Wheeze

Wheeze is a continuous, high pitched musical sound produced by airflow through narrowed intrathoracic airways, heard during expiration (typically) or both phases of respiration. It indicates airway narrowing but not its cause: asthma and chronic obstructive pulmonary disease dominate, but cardiac failure, aspiration, foreign body, anaphylaxis, tumours, pulmonary embolism and vocal cord dysfunction all wheeze. A single localised (monophonic) wheeze that does not clear on coughing suggests a fixed obstruction.

Clinical relevance. Wheeze affects about 10% to 15% of adults in the past year and is a leading reason for primary care visits. Missing cardiac asthma, a central airway tumour, foreign body or anaphylaxis because "all that wheezes is asthma" is a classic error. Persistent unilateral or fixed wheeze must be investigated. In children, wheeze phenotypes (viral episodic, multiple trigger, atopic) guide treatment.

Classification.

• By phase: expiratory (intrathoracic obstruction), inspiratory (extrathoracic or fixed central; this is stridor if loud and harsh), biphasic (fixed central obstruction).
• By character: polyphonic (multiple pitches starting at different times, diffuse small airway narrowing: asthma, chronic obstructive pulmonary disease, bronchiolitis, cardiac failure) and monophonic (single pitch, localised: tumour, foreign body, stenosis, mucus plug).
• By timeline: acute (infection, asthma exacerbation, anaphylaxis, aspiration, embolism, heart failure), recurrent or episodic (asthma, atopy, reflux, vocal cord dysfunction), chronic persistent (chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obliterative bronchiolitis, tracheomalacia, tumour).
• By cause group: airway, parenchymal, cardiac, vascular, allergic and drug related, aspiration, functional, mimics.

Mechanism. Wheeze arises when airway walls oscillate as flow velocity reaches a critical level in a narrowed segment (flow limitation), through bronchospasm, mucosal oedema, secretions, airway wall collapse or extrinsic compression.

History.

• Onset, duration, frequency, pattern (episodic or persistent), diurnal variation (nocturnal or early morning), triggers (viral illness, allergen, cold air, exercise, emotion, smoke, aspirin, NSAIDs, beta blockers, food, laughing), relief with bronchodilators, response to steroids.
• Associated: cough, sputum, breathlessness, chest tightness, nasal symptoms (rhinitis, polyps), eczema, hay fever, heartburn, regurgitation, swallowing difficulty, orthopnoea, ankle swelling, palpitations, haemoptysis, weight loss, fever, rash, flushing, diarrhoea (carcinoid), hoarseness, stridor, voice changes.
• Childhood wheeze, family history of atopy or asthma, smoking exposure, occupation (flour, isocyanates, latex, wood dust, laboratory animals, cleaning products), pets, damp housing, recent choking or aspiration, immunisation.
• Smoking history and pack years, vaping, cannabis, biomass exposure.
• Drugs: beta blockers (including eye drops), aspirin and NSAIDs, ACE inhibitors (cough), adenosine, cholinesterase inhibitors, immune checkpoint inhibitors, amiodarone, recent new inhaler, inhaler technique and adherence.
• Past history: eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchiectasis, heart failure, ischaemic heart disease, previous tuberculosis, lung cancer, thyroid goitre, sleep apnoea, reflux.

Examination.

• Respiratory distress signs: rate, accessory muscle use, ability to speak, pulsus paradoxus, saturation, peak expiratory flow (percentage of best or predicted).
• Chest: wheeze (diffuse polyphonic expiratory, localised monophonic), prolonged expiratory phase, hyperinflation, crackles, reduced breath sounds (silent chest in severe asthma), pleural effusion signs.
• Upper airway: nasal polyps, rhinitis, throat, stridor, voice, neck mass.
• Cardiac: third heart sound, raised jugular venous pressure, oedema, murmurs (mitral stenosis), arrhythmia.
• Skin: eczema, urticaria, angioedema, flushing, rash (vasculitis).
• Systemic: clubbing (bronchiectasis, cystic fibrosis, cancer), cachexia, lymph nodes, thyroid goitre.
• Observe the wheeze during forced expiration and while talking (vocal cord dysfunction wheeze is loudest over the larynx and neck).

Red flags.

• Silent chest, exhaustion, cyanosis, confusion, bradycardia, peak flow under 33% of best (life threatening asthma).
• Stridor, drooling, lip or tongue swelling, urticaria, hypotension (anaphylaxis or upper airway obstruction).
• Sudden onset after choking or in a young child (foreign body).
• Unilateral or fixed monophonic wheeze, haemoptysis, weight loss, clubbing, hoarseness (central airway tumour).
• Orthopnoea, oedema, crackles (cardiac asthma).
• Pleuritic pain, leg swelling (pulmonary embolism).
• Fever and sputum with systemic illness (pneumonia).
• Rash, neuropathy, sinus disease with high eosinophil count (eosinophilic granulomatosis with polyangiitis).
• Flushing, diarrhoea and wheeze (carcinoid syndrome).
• New wheeze at age over 40 without prior asthma and smoking history (chronic obstructive pulmonary disease or tumour).
• Recurrent infant wheeze with failure to thrive (cystic fibrosis, aspiration, vascular ring).

Airway disease. Asthma (allergic, non allergic, occupational, aspirin exacerbated, cough variant, exercise induced), chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, bronchiolitis (viral in infants, obliterative), allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, chronic eosinophilic pneumonia, tracheobronchomalacia, relapsing polychondritis.

Obstruction (localised monophonic wheeze). Foreign body, lung cancer (central), carcinoid and other endobronchial tumours, tracheal and bronchial stenosis (post intubation, tuberculosis, granulomatosis with polyangiitis, amyloidosis, sarcoidosis), extrinsic compression (lymph nodes, mediastinal mass, goitre, aortic aneurysm, vascular rings), mucus plug, bronchial granuloma.

Cardiac and vascular. Acute left heart failure (cardiac asthma), mitral stenosis, pulmonary embolism, pulmonary hypertension, superior vena cava obstruction.

Allergic and drug related. Anaphylaxis, angioedema, drug induced bronchospasm (beta blockers, aspirin and NSAIDs, adenosine, cholinesterase inhibitors), food and sulphite sensitivity, inhaled irritants and smoke. Infective and inflammatory. Viral infection and bronchiolitis, mycoplasma pneumonia, pertussis, pneumonia, tuberculosis, parasitic infection with pulmonary phase (tropical pulmonary eosinophilia, Ascaris, Strongyloides, Toxocara), aspiration, interstitial lung disease with airway involvement.

Upper airway and functional. Vocal cord dysfunction (inducible laryngeal obstruction), laryngeal oedema, laryngomalacia, epiglottitis, obstructive sleep apnoea, gastro-oesophageal reflux with microaspiration, dysfunctional breathing.

Metabolic and others. Carcinoid syndrome, thyroid goitre, pregnancy, obesity.

Mimics. Stridor, upper airway rattle (secretions), snoring, crackles, transmitted upper airway sounds, rhonchi.

1. Assess severity first (saturation, ability to speak, peak flow); treat acute severe cases immediately.
2. Peak expiratory flow (percentage of predicted or best) and spirometry with bronchodilator reversibility (increase in forced expiratory volume in 1 second of 12% and 200 mL or more; variability over 20% on 2 week diary supports asthma); flow volume loop (flattened expiratory or inspiratory limb suggests fixed or variable central obstruction).
3. Chest radiograph in all adults with new, persistent or unilateral wheeze: hyperinflation, infiltrates, mass, collapse, effusion, cardiomegaly, pulmonary oedema, mediastinal mass, foreign body (inspiratory and expiratory films).
4. Blood tests: full blood count with eosinophils, IgE (total and specific), natriuretic peptide, D-dimer when embolism possible, antineutrophil cytoplasmic antibody (perinuclear) for eosinophilic granulomatosis with polyangiitis, Aspergillus IgE and IgG, alpha 1 antitrypsin, urinary 5-hydroxyindoleacetic acid and chromogranin A for carcinoid, glucose, thyroid function.
5. Fractional exhaled nitric oxide (over 40 ppb in adults supports eosinophilic airway inflammation), methacholine or mannitol challenge when spirometry is normal and asthma is likely, skin prick tests, exercise challenge (exercise induced bronchoconstriction; fall in forced expiratory volume in 1 second of 10% or more), occupational peak flow monitoring.
6. CT chest (high resolution) for unilateral or fixed wheeze, suspected tumour, bronchiectasis, interstitial disease, tracheal stenosis, tracheobronchomalacia (dynamic expiratory scan), central airway; CT pulmonary angiography for embolism.
7. Bronchoscopy for localised wheeze, haemoptysis, suspected foreign body (rigid bronchoscopy), tumour or stenosis, and biopsy.
8. Laryngoscopy (flexible, during symptoms or continuous laryngoscopy during exercise) for vocal cord dysfunction; speech and language assessment.
9. Echocardiography and ECG for cardiac causes; oesophageal pH and impedance for reflux.
10. Sputum culture and cytology; stool and serology for parasites in endemic regions; cystic fibrosis sweat chloride test and genotype (sweat chloride over 60 mmol/L) in suspected cases.
11. Test of treatment with objective response measurement (peak flow, spirometry, symptom diary) at 4 to 8 weeks.

Limits. Wheeze is variable and may be absent between episodes; normal spirometry does not exclude asthma. Wheeze is not specific: cardiac and upper airway causes are mistaken for asthma. Chest radiograph misses central lesions and early bronchiectasis. Silent chest signals the most severe obstruction. Bronchodilator reversibility occurs in chronic obstructive pulmonary disease and does not prove asthma. Pulmonary function in children needs age appropriate methods.

Acute severe wheeze (any cause): immediate. Assess airway, breathing, circulation. Sit the patient upright. Give oxygen to saturation 94% to 98% (88% to 92% if chronic obstructive pulmonary disease with hypercapnia risk). Monitor. Call senior help early for life threatening features.

Acute asthma.

• Moderate: salbutamol 4 to 10 puffs by large volume spacer (100 micrograms for each puff) or 2.5 to 5 mg nebulised, repeated every 15 to 20 minutes as needed. Give prednisolone 40 to 50 mg orally immediately and daily for 5 days (no taper).
• Severe (peak flow 33% to 50% best, respiratory rate 25 or more, heart rate 110 or more, cannot complete sentences): salbutamol 5 mg nebulised continuously or every 15 minutes with ipratropium 500 micrograms every 4 to 6 hours. Give prednisolone 40 to 50 mg or hydrocortisone 100 mg intravenously every 6 hours, and magnesium sulphate 1.2 to 2 g intravenously over 20 minutes.
• Life threatening (peak flow under 33%, silent chest, cyanosis, exhaustion, confusion, bradycardia, hypotension, arrhythmia, saturation under 92%, PaO2 under 8 kPa, normal PaCO2 over 4.6 kPa): critical care.
• Life threatening asthma treatment: aminophylline 5 mg/kg loading over 20 minutes (omit if already on theophylline) then 0.5 to 0.7 mg/kg/hour. Consider intravenous salbutamol 5 micrograms/minute. Give adrenaline 0.5 mg intramuscularly if anaphylactic features.
• Life threatening asthma ventilation: non invasive ventilation as a bridge, then intubation (ketamine 1 to 2 mg/kg, avoid high ventilation rates), permissive hypercapnia, and repeat blood gas.
• Discharge when peak flow is over 75% best and stable 1 hour after last treatment. Supply a 5 day steroid course, check inhaler technique, give a written plan, and review in 2 working days. Prescribe inhaled corticosteroid.

Chronic asthma control.

• Inhaled corticosteroid with formoterol as maintenance and reliever: budesonide with formoterol 200/6 micrograms, 1 inhalation twice daily plus 1 as needed. Maximum 8 in 24 hours routine, 12 in emergencies.
• Step up with higher dose and add-on (tiotropium 2.5 micrograms 2 puffs daily, montelukast 10 mg daily).
• Biologics for severe disease: omalizumab 150 to 375 mg every 2 to 4 weeks by weight and IgE; mepolizumab 100 mg every 4 weeks; benralizumab 30 mg every 4 weeks for 3 doses then every 8 weeks; dupilumab 400 mg then 200 mg every 2 weeks; tezepelumab 210 mg every 4 weeks.
• Avoid triggers. Treat rhinitis (intranasal fluticasone 2 sprays in each nostril daily). Vaccinate. Advise weight loss and stopping smoking. Review technique, maintain a written plan, and reduce oral steroid exposure.

Chronic obstructive pulmonary disease.

• Smoking cessation
• Long acting bronchodilators (tiotropium 18 micrograms daily, umeclidinium 62.5 micrograms daily, indacaterol 150 micrograms daily)
• Add inhaled corticosteroid when eosinophils are over 0.3 x 10^9/L or exacerbations are frequent
• Pulmonary rehabilitation
• Exacerbation treatment: salbutamol 2.5 to 5 mg nebulised, ipratropium 500 micrograms, prednisolone 30 to 40 mg for 5 days. Give antibiotics when sputum is purulent (doxycycline 200 mg then 100 mg daily, or amoxicillin 500 mg three times daily, for 5 days)

Cardiac asthma and heart failure. Furosemide 40 to 80 mg intravenously, glyceryl trinitrate infusion 10 to 200 micrograms/minute (systolic pressure over 110 mmHg), continuous positive airway pressure, and treat the cause. Avoid beta blocker withdrawal in stable patients. Cardioselective beta blockers (bisoprolol) are safe in well controlled asthma and chronic obstructive pulmonary disease.

Anaphylaxis. Adrenaline 0.5 mg (0.5 mL of 1:1,000) intramuscularly into the anterolateral thigh, repeated after 5 minutes if needed. Give oxygen, intravenous fluid 500 to 1,000 mL, chlorphenamine 10 mg, hydrocortisone 200 mg, and nebulised salbutamol 5 mg. Observe at least 6 to 12 hours. Prescribe an adrenaline auto-injector 0.3 mg and refer to allergy.

Drug induced bronchospasm. Stop the drug (beta blockers including eye drops, aspirin and NSAIDs in aspirin exacerbated disease, adenosine). Use salbutamol and ipratropium. Use alternatives to aspirin, or aspirin desensitisation in selected patients. Avoid the drug in asthma.

Foreign body or central obstruction. Back blows and abdominal thrusts for complete obstruction. Urgent bronchoscopy (rigid for foreign body) or stent for tumour or stenosis. Steroids for oedema. Heliox 70:30 as a bridge.

Pulmonary embolism. Anticoagulation: rivaroxaban 15 mg twice daily for 21 days then 20 mg daily; or apixaban 10 mg twice daily for 7 days then 5 mg twice daily; enoxaparin 1 mg/kg twice daily. Alteplase 100 mg over 2 hours for shock.

Eosinophilic granulomatosis with polyangiitis and allergic bronchopulmonary aspergillosis.

• Eosinophilic granulomatosis with polyangiitis: prednisolone 0.5 to 1 mg/kg daily with taper over months, and immunosuppression (cyclophosphamide 15 mg/kg every 2 to 3 weeks, rituximab 375 mg/m2 weekly for 4 weeks, mepolizumab 300 mg every 4 weeks)
• Allergic bronchopulmonary aspergillosis: prednisolone 0.5 mg/kg daily for 2 to 4 weeks then taper over 3 to 6 months, with itraconazole 200 mg twice daily for 16 weeks or more

Bronchiectasis and cystic fibrosis. Airway clearance, hypertonic saline 7% nebulised twice daily, and antibiotics for exacerbations (amoxicillin 500 mg to 1 g three times daily or ciprofloxacin 500 to 750 mg twice daily for 14 days). Long term azithromycin 250 mg daily. Specialist cystic fibrosis care (elexacaftor-tezacaftor-ivacaftor where eligible).

