, and low health literacy). Globally, the World Health Organization has noted that more than 80% of all deaths from asthma happen in low- or lower-middle-income countries where asthma is less likely to be diagnosed and properly treated.

Public health responses operate on several fronts. Air quality regulation addresses the environmental exposures that drive both incidence and exacerbations, and experts have argued that reducing air pollution, improving housing quality and expanding access to medical care must proceed together (both the public and private sectors must reduce air pollution, improve housing quality, and enhance access to medical care). Tobacco control reduces another preventable exposure, since secondhand smoke is among the recognised triggers in children's exposure profiles. School-based and community programmes are a central delivery route because asthma is a major cause of school absence; a US study highlighted mobile asthma clinics and joint programmes with schools in high-prevalence areas as promising options (the study highlights the potential of targeted interventions, such as mobile asthma clinic programs and joint programs with schools where asthma prevalence is high. Asthma is a leading cause of school absence.). Surveillance of prevalence, hospital use and absenteeism allows authorities to track these gaps over time. Affordability of essential inhalers is the final lever: when reliever and controller inhalers are costly, adherence falls and the cost burden rises through avoidable emergency care.

Asthma also affects psychological wellbeing and quality of life, both in patients and in the people who care for them. In a study of children's caregivers, anxiety, social phobia, depression, acute and chronic psychological disorders, and poor quality of life related to mental health were significantly more prevalent in caregivers of asthmatic children. Those same conditions were linked to a higher risk of uncontrolled asthma, which suggests that the psychological state of families is itself a clinical variable. Patients show a similar pattern: anxiety is twice as prevalent in people with asthma than in the general population and is linked to poorer quality of life across all age groups. Stigma adds to this burden because it can delay recognition of depression and anxiety, which will not always be immediately obvious, and stigma is a barrier to identifying these conditions. Family routines are also disrupted by the unpredictability of attacks, which can weaken asthma control in turn. Psychological interventions have shown some benefit: mindfulness-based programmes have improved asthma-related quality of life and reduced anxiety and depressive symptoms in several trials.

Research Frontiers and Unresolved Questions

Diverging regional trends

Survey data do not show one global direction. The prevalence of current wheeze decreased in low-income countries and increased in lower-middle-income countries, based on the Global Asthma Network Phase I study, which was compared with earlier ISAAC surveys. Wheeze prevalence in children and adolescents has otherwise remained fairly stable from ISAAC Phases I to III and to GAN Phase I, though some individual centres have changed substantially. Explaining the rise in some low- and middle-income settings remains an open problem. Proposed drivers include urbanisation, dietary change and exposure to pollutants, and climate change is hypothesised to alter pollen seasons and lengthen allergen exposure. The relative weight of these factors is not established.

Measurement complicates interpretation. A meta-analysis covering 69 countries linked higher recorded prevalence to cleaner air, greater national wealth and better access to care, and its authors read the gap in poorer countries as partly reflecting underdiagnosis and underreporting. Weak reporting may also account for part of the apparent decline in the poorest countries.

Endotypes and precision treatment

Classification is moving from clinical labels toward molecular endotypes, but the biomarkers in routine use remain imperfect. Blood eosinophil counts and serum IgE help clinicians select biologic therapy, yet they predict treatment outcomes poorly for some patients and differ between racially and ethnically diverse populations. Stratification based on a few point-of-care markers produces considerable overlap between endotype groups and has not solved the incomplete response to type 2-targeted biologics. Some groups have proposed DNA methylation scores as a less biased alternative. Marker performance also varies by population: YKL-40 and IL-17 showed moderate predictive value in Western cohorts but performed markedly worse in validation studies in Asian cohorts.

Machine learning is widely expected to integrate multi-omic, imaging and digital data into more precise endotype definitions. However, microbiome-based response predictors remain unvalidated, and reviewers stress that model-derived signatures need testing in large cohorts. Cost, safety in particular groups and poor adherence also limit how far precision approaches can reach routine care.

Remission

Whether asthma can enter remission is contested, partly because there is no agreed definition. A scoping review of paediatric studies published between 2010 and 2024 found that most remission definitions relied on the absence of symptoms, while objective measures such as normal lung function were rarely included, and it called for consensus criteria suited to children. Reported rates vary widely: remission rates of childhood asthma have been reported between 16 and 60% by early adulthood, according to prior longitudinal studies, and the variation is attributed to differing study designs, follow-up periods and populations. In one US paediatric cohort, about a quarter of participants were in clinical remission by adulthood, but only 15% met a strict definition that also required normal airway responsiveness. In a small allergic-asthma cohort, more than half of those in clinical remission still had low lung function or bronchial hyperresponsiveness. Relapse is also common: up to half of children who appear to outgrow asthma may have symptoms return in adulthood, and remission should not be equated with cure.

