Asthma

• Asthma is a chronic inflammatory disease of the airways that produces episodes of wheeze, breathlessness, chest tightness and cough, driven by variable (usually reversible) airflow limitation and airway hyperresponsiveness.
• It is common worldwide and its burden falls most heavily on low- and middle-income countries, because diagnosis and inhaled treatment are often delayed or unavailable.
• Diagnosis rests on a compatible history plus objective evidence of variable airflow limitation, most often bronchodilator reversibility, but peak-flow variability, FeNO and bronchial challenge all have a place.
• Long-term treatment follows the GINA five-step approach: no-one should receive a short-acting beta-agonist (SABA) alone. The preferred Track 1 uses low-dose inhaled corticosteroid (ICS)-formoterol as the reliever at every step, either as needed in mild asthma or as maintenance-and-reliever therapy (MART) in moderate and severe asthma.
• Acute exacerbations are managed with controlled oxygen, repeated inhaled SABA (with ipratropium in severe attacks), early systemic corticosteroids, and intravenous magnesium for the severe cases that do not respond; hospitalise on clinical grounds.
• Because many asthma deaths occur in people with apparently mild disease, control, risk factors, triggers and inhaler technique need review at every visit.

By the end of this page you should be able to:

1. Define asthma and describe its typical symptom pattern and natural variability.
2. Explain the chain from airway inflammation and Th2 (type 2) inflammation to wheeze and reversible obstruction, and distinguish Th2 from non-Th2 phenotypes.
3. List the common triggers and the main differential diagnoses, with the feature that separates each.
4. Plan the investigation of suspected asthma and interpret the main diagnostic tests and their thresholds.
5. Classify asthma control and severity, and step long-term treatment according to the GINA tracks.
6. Manage an acute exacerbation in primary or acute care, including doses, admission criteria and signs of impending respiratory failure.
7. Adjust care for special groups (pregnancy, children, exercise, aspirin-sensitive, occupational asthma) and for low-resource settings.

Asthma is a heterogeneous disease defined by a history of respiratory symptoms (wheeze, shortness of breath, chest tightness and cough) that vary over time and in intensity, together with variable expiratory airflow limitation. Airflow may become persistently reduced in long-standing disease. The condition is usually associated with airway hyperresponsiveness and airway inflammation, but neither is necessary or sufficient for the diagnosis. ^[1]

Asthma is a syndrome rather than a single mechanism: clinical phenotypes (childhood-onset versus late-onset, allergic versus non-allergic) correlate only weakly with the underlying cellular process or with treatment response. ^[1]

A useful way to classify asthma for management is by inflammatory phenotype, because this guides the choice of add-on treatment in severe disease:

• Th2-high (type 2) asthma. The airway is infiltrated by eosinophils. Epithelial cytokines (interleukin-33 [IL-33] and thymic stromal lymphopoietin [TSLP]) drive dendritic cells and T helper 2 (Th2) cells, which release IL-4, IL-5 and IL-13; IL-5 recruits eosinophils, while IL-13 drives mucus and bronchial hyperresponsiveness. IgE class switching produces allergic sensitisation. Th2-high disease often shows raised FeNO, blood or sputum eosinophilia, childhood onset and allergy. ^[3]
• Th2-low (non-Th2) asthma. Usually neutrophilic or paucigranulocytic. It is more common in older adults, smokers and obese patients, is less responsive to ICS, and is the phenotype most likely to be severe and corticosteroid-refractory. ^[3]
• Aspirin-exacerbated respiratory disease. A severe phenotype, usually in adults, with asthma, chronic rhinosinusitis and nasal polyps, triggered by cyclo-oxygenase-1 (COX-1) inhibitors such as aspirin and other non-steroidal anti-inflammatory drugs. Patients need strict avoidance of COX-1 inhibitors and specialist care.

