Acute Severe Asthma in Adults

Clinical Overview

Summary

Acute severe asthma is a medical emergency characterised by progressive bronchospasm, airway inflammation, and mucus hypersecretion leading to rapid respiratory deterioration. It remains a significant cause of preventable death, with the UK National Review of Asthma Deaths identifying that 46% of asthma deaths could have been prevented with better management. [1] The hallmark of optimal management is early recognition of severity using the BTS/SIGN classification, aggressive bronchodilator therapy, systemic corticosteroids within 60 minutes of presentation, and timely escalation to intensive care when life-threatening features are present. [2]

The pathophysiology involves a cascade of bronchospasm (minutes), inflammatory oedema (hours), and mucus plugging (hours to days), all contributing to progressive airway obstruction. A rising or normal pCO2 in an acutely breathless patient represents a critical warning sign of impending respiratory arrest, as it indicates the patient is tiring and can no longer maintain compensatory hyperventilation. [3]

Key Facts

Clinical Pearls

O SHIT M — Oxygen, Salbutamol, Hydrocortisone (or prednisolone), Ipratropium, Theophylline, Magnesium. This mnemonic captures the essential first-line interventions in severe asthma.

A "normal" or rising pCO2 (> 4.6 kPa / 35 mmHg) in acute asthma is a sign of impending respiratory failure. The expected response to hypoxia is hyperventilation with LOW pCO2. A normal value means the patient is fatiguing. [3]

Always check inhaler technique before discharge — the National Review of Asthma Deaths found that 39% of patients who died had not been assessed for inhaler technique in primary care. [1]

The transition from wheeze to silent chest is ominous. Paradoxically, return of audible wheeze after bronchodilator treatment often indicates improvement (air is now moving).

Why This Matters Clinically

Acute asthma represents a unique window where rapid, protocolised intervention dramatically alters outcomes. Unlike many emergencies, the difference between good and poor outcomes is measured in minutes. The NRAD report demonstrated that:

• 43% of deaths occurred before medical help arrived or could be summoned
• 9% died in the emergency department or on arrival at hospital
• Only 4% died in ICU settings [1]

This highlights the critical importance of patient education, rapid recognition, and aggressive early treatment. Junior doctors must be confident to escalate early when life-threatening features are present and never delay treatment for investigations.

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Epidemiology

Global and UK Prevalence

Asthma affects approximately 339 million people worldwide, with significant geographic variation in prevalence. [8] The UK has one of the highest asthma prevalence rates globally, with significant implications for emergency presentations.

Demographics

Age Distribution:

• Bimodal distribution: childhood peak (5-10 years) and late-adult peak (50-70 years)
• Severe exacerbations peak in young adults (18-34 years) and elderly (> 65 years) [4]
• Higher mortality in the elderly (> 80% of deaths occur in those aged > 50)

Sex Differences:

• Female predominance in adults (approximately 2:1 ratio)
• More severe disease trajectory in adult females
• Hormonal factors implicated (premenstrual exacerbations documented) [9]

Ethnic Disparities:

• Higher prevalence in Black Caribbean populations (13.6%)
• Elevated rates in South Asian populations
• Higher mortality in Black ethnic groups (3-fold higher than White populations)
• Socioeconomic factors contribute significantly [10]

Risk Factors for Severe Exacerbation

Understanding risk factors allows identification of high-risk patients who require closer monitoring and more aggressive preventive strategies.