Prevention in early life

Whether asthma can be prevented in early life is unresolved. Early-life factors such as viral infections, allergen load, antibiotic use and the microbial environment have been implicated, but it is unclear whether modifying them prevents asthma or merely postpones symptoms. Long-term trials that follow children through childhood and adolescence are costly and slow, and predicting which children will develop persistent disease is itself difficult.

Diagnosis in young children and standardised definitions

Diagnosing asthma in preschool children remains especially hard, and asthma in infancy often goes unrecognized and thus untreated. Definitions also vary between studies. In a survey of adolescents in Durban, South Africa, fewer than half of those with current or severe symptoms had a doctor's diagnosis, illustrating how survey-based and clinical estimates can diverge. Because many countries do not report prevalence or do not have accurate statistics, the true global burden of asthma is difficult to determine. Harmonising questionnaires, clinical criteria and surveillance methods is therefore a precondition for comparing results across populations, and for judging whether the observed trends reflect real change in disease or change in how it is recognised.

References

1. FAQ - Global Initiative for Asthma - GINAginasthma.org
2. GINA 2025 1 Global Strategy for Asthma Management and Prevention (2025 update)ginasthma.org
3. GINA Definition of Asthma and Phenotypesuspharmacist.com
4. Asthma Management, Adults and Adolescents: GINA 2025 Guideline Summaryreference.medscape.com
5. 1. Introduction to Asthma - Children's Mercychildrensmercy.org
6. Epidemiology of asthma - UpToDateuptodate.com
7. GINA - At-A-Glance Asthma Management Referenceginasthma.org
8. Asthma remission: A path to cure?apjai-journal.org
9. The definition of asthma remission in children: A scoping review by the WAO Paediatric Asthma Committeencbi.nlm.nih.gov
10. Is remission a meaningful outcome in asthma? - ScienceDirectsciencedirect.com
11. Asthma Origins and Remission Studyclinicaltrials.gov
12. The definition of remission in asthma should be unique and specific - PMCpmc.ncbi.nlm.nih.gov
13. Pro: Clinical remission in asthmapublications.ersnet.org
14. Clinical Remission and Its Determinants in Adult Severe Asthma Patients Receiving Biologic Therapy: A Retrospective Analysisncbi.nlm.nih.gov
15. Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse modelsncbi.nlm.nih.gov
16. Childhood and Adult Asthma: Phenotype- and Endotype-Based Biomarkersintechopen.com
17. Neutrophils and Asthmancbi.nlm.nih.gov
18. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons - PMCpmc.ncbi.nlm.nih.gov
19. Neutrophilic asthma may not be a distinct endotypepublications.ersnet.org
20. Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choicencbi.nlm.nih.gov
21. Phenotypes and endotypes of adult asthma: Moving toward precision medicine - Journal of Allergy and Clinical Immunologyjacionline.org
22. Aspirin-exacerbated respiratory disease (AERD): Current understanding of AERD - ScienceDirectsciencedirect.com
23. Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease - Journal of Allergy and Clinical Immunologyjacionline.org
24. Pathogenesis of NSAID-induced reactions in aspirin-exacerbated respiratory disease - PMCpmc.ncbi.nlm.nih.gov
25. Aspirin-Exacerbated Respiratory Disease Requiring Desensitization Prior to Planned Percutaneous Catheterization Interventionncbi.nlm.nih.gov
26. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature - Journal of Allergy and Clinical Immunologyjacionline.org
27. Epidemic thunderstorm asthmaalfredhealth.org.au
28. Who's at risk of thunderstorm asthma? The ryegrass pollen trifecta and lessons learnt from the Melbourne thunderstorm epidemic - ScienceDirectsciencedirect.com
29. Airborne grass pollen and thunderstorms influence emergency department asthma presentations in a subtropical climate - ScienceDirectsciencedirect.com
30. Revisiting Type 2‐high and Type 2‐low airway inflammation in asthma: current knowledge and therapeutic implications - Robinson - 2017 - Clinical & Experimental Allergy - Wiley Online Libraryonlinelibrary.wiley.com
31. Type 2 inflammation in asthma and other airway diseasespublications.ersnet.org
32. Airway remodelling in asthma and the epithelium: on the edge of a new erapublications.ersnet.org