Vocal cord dysfunction. Speech and language therapy with breathing retraining (rescue breathing techniques), reassurance, treat reflux and rhinitis, avoid unnecessary steroids and bronchodilators, and give psychological support.

Carcinoid syndrome. Octreotide 100 to 200 micrograms subcutaneously three times daily or long acting octreotide 20 to 30 mg intramuscularly every 4 weeks. Avoid adrenaline and beta agonists as triggers if possible. Specialist care.

Infections.

• Viral wheeze: supportive care and bronchodilators
• Mycoplasma and pneumonia: antibiotics (doxycycline 200 mg then 100 mg daily, or clarithromycin 500 mg twice daily)
• Pertussis: azithromycin 500 mg then 250 mg daily for 4 days
• Parasitic infection: diethylcarbamazine 6 mg/kg/day in three doses for 12 to 21 days for tropical pulmonary eosinophilia; albendazole 400 mg for Ascaris and Toxocara (800 mg daily for 5 days); ivermectin 200 micrograms/kg for 2 days for Strongyloides

Disposition.

• Admit: severe or life threatening features, peak flow under 50% after treatment, saturation under 92%, failure to respond to treatment in 1 to 2 hours, wheeze with suspected embolism, heart failure, foreign body, anaphylaxis, infants with severe bronchiolitis, social factors.
• Critical care: silent chest, exhaustion, respiratory acidosis, need for ventilation.
• Community: mild to moderate wheeze with good response, reliable follow up within 2 working days, correct inhaler use, and written plan.
• Urgent specialist referral: unilateral or fixed wheeze, haemoptysis, weight loss, age over 40 with new wheeze, failure to respond to therapy, suspected vasculitis.

Monitoring. Peak flow diary twice daily (variability), symptom control questionnaire (Asthma Control Test, COPD Assessment Test), exacerbation frequency, spirometry at 3 months then annually, inhaler technique each review, blood eosinophils, oral steroid cumulative dose, bone density and adrenal suppression in long term steroid users, annual influenza vaccination.

Referral and escalation.

• Respiratory team: severe or uncontrolled asthma, unexplained or unilateral wheeze, chronic obstructive pulmonary disease with frequent exacerbations, allergic bronchopulmonary aspergillosis, vasculitis, bronchiectasis, carcinoid and interstitial disease
• ENT and speech therapy: vocal cord dysfunction
• Allergy: anaphylaxis and food or drug allergy
• Cardiology: cardiac asthma
• Occupational health: work related wheeze
• Thoracic surgery or interventional bronchoscopy: tracheal lesions and foreign body
• Paediatrics: child wheeze

Safety netting. Return urgently for wheeze with inability to speak in sentences, blue lips, silent or very tight chest, exhaustion, relief inhaler needed more often than every 4 hours, peak flow under the red zone of the plan, swelling of the face or tongue, fainting, or coughing blood. Use the written action plan, carry the reliever, avoid triggers and keep inhaler review.

Special groups.

• Infants and children: bronchiolitis (supportive care, oxygen, nasal suction, nasogastric feeding; no routine bronchodilators or steroids), viral wheeze (salbutamol via spacer, 6 puffs; oral prednisolone 1 to 2 mg/kg maximum 40 mg for 3 days if moderate to severe, montelukast), asthma, foreign body, cystic fibrosis, tracheomalacia, vascular ring, aspiration, congenital heart disease.
• Pregnancy: asthma control is vital. Continue inhaled corticosteroid and reliever. Avoid uncontrolled asthma (foetal hypoxia risk). Treat exacerbations as usual. Consider pulmonary embolism and peripartum cardiomyopathy as alternative causes.
• Older adults: overlap of chronic obstructive pulmonary disease, heart failure and aspiration. Use lower doses of beta agonist when arrhythmia is present.
• Occupational: remove from exposure early, notify.
• Smokers: cessation counselling.
• Endemic regions: tropical pulmonary eosinophilia, ascariasis, strongyloidiasis, tuberculosis, and biomass fuel exposure cause wheeze.