Recurrent chest infections

Recurrent chest infections are repeated lower respiratory tract infections in a patient who recovers between episodes. A working definition is 2 or more infections requiring antibiotics in 12 months, or 3 or more over a lifetime, or a single severe infection (empyema, bacteraemia, invasive pneumococcal disease) or an infection with an unusual organism.

The same pattern can reflect a single localised abnormality (recurrence in the same lobe), a diffuse airway problem (bronchiectasis), host immune deficiency, repeated aspiration, or a missed alternative diagnosis such as asthma, heart failure or tuberculosis.

Clinical relevance. A single episode of pneumonia in a smoker over 50 needs a follow-up radiograph. Repeated episodes need a complete work-up because the underlying cause is often treatable:

• immunoglobulin replacement in antibody deficiency
• airway clearance and prophylactic macrolide in bronchiectasis
• removal of an endobronchial obstruction
• swallowing therapy in aspiration

Missed diagnoses cause progressive structural lung damage and respiratory failure.

Classification.

• Recurrence in the same lung segment or lobe: local cause (endobronchial tumour, foreign body, bronchial stenosis, broncholithiasis, sequestration, congenital malformation, extrinsic compression by lymph nodes).
• Recurrence in different lung regions: generalised cause (bronchiectasis, immune deficiency, ciliary dysfunction, cystic fibrosis, aspiration, chronic obstructive disease, asthma, allergic bronchopulmonary aspergillosis, alpha-1 antitrypsin deficiency).
• Primary immunodeficiency: common variable immunodeficiency (the commonest symptomatic antibody deficiency in adults, with a peak presentation at 20 to 40 years), selective IgA deficiency (usually mild), IgG subclass deficiency, specific antibody deficiency, X-linked agammaglobulinaemia, complement deficiencies.
• Secondary immunodeficiency: chronic lymphocytic leukaemia, myeloma, lymphoma, HIV, cytotoxic chemotherapy, rituximab and other B cell depletion, long-term corticosteroids, protein-losing states (nephrotic syndrome, enteropathy), splenectomy or hyposplenism, diabetes, malnutrition.

Mechanism. Infection recurs when mucociliary clearance, structural airway integrity, protective airway reflexes or immune defences fail. Damaged airways (bronchiectasis) hold mucus, form a bacterial reservoir (Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus) and drive a cycle of infection, inflammation and further damage. Antibody deficiency impairs opsonisation of encapsulated bacteria. Aspiration introduces oral and gastric flora and chemical injury.

History.

• Number, dates and sites of infections; how each was diagnosed (radiograph or clinical), which antibiotics, response, and interval between episodes; hospital admissions and complications (empyema, lung abscess).
• Chronic daily productive cough with large volumes of mucopurulent sputum, haemoptysis, wheeze, chronic rhinosinusitis, hearing loss or otitis media (immune or ciliary disease).
• Childhood: severe pneumonia, whooping cough, measles, tuberculosis, neonatal respiratory distress, persistent wet cough, recurrent otitis, infertility or situs inversus (primary ciliary dyskinesia).
• Other infections: sinusitis, giardiasis, severe or recurrent bacterial infections, meningitis, zoster, thrush, diarrhoea; family history of immune deficiency or early death.
• Systemic disease: rheumatoid arthritis, inflammatory bowel disease, autoimmune cytopenias, granulomatous disease, lymphoma symptoms (night sweats, weight loss), HIV risk.
• Aspiration risk: dysphagia, neurological disease, reflux, alcohol or sedative use, dental disease, bulbar weakness, seizures, previous stroke, tracheostomy.
• Smoking, occupational exposure, immunosuppressive drugs, previous radiotherapy, travel and tuberculosis contact.
• Gastro-oesophageal reflux, nasal disease, allergy, asthma symptoms, fungal exposure.

Examination.

• Weight, BMI, nutrition, clubbing, cyanosis, lymphadenopathy, hepatosplenomegaly.
• Chest: coarse crackles, wheeze, bronchial breathing, reduced air entry, dullness, pleural rub.
• ENT: nasal polyps, purulent discharge, tympanic membrane scarring, dental caries.
• Skin and joints: eczema, vasculitic rash, joint changes.
• Neurology and swallow.
• Heart: murmurs and signs of heart failure.