33. Airway Remodeling in Asthmancbi.nlm.nih.gov
34. Type 2 Inflammation and the Evolving Profile of Uncontrolled Persistent Asthmaemjreviews.com
35. Epithelial alarmins TSLP, IL-33, and IL-25 in asthma pathogenesis: mechanistic roles and therapeutic implicationslink.springer.com
36. Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory responsencbi.nlm.nih.gov
37. Combined exposure to the alarmins TSLP, IL‐33 and IL‐25 enhances mast cell‐dependent contractions of human bronchi - Belikova - 2023 - Clinical & Experimental Allergy - Wiley Online Libraryonlinelibrary.wiley.com
38. The Role of Airway Epithelial Cell Alarmins in Asthmancbi.nlm.nih.gov
39. Sounding the alarmins—The role of alarmin cytokines in asthma - Gauvreau - 2023 - Allergy - Wiley Online Libraryonlinelibrary.wiley.com
40. Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targetsncbi.nlm.nih.gov
41. Frontiersfrontiersin.org
42. Chronic Allergen Challenge Induces Corticosteroid Insensitivity With Persistent Airway Remodeling and Type 2 Inflammationncbi.nlm.nih.gov
43. Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthmanature.com
44. The genetics of asthma and the promise of genomics-guided drug target discovery - ScienceDirectsciencedirect.com
45. Decoding the genetic and epigenetic basis of asthma - Stikker - 2023 - Allergy - Wiley Online Libraryonlinelibrary.wiley.com
46. The intersect of genetics, environment, and microbiota in asthma—perspectives and challenges - Journal of Allergy and Clinical Immunologyjacionline.org
47. Frontiersfrontiersin.org
48. Gene–environment interactions in asthma - PMCpmc.ncbi.nlm.nih.gov
49. Gene-environment interactions in asthma - Journal of Allergy and Clinical Immunologyjacionline.org
50. Gene–environment interactions in asthma - PMC - NIHpmc.ncbi.nlm.nih.gov
51. Genetics and Gene-Environment Interactions in Childhood and Adult Onset Asthma - PMCpmc.ncbi.nlm.nih.gov
52. Early life exposure to antibiotics and the risk of childhood allergic diseases: An update from the perspective of the hygiene hypothesis - ScienceDirectsciencedirect.com
53. Early-life microbiota exposure and prevention of childhood asthma: immunological mechanisms and intervention perspectives - PMCpmc.ncbi.nlm.nih.gov
54. The evolution of the hygiene hypothesis: The role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseasesresearchgate.net
55. Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies - ScienceDirectsciencedirect.com
56. Heritability and confirmation of genetic association studies for childhood asthma in twins - Ullemar - 2016 - Allergy - Wiley Online Libraryonlinelibrary.wiley.com
57. Genome-Wide Association Studies of Asthma - ScienceDirectsciencedirect.com
58. Global, regional, and national burden of asthma and atopic dermatitis, 1990–2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021healthdata.org
59. Frontiersinfrontiersin.org
60. (PDF) Global, regional, and national burden of asthma and atopic dermatitis, 1990-2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021academia.edu
61. Global, regional, and national burden of asthma from 1990 to 2021: A systematic analysis of the global burden of disease study 2021mednexus.org
62. Cross-country health inequality in the asthma burden: findings from the global burden of disease study 2021ncbi.nlm.nih.gov
63. Impact of gender on asthma in childhood and adolescence: a GA2LEN review - Almqvist - 2008 - Allergy - Wiley Online Libraryonlinelibrary.wiley.com
64. Global burden of asthma among children and adolescents with projections to 2050: a comprehensive review and forecasted modeling studye-cep.org
65. Sex discordance in asthma and wheeze prevalence in two longitudinal cohortsjournals.plos.org
66. Genetic and observational evidence supports a causal role of sex hormones on the development of asthmancbi.nlm.nih.gov
67. Global, regional, and national burden of chronic obstructive pulmonary disease and asthma from 1990 to present: risk attributions and projections to 2050 - PubMedpubmed.ncbi.nlm.nih.gov
68. Epidemiology of asthmaen.wikipedia.org
69. Global, regional, and national burden of asthma and atopic dermatitis, 1990–2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021researchgate.net
70. Cross-country health inequality in the asthma burden: findings from the global burden of disease study 2021 - PMCpmc.ncbi.nlm.nih.gov
