Respiratory Medicine

Key Facts

Acute severe asthma is a medical emergency characterised by progressive worsening of asthma symptoms with significant airflow limitation. It requires prompt recognition and aggressive treatment to prevent respiratory arrest.

Epidemiology

• ~77,000 emergency hospital admissions per year in the UK for asthma
• ~1,400 asthma deaths per year in the UK
• Higher mortality in females, ethnic minorities, and deprived areas
• Most deaths occur pre-hospital or within first 24 hours of admission

Aetiology

• Viral upper respiratory tract infection (most common trigger)
• Allergen exposure
• Poor medication adherence (especially ICS)
• Air pollution or irritant exposure
• Exercise
• Drugs: NSAIDs (in aspirin-sensitive asthma), beta-blockers
• Emotional stress
• Failure to recognise worsening symptoms

Pathophysiology

• Severe bronchospasm, mucosal oedema, and mucus plugging cause critical airflow obstruction
• Dynamic hyperinflation increases work of breathing
• V/Q mismatch initially causes hypoxaemia with hypocapnia (hyperventilation)
• Rising PaCO₂ indicates respiratory muscle fatigue and impending arrest
• Severe air trapping can cause pneumothorax or pneumomediastinum

Moderate Exacerbation

• Increasing symptoms, PEF 50-75% best/predicted
• No features of acute severe asthma

Acute Severe Asthma

• PEF 33-50% best or predicted
• Respiratory rate ≥25/min
• Heart rate ≥110/min
• Inability to complete sentences in one breath

Life-Threatening Asthma

• PEF <33% best or predicted
• SpO₂ <92%
• PaO₂ <8 kPa
• Normal PaCO₂ (4.6-6.0 kPa) - indicates failing ventilation
• Silent chest
• Cyanosis
• Poor respiratory effort
• Hypotension
• Exhaustion, altered consciousness
• Arrhythmia

Near-Fatal Asthma

• Raised PaCO₂ and/or requiring mechanical ventilation with raised inflation pressures

Red Flags

• Silent chest (no wheeze despite severe obstruction)
• Altered consciousness or confusion
• Bradycardia or hypotension
• Rising PaCO₂ on serial ABGs
• Failure to improve with initial treatment
• Previous near-fatal episode or ICU admission

Bedside

• PEF: compare to best or predicted - severity grading
• Pulse oximetry: continuous SpO₂ monitoring
• ABG: if SpO₂ <92% or life-threatening features - assess PaCO₂, PaO₂, pH, lactate
• ECG: arrhythmia, right heart strain

Bloods

• FBC: raised WCC (infection or steroid effect)
• CRP: infection assessment
• U&Es: hypokalaemia (salbutamol and steroid effect)
• Magnesium: hypomagnesaemia worsens bronchospasm
• Theophylline level: if already on theophylline before aminophylline
• Blood cultures: if sepsis suspected

Imaging

• Chest X-ray: hyperinflation, exclude pneumothorax, pneumomediastinum, consolidation

Special Tests

• Serial PEF: monitor response to treatment (15-30 minutely)
• Serial ABG: if initial PaCO₂ elevated or patient deteriorating
• Sputum culture: if infective exacerbation suspected

Non-pharmacological

• Sit patient upright
• High-flow oxygen via non-rebreathe mask (target SpO₂ 94-98%)
• Continuous pulse oximetry and cardiac monitoring
• Senior clinician review immediately for life-threatening features

Pharmacological

Immediate management (BTS/SIGN):

1. Oxygen: 15L/min via non-rebreathe mask (target SpO₂ 94-98%)
2. Nebulised salbutamol 5mg (oxygen-driven) - repeat every 15-30 min, or continuous nebulisation for severe/life-threatening
3. Nebulised ipratropium bromide 500mcg - add to salbutamol if poor initial response or life-threatening
4. Corticosteroids: prednisolone 40-50mg PO or hydrocortisone 100mg IV if unable to swallow - continue for at least 5 days
5. Magnesium sulphate 1.2-2g IV over 20 minutes: if life-threatening features or poor response to initial treatment
6. IV aminophylline: loading dose 5mg/kg over 20 min (omit if already on theophylline) then infusion 0.5-0.7mg/kg/hr - requires cardiac monitoring
7. IV salbutamol 250mcg slowly: if life-threatening and no response to nebulisers

Escalation if deteriorating:

• Involve ICU early
• Consider intubation and mechanical ventilation for near-fatal asthma
• Ketamine for bronchospasm in ventilated patients
• ECMO in refractory cases (specialist centres)

Surgical/Interventional

• Chest drain if pneumothorax develops
• Intubation and ventilation for respiratory arrest or near-fatal asthma

Referral Criteria

• ICU review: life-threatening or near-fatal features, deterioration despite treatment
• All patients admitted with acute severe asthma need respiratory follow-up within 2 working days of discharge
• Specialist referral if ≥2 admissions per year or any ICU admission

• In-hospital mortality for acute severe asthma: ~1-2%
• Near-fatal asthma: ICU mortality ~5-10%
• Previous ICU admission is the strongest predictor of future fatal asthma
• Most deaths occur pre-hospital - 75% are potentially preventable
• NRAD (2014): poor follow-up, lack of asthma action plans, and excessive SABA use are major factors in deaths
• Good recovery expected with prompt treatment and appropriate discharge planning

Acute Asthma Severity Classification (BTS/SIGN)

Discharge Criteria

Key Facts

Difficult asthma refers to asthma that appears uncontrolled despite treatment at Step 4/5 of the BTS/SIGN guidelines. Systematic assessment often reveals modifiable factors. True severe refractory asthma accounts for only a subset of these patients.

Epidemiology

• ~5-10% of asthma patients have difficult-to-treat asthma
• ~3.5% (~190,000 in the UK) have truly severe refractory asthma
• Severe asthma accounts for >50% of total asthma healthcare costs
• Higher prevalence in women, obesity, late-onset disease

Aetiology

Modifiable factors (difficult asthma):

• Poor inhaler technique (~70-80% of patients have errors)
• Non-adherence to ICS (~50% of difficult asthma)
• Untreated comorbidities: GORD, rhinosinusitis, obesity, OSA, anxiety/depression
• Ongoing allergen/occupational exposure
• Smoking
• Drug triggers: NSAIDs, beta-blockers

Severe refractory asthma:

• Persistent eosinophilic inflammation despite high-dose ICS
• Neutrophilic airway inflammation (poor steroid response)
• Airway remodelling with fixed obstruction

Pathophysiology

• Heterogeneous: multiple inflammatory endotypes
• Type 2 high: eosinophilic, elevated FeNO, IgE, IL-4/5/13 driven (~50-70%)
• Type 2 low: neutrophilic or paucigranulocytic, poor steroid response
• Airway remodelling leads to irreversible obstruction over time
• Mucus plugging, subepithelial fibrosis, and smooth muscle hypertrophy persist

Typical Presentation

• Persistent symptoms despite high-dose ICS/LABA
• Frequent exacerbations (≥2 requiring OCS per year)
• Recurrent hospital admissions
• Chronic OCS dependence
• Significant impact on quality of life and daily activities

Phenotypes

• Early-onset allergic: atopy, raised IgE, eosinophilia - responds to anti-IgE
• Late-onset eosinophilic: adult-onset, nasal polyps, no atopy, high blood eosinophils - responds to anti-IL-5
• Obesity-related: female predominance, poor response to standard therapy
• Aspirin-exacerbated respiratory disease (AERD): Samter triad (asthma, nasal polyps, aspirin sensitivity)

Red Flags

• Frequent OCS courses (≥2/year) - consider biologic therapy
• Maintenance OCS requirement
• Frequent ED attendances or admissions
• Ever requiring ICU admission or ventilation
• Rapid decline in lung function on serial spirometry

Bedside

• Inhaler technique assessment: observe and correct
• FeNO: elevated (≥25 ppb) suggests eosinophilic inflammation and steroid-responsive disease
• PEF diary: assess variability and adherence
• Pulse oximetry: baseline oxygen saturation

Bloods

• Blood eosinophil count: ≥300 cells/µL supports eosinophilic phenotype and biologic eligibility
• Total IgE: elevated in allergic asthma (guides omalizumab dosing)
• Specific IgE/skin prick tests: allergen identification
• Aspergillus IgE and IgG: exclude ABPA
• ANCA: exclude EGPA if eosinophilia + systemic features

Imaging

• HRCT chest: bronchiectasis, mucus plugging, air trapping, ground-glass opacity
• CT sinuses: chronic rhinosinusitis, nasal polyps

Special Tests

• Spirometry: assess for fixed airflow obstruction (post-BD FEV₁/FVC)
• Sputum induction: eosinophil vs neutrophil predominance for phenotyping
• Prescription refill monitoring: objective adherence assessment
• Fractional exhaled NO (FeNO): suppressed FeNO in patient claiming ICS use suggests non-adherence
• Prednisolone assay: confirm OCS adherence if concerns

Non-pharmacological

• Systematic assessment (BTS Difficult Asthma Protocol):
  1. Confirm diagnosis
  2. Assess and optimise inhaler technique
  3. Monitor and improve adherence
  4. Identify and treat comorbidities
  5. Eliminate triggers
• Weight management if BMI >30
• Treat rhinosinusitis, GORD, and OSA
• Psychological support for anxiety/depression
• Breathing pattern retraining if dysfunctional breathing

Pharmacological

Before biologics - optimise Step 4/5 therapy:

• High-dose ICS/LABA (e.g. budesonide/formoterol 400/12 mcg, 2 puffs BD)
• Add LTRA (montelukast 10mg ON)
• MART regimen if appropriate
• Trial of low-dose maintenance OCS (prednisolone 5-7.5mg/day) - minimise dose

Biologic therapies (NICE-approved):

• Omalizumab (anti-IgE): severe allergic asthma, IgE 30-1500 IU/mL, positive skin prick test (NICE TA278)
• Mepolizumab 100mg SC monthly (anti-IL-5): blood eosinophils ≥300 cells/µL (NICE TA431, MENSA/MUSCA trials)
• Benralizumab 30mg SC 4-weekly then 8-weekly (anti-IL-5Rα): blood eosinophils ≥300 (NICE TA565, SIROCCO/CALIMA trials)
• Dupilumab 200mg or 300mg SC 2-weekly (anti-IL-4Rα): type 2 inflammation, eosinophils ≥150 or FeNO ≥25 (NICE TA751, LIBERTY ASTHMA trials)
• Tezepelumab (anti-TSLP): broad severe asthma (NICE TA880, NAVIGATOR trial)

Surgical/Interventional

• Bronchial thermoplasty: considered in select refractory cases (NICE IPG635)
• Sinus surgery for refractory rhinosinusitis with nasal polyps

Referral Criteria

• All patients uncontrolled on Step 4 therapy should be referred to a specialist severe asthma centre
• MDT assessment for biologic eligibility
• Biologic trial (minimum 4 months) with objective response assessment

• Severe asthma has significantly higher morbidity and mortality than mild-moderate disease
• Biologic therapies reduce exacerbations by 50-70% and allow OCS dose reduction/cessation in ~50% of patients
• Chronic OCS use causes significant morbidity: osteoporosis (30-50%), diabetes (15-20%), adrenal suppression, cataracts
• Airway remodelling may cause irreversible obstruction
• Quality of life significantly impaired; 30-40% report severe impact on daily activities
• Good outcomes with early specialist referral and biologic therapy

Biologic Eligibility Summary

Difficult Asthma Systematic Assessment

Key Facts

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable condition characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response to noxious particles or gases, most commonly cigarette smoke.

Epidemiology

• ~1.2 million diagnosed with COPD in the UK; estimated 2 million undiagnosed
• 3rd leading cause of death globally; 5th in the UK (~30,000 deaths/year)
• Prevalence increases with age: ~10% in over-40s
• More common in men historically, but female rates increasing
• Strong association with socioeconomic deprivation

Aetiology

• Cigarette smoking: ~85-90% of UK COPD cases (~15-20% of smokers develop COPD)
• Occupational exposure: coal dust, silica, cadmium, grain dust (~15%)
• Alpha-1 antitrypsin deficiency: ~1-2% of cases; suspect if onset <45 years or non-smoker
• Biomass fuel exposure: significant cause in developing countries
• Air pollution: contributes to disease progression
• Childhood respiratory infections and low birth weight increase susceptibility

Pathophysiology

• Chronic bronchitis: mucus gland hypertrophy, goblet cell hyperplasia, chronic airway inflammation → productive cough, airway narrowing
• Emphysema: destruction of alveolar walls (loss of elastic recoil) by neutrophil elastase and oxidative stress → air trapping, hyperinflation, gas exchange impairment
• Protease-antiprotease imbalance: excess neutrophil elastase overwhelms alpha-1 antitrypsin
• Small airway fibrosis and mucus plugging contribute to fixed obstruction
• Progressive decline in FEV₁ (~50-80 mL/year vs ~30 mL/year in non-smokers)

Typical Presentation

• Chronic progressive breathlessness, initially on exertion
• Chronic cough, often productive with sputum (especially in chronic bronchitis phenotype)
• Wheeze
• Smoking history (usually ≥20 pack-years)
• Age typically >35 years at diagnosis
• Recurrent chest infections

Clinical Signs

• Barrel chest (hyperinflation)
• Pursed-lip breathing
• Use of accessory muscles
• Reduced chest expansion
• Hyperresonant percussion
• Reduced breath sounds, expiratory wheeze
• Peripheral oedema and raised JVP (cor pulmonale in advanced disease)

Phenotypes

• Pink puffer (predominantly emphysema): thin, tachypnoeic, pursed-lip breathing, minimal cyanosis
• Blue bloater (predominantly chronic bronchitis): overweight, cyanotic, oedematous, productive cough

Red Flags

• Rapid FEV₁ decline (>80 mL/year)
• Onset <45 years (consider alpha-1 antitrypsin deficiency)
• Frequent exacerbations (≥2/year)
• Signs of cor pulmonale
• Unexplained weight loss (consider lung cancer)
• Haemoptysis (exclude malignancy)

Bedside

• Post-bronchodilator spirometry: FEV₁/FVC <0.7 confirms airflow obstruction (NICE NG115)
• Pulse oximetry: baseline SpO₂
• BMI: nutritional status assessment
• MRC dyspnoea scale: grade 1-5 breathlessness

Bloods

• FBC: polycythaemia (chronic hypoxia), anaemia
• Alpha-1 antitrypsin level: all patients at diagnosis (NICE)
• U&Es: baseline
• CRP: if infective exacerbation suspected
• BNP/NT-proBNP: if cor pulmonale/heart failure suspected
• Eosinophil count: guides ICS use (≥300 cells/µL favours ICS)

Imaging

• Chest X-ray: hyperinflation, flattened diaphragms, bullae, exclude other pathology
• CT chest: emphysema distribution, bullae, bronchiectasis, lung cancer screening

Special Tests

• TLCO (transfer factor): reduced in emphysema; helps distinguish from asthma (normal TLCO)
• ABG: if SpO₂ ≤92% or GOLD 3-4 - assess for LTOT
• 6-minute walk test: exercise capacity and desaturation
• Full pulmonary function tests: lung volumes (increased RV/TLC in emphysema)
• Sputum culture: if persistent purulent sputum or frequent exacerbations
• ECG/Echo: right heart assessment if cor pulmonale suspected

Non-pharmacological

• Smoking cessation: most important intervention (offer NRT, varenicline 0.5mg OD for 3 days then 1mg BD for 12 weeks, or bupropion)
• Pulmonary rehabilitation: for MRC dyspnoea grade ≥3; 6-12 week supervised exercise and education programme
• Annual influenza and pneumococcal vaccination
• Nutritional support: if BMI <20 kg/m²
• Self-management plan with rescue pack (antibiotics + prednisolone)

Pharmacological

NICE NG115 stepwise approach:

Step 1: SABA (salbutamol 100-200mcg PRN) or SAMA (ipratropium 20-40mcg PRN)

Step 2 - based on phenotype:

• No asthmatic features/eosinophilia: LABA (salmeterol 50mcg BD) or LAMA (tiotropium 18mcg OD via HandiHaler or 5mcg via Respimat)
• Asthmatic features or eosinophils ≥300: LABA + ICS (e.g. budesonide/formoterol)

Step 3:

• Non-eosinophilic: LABA + LAMA (e.g. umeclidinium/vilanterol or tiotropium + olodaterol)
• Eosinophilic: LABA + LAMA + ICS triple therapy (e.g. fluticasone furoate/umeclidinium/vilanterol - Trelegy; IMPACT trial)

Additional therapies:

• Roflumilast 500mcg OD: PDE4 inhibitor for frequent exacerbations with FEV₁ <50% (REACT trial)
• Azithromycin 250mg 3×/week: prophylactic for frequent exacerbations (non-smokers, exclude QT prolongation)
• Mucolytics: carbocisteine 750mg TDS - consider if chronic productive cough

Oxygen therapy:

• LTOT: PaO₂ ≤7.3 kPa on 2 stable ABGs 3 weeks apart; or ≤8.0 kPa with cor pulmonale/polycythaemia
• Must use ≥15 hours/day; smoking cessation mandatory
• Ambulatory oxygen: if desaturation on exercise and benefit demonstrated

Surgical/Interventional

• Lung volume reduction surgery (LVRS): selected upper-lobe predominant emphysema with low exercise capacity (NETT trial)
• Endobronchial valves: heterogeneous emphysema with intact fissures (NICE IPG600; LIBERATE trial)
• Bullectomy: large bullae compressing functional lung
• Lung transplantation: end-stage COPD, BODE index 7-10, age <65

Referral Criteria

• Diagnostic uncertainty
• Rapid FEV₁ decline
• Frequent exacerbations (≥2/year) despite optimal therapy
• Suspected alpha-1 antitrypsin deficiency
• Assessment for LTOT, pulmonary rehab, LVRS, transplant
• Cor pulmonale or persistent hypoxia

• COPD is the 3rd leading cause of death globally
• BODE index predicts mortality: BMI, Obstruction (FEV₁), Dyspnoea (MRC), Exercise capacity (6MWT)
• FEV₁ <30% predicted: ~5-year survival ~50%
• Smoking cessation improves survival at any stage
• Frequent exacerbations (≥2/year) associated with faster FEV₁ decline and increased mortality
• Cor pulmonale carries poor prognosis (~50% 5-year mortality)
• LTOT improves survival in hypoxic COPD (MRC and NOTT trials: ~5-year survival improved by 20-30%)
• Lung transplant: median survival ~5-6 years post-transplant

GOLD Severity Classification

MRC Dyspnoea Scale

BODE Index

Key Facts

An acute exacerbation of COPD (AECOPD) is defined as a sustained worsening of the patient's symptoms from their usual stable state which is beyond normal day-to-day variations and is acute in onset, commonly requiring a change in regular medication.

Epidemiology

• Average 1-3 exacerbations per year per COPD patient
• ~115,000 COPD admissions per year in England
• Leading cause of emergency medical admission in the UK
• Winter predominance (viral triggers)
• 30-day readmission rate ~25%

Aetiology

• Viral infections (~50-70%): rhinovirus, influenza, parainfluenza, RSV, adenovirus
• Bacterial infections (~30-50%): Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas (if severe COPD/bronchiectasis)
• Environmental: air pollution, cold weather, allergens
• Non-infectious: PE (~25% of AECOPD admissions may have concurrent PE), pneumothorax, heart failure, non-adherence

Pathophysiology

• Infection or irritant triggers enhanced airway inflammation (neutrophilic)
• Increased mucus production and bronchospasm worsen airflow obstruction
• Dynamic hyperinflation increases work of breathing
• V/Q mismatch worsens causing hypoxaemia
• In severe cases, type 2 respiratory failure (hypoxia + hypercapnia) develops due to respiratory muscle fatigue

Typical Presentation

• Increased breathlessness beyond usual level
• Increased sputum volume and/or purulence
• Increased cough
• Wheeze
• Chest tightness
• Reduced exercise tolerance
• May have fever, confusion (hypercapnia), or ankle swelling (cor pulmonale)

Severity Assessment

• Mild: managed with increased bronchodilator use alone
• Moderate: requires systemic corticosteroids and/or antibiotics
• Severe: requires hospitalisation or ED attendance

Red Flags

• Confusion or reduced consciousness (CO₂ narcosis)
• SpO₂ <88% on air
• Respiratory rate >30/min
• Use of accessory muscles, paradoxical abdominal movement
• Cyanosis
• Peripheral oedema (acute cor pulmonale)
• Unable to speak in full sentences
• Failure to respond to initial treatment
• pH <7.35 (respiratory acidosis)
• Significant comorbidities (heart failure, pneumonia)

Bedside

• ABG: essential if SpO₂ <92% or severe exacerbation - assess pH, PaCO₂, PaO₂, HCO₃⁻, lactate
• Pulse oximetry: continuous; target SpO₂ 88-92%
• ECG: arrhythmia, right heart strain, exclude ACS
• Sputum colour chart: green/purulent suggests bacterial infection

Bloods

• FBC: WCC (infection), eosinophils, haemoglobin
• CRP: elevated in infective exacerbation
• U&Es: renal function, electrolytes
• Blood cultures: if pyrexial or severe sepsis
• BNP/NT-proBNP: if heart failure suspected
• Theophylline level: if on maintenance theophylline
• Procalcitonin: may help guide antibiotic decisions (reducing unnecessary antibiotics)

Imaging

• Chest X-ray: exclude pneumonia, pneumothorax, pleural effusion, pulmonary oedema
• CTPA: if PE suspected (25% of severe AECOPD have concurrent PE)

Special Tests

• Sputum MC&S: if frequent exacerbations, failure to respond to empirical antibiotics, or bronchiectasis
• Spirometry: NOT performed during acute exacerbation; reassess 4-6 weeks after recovery

Non-pharmacological

• Controlled oxygen therapy: 24% or 28% Venturi mask initially (target SpO₂ 88-92%)
• Titrate oxygen based on repeat ABG at 30-60 minutes
• Sit patient upright
• Chest physiotherapy for sputum clearance

Pharmacological

Bronchodilators:

• Nebulised salbutamol 2.5-5mg QDS (driven by compressed air in hypercapnic patients, with nasal O₂ at 2L/min)
• Nebulised ipratropium bromide 500mcg QDS

Corticosteroids:

• Prednisolone 30mg OD for 5 days (REDUCE trial showed 5 days equivalent to 14 days)
• IV hydrocortisone 100mg if unable to swallow

Antibiotics (if purulent sputum or consolidation):

• Amoxicillin 500mg TDS for 5 days (first-line)
• Doxycycline 200mg loading then 100mg OD or clarithromycin 500mg BD if penicillin allergic
• Co-amoxiclav 625mg TDS or piperacillin-tazobactam if Pseudomonas risk or severe

NIV (BiPAP):

• Indicated for persistent respiratory acidosis (pH 7.25-7.35, PaCO₂ >6 kPa) despite 1 hour of optimal medical therapy
• Typical settings: IPAP 12-20 cmH₂O, EPAP 4-6 cmH₂O, back-up rate 12-15
• If pH <7.25 or failure to improve - consider ITU referral for invasive ventilation

Other:

• VTE prophylaxis: LMWH (enoxaparin 40mg SC OD) unless contraindicated
• IV aminophylline: rarely used; consider if poor response (loading 5mg/kg over 20 min)

Surgical/Interventional

• Intubation and mechanical ventilation if NIV fails or pH <7.25
• Chest drain if pneumothorax

Referral Criteria

• ICU referral if pH <7.25 or failing NIV
• Respiratory team review for all admitted AECOPD patients
• Pulmonary rehabilitation referral within 4 weeks of discharge
• Specialist review if frequent exacerbations (≥2/year) or diagnostic uncertainty

• In-hospital mortality: ~5-10%
• 30-day mortality: ~10%
• 90-day mortality: ~15%
• 30-day readmission rate: ~25%
• 1-year mortality after hospitalised AECOPD: ~25%
• Each exacerbation associated with ~5-8% decline in FEV₁
• Frequent exacerbations (≥2/year) are an independent predictor of mortality
• Post-exacerbation pulmonary rehabilitation reduces readmissions by 30-50%
• NIV reduces mortality by ~50% in acidotic AECOPD (vs standard care)

DECAF Score (Hospital Mortality Predictor)

NIV Settings Summary

Key Facts

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema and liver disease in adults and children. It results from mutations in the SERPINA1 gene, leading to reduced circulating levels of the serine protease inhibitor alpha-1 antitrypsin.

Epidemiology

• PiZZ homozygosity: ~1 in 2,000-5,000 in Northern Europeans
• PiMZ heterozygotes: ~1 in 25 (usually asymptomatic carriers)
• Often underdiagnosed; average delay to diagnosis ~5-7 years
• Accounts for ~1-2% of COPD cases

Aetiology

• Mutations in SERPINA1 gene (chromosome 14)
• Normal allele: Pi*M (produces normal AAT levels)
• Deficient alleles: PiZ (Glu342Lys - most common severe), PiS (Glu264Val - moderate)
• PiZZ: AAT levels ~10-15% of normal (high risk of lung and liver disease)
• PiSZ: intermediate risk
• PiMZ: usually normal AAT function, slight increased risk with smoking

Pathophysiology

• Smoking massively increases neutrophil recruitment and oxidative inactivation of remaining AAT

Pulmonary Presentation

• Early-onset COPD/emphysema (<45 years)
• Progressive breathlessness and wheeze
• Basal predominant emphysema (unlike smoking-related apical emphysema)
• Disproportionate breathlessness for smoking history
• Recurrent chest infections
• May present as "difficult asthma" in younger patients

Hepatic Presentation

• Neonatal cholestasis (10-15% of PiZZ neonates)
• Childhood cirrhosis
• Adult cirrhosis (15-20% of PiZZ adults)
• Hepatocellular carcinoma risk

Other Manifestations

• Panniculitis: painful subcutaneous nodules, typically on thighs/buttocks
• Granulomatosis with polyangiitis (c-ANCA positive vasculitis - rare association)

Red Flags

• COPD/emphysema onset <45 years
• Emphysema in a non-smoker or minimal smoker
• Basal predominant emphysema on CT
• Family history of early COPD or liver disease
• Unexplained liver cirrhosis
• Panniculitis

Bedside

• Spirometry: obstructive pattern (FEV₁/FVC <0.7); may show significant gas trapping
• Pulse oximetry: baseline and exercise desaturation

Bloods

• Serum alpha-1 antitrypsin level: <11 µmol/L (or <0.8 g/L) confirms deficiency
• AAT phenotyping (isoelectric focusing) or genotyping: identifies allele combination (PiMM, PiMZ, PiSZ, PiZZ)
• LFTs: elevated in liver involvement
• FBC: polycythaemia if chronic hypoxia

Imaging

• HRCT chest: panacinar emphysema with basal predominance; bronchiectasis may coexist
• CT liver/USS liver: cirrhosis assessment

Special Tests

• TLCO: reduced (emphysema)
• Full lung function tests: increased RV/TLC (gas trapping)
• Liver biopsy: PAS-positive, diastase-resistant globules in hepatocytes (accumulated Z-protein)
• Liver elastography (FibroScan): non-invasive cirrhosis assessment
• Family screening: offer genotyping to first-degree relatives

Non-pharmacological

• Smoking cessation: absolutely essential - most important single intervention
• Avoidance of occupational dust/fume exposure
• Annual influenza and pneumococcal vaccination
• Pulmonary rehabilitation
• Registration with national AAT deficiency registry (ADAPT in UK)

Pharmacological

• Standard COPD management per NICE NG115 (bronchodilators, ICS if eosinophilic)
• IV augmentation therapy: pooled human alpha-1 antitrypsin (Respreeza 60mg/kg IV weekly)
  • RAPID trial: slowed progression of CT-measured emphysema
  • NICE HST24: approved for non-smoking adults with FEV₁ 35-70% predicted and evidence of progressive disease
  • Specialist centre initiation only
• Hepatoprotection: avoid hepatotoxic drugs, alcohol abstinence
• Ursodeoxycholic acid for cholestatic liver disease (limited evidence)

Surgical/Interventional

• Lung transplantation: for end-stage emphysema; AAT deficiency is a common indication for lung transplant in younger patients
• Liver transplantation: for end-stage liver disease (curative - donor liver produces normal AAT)
• Lung volume reduction surgery: selected cases

Referral Criteria

• All patients with confirmed AAT deficiency should be referred to a specialist centre
• Hepatology referral for liver involvement
• Genetic counselling for family members
• Transplant assessment when appropriate

• PiZZ smokers: mean age of emphysema onset ~32-41 years; significantly reduced life expectancy
• PiZZ non-smokers: may not develop clinically significant emphysema until 50-60 years
• Smoking is the strongest modifiable risk factor - cessation improves survival dramatically
• FEV₁ decline ~70-130 mL/year in PiZZ smokers vs ~50 mL/year in non-smoking PiZZ
• Liver cirrhosis develops in 15-20% of PiZZ adults
• Liver transplant is curative for both liver and lung disease (normalises AAT levels)
• 5-year survival post-lung transplant: ~50-60%
• Augmentation therapy slows CT emphysema progression by ~30%

AAT Phenotypes and Clinical Risk

Key Distinguishing Features from Smoking COPD

Key Facts

Pneumonia is an acute lower respiratory tract infection causing inflammation and consolidation of the lung parenchyma. It remains a major cause of morbidity and mortality, particularly in the elderly, immunocompromised, and those with chronic diseases.

Epidemiology

• Incidence: 5-11 per 1,000 adults per year in the UK
• ~300,000 adults diagnosed annually in the UK
• ~29,000 deaths per year in England and Wales from pneumonia
• 6th leading cause of death in the UK
• 5-10% mortality for hospitalised CAP; <1% for community-managed CAP

Aetiology

Community-acquired pneumonia (CAP):

• Streptococcus pneumoniae (30-40%) - most common
• Haemophilus influenzae (5-10%)
• Mycoplasma pneumoniae (5-15%, epidemic every 4 years)
• Staphylococcus aureus (1-5%, post-influenza)
• Legionella pneumophila (2-5%)
• Chlamydophila pneumoniae, Moraxella catarrhalis, respiratory viruses

Hospital-acquired pneumonia (HAP):

• Gram-negative bacilli (E. coli, Klebsiella, Pseudomonas)
• Staphylococcus aureus (including MRSA)
• Anaerobes

Pathophysiology

• Pathogen reaches alveoli via inhalation, aspiration, or haematogenous spread
• Alveolar macrophages and neutrophils mount inflammatory response

• Complications: parapneumonic effusion, empyema, lung abscess, ARDS, sepsis

Typical Presentation

• Cough (productive with purulent or rusty sputum)
• Fever and rigors
• Pleuritic chest pain
• Breathlessness
• Malaise and myalgia

Clinical Signs

• Pyrexia (>38°C)
• Tachypnoea, tachycardia
• Reduced chest expansion on affected side
• Dull percussion note
• Bronchial breathing over consolidation
• Increased tactile vocal fremitus
• Coarse crackles

Atypical Presentations

• Elderly: confusion, falls, functional decline without fever
• Immunocompromised: indolent course, atypical organisms
• Atypical pneumonia: dry cough, headache, myalgia, extrapulmonary features

Red Flags

• CURB-65 score ≥3 (severe pneumonia)
• SpO₂ <92% or PaO₂ <8 kPa
• Bilateral or multilobar involvement
• Systolic BP <90 mmHg
• Confusion (new onset)
• Age >65 years
• Significant comorbidities
• Failure to respond to initial antibiotics within 48-72 hours

Bedside

• Pulse oximetry: SpO₂ on air
• ABG: if SpO₂ <92% or severe pneumonia
• Urinary antigens: pneumococcal and Legionella (moderate-severe CAP)
• Sputum sample: MC&S before antibiotics if possible

Bloods

• FBC: leucocytosis (or leucopenia in severe sepsis)
• CRP: elevated; useful for monitoring response
• U&Es: urea (CURB-65 component), renal function
• LFTs: baseline; abnormal in Legionella, Mycoplasma
• Blood cultures: x2 before antibiotics in moderate-severe
• Procalcitonin: may guide antibiotic duration
• HIV test: consider in all pneumonia patients aged 15-59 (NICE)

Imaging

• Chest X-ray: within 4 hours of admission - lobar consolidation, air bronchograms, parapneumonic effusion
• Follow-up CXR at 6 weeks: confirm resolution, exclude underlying malignancy (especially smokers >50 years)
• CT chest: if non-resolving, complicated, or alternative diagnosis suspected

Special Tests

• Pleural fluid aspiration and analysis: if significant effusion (pH, glucose, protein, LDH, MC&S, cytology)
• Bronchoscopy with BAL: if immunocompromised, non-resolving, or unusual organism suspected
• Atypical serology: Mycoplasma IgM, Chlamydophila, Legionella if clinical suspicion

Non-pharmacological

• Oxygen therapy (target SpO₂ 94-98%, or 88-92% if at risk of hypercapnia)
• IV fluids if dehydrated or unable to take oral
• Chest physiotherapy for sputum clearance
• VTE prophylaxis for inpatients (enoxaparin 40mg SC OD)

Pharmacological

NICE CG191 - empirical antibiotics for CAP:

Low severity (CURB-65 0-1, treat in community):

• Amoxicillin 500mg TDS for 5 days
• If penicillin allergic: doxycycline 200mg loading then 100mg OD, or clarithromycin 500mg BD

Moderate severity (CURB-65 2, consider hospital):

• Amoxicillin 500mg TDS PO + clarithromycin 500mg BD PO for 5 days
• If penicillin allergic: doxycycline 200mg then 100mg OD

High severity (CURB-65 3-5, hospital/ICU):

• Co-amoxiclav 1.2g IV TDS + clarithromycin 500mg IV BD
• Or piperacillin-tazobactam 4.5g IV TDS + clarithromycin 500mg IV BD if very severe
• Step down to oral when improving (typically 48-72 hours)

Specific organisms:

• Legionella: clarithromycin/azithromycin ± rifampicin (notify PHE)
• MRSA: vancomycin or linezolid
• Pseudomonas: piperacillin-tazobactam or meropenem

Surgical/Interventional

• Chest drain: for empyema or large complicated parapneumonic effusion
• CT-guided drainage: for lung abscess not responding to antibiotics

Referral Criteria

• CURB-65 ≥2: hospital admission
• CURB-65 ≥3: ICU assessment
• Non-resolving pneumonia at 6 weeks: urgent CXR, consider CT and respiratory referral
• Recurrent pneumonia in same lobe: bronchoscopy to exclude obstruction

• Community-managed CAP: mortality <1%
• Hospitalised CAP: mortality 5-10%
• ICU-admitted CAP: mortality 25-50%
• 30-day mortality by CURB-65: score 0 (~0.7%), 1 (~3.2%), 2 (~13%), 3 (~17%), 4 (~41.5%), 5 (~57%)
• Pneumococcal bacteraemia increases mortality 2-3 fold
• Most patients show clinical improvement within 48-72 hours of appropriate antibiotics
• CXR changes may take 6-8 weeks to resolve completely
• Long-term: pneumonia survivors have increased cardiovascular risk for 1-2 years post-event

CURB-65 Score

Management by CURB-65 Score

Light's Criteria (Exudative Effusion)

Key Facts

Community-acquired pneumonia (CAP) is defined as an acute lower respiratory tract infection with radiological evidence of consolidation, acquired outside hospital or within 48 hours of admission. It is the most common infectious cause of death in developed countries.

Epidemiology

• Incidence: 5-11 per 1,000 adults per year in the UK
• Peak incidence in winter months
• Higher in extremes of age, immunosuppressed, chronic lung disease
• 22-42% require hospitalisation
• 5-10% of hospitalised CAP patients require ICU admission

Aetiology

• Streptococcus pneumoniae (~30-40%): most common; rusty sputum, lobar consolidation
• Haemophilus influenzae (~5-10%): COPD patients
• Mycoplasma pneumoniae (~5-15%): younger adults, 4-yearly epidemics, extrapulmonary features
• Legionella pneumophila (~2-5%): travel, cooling towers; hyponatraemia, deranged LFTs
• Staphylococcus aureus (~1-5%): post-influenza, IV drug users, cavitation
• Chlamydophila pneumoniae, psittaci: atypical pattern
• Viruses: influenza, SARS-CoV-2, RSV (~15-30% of cases)
• No organism identified in ~40-60% of cases

Pathophysiology

• Microaspiration of oropharyngeal organisms overwhelms local defences
• Alveolar macrophages and neutrophils initiate inflammatory response
• Exudate fills alveoli causing consolidation and impaired gas exchange
• Bacteraemia occurs in ~10-25% of pneumococcal pneumonia
• Parapneumonic effusion from pleural inflammation; empyema if infected

Typical (Bacterial) Presentation

• Acute onset productive cough (purulent or rusty sputum)
• High fever with rigors
• Pleuritic chest pain
• Dyspnoea
• Tachycardia, tachypnoea
• Signs of consolidation: bronchial breathing, dull percussion, increased vocal resonance

Atypical Presentation

• Dry cough, gradual onset
• Headache, myalgia, malaise
• Extrapulmonary features (M. pneumoniae: erythema multiforme, cold agglutinins; Legionella: confusion, hyponatraemia, diarrhoea)
• Patchy rather than lobar infiltrates

Elderly Presentation

• Confusion or functional decline may be sole presentation
• Often afebrile
• Falls

Red Flags

• CURB-65 ≥3
• SpO₂ <92%
• Bilateral or multilobar disease
• Haemodynamic instability
• Failure to improve after 48 hours of appropriate antibiotics
• Cavitation on CXR (abscess, TB, Klebsiella, Staph aureus)

Bedside

• Pulse oximetry: SpO₂ on air
• ABG: if SpO₂ <92% or severe features
• CURB-65 score: calculate on admission
• Urinary antigens: pneumococcal + Legionella (moderate-severe)

Bloods

• FBC: leucocytosis, or leucopenia (poor prognosis)
• CRP: elevated; monitor for treatment response
• U&Es: urea >7 (CURB-65), renal function
• LFTs: deranged in Legionella
• Blood cultures x2: before antibiotics in moderate-severe
• Procalcitonin: may guide antibiotic duration
• Lactate: if sepsis suspected

Imaging

• CXR PA: lobar consolidation, air bronchograms, parapneumonic effusion
• Repeat CXR at 6 weeks: essential in all patients to confirm resolution (NICE CG191)
• CT chest: non-resolving, complicated, or alternative diagnosis
• Pleural USS: guide aspiration of effusion

Special Tests

• Sputum MC&S: before antibiotics where possible
• Pleural fluid analysis: if significant effusion (pH, protein, LDH, glucose, MC&S, cytology)
• Mycoplasma serology: IgM (acute), complement fixation titre
• Legionella PCR: on respiratory samples
• Viral PCR: influenza, SARS-CoV-2, RSV (nasal/throat swab)
• Bronchoscopy with BAL: immunocompromised or non-resolving

Non-pharmacological

• Supplemental oxygen (target SpO₂ 94-98% or 88-92% if COPD risk)
• IV fluid resuscitation if septic or dehydrated
• Adequate analgesia for pleuritic pain (paracetamol, NSAIDs if no contraindication)
• VTE prophylaxis (enoxaparin 40mg SC OD)
• Nutritional support

Pharmacological

NICE CG191 empirical antibiotics:

Low severity (CURB-65 0-1):

• Amoxicillin 500mg TDS PO for 5 days
• Penicillin allergy: doxycycline 200mg then 100mg OD or clarithromycin 500mg BD

Moderate severity (CURB-65 2):

• Amoxicillin 500mg TDS PO + clarithromycin 500mg BD PO for 5 days
• Penicillin allergy: doxycycline 200mg then 100mg OD

High severity (CURB-65 3-5):

• Co-amoxiclav 1.2g IV TDS + clarithromycin 500mg IV BD
• Switch to oral at 48-72 hours when improving
• Total course: 7-10 days for severe (may be shorter for uncomplicated)

Specific pathogens:

• Legionella: fluoroquinolone or clarithromycin ± rifampicin; notifiable disease
• Influenza-associated: oseltamivir 75mg BD + anti-staphylococcal cover
• PVL-producing Staph aureus: linezolid + clindamycin (suppress toxin) + rifampicin

Surgical/Interventional

• Chest drain insertion for empyema (pH <7.2) or large complicated effusion
• Intrapleural fibrinolytics (alteplase 10mg + DNase 5mg BD) for loculated empyema
• CT-guided drainage for lung abscess not responding to antibiotics

Referral Criteria

• ICU if CURB-65 ≥3 or clinical deterioration
• Non-resolving pneumonia at 6 weeks: respiratory/radiology review
• Recurrent pneumonia same lobe: bronchoscopy to exclude obstruction
• Immunocompromised patients: early infectious diseases/respiratory input

• Outpatient CAP mortality: <1%
• Hospitalised CAP mortality: 5-10%
• ICU-admitted CAP: 25-50% mortality
• CURB-65 score 0: ~0.7% mortality; score 5: ~57% mortality
• Pneumococcal bacteraemia mortality: ~20%
• Most improve within 48-72 hours of appropriate antibiotics
• CXR resolution: 50% at 2 weeks, 75% at 6 weeks, 95% at 12 weeks
• Post-pneumonia cardiovascular events increased for 1-2 years
• Pneumococcal vaccination reduces invasive disease by ~50-80% in elderly

CURB-65 Score Interpretation

Common Organisms and Clues

Key Facts

Hospital-acquired pneumonia (HAP) is a lower respiratory tract infection that develops ≥48 hours after hospital admission and was not incubating at the time of admission. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infection.

Epidemiology

• Affects 0.5-1% of all hospital inpatients
• VAP affects 10-20% of mechanically ventilated patients
• Mortality: 20-50% (varies with organism and patient factors)
• Adds 7-10 days to hospital stay
• Estimated £1-2 billion annual cost to NHS

Aetiology

Early-onset HAP (<5 days):

• Streptococcus pneumoniae
• Haemophilus influenzae
• Staphylococcus aureus (MSSA)

Late-onset HAP (≥5 days):

• Pseudomonas aeruginosa
• Enterobacteriaceae (E. coli, Klebsiella)
• Acinetobacter baumannii
• MRSA
• Stenotrophomonas maltophilia
• Anaerobes

Pathophysiology

• Micro-aspiration of colonised oropharyngeal or gastric secretions is the primary mechanism
• Hospital environment promotes oropharyngeal colonisation with Gram-negative organisms
• Impaired mucociliary clearance (intubation, sedation, post-operative)
• Biofilm formation on endotracheal tubes (VAP)
• Reduced immune defences (critical illness, immunosuppression, malnutrition)

Typical Presentation

• New or worsening cough with purulent sputum
• Fever >38°C or hypothermia
• New radiographic infiltrate or consolidation
• Increasing oxygen requirements
• Rising inflammatory markers (CRP, WCC)
• Deterioration in general condition

Clinical Signs

• Pyrexia or hypothermia
• Tachypnoea, tachycardia
• New focal chest signs: crackles, bronchial breathing
• Increased volume/purulence of tracheal secretions (in ventilated patients)

Diagnostic Criteria (Clinical)

• New radiographic infiltrate PLUS at least 2 of: fever >38°C, leucocytosis/leucopenia, purulent secretions

Red Flags

• Sepsis (NEWS2 ≥5 or clinical concern)
• Requirement for new or increased ventilatory support
• Multi-organ dysfunction
• Known MDR organism colonisation
• Rapidly progressive infiltrates
• Immunocompromised patient

Bedside

• Pulse oximetry: new oxygen requirement or increasing FiO₂
• NEWS2 score: sepsis screening
• Sputum sample/tracheal aspirate: MC&S (before antibiotics)

Bloods

• FBC: leucocytosis or leucopenia
• CRP/procalcitonin: elevated; procalcitonin may guide antibiotic duration
• U&Es: renal function (antibiotic dosing)
• Blood cultures x2: before antibiotics
• Lactate: if sepsis suspected

Imaging

• Chest X-ray: new infiltrate, consolidation, cavitation
• CT chest: if CXR equivocal or non-resolving

Special Tests

• Bronchoalveolar lavage (BAL): gold standard for VAP diagnosis (≥10⁴ CFU/mL significant)
• Non-directed bronchial lavage: alternative if bronchoscopy not available
• Respiratory viral PCR: exclude viral cause
• Galactomannan/beta-D-glucan: if fungal infection suspected (immunocompromised)

Non-pharmacological

• Oxygen therapy (target SpO₂ 94-98% or 88-92% if COPD)
• IV fluids and nutritional support
• VTE prophylaxis
• Chest physiotherapy and early mobilisation
• Source control (remove/replace lines, NG tubes)

Pharmacological

NICE NG139 empirical antibiotics:

Non-severe HAP (early-onset, no MDR risk):

• Co-amoxiclav 625mg TDS PO for 5 days
• Penicillin allergy: doxycycline 200mg then 100mg OD

Severe or late-onset HAP (MDR risk):

• Piperacillin-tazobactam 4.5g IV TDS or meropenem 1g IV TDS
• Add vancomycin 15-20mg/kg IV BD (trough-guided) if MRSA risk
• Guided by local antibiogram and previous culture results

VAP:

• Piperacillin-tazobactam or meropenem + anti-MRSA cover (vancomycin/linezolid)
• De-escalate based on culture results within 48-72 hours
• Duration: 7-8 days (shorter courses non-inferior; longer if Pseudomonas)

Surgical/Interventional

• Chest drain for empyema
• Percutaneous or surgical drainage of lung abscess

Referral Criteria

• Microbiology advice for MDR organisms
• ICU if respiratory failure requiring escalation
• Infectious diseases input for complex/resistant infections

• HAP mortality: 20-50% (higher for VAP, MDR organisms, immunocompromised)
• VAP mortality: 25-50%
• Pseudomonas/Acinetobacter HAP carries highest mortality (~40-60%)
• Appropriate early antibiotics reduce mortality significantly
• Delays in appropriate antibiotic therapy increase mortality by 20-30%
• VAP prevention bundles reduce incidence by 40-50%
• Prolonged hospitalisation: average additional 7-10 days
• Increased risk of readmission and subsequent infections

VAP Prevention Bundle

HAP Antibiotic Summary

Key Facts

Aspiration pneumonia is a lung infection caused by the inhalation of colonised oropharyngeal or gastric contents into the lower respiratory tract. It should be distinguished from aspiration pneumonitis, which is a chemical inflammatory response to aspirated gastric acid without initial bacterial infection.

Epidemiology

• Accounts for ~5-15% of community-acquired pneumonia cases
• Up to 50% of pneumonias in nursing home residents
• Incidence increases markedly with age (>75 years) and institutional care
• Stroke patients: 30-50% aspirate; ~15-25% of these develop pneumonia

Aetiology

• Mixed oropharyngeal flora: anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus, Prevotella) + aerobes
• Community-acquired: S. pneumoniae, H. influenzae + anaerobes
• Hospital-acquired: Gram-negative bacilli, S. aureus, Pseudomonas + anaerobes
• Poor oral hygiene significantly increases anaerobic load

Pathophysiology

• Aspiration of oropharyngeal secretions colonised with pathogenic bacteria
• Normal protective mechanisms impaired: cough reflex, mucociliary clearance, epiglottic closure
• Gravity-dependent segments affected: right lower lobe (upright), posterior segments of upper lobes (supine)

Typical Presentation

• Cough with foul-smelling purulent sputum (anaerobic infection)
• Fever (may be low-grade initially)
• Breathlessness
• Witnessed aspiration event in some cases
• Usually in context of known risk factor (stroke, altered consciousness, dysphagia)

Clinical Signs

• Signs of consolidation, typically right lower lobe
• Pyrexia
• Tachypnoea, tachycardia
• Reduced SpO₂
• Poor dentition (significant risk factor)

Aspiration Pneumonitis vs Pneumonia

• Pneumonitis (Mendelson syndrome): acute chemical lung injury from gastric acid; rapid onset (hours), diffuse bilateral crackles, self-limiting in ~48-72 hours without antibiotics
• Pneumonia: bacterial infection; slower onset (24-72 hours post-aspiration), localised consolidation, purulent sputum

Red Flags

• Lung abscess (non-resolving consolidation, air-fluid level on CXR)
• Empyema
• Rapidly progressive necrotising pneumonia
• Recurrent aspiration events
• Inability to protect airway

Bedside

• Pulse oximetry: assess oxygenation
• ABG: if SpO₂ <92%
• SALT assessment: swallowing evaluation to prevent recurrence

Bloods

• FBC: leucocytosis
• CRP: elevated
• U&Es: renal function, hydration status
• Blood cultures: before antibiotics in moderate-severe
• Procalcitonin: distinguish pneumonitis from pneumonia

Imaging

• Chest X-ray: consolidation (typically right lower lobe), air-fluid level (abscess)
• CT chest: if abscess suspected, non-resolving, or to guide drainage

Special Tests

• Sputum MC&S: anaerobic and aerobic cultures
• Bronchoscopy: if foreign body suspected or non-resolving
• Video fluoroscopy/FEES: formal swallowing assessment
• Barium swallow: if oesophageal pathology or fistula suspected

Non-pharmacological

• Nil by mouth until SALT assessment
• Positioning: sit upright (30-45° head-of-bed elevation)
• Oral hygiene: regular mouth care, dental assessment
• Oxygen therapy (target SpO₂ 94-98%)
• IV fluids if nil by mouth or dehydrated
• NG tube feeding only after SALT assessment (NG tubes themselves increase aspiration risk)

Pharmacological

Antibiotics (must cover anaerobes):

• Co-amoxiclav 1.2g IV TDS (covers aerobes + anaerobes) - first-line
• Or amoxicillin 1g IV TDS + metronidazole 500mg IV TDS
• Penicillin allergy: clindamycin 600mg IV QDS or moxifloxacin 400mg OD
• Hospital-acquired aspiration: piperacillin-tazobactam 4.5g IV TDS
• Duration: 7-14 days (longer for abscess/empyema - up to 4-6 weeks)

Lung abscess:

• Prolonged antibiotics (4-6 weeks minimum)
• Co-amoxiclav or piperacillin-tazobactam
• CT-guided percutaneous drainage if >6cm or failed medical therapy

Surgical/Interventional

• Chest drain for empyema
• CT-guided drainage for lung abscess
• Tracheostomy for patients with recurrent aspiration and inability to protect airway
• PEG feeding: consider for chronic dysphagia (though does not eliminate aspiration risk)

Referral Criteria

• SALT assessment for all patients with aspiration pneumonia
• Respiratory referral for recurrent aspiration or lung abscess
• ENT/gastroenterology for structural causes of aspiration
• Palliative care if aspiration due to end-stage neurological disease

• Mortality: ~20-30% for hospitalised aspiration pneumonia
• Higher mortality in elderly, nursing home residents, and mechanically ventilated patients
• Lung abscess mortality: ~5-10% with appropriate treatment
• Recurrence rate is high (~30%) without addressing underlying cause
• Chronic aspiration leads to progressive lung damage and bronchiectasis
• Outcomes improve with early SALT assessment and dysphagia management

Risk Factors for Aspiration

Aspiration Pneumonitis vs Pneumonia

Key Facts

Atypical pneumonia refers to pneumonia caused by organisms that do not respond to beta-lactam antibiotics and are not identified on standard Gram stain or culture. The term reflects both the unusual clinical presentation (compared to typical lobar pneumonia) and the atypical organisms responsible.

Epidemiology

• Accounts for ~15-25% of all CAP cases
• Mycoplasma pneumoniae: most common; 4-yearly epidemic cycles, mainly affects ages 5-40
• Legionella: ~2-5% of CAP; higher in summer/autumn; travel-associated; outbreaks from cooling towers
• Chlamydophila pneumoniae: ~5-10%; mild illness, common in young adults
• Chlamydophila psittaci: occupational exposure to birds (psittacosis)
• Coxiella burnetii: Q fever; exposure to livestock/farm animals

Aetiology

• Mycoplasma pneumoniae: smallest free-living bacterium; lacks cell wall (hence beta-lactam resistance)
• Legionella pneumophila: Gram-negative rod; contaminated water, cooling towers, spa pools; serogroup 1 most common
• Chlamydophila pneumoniae/psittaci: obligate intracellular; person-to-person (C. pneumoniae) or bird-to-human (C. psittaci)
• Coxiella burnetii: obligate intracellular; livestock, placental tissue; Q fever

Pathophysiology

• Intracellular organisms evade standard immune defences
• Immune-mediated pathology contributes (Mycoplasma: cold agglutinins, autoimmune haemolysis, cross-reactive antibodies)
• Diffuse interstitial rather than alveolar inflammation → patchy bilateral infiltrates
• Extrapulmonary manifestations reflect systemic immune activation

General Atypical Features

• Gradual onset (over days)
• Dry (non-productive) cough
• Prominent systemic symptoms: headache, myalgia, malaise, fever
• Minimal chest signs despite CXR changes ("walking pneumonia")
• Extrapulmonary features common

Mycoplasma pneumoniae

• Young adults (5-40 years), campus/military outbreaks
• Dry cough, headache, malaise
• Extrapulmonary: erythema multiforme/Stevens-Johnson syndrome, cold agglutinins (autoimmune haemolytic anaemia), myocarditis, pericarditis, encephalitis, Guillain-Barré syndrome, arthritis, bullous myringitis

Legionella pneumophila

• Travel, contaminated water, outbreaks
• High fever, rigors, confusion
• Key triad: confusion, hyponatraemia, deranged LFTs
• GI symptoms: diarrhoea, abdominal pain, nausea
• Can cause severe pneumonia requiring ICU

Chlamydophila psittaci

• Bird exposure (parrots, pigeons, poultry workers)
• Pneumonia with hepatosplenomegaly, rash (Horder spots)

Q Fever (Coxiella burnetii)

• Farm/livestock exposure
• Pneumonia, hepatitis, endocarditis (chronic Q fever)

Red Flags

• Severe Legionella pneumonia (CURB-65 ≥3)
• Mycoplasma with neurological complications (encephalitis, GBS)
• Stevens-Johnson syndrome
• Multi-organ involvement
• Non-response to beta-lactam antibiotics

Bedside

• Pulse oximetry: SpO₂
• Urinary Legionella antigen: rapid result (sensitivity ~70-80% for serogroup 1 only)
• Urinary pneumococcal antigen: to identify co-infection
• CURB-65 score: severity assessment

Bloods

• FBC: leucocytosis or normal WCC; lymphopenia (viral); anaemia (cold agglutinins in Mycoplasma)
• CRP: elevated
• U&Es: hyponatraemia (Legionella)
• LFTs: deranged in Legionella, Q fever, psittacosis
• Cold agglutinins: positive in ~50% of Mycoplasma (IgM anti-I)
• Blood cultures x2: exclude typical organisms
• Mycoplasma IgM serology: acute infection
• Legionella PCR on respiratory sample: more sensitive than urinary antigen

Imaging

• CXR: patchy bilateral infiltrates, interstitial pattern, lower lobe predominance; may be worse than clinical signs suggest
• CT chest: ground-glass opacification, tree-in-bud, patchy consolidation

Special Tests

• Legionella culture (BCYE agar): takes 3-5 days; gold standard
• Mycoplasma PCR (throat swab/sputum): rapid, sensitive
• Paired serology (acute and convalescent, 2-4 weeks apart): 4-fold rise in titre confirms diagnosis
• Complement fixation tests: Mycoplasma, Chlamydophila, Q fever
• Bronchoscopy/BAL: if diagnostic uncertainty or immunocompromised

Non-pharmacological

• Oxygen therapy as needed
• IV fluids if dehydrated
• Isolate if Legionella suspected (prevent nosocomial spread from water systems)
• Notify PHE: Legionella, Q fever, psittacosis are notifiable diseases

Pharmacological

First-line antibiotics (atypical coverage):

• Clarithromycin 500mg BD PO/IV for 7-14 days (most atypicals)
• Or doxycycline 200mg loading then 100mg OD for 7-14 days

Severe Legionella:

• Levofloxacin 500mg OD/BD IV or azithromycin 500mg OD IV
• Consider adding rifampicin 600mg BD in severe/ICU cases
• Duration: 14-21 days

Mycoplasma pneumoniae:

• Clarithromycin 500mg BD or doxycycline 100mg BD for 7-14 days
• Severe/neurological: consider IV clarithromycin or azithromycin
• Corticosteroids for severe immune-mediated complications (encephalitis, SJS)

Chlamydophila/Psittacosis:

• Doxycycline 100mg BD for 14 days (first-line)
• Alternative: clarithromycin

Q Fever:

• Acute: doxycycline 100mg BD for 14 days
• Chronic (endocarditis): doxycycline + hydroxychloroquine for ≥18 months

Surgical/Interventional

• Not typically required
• Drain empyema if present

Referral Criteria

• PHE notification for Legionella, psittacosis, Q fever
• ICU for severe Legionella
• Infectious diseases for complex cases or chronic Q fever
• Environmental health investigation for Legionella outbreaks

• Mycoplasma pneumonia: usually self-limiting; mortality <1%; complications in 5-10%
• Legionella: mortality ~5-10% (up to 30% in immunocompromised or ICU)
• Psittacosis: mortality <1% with treatment; rarely fatal
• Q fever: acute infection usually self-limiting; chronic Q fever endocarditis has significant morbidity
• Overall atypical pneumonia has good prognosis with appropriate antibiotic therapy
• Neurological complications of Mycoplasma (GBS, encephalitis) may cause lasting disability

Atypical Pneumonia Organism Summary

Notifiable Atypical Pneumonia Organisms (UK)

Key Facts

Pulmonary embolism (PE) is the obstruction of one or more pulmonary arteries by material (usually thrombus) that has travelled from elsewhere in the body. It exists on a spectrum from small subsegmental PEs to massive saddle embolism causing cardiac arrest.

Epidemiology

• Annual incidence: ~60-70 per 100,000 population
• ~25,000 deaths per year in the UK attributed to VTE
• Leading cause of preventable hospital death
• Accounts for ~10% of in-hospital deaths
• Third most common cardiovascular cause of death after MI and stroke

Aetiology

Virchow's triad:

• Stasis: immobility (surgery, long-haul travel, bed rest), pregnancy
• Endothelial injury: surgery, trauma, central venous catheters
• Hypercoagulability: malignancy, thrombophilia (Factor V Leiden, prothrombin gene mutation, antiphospholipid syndrome), OCP/HRT, pregnancy, nephrotic syndrome

Pathophysiology

• Thrombus (usually from ileofemoral DVT) embolises to pulmonary arteries
• Obstruction increases pulmonary vascular resistance → right ventricular pressure overload

• V/Q mismatch → hypoxaemia

• Release of vasoactive mediators (serotonin, thromboxane) causes additional vasoconstriction

Typical Presentation

• Acute onset breathlessness (most common symptom)
• Pleuritic chest pain
• Haemoptysis
• Tachycardia, tachypnoea
• Often with identifiable risk factor

Massive PE

• Cardiovascular collapse: hypotension (SBP <90 mmHg), syncope
• Signs of acute RV failure: raised JVP, RV heave, loud P2
• Cyanosis
• Cardiac arrest (PEA most common rhythm)

Submassive PE

• Haemodynamically stable but with RV dysfunction on echo/CT
• Elevated troponin and/or BNP

Small/Subsegmental PE

• May be asymptomatic or mild dyspnoea only
• Incidental finding on CT

Red Flags

• Haemodynamic instability (massive PE)
• Syncope
• New-onset AF
• Signs of RV strain
• Cardiac arrest in context of VTE risk factors
• Pregnancy (PE is leading cause of direct maternal death)

Bedside

• Two-level Wells score: calculate before investigation
  • PE likely (>4): proceed to CTPA
  • PE unlikely (≤4): check D-dimer first
• ECG: sinus tachycardia (most common), S1Q3T3 (classic but uncommon), right axis deviation, RBBB, T-wave inversion V1-V4, AF
• ABG: hypoxaemia, hypocapnia (type 1 respiratory failure), raised A-a gradient
• Pulse oximetry: hypoxia

Bloods

• D-dimer: if Wells ≤4; negative D-dimer effectively excludes PE (high sensitivity, low specificity)
• Troponin: elevated in submassive/massive PE (RV strain)
• BNP/NT-proBNP: RV dysfunction marker, prognostic
• FBC, U&Es, coagulation screen: baseline
• Thrombophilia screen: if unprovoked PE (defer until 3 months after anticoagulation)

Imaging

• CTPA: gold standard; sensitivity >95%, specificity >95%
• V/Q scan: if CTPA contraindicated (contrast allergy, severe renal impairment, pregnancy - lower radiation dose to breast tissue)
• Echocardiography: RV dilation, McConnell sign (RV free wall hypokinesis with apical sparing), interventricular septum bowing
• Compression duplex USS legs: if DVT suspected concurrently
• CXR: often normal; may show Westermark sign (oligaemia), Hampton hump (wedge-shaped opacity), effusion, atelectasis

Special Tests

• RV/LV ratio on CT: >0.9 indicates RV strain
• CT lower limb venography: can be combined with CTPA
• Pulmonary angiography: rarely needed; historical gold standard

Non-pharmacological

• Haemodynamic support: IV fluids (cautious - avoid RV overload), vasopressors (noradrenaline) if needed
• Supplemental oxygen (target SpO₂ 94-98%)
• Early mobilisation (for stable PE)

Pharmacological

Anticoagulation (NICE NG158):

• Start treatment-dose anticoagulation immediately if clinical suspicion is high (don't wait for CTPA)

First-line (non-massive):

• Apixaban: 10mg BD for 7 days, then 5mg BD
• Or rivaroxaban: 15mg BD for 21 days, then 20mg OD
• Alternative: LMWH (e.g. enoxaparin 1.5mg/kg OD or 1mg/kg BD) for ≥5 days → warfarin (target INR 2-3)

Duration:

• Provoked PE (identifiable transient risk factor): 3 months
• Unprovoked PE: 6 months minimum, consider lifelong if low bleeding risk
• Recurrent VTE or strong thrombophilia: lifelong
• Cancer-associated: DOAC or LMWH; duration dependent on ongoing cancer treatment

Massive PE (haemodynamically unstable):

• Thrombolysis: alteplase 50mg IV bolus (cardiac arrest) or 100mg IV over 2 hours
• Followed by IV unfractionated heparin infusion
• Consider thrombolysis in cardiac arrest with suspected PE

Submassive PE (stable but RV dysfunction):

• Standard anticoagulation
• Close monitoring; some guidelines suggest considering thrombolysis if deteriorating

Surgical/Interventional

• Catheter-directed thrombolysis: massive PE where systemic thrombolysis contraindicated
• Surgical embolectomy: last resort for massive PE with failed thrombolysis
• IVC filter: if anticoagulation absolutely contraindicated (temporary, retrieve when possible)

Referral Criteria

• Massive PE: immediate ICU/critical care
• Ambulatory PE management: consider for low-risk PE (PESI class I-II) with appropriate follow-up
• Haematology: unprovoked PE for thrombophilia screening
• Oncology screening: consider occult malignancy in unprovoked PE

• Untreated PE mortality: ~30%
• Treated PE mortality: ~2-8% (depending on severity)
• Massive PE mortality: ~15-25% (even with treatment); ~65% if cardiac arrest
• Submassive PE: ~3-5% mortality
• VTE recurrence: ~5% per year while anticoagulated; ~10% per year after stopping
• Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 2-4% of PE survivors
• Post-PE syndrome: persistent dyspnoea and exercise limitation in ~50%
• Early anticoagulation dramatically improves survival

Two-Level Wells Score for PE

PESI Score (Prognostic)

Classic ECG Findings in PE

Key Facts

Pulmonary hypertension (PH) is defined as an elevation in mean pulmonary artery pressure ≥20 mmHg at rest, measured by right heart catheterisation. It encompasses a heterogeneous group of conditions classified into 5 WHO groups based on aetiology and haemodynamic profiles.

Epidemiology

• Group 2 (left heart disease) is the most common cause overall
• Idiopathic PAH (Group 1): incidence ~2-7 per million per year
• PAH prevalence: ~15-50 per million
• Female predominance in idiopathic PAH (~4:1)
• Mean age at diagnosis of idiopathic PAH: ~50 years
• CTEPH (Group 4): develops in ~2-4% of PE survivors

Aetiology

WHO Classification:

• Group 1 (PAH): idiopathic, heritable (BMPR2 mutation), drug-induced (anorexigens, methamphetamine), connective tissue disease (scleroderma), HIV, portal hypertension, congenital heart disease, schistosomiasis
• Group 2: left heart disease (HFrEF, HFpEF, valvular disease)
• Group 3: chronic lung disease (COPD, ILD, OSA, high altitude)
• Group 4: CTEPH
• Group 5: multifactorial/unclear (sarcoidosis, haematological disorders, metabolic)

Pathophysiology

• PAH (Group 1): pulmonary arterial vasoconstriction, vascular remodelling (intimal fibrosis, medial hypertrophy), in-situ thrombosis, plexiform lesions
• Endothelial dysfunction: reduced nitric oxide and prostacyclin, excess endothelin-1 and thromboxane

• Group 2: passive congestion from elevated left atrial pressure; may develop reactive (combined pre- and post-capillary) component
• Group 4: organised thrombus causes mechanical obstruction + secondary small vessel arteriopathy

Typical Presentation

• Progressive exertional dyspnoea (most common symptom)
• Fatigue and lethargy
• Exertional syncope or presyncope
• Chest pain (RV ischaemia)
• Peripheral oedema

Clinical Signs

• Raised JVP with prominent a-wave (RV hypertrophy) or v-wave (tricuspid regurgitation)
• Right ventricular heave (left parasternal)
• Loud P2 (pulmonary component of second heart sound)
• Pansystolic murmur of tricuspid regurgitation
• Hepatomegaly, ascites, peripheral oedema (right heart failure)
• Cyanosis in advanced disease

