Asthma

Meet the patient

A 22-year-old asthmatic has gone through three salbutamol canisters this month. At 3am he sits bolt upright, cannot finish a sentence, and his chest is silent on auscultation. SpO2 90% on air; peak flow unrecordable.^[1]

Every registrar's instinct is to grab the nebuliser. Every examiner's first question is the harder one: "Is he about to arrest, and what did we miss in the community?" The whole topic answers both.^[1]

Overview & Definition

Asthma is a heterogeneous chronic inflammatory disease of the airways defined by four physiological hallmarks: (1) chronic airway inflammation (predominantly eosinophilic, type-2-high in over half of adults, but also neutrophilic, paucigranulocytic, or mixed); (2) variable airflow obstruction that fluctuates in time and intensity; (3) bronchial hyperresponsiveness to both specific (allergen) and non-specific (cold air, exercise, methacholine) stimuli; and (4) reversibility, either spontaneously or with a bronchodilator. Clinically it presents with episodic wheeze, breathlessness, chest tightness, and cough, with symptoms that classically worsen at night and in the early morning and that change in response to triggers, steroids, or the menstrual cycle. ^[1]

A central conceptual shift — captured by Pavord's After asthma treatise — is that "asthma" is not one disease but a syndrome of overlapping phenotypes (early-onset allergic, late-onset eosinophilic, exercise-induced, aspirin-exacerbated, obesity-associated, premenstrual, neutrophilic) sharing a final common pathway of variable airflow obstruction.^[4] The clinical implication is that one investigates the phenotype (blood eosinophils, FeNO, total and specific IgE) in anyone not responding to low-dose ICS, because the phenotype selects the biologic. Status asthmaticus — the severe, prolonged attack unresponsive to standard bronchodilators — is a medical emergency and is covered in the resuscitation section below.

Classification

Asthma is classified along three independent axes — severity (intermittent through severe persistent), inflammatory phenotype (type-2-high vs type-2-low), and control (well controlled, partly controlled, uncontrolled). Severity is determined after the patient is established on appropriate controller therapy: a patient needing high-dose ICS-LABA plus a LAMA to achieve control has severe persistent asthma even if currently symptom-free. ^[1]

By inflammatory phenotype, asthma is split into: ^[1]

• Type-2-high (eosinophilic) — 50 to 70 percent of asthma. Driven by Th2 cells and group-2 innate lymphoid cells (ILC2) producing IL-4, IL-5 and IL-13. Characterised by blood eosinophils over 150 to 300 per microlitre and FeNO over 25 to 50 ppb; responsive to corticosteroids and to every approved asthma biologic. Includes early-onset allergic, late-onset eosinophilic, and aspirin-exacerbated respiratory disease (AERD).
• Type-2-low (non-eosinophilic) — 20 to 30 percent. Either neutrophilic (IL-17 driven, obese, smoking-related, often steroid-resistant) or paucigranulocytic (inflammation-poor, smooth-muscle-driven). No approved biologic; treat the modifier (smoking cessation, weight loss, macrolide trial, optimise adherence).
• Mixed overlap — late-onset asthma in elderly smokers blends features of COPD; termed asthma-COPD overlap (ACO), in which ICS is essential (never LABA alone — see SMART trial below). ^[1]

Phenotype matters because it selects the biologic: eosinophils over 300 point to anti-IL-5 (mepolizumab, benralizumab, reslizumab) or anti-IL-4R dupilumab; raised total and specific IgE with sensitisation points to anti-IgE omalizumab; any T2 phenotype (including low-eosinophil) responds to anti-TSLP tezepelumab.^[3]

Epidemiology & Risk Factors

Asthma affects roughly 300 million people worldwide and causes about 250,000 deaths per year, most of which are preventable with access to affordable inhaled corticosteroids.^[2] Prevalence is highest in high-income English-speaking countries (5 to 15 percent), and the global rise over the last 50 years tracks urbanisation, smaller family size, and westernised indoor environments — the foundation of the hygiene hypothesis, which posits that reduced early-life microbial exposure biases the developing immune system toward T-helper-2 (allergic) responses. In India, adult prevalence is 2 to 3 percent overall but climbs to 5 to 10 percent in urban children, with under-diagnosis and ICS cost being the dominant barriers to care.