71. The epidemiology of asthma and its attributable risk factors from 1990 to 2021: A systematic analysis based on the Global Burden of Disease Study 2021 and Mendelian Randomization Studies - ScienceDirectsciencedirect.com
72. Frontiersfrontiersin.org
73. Mechanisms driving gender differences in asthma - PMC - NIHpmc.ncbi.nlm.nih.gov
74. Office Spirometry: Indications and Interpretationaafp.org
75. Distinguishing Asthma and COPD in Primary Care: A Case-based Approachaafp.org
76. 1 SPIROMETRY FOR HEALTH CARE PROVIDERSgoldcopd.org
77. Immediate bronchodilator response in FEV1 as a diagnostic criterion for adult asthmapublications.ersnet.org
78. New spirometry interpretation algorithm: Primary Care Respiratory Alliance of Canada approach - PMCpmc.ncbi.nlm.nih.gov
79. Spirometry: Types, Interpretation, and Instructionspatient.info
80. Stop Diagnosing Asthma and COPD With a Reversibility Testdocwirenews.com
81. Assessment of Airway Bronchodilation by Spirometry Compared to Airway Obstruction in Young Children with Asthma - PMCpmc.ncbi.nlm.nih.gov
82. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthmancbi.nlm.nih.gov
83. Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatmentncbi.nlm.nih.gov
84. Bronchodilation Test with Inhaled Salbutamol Versus Bronchial Methacholine Challenge to Make an Asthma Diagnosis: Do They Provide the Same Information? - ScienceDirectsciencedirect.com
85. Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthmancbi.nlm.nih.gov
86. The Correlation Between Fractional Exhaled Nitric Oxide (FeNO), Blood Eosinophil Count, Immunoglobulin E Levels, and Spirometric Values in Patients With Asthmancbi.nlm.nih.gov
87. Fractional exhaled nitric oxide in monitoring biological treatment for severe asthma in adults: Clinical implications and future perspectives - ScienceDirectsciencedirect.com
88. Methacholine Challenge Testlung.org
89. 2025 Global Initiative for Asthma (GINA) Reportsfhp.org
90. Updated 2025 Updated November 2025 ©2025 Global Initiative for Asthmaginasthma.org
91. Summary Guide for Asthma Management and Preventionginasthma.org
92. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) updatencbi.nlm.nih.gov
93. Choosing the Right Biologic for the Right Patient With Severe Asthma - CHESTjournal.chestnet.org
94. Choosing the Right Biologic for the Right Patient With Severe Asthma - PMCpmc.ncbi.nlm.nih.gov
95. Tailored Biologics Selection in Severe Asthma - PMCpmc.ncbi.nlm.nih.gov
96. Head‐To‐Head Comparison of Biologic Efficacy in Asthma: What Have We Learned?ncbi.nlm.nih.gov
97. Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient - Respiratory Medicineresmedjournal.com
98. Frontiersfrontiersin.org
99. (PDF) Management of asthma: Adherence, inhaler technique and self-managementresearchgate.net
100. Knowledge, perceptions, facilitators, and barriers towards asthma self-management among patients: A systematic review of the literature - PMCpmc.ncbi.nlm.nih.gov
101. Guidelines from the National Asthma Education and Prevention Programnhlbi.nih.gov
102. Acute Asthma in the Pediatric Emergency Department: Infections Are the Main Triggers of Exacerbationsncbi.nlm.nih.gov
103. Management of Acute Asthma Exacerbationsaafp.org
104. Status asthmaticus in the medical intensive care unit: A 30-year experience - ScienceDirectsciencedirect.com
105. Management of life-threatening asthma in adults - Continuing Education in Anaesthesia, Critical Care and Painbjaed.org
106. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programmepublications.ersnet.org
107. Management of acute asthma in adults in the emergency department: nonventilatory management - PMCpmc.ncbi.nlm.nih.gov
108. Asthma Exacerbation in Adultsemergencycarebc.ca
109. Managing Acute Asthma Exacerbationsuspharmacist.com
110. Acute asthma exacerbation - Knowledge @ AMBOSSamboss.com
111. Clinical review: Severe asthma - PMC - NIHpmc.ncbi.nlm.nih.gov
112. Decapneization as supportive therapy for the treatment of status asthmaticus: a case reportncbi.nlm.nih.gov
113. Management of Life-Threatening Asthma - Chest Journaljournal.chestnet.org
114. “Tossing a coin:” defining the excessive use of short-acting beta2-agonists in asthma—the views of general practitioners and asthma experts in primary and secondary carencbi.nlm.nih.gov
115. Historical Review Summing up 100 years of asthmasciencedirect.com
116. A Brief History of Asthmahubpages.com