Asthma is one of the most common chronic diseases worldwide. GBD-based analyses estimate roughly 262 million people with asthma in 2019, about 21.6 million disability-adjusted life years, and about 461,069 deaths, of which roughly 90% of the burden is borne in low- and middle-income countries. ^[7] It causes morbidity at every age and in every country; the prevalence has risen in many countries, especially among children. ^[1]

Asthma arises from a gene-environment interaction. No single cause is identified for most cases. Recognised contributors and risk factors for developing asthma or for losing control include: ^[1]

• Atopy and allergy. Eczema, allergic rhinitis, food allergy and a family history of asthma are strong risk factors, particularly for childhood-onset allergic asthma.
• Infections in early life. Viral wheeze in infancy and severe respiratory infections are associated with later asthma, although the direction of causation is debated.
• Environmental exposures. Tobacco smoke (prenatal and postnatal), indoor and outdoor air pollution, allergens (dust mite, pollen, moulds, animal dander) and occupational agents (biological and chemical sensitizers such as flour, enzymes, isocyanates, wood dusts, latex).
• Hormonal and mechanical factors. Female sex after puberty, obesity and early gestational exposures.
• Modifiable triggers for exacerbations. Viral respiratory infections, poor adherence to ICS, SABA overuse, smoking, air pollution, weather change and emotional stress.

Everything in asthma follows from four linked processes. ^[1]

1. Airway inflammation. Inflammatory cells infiltrate the airway wall and lumen, amplifying mucus production and microvascular leak. In Th2-high disease this is eosinophilic; in other forms it can be neutrophilic.
2. Airway hyperresponsiveness. The inflamed airway narrows excessively in response to stimuli that would not affect a normal airway, so that cold air, exercise, allergen or irritant produces bronchospasm out of proportion to the stimulus.
3. Variable airflow limitation. Bronchospasm, mucus and inflammatory swelling narrow the lumen; airways are more obstructed at low lung volumes, which is why wheeze is worse in expiration and at night. The limitation is variable, often reversing spontaneously or with a bronchodilator, especially early in the disease.
4. Airway remodelling. In long-standing asthma, structural change (goblet-cell hyperplasia, subepithelial fibrosis, smooth-muscle hypertrophy) can make airflow limitation partially fixed, which is why poorly controlled asthma loses the very reversibility that defines it.

The wheeze itself is produced by turbulent flow through narrowed airways. Cough occurs because mucus and inflamed receptors trigger the cough reflex. Nocturnal symptoms reflect the normal overnight fall in catecholamines and peak of vagal tone, amplified by airway inflammation. ^[1]

• Episodic wheeze, breathlessness, chest tightness and cough, often worse at night or in the early morning. ^[1]
• Triggers: exercise, cold air, allergens, viral infections, smoke, strong smells, emotions, hormonal change.
• Variability is the hallmark: good days and bad days, diurnal variation, and periods of complete wellness between episodes.
• Past admissions, any need for oral corticosteroids, any previous intubation or ICU care, and any hospitalisation or emergency visit in the last year are risk factors for asthma death. ^[1]
• Co-morbidities that worsen control: allergic rhinitis, chronic rhinosinusitis with or without nasal polyps, obesity, gastro-oesophageal reflux disease, inducible laryngeal obstruction (vocal cord dysfunction), anxiety and depression.
• Atopic disease in the patient or family.

Examination may be entirely normal between attacks. ^[1]

• During an attack: tachypnoea, accessory muscle use, tripod posture, cyanosis only late, expiratory wheeze (which can become inaudible in very severe air trapping), prolonged expiration. A "silent chest" is ominous.
• Signs between attacks: none, or wheeze on forced expiration.
• Extrapulmonary: atopic features (eczema, allergic rhinitis, nasal polyps), clubbing does not fit asthma and should prompt a search for another diagnosis.
• Measurements to record: oxygen saturation, heart rate (tachycardia in severe attack), peak expiratory flow compared with the patient's own best, blood pressure.

Several conditions mimic asthma. Each is settled by history, objective testing or response to treatment.

Record spirometry before and after a bronchodilator. Most asthma guidelines use a relative increase in FEV1 and/or FVC of at least 12% and at least 200 mL from baseline after a bronchodilator as evidence of significant reversibility. ^[5][6] A peak flow or spirometric pattern that returns to normal, or near normal, between episodes supports the diagnosis. ^[1]

Detailed thresholds and reference ranges vary by guideline (ERS/ATS interpretations are evolving), which is one reason the asthma diagnosis should be confirmed before treatment whenever possible. ^[2]

Serial home peak-flow monitoring can reveal excessive diurnal variability, which indicates variable airway obstruction. Record the patient's own best value and compare future readings to it rather than to predicted values. ^[1]

FeNO is higher in asthma with type 2 (Th2-high) airway inflammation, but it is also raised by atopy, allergic rhinitis, eczema and eosinophilic bronchitis, and it can be lowered during bronchospasm or in some non-Th2 phenotypes. It is therefore a clue to phenotype, not a stand-alone diagnostic test. ^[1] In diagnostic studies it has been applied as a supportive type 2 biomarker (thresholds vary between studies: FeNO above 25 ppb in some, above 50 ppb in others, together with a raised blood eosinophil count) to improve sensitivity when other tests are negative. ^[2]

When the diagnosis is uncertain and baseline tests are normal, a bronchial challenge can demonstrate airway hyperresponsiveness. It is positive when the provocative concentration causing a 20% fall in FEV1 (PC20) is low (less than 16 mg/mL in the commonly used protocol). ^[6] Challenge testing should only be performed where resuscitation is available.

• Asthma control questionnaires. Asthma Control Test or the five-item Asthma Control Questionnaire, used to score control. ^[1]
• Atopy testing. Skin-prick tests or specific IgE for allergic asthma and allergen avoidance planning.
• For severe or atypical disease. Chest radiograph, CT, immunoglobulins (especially for ABPA), eosinophil counts, induced sputum. ^[3]
• After treatment has started. Repeat spirometry 3 to 6 months after starting treatment and periodically, because lung function guides stepped care and detects decline. ^[1]

Control is assessed in two domains: symptom control and future risk of exacerbations and decline in lung function. Severity is judged retrospectively, after 2 to 3 months of treatment, from the level of treatment needed to control the disease. ^[1]

Severe asthma is asthma that remains uncontrolled despite optimised high-dose ICS-long-acting beta-agonist (LABA) therapy, or that requires such treatment to prevent it becoming uncontrolled. Difficult-to-treat asthma looks severe but is actually uncontrolled because of modifiable factors (wrong technique, poor adherence, comorbidity, exposure). About 3% to 10% of people with asthma have severe asthma. ^[1]

Risk factors for asthma-related death must be sought specifically, even in patients with few symptoms: a previous need for intubation and mechanical ventilation, a hospitalisation or emergency visit in the past year, not using or poorly adherent with ICS-containing therapy, SABA overuse, psychiatric or psychosocial problems, concomitant food allergy, and current or recently stopped oral corticosteroids. ^[1]

Exacerbations are acute or sub-acute worsening of symptoms and lung function from the patient's usual state. They share the goal of every asthma visit: reduce preventable attacks, avoid oral corticosteroids where possible, and keep the patient out of hospital. ^[1]

• Oxygen. Give controlled-flow oxygen rather than 100% oxygen: sufficient flow to maintain saturation 93 to 95% in adults and 94 to 98% in children 6 to 11 years. Controlled oxygen carries lower mortality and better outcomes than high-concentration (100%) oxygen. ^[1]
• Bronchodilator. Repeated albuterol (salbutamol) by pressurised metered-dose inhaler and spacer every 20 minutes in the first hour (GINA: 4 to 10 puffs; local protocols set their own maximum) is effective for rapidly reversing airflow limitation. Avoid nebulisation except for life-threatening asthma (or where it cannot be avoided); a metered-dose inhaler plus spacer has equivalent efficacy to nebulisation with fewer adverse effects. ^[1][3]
• Ipratropium bromide. Give only for severe exacerbations. ^[1]
• Systemic corticosteroid. Start early after presentation. Adults: prednisolone 40 to 50 mg per day (or equivalent) for 5 to 7 days. Children: prednisolone 1 to 2 mg/kg (maximum 40 mg) for 3 to 5 days. No taper is needed if treatment is under 2 weeks. Single-dose dexamethasone is a practical alternative to multi-day prednisolone with similar relapse outcomes. ^[1][3]
• Magnesium. Consider intravenous magnesium sulphate for severe exacerbations not responding to initial treatment. ^[1][3]
• What not to do. Do not routinely request chest radiography or routinely prescribe antibiotics for an asthma exacerbation. ^[1]

• Red flags requiring urgent transfer or intensive care: drowsiness or confusion (a sign of hypercapnia), a silent chest, inability to maintain oxygen saturation on the oxygen given, a rising heart rate with exhaustion, or marked airflow limitation that does not improve. ^[1]
• Criteria for hospitalisation: clinical status, lung function, response to initial treatment, recent and past exacerbation history (especially previous intubation or ventilation), social support and ability to manage at home. ^[1]

The aim is to control symptoms, relieve them when they occur, and minimise exacerbations, asthma-related death and treatment side effects, using the GINA five-step framework and a shared decision with the patient. ^[1]

Asthma in adults and adolescents should no longer be treated with a SABA alone. All adults and adolescents should receive ICS-containing therapy, either regularly or, in mild asthma, taken as needed for symptom relief. ^[1] For children 6 to 11 years, ICS-containing treatment is also recommended, either regularly or, in mild asthma, whenever a SABA is taken. ^[1]

The reason is the risk of death and urgent care use with SABA monotherapy, and the evidence that ICS, even in small as-needed doses, cuts severe exacerbations. As-needed ICS-formoterol reduces severe exacerbations needing oral corticosteroids by at least 60% compared with SABA alone in mild asthma, with similar symptom control, lung function and inflammatory outcomes. ^[1][4]

GINA divides steps 1 to 5 into two tracks according to the reliever used. ^[1]

• Track 1 (preferred): low-dose ICS-formoterol as the reliever at every step. In steps 1 to 2 it is taken only as needed, without daily maintenance treatment. In steps 3 to 5 it is taken as daily maintenance plus as needed (maintenance-and-reliever therapy, MART).
• Track 2 (alternative): as-needed SABA at every step plus a regular controller (regular ICS at step 2, ICS-LABA at steps 3 to 5), for example where ICS-formoterol is unavailable or not preferred by a patient with no exacerbation in the past year.

Notes that follow from the source:

• ICS-formoterol should not be used as the reliever for patients on a maintenance combination of a non-formoterol ICS-LABA, with or without a LAMA; their reliever is a SABA. ^[1]
• In clinical trials, patients with mild asthma using as-needed budesonide-formoterol averaged only 3 to 4 inhalations per week; fewer than 0.1% took more than 8 inhalations on more than one day over 12 months. The maximum temporary daily total (reliever plus maintenance) is 12 inhalations for adults and adolescents and 8 inhalations for children 4 to 11 years (budesonide-formoterol) or 8 inhalations for adults (beclometasone-formoterol); if more than this is needed, seek medical help the same day. ^[1]
• For severe asthma and difficult-to-treat asthma, assessment must first confirm the diagnosis and optimise inhaler technique, adherence, trigger control and comorbidities before simply adding drugs. ^[1]

• LAMA. Adding tiotropium provides a modest improvement in lung function (exacerbation reduction in some studies), and should generally be considered after MART has been tried. Triple ICS-LABA-LAMA is an adult (18 years and over) option. ^[1]
• Azithromycin. Low-dose azithromycin is an option after specialist referral, but risks of antibiotic resistance and QT prolongation need to be weighed. ^[1]
• Biologics for severe disease, selected by inflammatory phenotype (blood eosinophils, FeNO, IgE, exacerbation history and comorbidity such as nasal polyps): ^[1][3]
  • Anti-IgE: omalizumab, for severe allergic asthma with raised IgE.
  • Anti-IL-5 / anti-IL-5 receptor: mepolizumab, reslizumab, and benralizumab (the last depletes eosinophils).
  • Anti-IL-4 receptor alpha: dupilumab, which blocks both IL-4 and IL-13 and has broader type 2 targeting.
  • Anti-TSLP: tezepelumab, acting on an upstream epithelial cytokine and useful in both type 2-high and some type 2-low phenotypes.
  • Their main benefits are substantial reduction in severe exacerbations and reduced oral corticosteroid exposure.
• Oral corticosteroids for maintenance should be avoided wherever possible given their serious long-term effects (osteoporosis, diabetes, cataract, weight gain, adrenal suppression). ^[1]
• Other tools: sputum-guided ICS adjustment improves outcomes but is not widely available; allergen immunotherapy is an option in selected allergic asthma; bronchial thermoplasty is specialist and in evidence gaps. ^[1]

Children follow a similar stepwise approach with age-appropriate ICS doses, with ICS-containing therapy at every step and MART (ICS-formoterol) as an option at steps 3 to 4. ICS-formoterol as AIR or MART is currently not recommended for children under 5 years because of insufficient evidence. ^[1][3]

Children under 5 years with frequent wheeze are managed initially with inhaled SABA, and a controller trial (for about 3 months) is considered if the symptom pattern suggests asthma, alternative diagnoses have been excluded and episodes are frequent or severe. ^[1]

• Before stepping up, confirm the symptoms are due to asthma, check inhaler technique, adherence and triggers, treat comorbidities and educate the patient. ^[1]
• Once good control has been maintained for 2 to 3 months, step down gradually to find the minimum effective dose, with frequent review. ^[1]
• Review at least yearly (more often in moderate and severe asthma), after any exacerbation and after a treatment change. ^[1]
• Provide a written asthma action plan to every patient, tailored to health literacy, so they know how to recognise and respond to worsening asthma. ^[1]

• Train inhaler technique and check it frequently; poor technique is itself a cause of poor control. ^[1]
• Identify and mitigate triggers and exposures, stop smoking, and avoid indoor air pollution and allergens where feasible. ^[1]
• Treat comorbidities (rhinitis, rhinosinusitis, obesity, reflux, inducible laryngeal obstruction) because they worsen control. ^[1][3]
• Encourage regular exercise; it is associated with better lung function and symptoms. ^[3]
• Allergen-specific immunotherapy is an option in selected allergic asthma; bronchial thermoplasty is specialist and in evidence gaps. ^[1]

Pregnancy. The benefits of actively treating asthma in pregnancy to avoid exacerbations markedly outweigh any potential adverse effects of usual controller and reliever medicines. Continue the usual inhaled treatment, optimise control, and review more frequently. ^[1]

Exercise-induced bronchospasm. Distinguish exercise-induced bronchospasm from deconditioning, obesity or inducible laryngeal obstruction. Treat with ICS-containing therapy and advise a proper warm-up. Patients on Track 1 can take their ICS-formoterol before exercise if needed and do not need a separate SABA inhaler. ^[1]

Aspirin-exacerbated respiratory disease. Severe phenotype with asthma, chronic rhinosinusitis and nasal polyps; COX-1 inhibitors precipitate attacks, so they must be avoided. Management is specialist and includes the standard stepwise asthma pathway plus targeted biologic therapy or aspirin desensitisation where available.

Occupational asthma. Suspect it when work-related worsening is present; refer, and remove exposure early. Any patient needing urgent care or oral corticosteroids more than once a year should be referred. ^[1]

Older adults. Spirometry may be harder to interpret; smoking and COPD features are more common, but late-onset asthma still needs ICS rather than bronchodilator-only treatment. ^[1]

Children under 5. See the management section above.

The majority of asthma morbidity and mortality occurs in low- and middle-income countries, where essential inhaled medicines are often unavailable or unaffordable and diagnosis is late. ^[7]

• A clinical diagnosis based on history and a trial of treatment is acceptable where spirometry or biomarkers are unavailable, but every effort should be made to confirm variable obstruction with low-cost peak-flow monitoring.
• Use spacer devices (including locally made bottle spacers) with metered-dose inhalers rather than nebulisers, which waste drug and can transmit infection.
• Prioritise availability of low-dose ICS and combination ICS-formoterol if supply allows; where ICS-formoterol is unavailable, use regular low-dose ICS with as-needed SABA rather than SABA alone.
• Systemic corticosteroids are inexpensive and save lives in severe attacks; magnesium sulphate and oxygen are the priorities after bronchodilators.
• Educate caregivers, simplify regimens, and use large, cheap reusable action plans.

• Fatal or near-fatal attacks, most often when warning signs are missed or treatment is delayed.
• Oral corticosteroid toxicity from repeated courses (osteoporosis, diabetes, cataract, adrenal suppression, weight gain). ^[1]
• Fixed airflow limitation from untreated airway remodelling.
• Psychological morbidity and impaired quality of life, school and work absence.

With appropriate ICS-containing treatment, most patients achieve good control and a near-normal life. Poor control early in life tracks into adulthood, and severe exacerbations recur unless the causes (non-adherence, ongoing exposures, comorbidities) are addressed. ^[1]

There is no proven way to prevent asthma developing in most people, but avoiding tobacco smoke in pregnancy and childhood, and reducing indoor and outdoor air pollution, materially reduce risk. Early identification of viral wheeze with asthma features, and treatment with ICS rather than repeated bronchodilators alone, reduces harm. ^[1]

• Asthma is a variable, inflammatory, (usually) reversible airway disease defined by history and objective evidence of variable airflow limitation.
• Most asthma is Th2 (type 2) inflammation driven by epithelial cytokines (IL-33, TSLP), Th2 cells and IL-4/5/13; eosinophils and IgE characterise one phenotype, neutrophilic the other.
• The classic signs are wheeze, breathlessness and cough, worse at night or early morning, with exercise or viral infection as triggers.
• Reversibility of at least 12% and at least 200 mL in FEV1 after bronchodilator is the standard spirometric evidence; other tests include peak-flow variability, FeNO (a type 2 marker) and methacholine challenge (positive at low PC20, less than 16 mg/mL).
• Severity is retrospective; control is the day-to-day metric; severe asthma is 3% to 10% of cases but causes most harm.
• Risk of severe and fatal exacerbation exists even in mild, well-controlled asthma, so risk factors must be checked separately from symptoms.
• Everyone now needs ICS-containing treatment: no patient should receive a SABA alone. Preferred Track 1 uses low-dose ICS-formoterol as the reliever always.
• MART (maintenance plus as-needed ICS-formoterol) reduces exacerbations in moderate and severe asthma; ICS-formoterol cannot be used as reliever with non-formoterol ICS-LABA.
• Acute care: controlled oxygen 93 to 95% (adults) / 94 to 98% (children), repeated inhaled SABA, early systemic corticosteroid (prednisolone 40 to 50 mg for 5 to 7 days adults; 1 to 2 mg/kg, max 40 mg, for 3 to 5 days children), ipratropium only for severe cases, intravenous magnesium if refractory.
• Red flags are drowsiness, confusion, silent chest and failure to maintain saturation; hospitalise on clinical grounds.
• Special groups (pregnancy, children, exercise, NSAID-sensitive, occupational) need the same ICS-based approach plus targeted measures; in low-resource settings, spacer-delivered MDI, ICS availability and cheap corticosteroid kits save lives.
• Biologics (anti-IgE, anti-IL-5, anti-IL-4R, anti-TSLP) are the major Step 5 advance and should be selected by phenotype, with avoidance of maintenance oral steroids.

• Chronic obstructive pulmonary disease
• Acute respiratory failure and ventilation
• Allergic rhinitis and chronic rhinosinusitis
• Gastro-oesophageal reflux disease