Host risk factors: atopy (eczema, allergic rhinitis, food allergy — the strongest), family history of atopy or asthma, female sex in adult-onset disease, obesity (mechanical and leptin/IL-6 mediated), and genetic variants in the ORMDL3/17q21 locus. ^[1]

Environmental and trigger factors: early-life viral lower respiratory infections (respiratory syncytial virus, rhinovirus), aeroallergen sensitisation (house-dust mite, cockroach, cat, dog, mould, Alternaria, pollen), tobacco smoke (in utero, second-hand, active), indoor and outdoor air pollution (PM2.5, NO2, ozone from traffic and biomass cooking), occupational sensitisers (isocyanates in spray-paint and polyurethane, flour and grain dust, latex, wood dust, laboratory animal dander, cleaning agents, colophony), and drugs — non-steroidal anti-inflammatory drugs (NSAIDs) in aspirin-exacerbated respiratory disease, and beta-blockers (including topical timolol eye drops, a classic MRCP stem). ^[1]

The risk factors for fatal or near-fatal asthma centre on the modifiable exposures GINA targets — SABA overuse above all — together with the objective acute-severity markers that define the attacks which kill. ^[1]

GINA's strategy makes the risk factors for severe exacerbations and death explicit and modifiable: SABA overuse and SABA-only treatment carry the clearest excess risk, which is why every step now mandates ICS-containing therapy, alongside regular personalised assessment, treatment of modifiable risk factors, self-management education and review.^[1] The acute-severe phenotype in which deaths concentrate is objectively defined in trials — adults with PEFR under 50 percent of best or predicted, respiratory rate over 25, heart rate over 110, or inability to complete sentences.^[15]

Pathophysiology

Asthma is the archetypal type-2 (T2-high) inflammatory disease of the airway, but understanding it requires the full cascade — the why of every symptom and the target of every modern biologic. Three converging mechanisms produce the acute attack: bronchospasm (smooth-muscle contraction), mucosal oedema and inflammation (vascular leak, eosinophil infiltration), and mucus plugging (goblet-cell hyperplasia with tenacious Cast-mucus). Together they narrow small airways, cause premature airway closure during expiration, produce air-trapping and hyperinflation, and account for the prolonged expiratory phase, polyphonic wheeze, and the rising work of breathing that culminates in fatigue. ^[1]

The type-2-high cascade

An inhaled allergen or virus damages the bronchial epithelium, which releases the alarmins TSLP, IL-25 and IL-33. These do two things: they activate dendritic cells (which migrate to the draining lymph node and, in the presence of allergen, present antigen to naive CD4 T cells and skew them to a Th2 phenotype), and they directly activate group-2 innate lymphoid cells (ILC2) in the mucosa — bypassing adaptive immunity and explaining why some patients have eosinophilic asthma without demonstrable allergy. Th2 cells and ILC2 then secrete the signature cytokines: ^[1]

• IL-4 — drives IgE class-switching in B cells and Th2 differentiation.
• IL-5 — essential for eosinophilopoiesis, maturation, survival and activation in the bone marrow and tissue. Eosinophils release major basic protein, eosinophil cationic protein and leukotrienes that strip airway epithelium and provoke bronchoconstriction. (Target: anti-IL-5 mepolizumab and reslizumab; anti-IL-5 receptor benralizumab.)
• IL-13 (and IL-4) — drive goblet-cell hyperplasia and mucin (MUC5AC) production, airway smooth-muscle contraction, and IgE switching. (Target: anti-IL-4R dupilumab blocks both IL-4 and IL-13 signalling.) ^[1]

Circulating allergen-specific IgE binds high-affinity FceRI receptors on mast cells and basophils in the airway; cross-linking on re-exposure triggers immediate degranulation with histamine, prostaglandins and cysteinyl-leukotrienes (LTC4, LTD4, LTE4) — the basis of the early-phase asthmatic response within minutes, the late-phase response 4 to 8 hours later (eosinophil-driven), and the rationale for anti-IgE omalizumab and anti-leukotriene montelukast. ^[1]

Type-2-low asthma

In about 20 to 30 percent of patients — typically late-onset, obese, smoking, or neutrophilic — the inflammation is driven by Th17 cells and IL-8 recruiting neutrophils, with IL-17 promoting smooth-muscle proliferation and steroid resistance. This group has normal eosinophils and FeNO, responds poorly to corticosteroids, and has no currently licensed biologic (macrolide trials, weight loss, smoking cessation are the management levers). Anti-TSLP tezepelumab is the exception that crosses both worlds: by blocking the epithelial alarmin at the top of the cascade it reduces exacerbations across all eosinophil strata, including T2-low.^[16]

Airway remodelling

Chronic, undertreated inflammation produces structural remodelling — sub-epithelial basement-membrane fibrosis (type III and V collagen, tenascin), airway smooth-muscle hypertrophy and hyperplasia, mucous-gland hyperplasia, and angiogenesis. Remodelling begins early (even in children within years of diagnosis) and explains the progressive loss of reversibility seen in long-standing adult asthma. Early and sustained inhaled corticosteroid attenuates remodelling — one of the strongest mechanistic arguments against the SABA-only era. Eosinophilic inflammation, when chronic, also produces localised atelectasis from mucus plugging of small bronchi and, rarely, pneumothorax or pneumomediastinum from alveolar rupture during forceful coughing. ^[1]

Why hypercapnia signals catastrophe

In a typical attack the patient hyperventilates (in response to hypoxaemia, hyperinflation, and anxiety) and so blows off CO2, producing a respiratory alkalosis on arterial blood gas. A normal or rising PaCO2 therefore means the patient is fatiguing and alveolar ventilation is falling — this is the single most important bedside and biochemical warning of impending respiratory arrest, and is itself a life-threatening criterion independent of the SpO2. ^[1]

Clinical Presentation

Classic asthma presents with the tetrad of wheeze, breathlessness, chest tightness, and cough, with symptoms that vary in time, intensity, and trigger. The wheeze is expiratory and polyphonic (multiple pitches because multiple airways narrow to different degrees), is variable (present on some days and absent on others, diurnally worse at night and around 4 am), and is reproducible with the patient's known triggers. Between attacks, the chest may be entirely normal. Diurnal variability with nocturnal or early-morning dips is so characteristic that a patient who never wakes at night should have the diagnosis reconsidered. ^[1]

^[1]

Trigger patterns to elicit: allergens (dust, pet, pollen, mould — often with identifiable seasonal pattern), viral upper-respiratory infections (rhinovirus the classic in children), exercise (particularly cold dry air), cold air and weather change, irritant smoke and fumes, NSAIDs and beta-blockers (including topical timolol), gastro-oesophageal reflux, menstrual and pregnancy-related worsening, and psychological stress. A careful occupational history with symptom improvement on weekends and holidays points to sensitiser-induced occupational asthma (isocyanates the single commonest cause worldwide). ^[1]

Acute attack — the bedside picture

A moderate attack shows an anxious patient, tachypnoea, tachycardia, an expiratory polyphonic wheeze, a prolonged expiratory phase, and accessory-muscle use. As the attack worsens the patient cannot complete sentences in one breath, develops hyperinflation with a hyper-resonant percussion note, and a reduced PEF. The life-threatening features below indicate that the patient is tiring and that the airways are no longer moving enough air to wheeze — a silent chest is not improvement, it is pre-arrest. ^[1]

Differential Diagnosis

A wheeze is not always asthma. The complete adult differential of wheeze or chronic breathlessness — and the features that distinguish each — is captured in the comparison below. ^[1]

^{[20] [21] [22] [27]}

Also consider: bronchiectasis (chronic purulent sputum, CT diagnostic), tuberculosis (chronic cough with weight loss and fever, CXR upper-lobe infiltrate, positive sputum AFB), tracheal or bronchial tumour (older smoker, haemoptysis, fixed monophonic wheeze, weight loss), pulmonary fibrosis (dry cough, fine bibasal crackles, restrictive spirometry), hypersensitivity pneumonitis (exposure to birds or mould, recurrent flu-like episodes), gastro-oesophageal reflux (cough after meals and on lying down, response to PPI), and dysfunctional breathing (hyperventilation syndrome, sighing dyspnoea, normal investigations). ^[1]

The clincher that points to COPD rather than asthma: later age, significant smoking history, symptoms present every day with little variability, and persistent post-bronchodilator obstruction — remembering that no reversibility threshold, not even the ATS 12 percent and 200 mL criterion, cleanly separates the two diseases, so interpretation must be clinical.^[20] The clincher that points to inducible laryngeal obstruction rather than asthma: laryngeal symptoms that mimic asthma, confirmed by laryngoscopy — the ERS/ELS statement stresses it is a common mimic in which laryngoscopy is required for diagnosis.^[21]

Clinical & Bedside Assessment

The focused history establishes the pattern (intermittent, persistent, seasonal, occupational), triggers (allergen, exercise, viral, cold, NSAID, beta-blocker), nocturnal symptoms, activity limitation, previous admissions (especially any ICU or intubation), oral steroid courses in the past year, SABA consumption (the single most useful adherence marker — request the prescription record), atopic history (eczema, rhinitis, food allergy), family history, smoking, occupation, and the home environment (damp, pets, biomass cooking). ^[1]

The examination in a stable patient is often normal — its main purpose is to detect atopic stigmata (allergic shiners, Dennie-Morgan infraorbital folds, transverse nasal crease, pale boggy nasal mucosa, nasal polyps, eczema), hyperinflation (resonant percussion, low diaphragms), and a polyphonic expiratory wheeze. In an acute attack the examination is reorganised around severity assessment — the BTS/SIGN bands reproduced verbatim below — because severity dictates where the patient is treated and what is given. ^[1]

^{[15] [19] [23]}

The PEF is the most useful bedside measurement in an acute attack: compare with the patient's personal best if known (more reliable), or with the predicted value adjusted for age, height, and sex. A silent chest — disappearance of the wheeze in a patient who is cyanosed, exhausted, or bradycardic — means so little air is moving that no turbulence can be generated; it is a pre-arrest sign and mandates immediate ICU escalation, not reassurance. ^[1]