117. The GINA asthma strategy report: what’s new for primary care?nature.com
118. History of guidelines for the diagnosis and management of asthma: from opinion to control - PubMedpubmed.ncbi.nlm.nih.gov
119. (PDF) Global Initiative for Asthma (GINA) guidelines: 15 years of applicationresearchgate.net
120. Transition to CFC-free metered dose inhalers — into the new millennium - ScienceDirectsciencedirect.com
121. MONTREAL PROTOCOL ON SUBSTANCES THAT DEPLETE THE OZONE LAYER UNEPozone.unep.org
122. FDA Ban on CFCs in Asthma Inhalers Raised Costs for Patients, New Study Findsraps.org
123. Hydrofluorocarbons, Climate, and Health — Moving the Montreal Protocol beyond Ozone-Layer Recoverynejm.org
124. Asthma - New World Encyclopedianewworldencyclopedia.org
125. The First Description of Asthma Due to Heart Conditions in the History of Medicine - CHESTjournal.chestnet.org
126. Definition of Asthma in the Middle Ages - PMCpmc.ncbi.nlm.nih.gov
127. Economic Burden of Asthma in the United States, 2008–2013academic.oup.com
128. Asthma costs the US economy more than $80 billion per yearsciencedaily.com
129. Full article: Medical Costs and Productivity Loss Due to Mild, Moderate, and Severe Asthma in the United Statestandfonline.com
130. Perceived Stress in the Primary Caregivers of Adolescents with Asthma: A Cross-Sectional Study - PMCpmc.ncbi.nlm.nih.gov
131. State-level medical and absenteeism cost of asthma in the United States: Journal of Asthma: Vol 54, No 4tandfonline.com
132. Asthma and the social determinants of health - Annals of Allergy, Asthma & Immunologyannallergy.org
133. Asthma and the Social Determinants of Health - PMC - NIHpmc.ncbi.nlm.nih.gov
134. Housing Disparities and Asthma: Reinvesting in Neighborhoods to Promote Health Equitypolicylab.chop.edu
135. NHLBI IN THE PRESSnhlbi.nih.gov
136. Community Asthma Initiative to Improve Health Outcomes and Reduce Disparities Among Children with Asthmacdc.gov
137. asthma socioeconomicwebmd.com
138. Relationship between pediatric asthma and psychosocial status of caregivers - PubMedpubmed.ncbi.nlm.nih.gov
139. Desktop Helper No. 21 - Asthma and mental health: holistic and practical guidance for primary care - online versionipcrg.org
140. CDC Study Puts Economic Burden of Asthma at More Than $80 Billion Per Yearajmc.com
141. Managing Asthma in Low-Income, Underrepresented Minority, and Other Disadvantaged Pediatric Populations: Closing the Gap - PMCpmc.ncbi.nlm.nih.gov
142. Review on the relationship of asthma and mental disorders - ScienceDirectsciencedirect.com
143. ED-Initiated School-based Asthma Medication Supervisioncdn.clinicaltrials.gov
144. Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study - The Lancetthelancet.com
145. Global Burden of Disease due to Asthmaglobalasthmareport.org
146. Asthma in Children and Adults—What Are the Differences and What Can They Tell us About Asthma? - PMCpmc.ncbi.nlm.nih.gov
147. Allergic diseases and asthma: a global public health concern and a call to actionncbi.nlm.nih.gov
148. The Global Impact of Asthma in Adult Populationsannalsofglobalhealth.org
149. Low Estimated Burden of Asthma in Low- and Middle-Income Countries Likely Reflects Underdiagnosis, Underreportingpatientcareonline.com
150. Epigenetic patient stratification via contrastive machine learning refines hallmark biomarkers in minoritized children with asthmancbi.nlm.nih.gov
151. Asthma endotypes and theratypes - ScienceDirectsciencedirect.com
152. Multiomics and Machine Learning Reveal Distinct Immune-Metabolic Signatures and Diagnostic Biomarkers for Asthma Inflammatory Endotypes - PMCpmc.ncbi.nlm.nih.gov
153. Are We Meeting the Promise of Endotypes and Precision Medicine in Asthma?journals.physiology.org
154. Microbiome-driven precision medicine in asthma: Roles of targeted therapies and artificial intelligence - PubMedpubmed.ncbi.nlm.nih.gov
155. Precision medicine in asthma: endotype stratification, biomarker-guided biologics, and emerging therapeutic strategies - PubMedpubmed.ncbi.nlm.nih.gov
156. Pediatric Asthma Lung Function Could Predict Adult Remissionhcplive.com
157. Does Childhood Asthma Go Away?myasthmateam.com
158. Can Asthma Go Away? Remission, Cure & Long-Term Controldmvallergy.com
159. Persistence and Remission in Childhood Asthma: A Population-Based Asthma Birth Cohort Studyjamanetwork.com
160. pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov