3.1 Asthma: Diagnostic Criteria, Chronic Stepping & Acute Exacerbations

3.1 Asthma: Diagnostic Criteria, Chronic Stepping & Acute Exacerbations

Asthma is a chronic inflammatory disorder of the conducting airways characterized by bronchial hyperresponsiveness, reversible airflow limitation, and airway remodeling. In clinical practice and UK licensing examinations, mastery of objective diagnostic thresholds, stepwise maintenance titration, and structured emergency resuscitation is essential.

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1. Pathophysiology and Clinical Presentation

The hallmark of asthma is chronic eosinophilic or non-eosinophilic airway inflammation mediated by T-helper 2 (Th2) lymphocytes, interleukin cytokines (IL-4, IL-5, IL-13), and mast cell degranulation. Release of histamine, leukotrienes, and prostaglandins produces smooth muscle bronchospasm, mucosal oedema, and hypersecretion of thick, tenacious mucus.

Typical Clinical Features

Patients typically present with variable and episodic respiratory symptoms that fluctuate over time and intensity:

• Wheezing: Expiratory, high-pitched, polyphonic wheezing across bilateral lung zones.
• Breathlessness and Chest Tightness: Often worse in the early morning, during nocturnal waking, or following physical exertion.
• Dry Cough: Frequently nocturnal or precipitated by cold air, aerosol irritants, viral upper respiratory tract infections, and exercise.
• Personal or Family Atopy: Strong association with allergic rhinitis, atopic eczema, and seasonal pollen allergies.

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2. Objective Diagnostic Pathway (BTS/NICE/SIGN NG245, 2024)

The joint British Thoracic Society, NICE and SIGN guideline NG245 (Asthma: diagnosis, monitoring and chronic asthma management, November 2024) replaced the separate NICE NG80 and BTS/SIGN pathways. Clinical diagnosis alone is not enough: objective tests are used in sequence. If a person is acutely unwell or highly symptomatic, treat them immediately and do whatever tests are available (for example eosinophil count, FeNO, or spirometry/PEF before and after a bronchodilator).

Adults (17 and Over)

1. Blood eosinophil count or FeNO first: diagnose asthma if the eosinophil count is above the laboratory reference range or the FeNO level is 50 ppb or more. FeNO measures eosinophilic airway inflammation (nitric oxide from inducible nitric oxide synthase in the bronchial epithelium).
2. Bronchodilator reversibility (BDR) with spirometry if not confirmed: diagnose asthma if $\text{FEV}_1$ rises by 12% or more AND 200 mL or more from the pre-bronchodilator value, or by 10% or more of the predicted normal $\text{FEV}_1$. Spirometry often shows obstruction ($\text{FEV}_1/\text{FVC}$ below the lower limit of normal or 0.70), but normal spirometry between attacks does not exclude asthma.
3. Peak expiratory flow (PEF) variability if spirometry is unavailable or delayed: measure PEF twice daily for 2 weeks; diagnose asthma if variability (amplitude percentage mean) is 20% or more.
4. Bronchial challenge test if asthma is still suspected clinically: refer for a test (for example methacholine, histamine or mannitol); bronchial hyper-responsiveness confirms asthma.

Children (5 to 16)

1. FeNO first: diagnose asthma if FeNO is 35 ppb or more.
2. BDR: an $\text{FEV}_1$ rise of 12% or more (or 10% or more of predicted) confirms asthma.
3. PEF variability: twice daily for 2 weeks; 20% or more is diagnostic.
4. Atopy and eosinophils: if still suspected, skin prick testing to house dust mite or total IgE, plus blood eosinophil count; diagnose if there is sensitisation or a raised IgE and eosinophils above $0.5 \times 10^9$/L. If doubt remains, refer to a paediatric specialist (including bronchial challenge).

Children under 5 cannot reliably do the tests: treat on clinical judgement as "suspected asthma" (for example an 8–12 week trial of paediatric low-dose ICS) and review.

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3. Chronic Pharmacological Management (NG245)

The goal is control of symptoms, prevention of exacerbations and the lowest effective treatment. NG245 makes inhaled corticosteroid–formoterol (ICS/formoterol) combination inhalers the backbone of treatment from age 12 and ends SABA-only treatment.

People Aged 12 and Over

1. As-needed AIR therapy: newly diagnosed asthma starts with a low-dose ICS/formoterol inhaler taken as needed for symptom relief (anti-inflammatory reliever, "AIR"; in the UK, licensed products are budesonide/formoterol). Anyone with confirmed asthma using a SABA alone is switched to as-needed AIR.
2. Low-dose MART: if not controlled, use the same ICS/formoterol inhaler every day as maintenance and also as the reliever (maintenance and reliever therapy). Start directly at low-dose MART if the person is highly symptomatic (for example regular night waking) or presents with a severe exacerbation (with oral corticosteroids as needed).
3. Moderate-dose MART: if still not controlled.
4. Check FeNO and blood eosinophils: if either is raised, refer to a specialist in asthma care. If neither is raised, try a leukotriene receptor antagonist (LTRA, e.g. montelukast) or a long-acting muscarinic antagonist (LAMA) added to moderate-dose MART for 8–12 weeks, then keep, swap or add the other agent depending on response.
5. Specialist referral: asthma not controlled despite moderate-dose MART and trials of both an LTRA and a LAMA. Specialists consider biologics (omalizumab for severe allergic asthma; mepolizumab, benralizumab or reslizumab for severe eosinophilic asthma; dupilumab or tezepelumab) and, as a last resort, maintenance oral corticosteroids.

People already well controlled on regular ICS plus SABA, or ICS/LABA plus SABA, do not have to switch; NG245 says consider moving them to low- or moderate-dose MART if control is inadequate. People on MART do not normally need a separate SABA.

Children Aged 5 to 11

1. Twice-daily paediatric low-dose ICS with a SABA as needed.
2. If not controlled: paediatric low-dose MART if the child can manage the regimen; otherwise add an LTRA (8–12 week trial) or switch to a twice-daily paediatric low-dose ICS/LABA inhaler plus SABA.
3. Then paediatric moderate-dose MART (or moderate-dose ICS/LABA plus SABA).
4. Refer to a specialist in asthma care if still not controlled.

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4. Acute Asthma Exacerbations: Clinical Severity Grading

An acute exacerbation is characterized by progressive breathlessness, cough, wheezing, and rapid reduction in PEF. Objective clinical triage using standardized British Thoracic Society (BTS/SIGN) criteria dictates the level of monitoring and immediate interventions required.

The "Normal" PaCO2 Clinical Trap

During an acute asthma attack, hyperventilation driven by hypoxia and airway irritation typically blows off carbon dioxide, producing a low arterial $\text{PaCO}_2$ ($< 4.5\text{ kPa}$) and respiratory alkalosis.

Finding a "normal" $\text{PaCO}_2$ ($4.5\text{--}6.0\text{ kPa}$) or elevated $\text{PaCO}_2$ ($> 6.0\text{ kPa}$) in an exhausted asthmatic indicates that the respiratory muscles have failed. The patient can no longer maintain minute ventilation. This constitutes an immediate life-threatening emergency signalling impending cardiorespiratory arrest.

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5. Emergency Resuscitation Protocol

Emergency management follows the structured "O-S-H-I-M" protocol under continuous monitoring:

1. Oxygen Therapy:

   • Deliver high-flow humidified oxygen via a non-rebreathe reservoir bag mask.
   • Target Oxygen Saturation: $94\text{--}98\%$ (unlike COPD, asthmatics are rarely at risk of hypercapnic oxygen suppression).

2. High-Dose Inhaled Bronchodilators (Salbutamol):

   • Salbutamol $5\text{ mg}$ nebulised, driven by $6\text{--}8\text{ L/min}$ of high-flow oxygen.
   • Repeat every $15\text{--}30\text{ minutes}$, or administer continuous nebulisation ($10\text{ mg/hr}$) for severe refractory obstruction.

3. Systemic Corticosteroids:

   • Oral prednisolone $40\text{--}50\text{ mg}$ once daily for at least 5 days (or until full recovery).
   • If the patient is vomiting, unconscious, or in severe distress, administer intravenous hydrocortisone $100\text{ mg}$ every 6 hours.

4. Inhaled Anticholinergics (Ipratropium Bromide):

   • Add nebulised ipratropium bromide $0.5\text{ mg}$ to salbutamol.
   • Administer every $4\text{--}6\text{ hours}$ in acute severe asthma, or every $20\text{ minutes}$ during the first hour of resuscitation in life-threatening presentations.

5. Intravenous Magnesium Sulphate:

   • Indicated for acute severe asthma unresponsive to initial nebulised therapy, or any life-threatening presentation.
   • Dose: Magnesium sulphate $1.2\text{--}2.0\text{ g}$ IV infused over 20 minutes.
   • Mechanism: Promotes bronchial smooth muscle relaxation by competing with calcium channels.

6. Second-Line Adjuncts (Under Senior Guidance):

   • Intravenous aminophylline loading dose ($5\text{ mg/kg}$ over 30 minutes, omitted if on oral theophylline) followed by maintenance infusion.
   • Intravenous salbutamol infusion under telemetry monitoring.

Indications for Urgent Senior Anaesthetic / Intensive Care (ICU) Referral

• Deteriorating or failing PEF despite maximal nebulisers.
• Normal or rising $\text{PaCO}_2$ or severe metabolic/respiratory acidosis ($\text{pH} < 7.35$).
• Persistent or worsening hypoxaemia ($\text{PaO}_2 < 8.0\text{ kPa}$) despite maximal supplemental oxygen.
• Signs of physical exhaustion, altered consciousness, confusion, or bradypnoea.
• Cardiorespiratory arrest.

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6. Discharge Criteria and Secondary Prevention

Patients may be considered for discharge when clinically stable on their discharge regimen for at least 12–24 hours:

• Peak expiratory flow $> 75\%$ of personal best or predicted.
• Inhaler technique observed and confirmed correct with a spacer.
• Completed minimum 5-day course of oral prednisolone ($40\text{--}50\text{ mg}$ daily).
• Review and update of a personalized Written Asthma Action Plan (WAAP).
• General practice follow-up arranged within 48 hours of discharge.
• Specialist respiratory outpatient clinic follow-up within 4 weeks for all admissions.