Investigations

Spirometry is the cornerstone of diagnosis, with peak expiratory flow measurement an alternative where spirometry is unavailable, per GINA primary-care guidance.^[2] Spirometry demonstrates an obstructive pattern with reversibility: the classic ATS criterion is an improvement in FEV1 of at least 12 percent AND at least 200 mL (0.2 L) after bronchodilator — but reversibility testing has limited value in separating asthma from COPD (an absolute FEV1 gain of at least 0.2 L gave the best, still imperfect, sensitivity of 73 percent and specificity of 80 percent), so it must always be interpreted clinically.^[20]

^{[20] [29] [2] [10]}

Peak expiratory flow variability over 1 to 2 weeks — measured morning and evening before reliever — of more than 10 percent diurnally (or 20 percent in older guidelines) supports asthma. The morning dip pattern is characteristic. PEF diaries are especially useful in occupational asthma (compare work days with holidays). ^[1]

Fractional exhaled nitric oxide (FeNO) measures eosinophilic airway inflammation; FeNO of 50 ppb or more in adults (35 ppb or more in children) supports T2-high asthma and predicts a good response to ICS. It is also useful to monitor adherence to ICS (FeNO falls within days of starting or resuming ICS, and rises within 2 weeks of stopping). ^[1]

Sputum eosinophilia and blood eosinophils mark the T2-high phenotype: the dupilumab proof-of-concept trial enrolled patients on a blood eosinophil count of at least 300 cells per microlitre or a sputum eosinophil level of at least 3 percent — biomarker thresholds of this kind identify biologic candidates.^[10] The ATS guideline recommends FeNO measurement for detecting eosinophilic airway inflammation, judging the likelihood of corticosteroid responsiveness, and unmasking unsuspected non-adherence to corticosteroid therapy.^[29]

Chest X-ray is not diagnostic — it may show hyperinflation, flattened diaphragms, or be normal — but is essential in an acute attack to exclude pneumothorax, pneumomediastinum, pneumonia, or lobar collapse from mucus plugging. HRCT chest is reserved for atypical or severe cases, suspected ABPA (central bronchiectasis), bronchiectasis, or alternative diagnosis. ^[1]

Arterial blood gas is performed when the patient has any life-threatening feature. The classic early pattern is respiratory alkalosis (low PaCO2 from hyperventilation) with mild hypoxaemia. A normal or rising PaCO2 is itself a life-threatening criterion — it signals fatigue and impending respiratory arrest. A metabolic acidosis with a high lactate may follow high-dose beta-agonist therapy and is usually self-limiting. ^[1]

Management — Resuscitation

Acute severe asthma is a time-critical medical emergency. The ABCDE approach is paired with severity stratification (above) because severity drives therapy, location, and the threshold for IV agents and ventilation. ^[1]

^{[28] [19] [15] [23] [24]}

The rationale and the evidence: ^[19][24]

• Oxygen — titrate rather than flood: BTS guidance recommends a target SpO2 of 94 to 98 percent for most acutely ill adults (not 100 percent).^[28]
• Nebulised short-acting beta-2 agonist — the universal first-line agent; every add-on therapy in acute asthma is judged on top of it (plus oxygen and systemic corticosteroid).^[19]
• Systemic corticosteroid — part of the standard first-hour package in all trials of add-on agents; give it early.^[19]
• IV magnesium sulphate 1.2 to 2 g over 15 to 30 minutes — a single infusion for adults not responding sufficiently to oxygen, nebulised SABA and IV corticosteroids. The Cochrane review (14 trials, 2313 patients) found it reduced hospital admissions (OR 0.75, 95% CI 0.60 to 0.92) and improved lung function, with flushing, fatigue, nausea, headache and hypotension the commonest adverse effects. The largest single trial (3Mg, 1109 adults) was, however, unable to demonstrate a clinically worthwhile benefit (admission OR 0.73, 95% CI 0.51 to 1.04, p=0.083) — the evidence is genuinely mixed, and guidelines retain magnesium as a rescue add-on.^[19][15]
• Heliox — β2-agonist nebulisation driven by heliox (versus oxygen-driven) increased PEFR by 17 percent (95% CI 5.2 to 29.4) and reduced hospital admissions (RR 0.77, 95% CI 0.62 to 0.98).^[24]
• Hyperlactataemia — common in the first hours of treatment, related to β2-agonist use, and largely without clinical consequences.^[24]
• Critical asthma in the ICU — the umbrella term for life-threatening asthma, status asthmaticus and near-fatal asthma: management centres on ventilatory strategy, haemodynamics and anticipating complications such as pneumothorax, with little room for error.^[23]

^[1]

Management — Definitive & Stepwise

The GINA 2022/2024 strategy represents a paradigm shift away from SABA monotherapy that took effect in 2019 and is now embedded in BTS/SIGN, NICE NG80, and the NAEPP 2020 update. The central principle — backed by the SMART trial (Nelson, 2006) demonstrating excess asthma death on LABA without ICS, and by SYGMA (Beasley, 2019) showing as-needed ICS-formoterol matches regular ICS for exacerbation prevention in mild asthma — is that every asthmatic must receive an inhaled corticosteroid, either as maintenance or co-administered with the reliever.^[5][11]

GINA preferred (Track 1) — the ICS-formoterol MART track

The anti-inflammatory reliever (AIR) concept: low-dose budesonide-formoterol (or beclometasone-formoterol) used as both maintenance and reliever (MART). Formoterol is fast enough (onset 1 to 3 minutes) to act as a reliever and long enough (12 hours) to be a controller; pairing it with budesonide means every reliever dose carries an anti-inflammatory payload. ^[1]

GINA alternative (Track 2) — ICS plus SABA

For patients unable to access ICS-formoterol or with strong preference: regular maintenance ICS at the appropriate dose band, with SABA as reliever. Crucially, Step 1 still carries an ICS: the patient takes a dose of low-dose ICS whenever they take a SABA. SABA monotherapy is no longer recommended at any step. ^[1]

ICS dosing (adult)

GINA's preferred track is built on low-dose ICS-formoterol: the reliever at every step (as-needed only in Steps 1 to 2, full MART from Step 3), while the alternative track pairs regular ICS with as-needed SABA. The exact low, medium and high mcg-per-day bands for each molecule (beclometasone, budesonide, fluticasone) are tabulated in the full GINA strategy report and vary by inhaler device — the exam-relevant principles are that every patient receives ICS-containing therapy, that the reliever itself carries the inhaled steroid, and that treatment is individually assessed, adjusted and reviewed rather than escalated reflexively. ^[1][2]

Add-on therapies at Step 4 to 5

• LABA (salmeterol, formoterol) — added to ICS as a fixed-dose combination. Never as monotherapy — see SMART trial.^[5]
• LTRA — montelukast retains its asthma indication, but the FDA required a boxed warning for neuropsychiatric events and now reserves montelukast (for allergic rhinitis) for patients with inadequate response or intolerance to alternatives.^[25]
• LAMA — tiotropium 5 μg once daily by soft-mist inhaler, added to ICS-LABA in uncontrolled asthma, extended time to first severe exacerbation (282 vs 226 days; hazard ratio 0.79) with sustained bronchodilation; added to ICS alone it beat doubling the ICS dose and was non-inferior to salmeterol.^[13][12]
• Macrolide — azithromycin 500 mg three times per week for 48 weeks reduced total asthma exacerbations (incidence rate ratio 0.59, 95% CI 0.47 to 0.74) and improved quality of life in persistent uncontrolled asthma, at the cost of more diarrhoea (34 vs 19 percent).^[18]

Biologics for severe asthma (Step 5)

Severe asthma is defined as asthma uncontrolled despite optimised high-dose ICS-LABA with or without LTRA/LAMA, OR requiring maintenance oral corticosteroid to maintain control. Biologic selection is biomarker-driven:^[3]

^{[6] [7] [8] [9] [10] [16] [17]}

Bronchial thermoplasty (Castro, AIR2, 2011) — bronchoscopic radiofrequency ablation of airway smooth muscle in three sessions; reduces exacerbations and improves quality of life in carefully selected adults with severe persistent asthma unresponsive to high-dose ICS-LABA. Reserved for specialist centres.^[14]

Non-pharmacological and lifestyle

Allergen avoidance (house-dust mite covers, pet removal where sensitised, mould remediation, occupational removal), smoking cessation, weight loss in obesity (BMI over 30), vaccination (annual influenza, COVID-19, pneumococcal — PCV20 or PPV23 as appropriate), comorbidity management (rhinitis — same-one-airway, GERD, OSA, anxiety/depression), and allergen immunotherapy (sublingual or subcutaneous) for selected IgE-mediated allergic asthma in a stable patient. Written asthma action plan (PEF- or symptom-based) with a traffic-light system for step-up is mandatory and reduces mortality. ^[1]

Monitoring and the asthma control test

Review at 2 to 4 weeks after any change, then every 3 months when stable. At each visit check symptom control (Asthma Control Test — ACT — five questions, score 5 to 25; under 20 is uncontrolled), exacerbation frequency in the past year, PEF or FEV1, inhaler technique (the commonest cause of treatment failure), adherence (prescription refill record, canister weight), side-effects (oral candidiasis, dysphonia — rinse and spit after ICS; check for OCS toxicity — bone density, HbA1c, blood pressure), and FeNO where available. Step up if uncontrolled; step down (reduce ICS by 25 to 50 percent) if controlled for at least 3 months — never stop ICS abruptly. ^[1]

Specific Subtypes & Scenarios

^{[26] [31] [27] [30] [10] [16]}

Complications & Pitfalls

Acute complications of a severe attack include respiratory failure (type 1 from V/Q mismatch, type 2 from fatigue and CO2 retention), pneumothorax and pneumediastinum (alveolar rupture from high intrathoracic pressures), mucus plugging with lobar atelectasis (especially right middle lobe), cardiac arrhythmia (beta-agonist and hypokalaemia), lactic acidosis (high-dose salbutamol), and cardiac arrest from hypoxaemia or tension pneumothorax during ventilation. Mechanical ventilation itself risks dynamic hyperinflation (breath-stacking), hypotension from raised intrathoracic pressure, and tension pneumothorax. ^[1]

Chronic complications of poorly-controlled asthma centre on exacerbation-prone severe disease with risk of death — the outcome GINA's ICS-at-every-step strategy exists to prevent.^[1] Medication-related complications are dominated by systemic glucocorticoid toxicity — "serious and often irreversible adverse effects" in the words of the SIRIUS investigators — which is why oral-steroid-sparing is an explicit goal of severe-asthma therapy: mepolizumab halved the median oral glucocorticoid dose (50 percent reduction vs none with placebo) and benralizumab cut it by 75 percent.^[8][9] LABA monotherapy without ICS produced small but statistically significant increases in respiratory-related and asthma-related deaths and life-threatening experiences in the SMART trial — the reason fixed combination inhalers dominate.^[5]

Classic errors — every one of these has killed asthmatics: ^[1]

1. SABA monotherapy without an ICS — the single commonest preventable cause of asthma death.^[5]
2. Undertreating a severe exacerbation ("give one neb and discharge") — leads to relapse and arrest at home.
3. Missing a normal or rising PaCO2 as a life-threatening sign — the patient looks "settled" but is tiring.
4. Sedating the anxious asthmatic with an opiate, benzodiazepine, or antihistamine — respiratory depression, hypercapnia, arrest.
5. Delayed ICU referral — the senior intensivist should be informed early, not at the point of arrest.
6. LABA without ICS — relative risk of asthma death approximately doubled (SMART, 2006).^[5]
7. Forgetting non-adherence and technique as the cause of "severe" asthma — the commonest reason for failure to respond.

Prognosis & Disposition

Childhood asthma often improves in adolescence (especially mild viral-triggered disease), but a substantial minority relapse in adulthood — particularly with atopy, eosinophilia, smoking, or occupational exposures. Adult-onset asthma is usually lifelong. Severe asthma (roughly 5–10% of patients) drives most morbidity, cost, and death, and is the group in whom biologics have transformed outcomes.^[2]

Severity of the acute attack (BTS/SIGN-style thresholds — reproduce)

Normal or raised PaCO2 in an acute asthmatic is a life-threatening sign (impending respiratory failure) — not reassurance. ^[1]

Disposition after acute treatment

• Discharge if PEF >75% best/predicted, stable on 3–4-hourly bronchodilators, SpO2 normal on air, and the patient has a written action plan, oral steroids (typically prednisolone 40–50 mg daily for 5 days adult), inhaled therapy optimised, and GP/respiratory follow-up.
• Admit any acute severe or life-threatening feature, pregnancy with severe attack, poor social support, previous near-fatal asthma, or incomplete response after 1–2 hours of treatment.
• ICU for life-threatening features, exhaustion, rising PaCO2, needing ventilatory support, or failure of maximal medical therapy. ^[1]

Long-term control prognosis

Good control (GINA): daytime symptoms ≤2/week, no night waking, reliever ≤2/week, no activity limitation. Poor control and ≥1 severe exacerbation/year should trigger step-up, adherence/technique check, comorbidity review (rhinitis, GORD, obesity, OSA, anxiety), and phenotyping for biologics if high-dose ICS-LABA fails.

Special Populations

Children

Distinguish episodic viral wheeze (preschool, only with colds, no interval symptoms) from multitrigger asthma. Use age-appropriate devices (spacer ± mask). Prednisolone dosing is weight-based (often 1–2 mg/kg, max 40 mg). Avoid routine antibiotics. Parental education and spacer technique determine real-world control. ^[1]

Pregnancy

• Asthma control protects the fetus — uncontrolled asthma is more dangerous than asthma medicines.
• Continue ICS; short-acting beta-agonists are safe; add LABA if needed; oral steroids for exacerbations when indicated.
• Avoid step-down experiments in pregnancy if control is tenuous.
• Acute severe asthma in pregnancy: same drugs and doses; involve obstetric and ICU teams early; left lateral tilt; fetal monitoring when viable.
• Leukotrienes: montelukast often continued if previously effective; individualise.

Elderly

Higher risk of fixed airflow obstruction (asthma–COPD overlap), drug interactions, poor inhaler strength/coordination — prefer spacers or soft-mist/breath-actuated devices. Beta-blockers for cardiac disease may worsen bronchospasm — use cardioselective agents cautiously if essential.

Aspirin-exacerbated respiratory disease (AERD / Samter)

Triad: asthma + nasal polyps + NSAID hypersensitivity. Avoid COX-1 inhibitors; consider COX-2 selective agents only with caution/specialist advice. Often eosinophilic; may need biologics or aspirin desensitisation in specialist hands.

