Sputum production

Sputum is material expectorated from the lower airways. It includes purulent sputum and the complaint of chest congestion. Normal airways produce about 10 to 100 mL of mucus each day, swallowed unnoticed; sputum production means the amount or character has changed. Its colour, volume, consistency, smell and blood content narrow the cause, but colour alone does not separate viral from bacterial infection.

Clinical relevance. Chronic productive cough on most days for 3 months in 2 consecutive years defines chronic bronchitis. Daily purulent sputum of more than 30 mL points to bronchiectasis. Large volumes of frothy sputum suggest pulmonary oedema or mucinous adenocarcinoma; foul smelling sputum suggests anaerobic lung abscess or necrotising infection. Sputum is also the best sample for diagnosing tuberculosis, which makes collection technique a clinical issue in its own right.

Classification.

• By appearance:
  • Mucoid (clear or white; asthma, chronic bronchitis, viral infection).
  • Mucopurulent and purulent (yellow or green; infection, inflammation, eosinophils or neutrophils).
  • Rusty (pneumococcal pneumonia).
  • Redcurrant jelly (Klebsiella).
  • Pink frothy (pulmonary oedema).
  • Black (smoke, coal dust).
  • Brown plugs (allergic bronchopulmonary aspergillosis).
  • Blood stained (cancer, tuberculosis, bronchiectasis, embolism).
  • Foul smelling (anaerobic abscess, bronchiectasis).
  • Copious watery (bronchorrhoea; mucinous adenocarcinoma in situ).
  • Gelatinous casts (plastic bronchitis).
• By volume: scant (under 10 mL a day), moderate (10 to 30 mL), large (over 30 mL; bronchiectasis, abscess, bronchopleural fistula, bronchorrhoea).
• By timeline: acute (infection, aspiration, oedema), recurrent (asthma, bronchiectasis, cystic fibrosis), chronic (chronic bronchitis, bronchiectasis, chronic infection, cancer).
• Pseudosputum: saliva, postnasal drip, vomitus, blood from the nose or mouth.

Mechanism. Goblet cell and submucosal gland hyperplasia, impaired mucociliary clearance, airway wall inflammation, infection and transudation of fluid raise the volume and viscosity of airway secretions.

History.

• Volume (teaspoons, cupfuls, 24 hour estimate), colour, consistency, odour, time of day (morning predominance in chronic bronchitis and bronchiectasis), blood, taste, effort to expectorate, effect of posture (large volume when lying on one side suggests bronchiectasis or abscess).
• Duration and pattern: acute versus chronic, recurrent chest infections, childhood chest illness, whooping cough, measles, tuberculosis, pneumonia.
• Associated symptoms: fever, rigors, night sweats, weight loss, breathlessness, wheeze, pleuritic pain, haemoptysis, sinus symptoms, postnasal drip, heartburn and regurgitation, swallowing difficulty, orthopnoea, ankle swelling, infertility or diarrhoea (cystic fibrosis), halitosis.
• Smoking (pack years), vaping, occupational dusts, mould, birds, biomass fuel exposure, alcohol, injecting drug use, recent anaesthesia or reduced consciousness (aspiration), dental disease.
• Past history: asthma, chronic obstructive pulmonary disease, cystic fibrosis, immunodeficiency, HIV, rheumatoid arthritis, inflammatory bowel disease, previous severe pneumonia, foreign body, recent stroke, heart failure.
• Drugs: ACE inhibitors, inhaled agents, immunosuppressants, amiodarone, nitrofurantoin; adherence to airway clearance and inhalers.

Examination.

• Vital signs: temperature, respiratory rate, saturation, heart rate, blood pressure, ability to speak.
• Look at the sputum yourself in a clear container: colour, consistency, blood, plugs, layers (three layers of froth, mucus and pus in bronchiectasis).
• Chest: coarse crackles (bronchiectasis, bronchitis), early inspiratory crackles in chronic obstructive pulmonary disease, wheeze, bronchial breathing, dullness, hyperinflation, pleural rub.
• Clubbing (bronchiectasis, abscess, cancer, cystic fibrosis), cyanosis, lymphadenopathy, nasal polyps, sinus tenderness, teeth and gums, swallowing, signs of heart failure (raised jugular venous pressure, oedema, third heart sound), signs of connective tissue disease.

Red flags.

• Haemoptysis, weight loss, night sweats, fever over 2 weeks, tuberculosis contact (tuberculosis, cancer).
• Smoker over 40 with change in sputum, hoarseness, clubbing, supraclavicular nodes.
• Foul smelling sputum with fever and poor dental hygiene (lung abscess, empyema).
• Large volume daily purulent sputum with recurrent pneumonia (bronchiectasis, immunodeficiency, cystic fibrosis).
• Respiratory rate 30 or more, saturation under 92%, confusion, hypotension (severe pneumonia, sepsis).
• Pink frothy sputum with breathlessness (pulmonary oedema).
• Sputum with choking or aspiration risk (stroke, bulbar disease, alcohol, seizures).
• Immunosuppression, HIV, transplant, chemotherapy.
• Sputum production in a child with failure to thrive (cystic fibrosis, ciliary dyskinesia, aspiration).

Airway disease. Chronic bronchitis and chronic obstructive pulmonary disease, bronchiectasis (post infective, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, immunodeficiency, rheumatoid arthritis, post tuberculous, obstructive), asthma (eosinophilic mucus plugs), acute bronchitis, bronchiolitis, tracheobronchitis, plastic bronchitis.

Infection. Community acquired pneumonia, hospital acquired and ventilator associated pneumonia, aspiration pneumonia, lung abscess, empyema with bronchopleural fistula, tuberculosis and nontuberculous mycobacteria, fungal infection (aspergillosis, histoplasmosis), parasitic disease (paragonimiasis, hydatid cyst rupture, amoebic liver abscess rupturing into the lung), pertussis.

Neoplastic. Lung cancer (squamous, adenocarcinoma including mucinous), endobronchial tumour with distal obstruction, bronchorrhoea.

Cardiac and vascular. Pulmonary oedema, mitral stenosis, pulmonary embolism with infarction.

Upper airway and others. Chronic rhinosinusitis with postnasal drip, gastro-oesophageal reflux with aspiration, foreign body, smoke and dust inhalation, drug induced lung disease, eosinophilic lung disease, sarcoidosis (endobronchial), chronic aspiration from dysphagia.

Pseudosputum. Saliva, nasal secretions, vomit, haematemesis.

1. Inspect the sample; confirm it is lower airway sputum, not saliva.
2. Assess severity at once: respiratory rate, saturation, heart rate, blood pressure, temperature, mental state; use CURB-65 (confusion, urea over 7 mmol/L, respiratory rate 30 or more, systolic pressure under 90 mmHg or diastolic 60 mmHg or under, age 65 or over) in pneumonia.
3. Chest radiograph in all with persistent, purulent, bloody or large volume sputum, or any systemic features (consolidation, cavity with air fluid level, tram tracks, ring shadows, mass, effusion, oedema, hyperinflation).
4. Sputum samples before antibiotics:
   • Gram stain and bacterial culture with sensitivities.
   • If no spontaneous sputum, use hypertonic saline (3% to 5%) nebulised induction.
   • Mycobacterial smear, culture and nucleic acid amplification test (3 early morning samples, at least one before treatment).
   • Fungal culture and Aspergillus tests.
   • Cytology (3 samples).
   • Eosinophil count (3% or more suggests eosinophilic airway disease).
   • Respiratory virus polymerase chain reaction.
5. Blood tests:
   • Full blood count with differential (eosinophilia, neutrophilia).
   • C reactive protein (over 100 mg/L supports pneumonia; under 20 mg/L makes it unlikely).
   • Urea, creatinine, electrolytes, liver function.
   • Blood cultures in moderate or severe illness.
   • HIV test.
   • Immunoglobulins (IgG, IgA, IgM) and specific antibody responses to pneumococcus and tetanus.
   • Total IgE and Aspergillus specific IgE or IgG.
   • Alpha 1 antitrypsin, rheumatoid factor and anti cyclic citrullinated peptide.
6. High resolution CT chest for bronchiectasis (bronchus wider than its artery, no tapering, visible airways near the pleura), mucus plugging, abscess, tumour, interstitial disease and unexplained sputum with a normal radiograph.
7. Spirometry with bronchodilator response; fractional exhaled nitric oxide; sweat chloride (over 60 mmol/L diagnostic) and cystic fibrosis genotype; nasal nitric oxide, ciliary biopsy and genetic testing for ciliary dyskinesia.
8. Bronchoscopy with bronchoalveolar lavage and biopsy for localised disease, suspected tumour, foreign body, unexplained infection in the immunosuppressed, or failure to find a cause.
9. Swallowing assessment (bedside, video fluoroscopy) when aspiration is suspected; oesophageal investigation for reflux.
10. Heart failure: natriuretic peptide and echocardiography.

Limits. Sputum colour and purulence do not predict bacterial cause well (peroxidase from neutrophils makes it green). Cultures are often contaminated with oral flora; a good sample has more than 25 neutrophils and fewer than 10 squamous cells in each low magnification field. Prior antibiotics reduce the yield of pathogens. Mycobacterial smear is positive in only about 50% to 60% of culture positive disease, so a single negative smear does not exclude tuberculosis. Radiograph can be normal in early bronchiectasis.

Immediate priorities. Treat hypoxia, sepsis and airway compromise first. Give oxygen to keep saturation at 94% to 98% (88% to 92% if at risk of hypercapnia). Obtain blood cultures and sputum before antibiotics when this does not delay treatment. Start intravenous antibiotics within 1 hour for sepsis or severe pneumonia.

Airway clearance (all patients with chronic or copious sputum).

• Hydration and humidification.
• Physiotherapy: active cycle of breathing technique 10 to 30 minutes twice daily, postural drainage, autogenic drainage, oscillating positive expiratory pressure devices (Flutter, Acapella), high frequency chest wall oscillation; cough assist for neuromuscular weakness.
• Mucoactive agents:
  • Nebulised hypertonic saline 7% (4 mL) twice daily after a bronchodilator in bronchiectasis and cystic fibrosis.
  • Carbocisteine 750 mg three times daily then 750 mg twice daily in chronic obstructive pulmonary disease with chronic bronchitis.
  • Mannitol dry powder 400 mg twice daily in selected bronchiectasis.
  • Dornase alfa 2.5 mg nebulised daily in cystic fibrosis (not in non cystic fibrosis bronchiectasis).
• Pulmonary rehabilitation and exercise; stop smoking.

Chronic bronchitis and chronic obstructive pulmonary disease.

• Smoking cessation:
  • Nicotine replacement patch 21 mg daily for 6 weeks, then 14 mg for 2 weeks and 7 mg for 2 weeks, with gum or lozenge.
  • Or varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks.
• Long acting muscarinic antagonist (tiotropium 18 micrograms daily, umeclidinium 62.5 micrograms daily) and long acting beta agonist (indacaterol 150 micrograms daily, formoterol 12 micrograms twice daily).
• Add inhaled corticosteroid when exacerbations are frequent and blood eosinophils are over 0.3 x 10^9/L.
• Roflumilast 500 micrograms daily for chronic bronchitis with frequent exacerbations.
• Azithromycin 250 mg daily in former smokers with frequent exacerbations (check ECG QTc, hearing, and exclude nontuberculous mycobacteria).
• Exacerbation with purulent sputum:
  • Antibiotics for 5 days (amoxicillin 500 mg three times daily, or doxycycline 200 mg on day 1 then 100 mg daily, or clarithromycin 500 mg twice daily; co-amoxiclav 625 mg three times daily if severe or previous failure).
  • Prednisolone 30 to 40 mg daily for 5 days.
  • Nebulised salbutamol 2.5 to 5 mg and ipratropium 500 micrograms.

Bronchiectasis.

• Exacerbation (increased volume or purulence): culture first, then treat for 14 days:
  • Amoxicillin 500 mg to 1 g three times daily, or doxycycline 200 mg then 100 mg daily, or clarithromycin 500 mg twice daily.
  • Ciprofloxacin 500 to 750 mg twice daily if Pseudomonas aeruginosa.
  • For severe disease: intravenous ceftazidime 2 g every 8 hours, piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours, with an aminoglycoside (gentamicin 5 to 7 mg/kg once daily or tobramycin 5 to 7 mg/kg once daily).
• Prevention for 3 or more exacerbations in a year:
  • Long term macrolide (azithromycin 250 mg daily or 500 mg three times weekly; ECG QTc, hearing and mycobacterial cultures first).
  • Or inhaled antibiotics for chronic Pseudomonas infection (colistimethate 1 to 2 million units twice daily, tobramycin 300 mg twice daily on alternate months, or aztreonam).
  • Eradication of first Pseudomonas isolate (ciprofloxacin 750 mg twice daily for 2 weeks plus inhaled colistin or tobramycin for 3 months).
• Treat the cause:
  • Immunoglobulin replacement (0.4 g/kg every 4 weeks) for antibody deficiency.
  • 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).
  • Reflux treatment.
  • Treat nontuberculous mycobacteria (clarithromycin or azithromycin with rifampicin and ethambutol for 12 months after culture negativity).
• Vaccinations: influenza yearly, pneumococcal, COVID-19, RSV.

Cystic fibrosis. Specialist centre care.

• Elexacaftor 200 mg with tezacaftor 100 mg and ivacaftor 150 mg each morning plus ivacaftor 150 mg each evening (adult dose) where eligible.
• Airway clearance, hypertonic saline, dornase alfa, nutrition and pancreatic enzymes.
• Exacerbations treated with two intravenous antipseudomonal antibiotics for 14 days.

Community and hospital acquired pneumonia.