Red flags.

• Haemoptysis, weight loss, night sweats, hoarseness, or a persistent focal radiographic shadow (malignancy, tuberculosis).
• Unusual organisms (Pneumocystis, Aspergillus, nontuberculous mycobacteria, Nocardia) or infections at multiple sites.
• Severe or invasive infections: empyema, sepsis, meningitis, bacteraemia, lung abscess.
• Hypoxaemia, chronic respiratory failure, cor pulmonale.
• Lymphopenia, small globulin gap, or unexplained cytopenias.
• Young adult with chronic purulent sputum, sinusitis and infertility.
• Recurrent aspiration with progressive neurological disease.
• Immunosuppressive therapy or HIV.

• Structural airway disease: bronchiectasis (post-infective, post-tuberculous, allergic bronchopulmonary aspergillosis, cystic fibrosis, primary ciliary dyskinesia, alpha-1 antitrypsin deficiency, rheumatoid arthritis, inflammatory bowel disease, immune deficiency, yellow nail syndrome, Mounier-Kuhn syndrome), chronic obstructive pulmonary disease, severe asthma with mucus plugging.
• Local obstruction: bronchial carcinoma or carcinoid, foreign body, broncholith, post-tuberculous stenosis, extrinsic nodal compression, middle lobe syndrome, pulmonary sequestration, congenital cystic malformation, bronchial atresia.
• Immune deficiency: common variable immunodeficiency, X-linked agammaglobulinaemia, IgG subclass deficiency, specific antibody deficiency, selective IgA deficiency with additional defects, HIV, CLL, myeloma, drug-induced hypogammaglobulinaemia (rituximab, high-dose corticosteroids, some antiepileptics), complement deficiency, hyposplenism.
• Aspiration: dysphagia from neurological disease, achalasia, pharyngeal pouch, oesophageal stricture, severe reflux, impaired consciousness, alcohol, tracheo-oesophageal fistula, bulbar palsy.
• Persistent infections: tuberculosis, nontuberculous mycobacteria, chronic fungal infection, Nocardia.
• Mimics: pulmonary oedema or heart failure, interstitial lung disease, eosinophilic pneumonia, organising pneumonia, vasculitis (granulomatosis with polyangiitis), pulmonary embolism with infarction, sarcoidosis, lung cancer with post-obstructive pneumonia.

1. Confirm the infections: gather previous chest radiographs, sputum cultures and antibiotic history. Many labelled "chest infections" are exacerbations of asthma, COPD or heart failure.
2. Chest radiograph now and, in a smoker or anyone with a focal shadow, a repeat after 6 weeks of treatment; compare with old films to establish whether the lesion is in the same site.
3. High resolution CT of the chest for any patient with 2 or more infections a year, productive cough, or persistent abnormality. Findings:
   • bronchiectasis (bronchial-artery ratio over 1, lack of tapering, bronchi visible within 1 cm of the pleura, signet ring sign)
   • mucus plugging
   • tree-in-bud (infection)
   • air trapping (small airway disease)
   • focal obstruction, cavities, nodules, lymphadenopathy, emphysema pattern
4. Sputum: bacterial culture each episode, mycobacterial smear and culture (three early morning samples, including nontuberculous mycobacteria), fungal culture; induced sputum or bronchoalveolar lavage if non-productive.
5. Blood tests: full blood count with differential (lymphopenia, neutropenia, eosinophilia), urea and electrolytes, liver profile, albumin, globulin gap (total protein minus albumin under 18 g/L suggests antibody deficiency), HIV test, HbA1c, C-reactive protein.
6. Immunoglobulins IgG, IgA, IgM and serum protein electrophoresis with free light chains (low IgG, or low IgG with low IgA or IgM suggests common variable immunodeficiency; also exclude secondary causes).
   • If IgG is normal or only mildly low but infections are recurrent, test specific antibody titres to tetanus and pneumococcus before and 4 to 6 weeks after a polysaccharide pneumococcal vaccine (a poor response is a rise of under 2 fold, or protective titres in under about 50% of serotypes).
   • Lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/56).
   • Complement CH50.
7. Allergic bronchopulmonary aspergillosis: total IgE (over 1000 IU/mL is highly suggestive), Aspergillus-specific IgE and IgG, blood eosinophil count, and skin prick test.
8. Cystic fibrosis and ciliary disease: sweat chloride (60 mmol/L or more is diagnostic; 30 to 59 is intermediate) and CFTR genotype; nasal nitric oxide (low in primary ciliary dyskinesia), high-speed video microscopy of ciliary beat, and genetic testing.
9. Alpha-1 antitrypsin level (under 1.1 g/L, or under 11 micromol/L, requires phenotype or genotype).
10. Spirometry with bronchodilator reversibility; fractional exhaled nitric oxide for asthma.
11. Swallow assessment (speech and language therapy bedside assessment, videofluoroscopy), upper gastrointestinal endoscopy or barium study, and oesophageal pH and manometry where reflux or dysmotility is suspected.
12. Bronchoscopy for focal abnormalities, haemoptysis, suspected foreign body or tumour, or to obtain lavage.
13. Echocardiogram if heart failure or shunt is suspected; rheumatoid factor, anti-CCP and connective tissue serology if systemic disease is suspected.

Limits. Immunoglobulin levels can be transiently low in acute illness, in nephrotic syndrome and after high dose steroids, and the reference range varies by age. Specific antibody testing has no uniform thresholds. High resolution CT detects bronchiectasis in some older and smoking patients without clinical relevance. Sputum cultures may be negative on antibiotics or in swallowing disorders, and nontuberculous mycobacteria should be isolated on at least two samples before treatment is considered.

Acute infection.

• Treat the current episode with sputum culture taken first.
• Community-acquired pneumonia low severity (CURB-65 score 0 to 1): amoxicillin 500 mg every 8 hours for 5 days; doxycycline 200 mg then 100 mg daily if penicillin allergic.
• Moderate (score 2): amoxicillin 500 mg every 8 hours with clarithromycin 500 mg twice daily for 7 days.
• Severe (score 3 to 5): co-amoxiclav 1.2 g every 8 hours intravenously plus clarithromycin 500 mg twice daily for 7 to 10 days.
• Bronchiectasis exacerbation: 14 days of antibiotics chosen by prior culture:
  • amoxicillin 500 mg to 1 g every 8 hours or doxycycline 100 mg twice daily for Haemophilus
  • ciprofloxacin 500 to 750 mg twice daily for Pseudomonas aeruginosa
  • flucloxacillin 1 g every 6 hours for methicillin-sensitive Staphylococcus aureus
• For frequent exacerbations, intravenous antipseudomonal therapy (ceftazidime 2 g every 8 hours with or without an aminoglycoside) may be needed.
• Aspiration: antibiotics with oral flora cover (co-amoxiclav 625 mg every 8 hours orally for 5 to 7 days) and stop precipitating factors.
• Oxygen to hold saturation at 94 to 98% (88 to 92% if at risk of hypercapnia); fluids; analgesia (paracetamol 1 g every 6 hours, maximum 4 g/day, or 3 g/day if frail or under 50 kg).

Prevent recurrence.

• Airway clearance: physiotherapist-taught active cycle of breathing techniques, positive expiratory pressure devices or oscillating devices for 10 to 30 minutes once or twice daily and during exacerbations.
• Mucoactive therapy: nebulised hypertonic saline 7% 4 mL twice daily after a test dose with a bronchodilator to check for bronchospasm (salbutamol 2.5 to 5 mg beforehand); carbocisteine 750 mg three times daily reducing to twice daily as improved.
• Long term macrolide for bronchiectasis with 3 or more exacerbations in the preceding 12 months: azithromycin 250 mg daily or 500 mg three times weekly for 6 to 12 months.
• Before starting a macrolide: exclude nontuberculous mycobacteria (negative sputum cultures), check QTc (under 450 ms in men, under 470 ms in women) and liver function, and counsel about hearing and gastrointestinal effects.
• Inhaled colistin 1 million units twice daily or inhaled gentamicin for chronic Pseudomonas aeruginosa infection with frequent exacerbations.
• Immunoglobulin replacement for primary antibody deficiency with recurrent infections: intravenous 0.4 to 0.6 g/kg every 3 to 4 weeks or subcutaneous 0.1 to 0.15 g/kg weekly to maintain a trough IgG in the normal range (at least 6 g/L, with higher targets of 8 to 10 g/L when bronchiectasis is present).
• Prophylactic antibiotics (azithromycin 250 mg daily, or amoxicillin 500 mg twice daily) in persistent infections despite replacement.
• Allergic bronchopulmonary aspergillosis: prednisolone 0.5 mg/kg daily for 2 weeks, then on alternate days, tapering over 3 to 6 months, or itraconazole 200 mg twice daily for 16 weeks with drug level checks.
• Reflux and aspiration: head elevation, proton pump inhibitor (omeprazole 20 mg daily), speech and language therapy, texture-modified diet, enteral feeding decisions in selected cases.
• Remove local obstruction: bronchoscopic foreign body removal, stent, resection of tumour, lobectomy for localised destroyed lung with recurrent infection.
• Vaccination: annual influenza, pneumococcal conjugate vaccine, COVID-19 and respiratory syncytial virus vaccines as eligible; avoid live vaccines in significant immune deficiency.
• Smoking cessation: nicotine patch 21 mg/24 hours for 6 weeks, 14 mg for 2 weeks, then 7 mg for 2 weeks; 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.
• Also pulmonary rehabilitation and nutrition support.
• Treat comorbid asthma and COPD with inhaled therapy; treat rhinosinusitis with saline irrigation and intranasal steroid.

Monitoring. Exacerbation frequency, sputum microbiology every 3 to 6 months, spirometry annually (twice yearly for fast decliners), IgG trough every 6 months on replacement, liver profile and ECG on macrolide, CT chest repeated for new symptoms rather than routinely, and drug levels on azoles.

Referral and escalation.

• Respiratory team for bronchiectasis, aspergillosis, nontuberculous mycobacteria or diagnostic uncertainty.
• Immunology for suspected immune deficiency (low immunoglobulins, poor vaccine response, unusual or severe infections).
• Haematology for cytopenias, lymphoproliferative disease and myeloma.
• Cystic fibrosis or primary ciliary dyskinesia specialist centres for confirmed or suspected disease.
• Thoracic surgery for localised disease; ENT for chronic rhinosinusitis; gastroenterology and speech and language therapy for aspiration; oncology for malignancy.
• Infectious diseases for tuberculosis, atypical mycobacteria, fungal or HIV infection.

Admission or disposition. Admit for hypoxaemia, sepsis, haemodynamic instability, confusion, severe comorbidity, inability to take oral therapy, failure of oral treatment, haemoptysis (over 100 mL/24 hours is massive; over 240 mL is life threatening) or pleural infection. Most others are managed in the community with review in 48 to 72 hours. Follow-up radiograph at 6 weeks in a smoker over 50 or with persistent symptoms.

Safety netting. Return urgently for breathlessness, chest pain, haemoptysis, confusion, fever with rigors, inability to take fluids or antibiotics, drowsiness, a rising sputum volume, or failure of improvement after 48 to 72 hours of antibiotics. Give a written action plan for bronchiectasis (sputum sample at first sign, rescue antibiotic supply where agreed). Keep an up-to-date vaccine record; avoid contact with sick people where immunocompromised.

Special groups.

• Pregnancy: avoid tetracyclines, fluoroquinolones and aminoglycosides unless essential; amoxicillin and macrolides (except clarithromycin in the first trimester when alternatives exist) are preferred; immunoglobulin is safe.
• Older adults: aspiration and swallowing disorders are common, so assess swallowing and oral hygiene; reassess goals of care.
• Immunosuppressed patients: lower threshold for bronchoscopy and for broad spectrum cover, and discuss with immunology or infectious disease specialists.
• Children and adolescents transitioning: continuity with paediatric services for cystic fibrosis, primary ciliary dyskinesia and immunodeficiency.
• HIV: viral load and CD4 count; start antiretroviral therapy; pneumocystis prophylaxis (co-trimoxazole 960 mg daily) when CD4 is under 200 cells/microlitre.