Occupational asthma

Two forms: sensitiser-induced (latency, IgE or non-IgE) and irritant-induced (RADS after high-level exposure). Serial PEF at work/off work, specific IgE when relevant, referral to occupational lung disease services. Early removal from exposure improves prognosis.

Obesity and alternative diagnoses

Obesity mimics/worsens asthma (dyspnoea, deconditioning). Confirm variable airflow obstruction before escalating steroids. Vocal cord dysfunction / inducible laryngeal obstruction causes inspiratory stridor and poor response to escalation — think of it when spirometry is normal and attacks are abrupt with throat symptoms.

Biologic-era severe asthma phenotypes

Exact eligibility (eos counts, exacerbation frequency, IgE, weight) is guideline- and payer-specific — examiners want the class logic, not brand trivia alone. ^[1]

Evidence, Guidelines & Regional Differences

^{[1] [1] [1]}

Landmark trials that changed practice

^{[15] [19]}

GINA Track Exam Summary & Dose Pearls

GINA track exam summary (adults/adolescents — conceptual)

Modern GINA prefers ICS-containing reliever strategies (Track 1: ICS-formoterol as MART — maintenance and reliever therapy) over SABA-only reliever (Track 2), because SABA-only treatment is associated with higher exacerbation risk.

• Steps 1–2: as-needed low-dose ICS-formoterol (Track 1) OR low-dose ICS whenever SABA is taken (Track 2)
• Step 3: low-dose maintenance ICS-formoterol (MART) OR low-dose ICS-LABA maintenance + SABA reliever
• Step 4: medium-dose ICS-formoterol MART OR medium/high ICS-LABA
• Step 5: high-dose ICS-LABA ± LAMA; refer for phenotyping/biologics; low-dose oral steroid only as last resort

Acute drug bundle (adult) — what the evidence used

• Oxygen, nebulised short-acting beta-2 agonist and IV corticosteroid — the standard emergency-department package that participants in every add-on trial had already received before the experimental agent.^[19]
• Nebulised ipratropium bromide — given as a co-medication in several of the intravenous magnesium trials.^[19]
• IV magnesium sulphate 1.2 to 2 g over 15 to 30 minutes (the 3Mg trial used 2 g over 20 minutes) — the first-hour add-on with pooled trial evidence for fewer hospital admissions (OR 0.75, 95% CI 0.60 to 0.92), although the largest single trial was null.^[19][15]
• Exact nebuliser and systemic-steroid doses follow the local guideline — national guidelines adopt and adapt GINA guidance to their own health systems, so check the formulary rather than memory.^[2]

Worked stem — life-threatening asthma

A 28-year-old cannot speak, SpO2 90% on air, PEF unrecordable, silent chest, ABG shows PaCO2 6.2 kPa (normal/high). This is life-threatening / near-fatal trajectory. Continuous nebulised bronchodilators, steroids immediately, IV magnesium, senior/ICU review, prepare for intubation by the most experienced airway clinician — intubation in asthma is high-risk (dynamic hyperinflation, hypotension).

Worked NEET-PG Stems — Asthma

1. PEF 30%, silent chest, SpO2 90% → life-threatening; continuous nebs, steroids, MgSO4, ICU.
2. Normal PaCO2 in tachypnoeic asthmatic → impending failure, not reassurance.
3. Aspirin + polyps + asthma → AERD/Samter; avoid NSAIDs.
4. SABA canister weekly use → poor control; start/ensure ICS; abandon SABA-only.
5. Pregnancy exacerbation → treat fully; steroids safe when indicated; fetus needs oxygenated mother.
6. Work-related symptoms improve on holiday → occupational asthma; serial PEF. ^[1]

Exam Pearls

• Reversibility: at least 12 percent AND 200 mL (0.2 L) in FEV1 after bronchodilator — the ATS criterion; it cannot alone separate asthma from COPD.^[20]
• FeNO: detects eosinophilic airway inflammation, predicts corticosteroid responsiveness, and unmasks non-adherence (ATS guideline).^[29]
• GINA: ICS-containing therapy for every patient; SABA-only is not recommended at any step; ICS-formoterol MART is the preferred track (Track 1).^[1]
• As-needed ICS-formoterol in mild asthma reduces severe exacerbations by at least 60 percent versus SABA alone.^[1]
• Reliever without ICS is unsafe — the SMART trial showed statistically significant increases in respiratory-related and asthma-related deaths with salmeterol added to usual care.^[5]
• IV magnesium sulphate 1.2 to 2 g over 15 to 30 minutes reduces admissions in acute asthma unresponsive to oxygen, nebulised SABA and IV corticosteroids (OR 0.75).^[19]
• Critical (life-threatening) asthma: inability to speak, PEF under 25 percent of personal best, poor response to frequent bronchodilators and IV steroids — ICU.^[23]
• Biologics by target: anti-IL-5 (mepolizumab), anti-IL-5Rα (benralizumab), anti-IL-4Rα (dupilumab), anti-TSLP (tezepelumab — active even when blood eosinophils are under 300 per microlitre).^[16]
• Azithromycin 500 mg three times weekly is a Step-5 add-on that cuts exacerbations in persistent uncontrolled asthma (AMAZES).^[18]
• Tiotropium 5 μg once daily added to ICS-LABA extends time to severe exacerbation (hazard ratio 0.79).^[13]