• Low severity (CURB-65 0 to 1): amoxicillin 500 mg to 1 g three times daily for 5 days; doxycycline 200 mg on day 1 then 100 mg daily for penicillin allergy.
• Moderate (CURB-65 2): amoxicillin 500 mg to 1 g three times daily with clarithromycin 500 mg twice daily for 7 days.
• Severe (CURB-65 3 to 5):
  • Co-amoxiclav 1.2 g intravenously every 8 hours (or ceftriaxone 2 g daily) with clarithromycin 500 mg intravenously twice daily for 7 to 10 days.
  • Add flucloxacillin 2 g every 6 hours or vancomycin 15 to 20 mg/kg every 8 to 12 hours when Staphylococcus aureus is suspected.
  • Piperacillin-tazobactam 4.5 g every 6 hours if Pseudomonas risk.
• Aspiration: co-amoxiclav 625 mg three times daily orally or 1.2 g every 8 hours intravenously, or ceftriaxone 2 g daily with metronidazole 500 mg every 8 hours; swallowing assessment, positioning, dental care.
• Lung abscess: co-amoxiclav 1.2 g every 8 hours intravenously, or clindamycin 600 mg every 6 hours, then oral for 4 to 6 weeks until the cavity resolves; drainage if no response in 7 days or empyema; bronchoscopy to exclude obstruction.
• Empyema: chest drain, intrapleural alteplase 10 mg with dornase alfa 5 mg twice daily for 3 days when loculated, surgical decortication if failure.

Tuberculosis. Isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg for 2 months, then isoniazid and rifampicin for 4 months, with pyridoxine 10 mg daily.

• Liver function at baseline and 2 weeks.
• Isolation until non infectious (usually 2 weeks of effective treatment).
• Notify.
• Contact tracing.
• HIV test.

Pulmonary oedema. Sit upright; furosemide 40 to 80 mg intravenously; glyceryl trinitrate infusion 10 to 200 micrograms/minute if systolic pressure over 110 mmHg; continuous positive airway pressure 5 to 10 cmH2O; treat the precipitant.

Mucinous bronchorrhoea. Oncology referral; inhaled steroid and macrolide (clarithromycin 250 mg twice daily) have limited effect; surgery for localised disease.

Upper airway and reflux. Intranasal fluticasone 2 sprays in each nostril daily, saline irrigation, omeprazole 20 to 40 mg daily, antibiotic for bacterial sinusitis.

Foreign body or tumour. Bronchoscopic removal or debulking; oncology for cancer.

Disposition.

• Admit: sepsis, hypoxia, CURB-65 of 2 or more, large haemoptysis, lung abscess, empyema, suspected tuberculosis needing isolation, aspiration with deterioration, failure of oral therapy, immunosuppression, social concerns.
• Community: stable chronic sputum production with a clear cause, reliable follow up in 1 to 2 weeks, airway clearance taught.
• Urgent referral (2 week suspected cancer) for smokers over 40 with changed sputum, haemoptysis or abnormal radiograph.

Monitoring. Sputum volume and colour diary; exacerbation count; spirometry yearly; microbiology every 3 to 6 months in bronchiectasis (annual culture of mycobacteria); weight and nutrition; chest radiograph at 6 weeks after pneumonia in smokers and those over 50; liver function on antituberculous drugs; ECG on macrolides.

Referral and escalation. Respiratory team for bronchiectasis, recurrent infection, haemoptysis and unexplained sputum; cystic fibrosis centre; immunology for recurrent infection; infectious diseases for tuberculosis; physiotherapy; ENT for sinus disease; speech and language therapy for swallowing; thoracic surgery for abscess or localised bronchiectasis; oncology.

Safety netting. Return urgently for coughing blood, fever with rigors, breathlessness, chest pain, confusion, a rapid rise in sputum volume or foul smell, or unexplained weight loss. Use the airway clearance routine daily and keep vaccinations current.

Special groups. Children: protracted bacterial bronchitis (amoxicillin-clavulanate 14 days), cystic fibrosis, ciliary dyskinesia, foreign body, immunodeficiency, aspiration; children swallow sputum, so cough character is the main clue. Pregnancy: treat infection promptly (amoxicillin, azithromycin), avoid doxycycline and fluoroquinolones, continue airway clearance.

Older adults: aspiration, dysphagia, poor expectoration; dehydration thickens secretions. Immunosuppressed and HIV: tuberculosis, fungal infection, pneumocystis pneumonia (co-trimoxazole 120 mg/kg/day in divided doses for 21 days with prednisolone for hypoxia), nocardia. Smokers: bronchitis and cancer. Endemic regions: tuberculosis, paragonimiasis, hydatid disease, melioidosis, amoebic abscess and biomass fuel related disease are common causes.