Seasonal Variation

Triggers for Acute Exacerbation

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Pathophysiology

Overview

Acute asthma exacerbation represents acute-on-chronic failure of the inflamed airway to cope with additional triggers. The underlying chronic airway inflammation primes the airway for an exaggerated response. The pathophysiology involves three key mechanisms working in concert, each with different temporal profiles and therapeutic implications. [15]

Mechanism Cascade

1. Bronchospasm (Onset: Minutes)

The immediate response to trigger exposure:

• Allergen/irritant binds to IgE on mast cell surface
• Mast cell degranulation releases preformed mediators:
  • "Histamine: Direct smooth muscle contraction"
  • "Tryptase: Airway remodelling, protease activation"
  • "Prostaglandin D2: Bronchoconstriction, vasodilation"
• Newly synthesised mediators:
  • "Leukotrienes (LTC4, LTD4, LTE4): Potent bronchoconstrictors (100-1000x histamine)"
  • "Platelet-activating factor (PAF): Bronchospasm, mucus secretion"
• Smooth muscle contraction → Acute airway narrowing
• Reversible with β2-agonists (therapeutic target)

Exam Detail: Cellular Mechanisms of Bronchospasm:

The β2-adrenergic receptor is a Gs protein-coupled receptor. Agonist binding activates adenylyl cyclase, increasing intracellular cAMP. This:

1. Activates protein kinase A (PKA)
2. Phosphorylates myosin light chain kinase → reduced contractility
3. Opens large-conductance Ca2+-activated K+ channels → hyperpolarisation
4. Reduces intracellular Ca2+ → smooth muscle relaxation

Desensitisation occurs with chronic SABA use through:

• Receptor phosphorylation by β-adrenergic receptor kinase (βARK)
• β-arrestin binding and receptor internalisation
• Uncoupling from Gs protein

This explains reduced bronchodilator response in patients overusing SABA.

2. Airway Inflammation (Onset: Hours)

The late-phase inflammatory response:

• Th2-mediated eosinophilic inflammation predominates
• Key cytokine profile:
  • "IL-4: B-cell IgE class switching"
  • "IL-5: Eosinophil recruitment, survival, activation"
  • "IL-13: Mucus hypersecretion, airway hyperresponsiveness"
• Cellular infiltration:
  • Eosinophils (hallmark cell)
  • Mast cells (increased in smooth muscle)
  • Th2 lymphocytes
  • Basophils
• Consequences:
  • Mucosal oedema
  • Vascular leak and plasma exudation
  • Epithelial shedding
  • Nerve ending exposure → enhanced cough reflex
• Requires corticosteroids for resolution (therapeutic target)

Exam Detail: The Eosinophil in Asthma:

Eosinophils release:

• Major basic protein (MBP): Epithelial damage, hyperreactivity
• Eosinophil cationic protein (ECP): Ciliary dysfunction
• Eosinophil peroxidase (EPO): Oxidative damage
• Leukotriene C4: Bronchoconstriction, mucus

Eosinophil counts correlate with:

• Asthma severity
• Risk of exacerbation
• Response to corticosteroids (Type 2 high phenotype)

This is the therapeutic target for biological agents:

• Mepolizumab/Benralizumab: Anti-IL-5/IL-5R
• Dupilumab: Anti-IL-4Rα (blocks IL-4 and IL-13)

3. Mucus Hypersecretion (Onset: Hours to Days)

The prolonged component contributing to persistent symptoms:

• Goblet cell hyperplasia (chronic) and metaplasia (acute)
• Submucosal gland hypertrophy
• Production of thick, tenacious mucus with altered rheology:
  • Increased MUC5AC glycoprotein
  • Reduced mucociliary clearance
• Mucus plug formation → segmental/lobar collapse
• May persist despite bronchodilation
• Contributes to post-exacerbation symptoms

Physiological Consequences

Dynamic Hyperinflation

A critical concept in severe asthma:

1. Prolonged expiratory time constant due to airway obstruction
2. Tachypnoea prevents complete exhalation
3. Progressive air trapping increases FRC
4. Diaphragm flattens → mechanical disadvantage
5. Intrinsic PEEP (auto-PEEP) develops
6. Patient must generate more negative intrathoracic pressure to initiate inspiration
7. Increased work of breathing → respiratory muscle fatigue

Clinical Implications:

• Explains paradoxical worsening with agitation/tachypnoea
• Rationale for controlled breathing techniques
• Ventilator management: low rates, prolonged expiration, permissive hypercapnia

The "Silent Chest" Phenomenon

The most ominous clinical sign in acute asthma:

Paradox: Improving wheeze after bronchodilator treatment often indicates therapeutic response, not deterioration. Conversely, "quiet" chest in a distressed patient is a critical emergency requiring immediate escalation.

Phenotypes of Severe Asthma

Understanding phenotypes guides biological therapy selection:

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BTS/SIGN Severity Classification

Overview

The British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) classification is the UK standard for grading acute asthma severity. [2] This classification determines management intensity, disposition, and escalation thresholds. It is critical to recognise that any single life-threatening feature mandates treatment as life-threatening asthma.

Complete Classification Table

Life-Threatening Features (CHESS VP)

A useful mnemonic for life-threatening features:

Near-Fatal Asthma Definition

Near-fatal asthma is defined as:

• Raised PaCO2 (respiratory acidosis) AND/OR
• Requiring mechanical ventilation with raised inflation pressures

Patients with near-fatal asthma have a significantly elevated risk of future fatal attacks and require:

• Specialist respiratory follow-up
• Written asthma action plan
• Consideration for biological therapy
• Psychological assessment (high rates of denial, depression)

Disposition by Severity

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Clinical Assessment

History (AMPLE + Asthma-Specific)

Standard AMPLE:

• Allergies: Known triggers, drug allergies (especially NSAIDs, beta-blockers)
• Medications: Current inhalers, compliance, recent SABA use, oral steroids
• Past medical history: Previous ICU admission, intubation, hospitalisations
• Last meal: Relevant if intubation considered
• Events leading: Onset (rapid vs gradual), triggers identified

Asthma-Specific History:

High-Risk Features on History:

• More than 3 hospitalisations in past year
• Any previous ICU admission or intubation
• Current or recent oral corticosteroid use
• Use of > 1 SABA canister per month [12]
• Non-compliance with inhaled corticosteroids
• Psychosocial problems (denial, depression, poor healthcare access)
• Food allergy (especially peanut, tree nuts)

Physical Examination

General Inspection:

Respiratory Examination:

Pulsus Paradoxus:

• Exaggerated fall in systolic BP (> 10 mmHg) during inspiration
• Caused by increased negative intrathoracic pressure and ventricular interdependence
• Correlates with severity of obstruction
• Difficult to measure in clinical practice; presence suggests severe disease

Cardiovascular Examination:

Examination Red Flags

[!DANGER] Any ONE of these = Life-Threatening Asthma:

• Silent chest on auscultation
• Central cyanosis
• Bradycardia (less than 60 bpm) or arrhythmia
• Hypotension (SBP less than 90 mmHg)
• Exhaustion / poor respiratory effort
• Altered consciousness (confusion, drowsiness, coma)
• SpO2 less than 92% despite oxygen

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Investigations

Immediate Bedside Tests

1. Peak Expiratory Flow Rate (PEFR)

The cornerstone of severity assessment:

Practical Points:

• Use patient's best (not predicted) if known
• Serial measurements every 15-30 minutes guide response
• May be unmeasurable in severe cases — do not delay treatment
• Post-bronchodilator improvement > 60 L/min suggests good response

2. Pulse Oximetry (SpO2)

Note: SpO2 can be falsely reassuring in CO2 retainers — always correlate with clinical picture and ABG.

3. Arterial Blood Gas (ABG)

Essential in severe and life-threatening asthma. [3]

[!WARNING] A normal or rising PaCO2 in acute asthma is an ominous sign. It indicates respiratory muscle fatigue and impending respiratory arrest. Immediate senior review and ICU referral required.

Interpreting the ABG:

Laboratory Investigations

Salbutamol-Induced Hypokalaemia:

• β2-agonists drive potassium intracellularly via Na+/K+-ATPase stimulation
• May drop K+ by 0.5-1.0 mmol/L with nebulised treatment
• Monitor K+ every 4-6 hours during continuous nebulisation
• Replace if less than 3.5 mmol/L (arrhythmia risk, especially with hypoxia)

Imaging

Chest X-ray — When to Order:

CXR is NOT routine in acute asthma. [2] Indications:

Expected CXR Findings in Asthma:

[!NOTE] An abnormal CXR in a known asthmatic should prompt consideration of alternative or additional diagnosis (pneumonia, pneumothorax, cardiac failure).

What NOT to Do

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Emergency Management

Immediate Actions: O SHIT M Protocol (First 15 Minutes)

This protocol must be initiated immediately upon recognition of acute severe asthma. Do not delay for investigations. [2]

1. Oxygen (O)

[!IMPORTANT] Do NOT withhold oxygen for fear of CO2 retention. This is a COPD concern, not asthma. Hypoxia kills faster than hypercapnia.

2. Salbutamol (S)

Nebuliser Considerations:

• Use oxygen-driven nebuliser (6-8 L/min flow)
• Air-driven acceptable if hypercapnic COPD coexists
• MDI + spacer (10 puffs) equivalent to nebuliser in moderate asthma [17]
• Monitor for side effects: tremor, tachycardia, hypokalaemia

3. Hydrocortisone / Prednisolone (H)

Evidence Base:

• Systemic corticosteroids reduce relapses by 50% [6]
• Effect begins at 4-6 hours (too late if delayed)
• Earlier administration = better outcomes
• Oral as effective as IV if patient can swallow [6]

[!WARNING] Do not delay steroids. The benefit is time-dependent. Oral prednisolone is as effective as IV hydrocortisone if the patient can swallow.

4. Ipratropium Bromide (I)

Indications:

• Add early in severe and life-threatening asthma
• Synergistic effect with β2-agonists
• Cochrane review: reduces hospital admissions (NNT 11) [18]
• Less effective alone; always combine with SABA

5. Theophylline / Aminophylline (T)

Toxicity Features:

• Nausea, vomiting (early)
• Tachycardia, arrhythmias
• Seizures (at high levels)
• Therapeutic range: 10-20 mg/L (55-110 µmol/L)

Evidence:

• Systematic review shows modest bronchodilator effect [19]
• Associated with increased side effects
• Reserve for patients failing standard therapy

6. Magnesium Sulphate (M)

Mechanism:

• Smooth muscle relaxation via Ca2+ channel blocking
• Inhibits mast cell degranulation
• Reduces acetylcholine release at neuromuscular junction

3Mg Trial Summary: [7]

• 1,109 adults with severe acute asthma (PEF less than 50%)
• 2 g IV MgSO4 vs placebo
• 10% absolute reduction in hospital admission
• Most benefit in severe/life-threatening subgroup
• Safe with minimal side effects

Side Effects:

• Flushing, warmth
• Hypotension (infuse slowly)
• Hyporeflexia (if toxic)

Treatment Algorithm by Severity

Moderate Exacerbation (PEF 50-75%):

1. Salbutamol 5 mg nebulised (or 10 puffs via spacer)
2. Prednisolone 40 mg PO
3. Reassess at 15-30 minutes
4. If PEF > 75% and stable → consider discharge
5. Provide written action plan

Severe Exacerbation (PEF 33-50% OR any severe feature):

1. High-flow O2 15 L/min via NRB
2. Salbutamol 5 mg nebulised — repeat PRN every 15-30 min
3. Ipratropium 0.5 mg nebulised
4. Prednisolone 40-50 mg PO OR Hydrocortisone 100 mg IV
5. Monitor: SpO2, PEF, clinical response
6. If inadequate response at 30-60 min:
   - Add MgSO4 2 g IV over 20 minutes
   - Consider ABG
7. Admit for observation

Life-Threatening (PEF less than 33% OR any life-threatening feature):

1. Call for senior help immediately
2. Call ICU outreach / Critical Care
3. High-flow O2 15 L/min NRB
4. Back-to-back salbutamol nebulisers (continuous)
5. Ipratropium 0.5 mg nebulised
6. Hydrocortisone 100 mg IV
7. MgSO4 2 g IV over 20 minutes
8. ABG — assess for hypercapnia
9. Prepare for intubation if deteriorating
10. Do NOT sedate the patient

Near-Fatal / ICU-Bound:

1. ICU admission mandatory
2. Senior anaesthetic review for intubation decision
3. Consider:
   - IV salbutamol (15-20 mcg/min) if poor inhaled response
   - IV aminophylline (5 mg/kg load if not on theophylline)
   - NIV (controversial, specialist decision)
   - Ketamine (bronchodilator properties, RSI agent)
4. Intubation and ventilation if:
   - Respiratory arrest
   - Coma / obtunded
   - Exhaustion despite maximal therapy
   - Rising PaCO2 with acidosis

Ventilation in Severe Asthma

Pre-Intubation Considerations:

• Intubation is high-risk in asthma (high intrinsic PEEP, difficult ventilation)
• Should be performed by most senior available anaesthetist
• Prepare for post-intubation hypotension (loss of sympathetic drive)
• Have vasopressors ready

Induction Agents:

Ventilation Strategy:

• Low respiratory rate (8-12/min) to allow long expiratory time
• Low tidal volumes (6-8 mL/kg)
• Prolonged I:E ratio (1:3 or 1:4)
• Accept permissive hypercapnia (pH > 7.2)
• Target low plateau pressures (less than 30 cmH2O)
• Avoid breath stacking and auto-PEEP

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Discharge Criteria and Planning

Safe Discharge Criteria

All criteria must be met before discharge: [2]

Discharge Medications

Follow-Up Requirements

Admission Criteria

Admit if ANY of the following:

Peak Flow Diary

Provide peak flow meter and diary with instructions:

Traffic Light Zones:

• Green (80-100%): All clear, continue preventers
• Amber (50-80%): Increase reliever, consider doubling ICS, seek review
• Red (less than 50%): Medical emergency, start action plan, seek urgent help

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Complications

Acute Complications

Medication-Related Complications

Long-Term Consequences

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Prognosis and Outcomes

Mortality Statistics

Prognostic Factors

Good Prognostic Indicators:

• Rapid response to initial bronchodilators (PEF > 50% at 30 min)
• Good inhaler technique demonstrated
• Written asthma action plan
• Regular preventer use with good adherence
• Never smoked
• No prior ICU admission
• Identifiable and avoidable trigger
• Good social support

Poor Prognostic Indicators:

• Previous near-fatal attack
• Multiple hospitalisations (≥3/year)
• Psychosocial dysfunction (denial, depression)
• Frequent oral steroid courses (≥3/year)
• Heavy SABA use (> 1 canister/month)
• Poor medication adherence
• Obesity
• Active smoking
• Comorbid COPD overlap
• Food allergy (anaphylaxis risk)

Long-Term Outcomes After Hospitalisation

Quality of Life Impact

Patients hospitalised for acute asthma have:

• Reduced health-related quality of life for 3-6 months
• Increased anxiety and fear of future attacks
• Work/school absenteeism
• Sleep disturbance
• Activity limitation

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Prevention and Discharge Education

Primary Prevention of Exacerbations

Written Asthma Action Plan Components

Every discharged patient must receive a personalised asthma action plan:

Inhaler Technique Assessment

Poor inhaler technique is a major cause of treatment failure. [1]

MDI + Spacer Steps:

1. Remove cap, shake inhaler
2. Insert into spacer
3. Exhale fully
4. Seal lips around mouthpiece
5. Fire canister ONCE
6. Breathe in slowly and deeply
7. Hold breath 10 seconds
8. Wait 30 seconds between puffs
9. Rinse mouth after ICS

Common Errors:

• Firing before inhalation
• Multiple puffs without breathing
• Too fast inspiration
• Not holding breath
• Not using spacer (reduces deposition by 80%)

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Special Populations

Pregnancy

Elderly

Obesity

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Exam-Focused Content

Common Viva Questions

Q: "A 28-year-old woman presents with acute severe asthma. Describe your initial management."

Model Answer: "I would immediately assess ABC and call for senior help if life-threatening features are present. My initial management follows the O SHIT M protocol. I would give high-flow oxygen via non-rebreathe mask targeting saturations 94-98%. Simultaneously, I would administer nebulised salbutamol 5 mg driven by oxygen, adding ipratropium 0.5 mg. I would give oral prednisolone 40 mg immediately — or IV hydrocortisone 100 mg if she cannot swallow. I would rapidly assess severity using PEF, SpO2, speech, and consciousness level according to BTS/SIGN classification. If severe or life-threatening, I would add IV magnesium sulphate 2 g over 20 minutes. I would monitor PEF every 15-30 minutes and obtain an ABG if there's inadequate response, specifically looking for a normal or rising pCO2 which would indicate impending respiratory failure requiring ICU referral."

Q: "What are the life-threatening features of acute asthma?"

Model Answer: "Life-threatening features can be remembered using CHESS VP: Cyanosis, Hypotension, Exhaustion, Silent chest, SpO2 less than 92%, arrhythmia or bradycardia (Vital signs), and PEF less than 33%. Additionally, I look for altered consciousness, poor respiratory effort, and critically, a normal or raised PaCO2 on blood gas. Any single life-threatening feature mandates treatment as life-threatening asthma and ICU referral."

Q: "Why is a normal pCO2 concerning in acute asthma?"

Model Answer: "In acute asthma, the physiological response to hypoxia is hyperventilation, which should cause a low pCO2 — typically below 4.5 kPa. A normal pCO2 of 4.6 to 5.5 kPa indicates that the patient is no longer able to maintain this compensatory hyperventilation — they are tiring. A rising or elevated pCO2 represents impending respiratory failure and respiratory arrest. This patient needs immediate ICU referral and preparation for intubation."

Common Examiner Follow-Ups

What Gets You Failed

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Key Guidelines

Primary Guidelines

Landmark Trials

3Mg Trial (Goodacre et al., 2014) [7]

• RCT: 1,109 adults with severe asthma (PEF less than 50%)
• Intervention: 2 g IV MgSO4 vs placebo
• Outcome: 10% absolute reduction in hospital admission
• NNT: 10 overall; 7 for severe/life-threatening
• Conclusion: Use MgSO4 early in severe/life-threatening cases

Rowe et al., Cochrane Review (2014) [6]

• Systematic review: Early corticosteroids in acute asthma
• Finding: Reduces admission rates by 25%
• Reduces relapse at 7-10 days by 50%
• Oral as effective as IV if tolerated

Kew et al., Cochrane Review (2014) [18]

• Systematic review: Ipratropium bromide in acute asthma
• Finding: Reduces hospital admissions (NNT 11)
• Most benefit when added to SABA in severe cases

Evidence Summary by Intervention

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Patient Information

What is an Asthma Attack?

An asthma attack happens when your airways suddenly become very narrow and inflamed. This makes it hard to breathe. During an attack, you may feel:

• Very short of breath
• Tightness in your chest
• Wheezing (a whistling sound when you breathe)
• Unable to speak in full sentences
• Frightened or anxious

What Causes an Attack?

Common triggers include:

What To Do During an Attack

Step 1: Sit upright — don't lie down

Step 2: Take your blue reliever inhaler — 1 puff every 30-60 seconds, up to 10 puffs

Step 3: If you're not better after 10 puffs, or feel worse — call 999

Step 4: If the ambulance hasn't arrived in 15 minutes — repeat 10 puffs

Step 5: Stay calm and try to breathe slowly

Warning Signs to Call 999 Immediately

• You can't speak in full sentences
• Your lips or fingernails are turning blue
• Your blue inhaler isn't helping
• You feel exhausted or confused
• You're getting worse despite treatment

After Your Hospital Visit

You will be given:

• Steroid tablets to take for 5-7 days (this is safe and important)
• A follow-up appointment with your GP within 48-72 hours
• An appointment at the asthma clinic within 4-6 weeks
• An asthma action plan explaining what to do next time

Preventing Future Attacks

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References

1. Royal College of Physicians. Why Asthma Still Kills: The National Review of Asthma Deaths (NRAD). London: RCP; 2014. Available from: https://www.rcplondon.ac.uk/projects/outputs/why-asthma-still-kills

2. British Thoracic Society / Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma. Thorax. 2019;74(Suppl 1):1-69. doi:10.1136/thorax-2019-BTSguidelines

3. McFadden ER Jr, Lyons HA. Arterial-blood gas tension in asthma. N Engl J Med. 1968;278(19):1027-1032. doi:10.1056/NEJM196805092781901

4. Mukherjee M, Stoddart A, Gupta RP, et al. The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases. BMC Med. 2016;14(1):113. doi:10.1186/s12916-016-0657-8

5. Brenner B, Corbridge T, Kazzi A. Intubation and mechanical ventilation of the asthmatic patient in respiratory failure. J Allergy Clin Immunol. 2009;124(2 Suppl):S222-S228. doi:10.1016/j.jaci.2009.05.013

6. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178. doi:10.1002/14651858.CD002178

7. Goodacre S, Cohen J, Bradburn M, et al. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. Lancet Respir Med. 2013;1(4):293-300. doi:10.1016/S2213-2600(13)70070-5

8. Global Asthma Network. The Global Asthma Report 2022. Int J Tuberc Lung Dis. 2022;26(Suppl 1):S1-S102. doi:10.5588/ijtld.22.1010

9. Leynaert B, Sunyer J, Garcia-Esteban R, et al. Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort. Thorax. 2012;67(7):625-631. doi:10.1136/thoraxjnl-2011-201249

10. Sheikh A, Alves B, Dhami S. Ethnic disparities in asthma prevalence and mortality: a systematic review. Prim Care Respir J. 2007;16(4):209-219. doi:10.3132/pcrj.2007.00058

11. Hasegawa K, Sullivan AF, Tober ME, et al. A multicenter observational study of US adults with acute asthma: who are the frequent visitors to the emergency department?. J Allergy Clin Immunol Pract. 2014;2(6):733-740. doi:10.1016/j.jaip.2014.06.012

12. Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994;149(3 Pt 1):604-610. doi:10.1164/ajrccm.149.3.8118625

13. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ. 1993;307(6910):982-986. doi:10.1136/bmj.307.6910.982

14. Thien F, Beggs PJ, Csutoros D, et al. The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors. Lancet Planet Health. 2018;2(6):e255-e263. doi:10.1016/S2542-5196(18)30120-7

15. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18(5):673-683. doi:10.1038/nm.2731

16. O'Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(Suppl 1):ii1-ii90. doi:10.1136/thoraxjnl-2016-209729

17. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;(9):CD000052. doi:10.1002/14651858.CD000052.pub3

18. Stoodley RG, Aaron SD, Dales RE. The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials. Ann Emerg Med. 1999;34(1):8-18. doi:10.1016/S0196-0644(99)70266-2

19. Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database Syst Rev. 2000;(4):CD002742. doi:10.1002/14651858.CD002742

20. Rodrigo GJ, Rodrigo C, Hall JB. Acute asthma in adults: a review. Chest. 2004;125(3):1081-1102. doi:10.1378/chest.125.3.1081

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