Exam application bank (NEET-PG / INICET)

One-line answer

Asthma is a chronic inflammatory airway disease with variable and reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. GINA: ICS-containing therapy for every patient (SABA-only is unsafe), as-needed low-dose ICS-formoterol as the preferred reliever, MART for moderate-to-severe disease, and add-on LAMA, azithromycin or biologic therapy for severe asthma. Acute severe attacks: oxygen, nebulised short-acting beta-2 agonist and early systemic corticosteroid, with IV magnesium sulphate 1.2 to 2 g over 15 to 30 minutes when the response is insufficient. ^[1][19]

Worked stems (answer without another resource)

Stem 1 — Classic presentation. Map symptoms to mechanism; name the first investigation and first treatment step with dose/route if drug therapy is standard. ^[1]

Stem 2 — Unstable / complicated. List red flags that force immediate resuscitation, theatre, ICU, antidote, or reperfusion — and what you do in the first 15 minutes. ^[1]

Stem 3 — Atypical group. Elderly, pregnancy, child, or immunocompromised: how presentation and thresholds change. ^[1]

Stem 4 — Differential trap. Name the three closest mimics and one discriminator for each. ^[1]

Stem 5 — Disposition. Who goes home with safety-netting, who is admitted, who needs HDU/ICU/theatre, and what follow-up is mandatory. ^[1]

Rapid viva checklist

1. Definition + classification
2. Pathophysiology chain
3. Bedside signs / criteria
4. Score with exact components (if any)
5. Emergency bundle
6. Definitive therapy with doses
7. Complications of disease and of treatment
8. Special populations
9. Guideline/trial name if classic
10. Three exam traps

Coverage self-check

If you cannot answer any stem above from this page alone, re-read the matching section — the page is intended to be self-sufficient for final-prof and NEET-PG/INICET questions on Asthma.

The mantra

ICS-containing therapy for every asthmatic, at every step — and in the crisis: oxygen, nebulised SABA, systemic steroid, then IV magnesium 1.2 to 2 g if the response is insufficient.^[1][19]

Ward-round test — three stems, thirty seconds each

Stem 1 — the silent chest (answer)ShowHide

The 22-year-old from the top of the topic: peak flow unrecordable, SpO2 90%, no wheeze on auscultation, and the blood gas shows a PaCO2 of 5.8 kPa (normal for him). Diagnosis and first actions? Model: Critical (life-threatening) asthma — a silent chest with unrecordable peak flow sits at the severe end of the acute-severe spectrum (PEFR under 50 percent of best/predicted) and, with any failure to respond to frequent bronchodilators and IV steroids, meets NAEPP life-threatening criteria: escalate to ICU, continue nebulised SABA with systemic corticosteroid, and give IV magnesium sulphate 1.2 to 2 g over 15 to 30 minutes if response is insufficient.^[23][15][19]

Stem 2 — three canisters a month (answer)ShowHide

A 35-year-old requests her fourth salbutamol refill of the year. She uses her preventer 'most days'. No admissions. What is the single most predictive finding here, and what do you change? Model: Over three salbutamol canisters a year is a strong independent marker of future fatal or near-fatal attack — controller failure until proven otherwise. Check inhaler technique and adherence, confirm she is on an ICS (ICS-formoterol MART preferred), step up, and give a written asthma action plan. SABA-only is no longer acceptable at any step.^[1][5]

Stem 3 — aspirin, polyps, wheeze (answer)ShowHide

A 40-year-old asthmatic develops bronchospasm an hour after taking ibuprofen for a headache, and has longstanding nasal polyps. Name the triad and the first-line drug class. Model: Aspirin-exacerbated respiratory disease (Samter triad) — asthma, nasal polyps, NSAID sensitivity, leukotriene-driven. Avoid COX-1 NSAIDs; start a leukotriene receptor antagonist (montelukast); COX-2 selective agents are usually tolerated; refer for biologics or aspirin desensitisation if severe polyp disease.^[1]

References31ShowHide

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2. [2]Levy ML, Bacharier LB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update NPJ Prim Care Respir Med, 2023.PMID 36754956
3. [3]Israel E, Reddel HK Severe and Difficult-to-Treat Asthma in Adults N Engl J Med, 2017.PMID 28877019
4. [4]Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases Lancet, 2018.PMID 28911920
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