WHO Functional Classification

• Class I: no limitation of physical activity
• Class II: slight limitation; comfortable at rest
• Class III: marked limitation; comfortable only at rest
• Class IV: symptoms at rest; unable to carry out any physical activity

Red Flags

• Syncope (indicates severe disease/low cardiac output)
• Rapidly progressive symptoms
• Signs of decompensated RV failure
• Pericardial effusion on echo
• Low cardiac output (cool peripheries, low BP, oliguria)

Bedside

• ECG: right axis deviation, RV hypertrophy (tall R waves V1-V3), P pulmonale, RBBB
• Pulse oximetry: desaturation (especially on exercise)
• 6-minute walk test: functional capacity and prognosis

Bloods

• BNP/NT-proBNP: elevated in RV dysfunction; prognostic marker
• FBC: polycythaemia (chronic hypoxia)
• Autoimmune screen: ANA, anti-centromere, anti-Scl-70, RF (connective tissue disease)
• TFTs: thyroid disease associated with PAH
• HIV test: HIV-associated PAH
• LFTs: hepatic congestion, portopulmonary hypertension screen
• Thrombophilia screen: if CTEPH suspected

Imaging

• Echocardiography: screening tool; estimates PA systolic pressure (PASP) from tricuspid regurgitation velocity, RV size/function, RA size, septal bowing, pericardial effusion
• CTPA: exclude CTEPH, assess cardiac chambers
• V/Q scan: gold standard to screen for CTEPH (higher sensitivity than CTPA for chronic thrombus)
• HRCT: parenchymal lung disease (Group 3)
• CXR: enlarged pulmonary arteries, pruning of peripheral vessels, RV enlargement

Special Tests

• Right heart catheterisation (RHC): gold standard for diagnosis and classification
  • mPAP ≥20 mmHg confirms PH
  • PAWP ≤15 mmHg: pre-capillary (Groups 1, 3, 4, 5)
  • PAWP >15 mmHg: post-capillary (Group 2)
  • PVR ≥2 Wood units: confirms elevated resistance
• Vasoreactivity testing: during RHC for idiopathic PAH; positive if mPAP drops ≥10 mmHg to ≤40 mmHg with preserved cardiac output (inhaled NO or IV epoprostenol)
• Pulmonary function tests: spirometry, TLCO, lung volumes
• Cardiac MRI: gold standard for RV assessment

Non-pharmacological

• Specialist PH centre referral for all suspected PAH/CTEPH
• Supervised exercise rehabilitation (improves functional capacity)
• Supplemental oxygen if PaO₂ <8 kPa
• Fluid restriction and low-salt diet
• Avoid pregnancy (high mortality risk 30-50%)
• Contraception counselling (avoid oestrogen-containing)
• Annual influenza and pneumococcal vaccination

Pharmacological

Group 1 (PAH) - targeted therapy:

Vasoreactive patients: high-dose CCB (nifedipine 120-240mg/day or diltiazem 240-720mg/day) - only ~10% of idiopathic PAH

Non-vasoreactive (majority):

• PDE5 inhibitors: sildenafil 20mg TDS (SUPER-1 trial) or tadalafil 40mg OD
• Endothelin receptor antagonists (ERAs): bosentan 125mg BD (BREATHE-1 trial), ambrisentan 5-10mg OD, macitentan 10mg OD (SERAPHIN trial)
• Prostanoids: epoprostenol IV continuous (gold standard for severe PAH), iloprost nebulised, treprostinil SC/IV/inhaled, selexipag PO (GRIPHON trial)
• sGC stimulator: riociguat 2.5mg TDS (PATENT-1 trial) - for PAH or inoperable CTEPH
• Combination therapy: initial or sequential combination is standard of care (AMBITION trial: ambrisentan + tadalafil superior to monotherapy)

Group 2 (left heart disease): treat underlying cardiac condition; PAH-specific therapies not recommended

Group 3 (lung disease): optimise treatment of underlying lung disease; supplemental oxygen; inhaled treprostinil for PH-ILD (INCREASE trial)

Group 4 (CTEPH):

• Pulmonary endarterectomy (PEA): potentially curative; gold standard for operable CTEPH
• Balloon pulmonary angioplasty (BPA): for inoperable CTEPH
• Riociguat: for inoperable/persistent CTEPH (CHEST-1 trial)

Surgical/Interventional

• Pulmonary endarterectomy for CTEPH (specialist centres; UK: Papworth)
• Balloon pulmonary angioplasty
• Atrial septostomy: palliative, creates R→L shunt to decompress RV
• Lung transplantation: end-stage PAH refractory to medical therapy
• Heart-lung transplantation: Eisenmenger syndrome

Referral Criteria

• All suspected PH: echocardiography → if PASP >40 mmHg or RV dysfunction, refer to specialist PH centre
• National PH centres in UK: Papworth, Hammersmith, Sheffield, Newcastle, Glasgow, Cardiff
• Urgent referral for syncope, rapid functional decline, or signs of RV failure

• Untreated idiopathic PAH: median survival ~2.8 years
• With modern combination therapy: median survival >7 years
• WHO FC I/II at diagnosis: better prognosis than FC III/IV
• 6MWD <300m, BNP >300 pg/mL, cardiac index <2 L/min/m²: poor prognostic markers
• CTEPH: PEA has ~95% 10-year survival if successful
• Scleroderma-associated PAH: worse prognosis than idiopathic PAH (~3-year survival ~50%)
• Group 2 PH: prognosis determined by underlying cardiac disease
• Pregnancy in PAH: maternal mortality ~30-50%; strongly advised against

WHO PH Classification Summary

Targeted PAH Drug Classes

Key Facts

Lung cancer is the most common cause of cancer-related death in the UK and worldwide. It is classified into non-small cell lung cancer (NSCLC, ~85%) and small cell lung cancer (SCLC, ~15%), with distinct management approaches and prognoses.

Epidemiology

• ~48,000 new cases per year in the UK
• ~35,000 deaths per year (leading cancer killer)
• Male:female ratio ~1.2:1 (gap narrowing)
• Peak incidence: age 70-80
• 5-year survival: overall ~16% (improving with targeted/immunotherapy)
• NHS lung cancer screening: targeted screening with LDCT for high-risk populations being rolled out

Aetiology

• Smoking: ~85% of lung cancers; risk increases with pack-years; cessation reduces but never eliminates risk
• Passive smoking: 20-30% increased risk
• Occupational: asbestos (synergistic with smoking), radon gas, chromium, arsenic, nickel, silica
• Genetics: family history increases risk 2-3 fold
• Pre-existing lung disease: COPD, pulmonary fibrosis (increased adenocarcinoma risk)
• Air pollution: contributes to ~1-2% of cases

Pathophysiology

NSCLC:

• Squamous cell carcinoma: central, arises from bronchial epithelium; associated with smoking, cavitation, hypercalcaemia (PTHrP)
• Adenocarcinoma: peripheral, commonest overall (especially in non-smokers and women); arises from glandular epithelium
• Large cell carcinoma: peripheral, undifferentiated; poor prognosis

SCLC:

• Neuroendocrine origin; central location
• Extremely aggressive: rapid doubling time, early widespread metastasis
• Highly chemosensitive initially but rapid relapse
• Strong association with paraneoplastic syndromes (SIADH, ectopic ACTH, Lambert-Eaton)

Typical Presentation

• Persistent cough (>3 weeks) or change in chronic cough
• Haemoptysis
• Chest pain
• Breathlessness
• Recurrent pneumonia (same lobe)
• Weight loss, anorexia, fatigue
• Hoarseness (recurrent laryngeal nerve palsy)

Local Invasion

• SVC obstruction: facial/arm oedema, distended neck veins, headache, plethora
• Pancoast tumour (apex): shoulder pain radiating down arm, Horner syndrome (miosis, ptosis, anhidrosis, enophthalmos)
• Phrenic nerve palsy: elevated hemidiaphragm, breathlessness
• Recurrent laryngeal nerve palsy: hoarse voice (left > right)
• Oesophageal compression: dysphagia

Paraneoplastic Syndromes

• Hypercalcaemia: PTHrP (squamous cell)
• SIADH: ADH secretion → hyponatraemia (SCLC)
• Ectopic ACTH: Cushing syndrome (SCLC)
• Lambert-Eaton myasthenic syndrome: proximal weakness improving with use (SCLC)
• Hypertrophic pulmonary osteoarthropathy (HPOA): finger clubbing, painful wrists/ankles
• Dermatomyositis/polymyositis: proximal weakness, skin rash

Red Flags

• Haemoptysis in smoker/ex-smoker >40 years - urgent 2WW referral
• CXR suspicious for lung cancer - urgent 2WW referral
• Persistent unexplained cough >3 weeks in high-risk patient
• Non-resolving pneumonia
• New finger clubbing
• SVC obstruction (medical emergency)

Bedside

• CXR: first-line - mass lesion, hilar lymphadenopathy, collapse, effusion, non-resolving consolidation
• Pulse oximetry: baseline

Bloods

• FBC: anaemia of chronic disease
• U&Es: hyponatraemia (SIADH)
• Calcium: hypercalcaemia (squamous cell, bone metastases)
• LFTs: hepatic metastases
• Coagulation: pre-biopsy

Imaging

• CT chest/abdomen/pelvis with contrast: staging - tumour size, lymph nodes, metastases
• PET-CT: metabolic staging; assess mediastinal nodes and distant metastases
• CT/MRI brain: staging for advanced disease or SCLC
• Bone scan: if bone pain or elevated ALP

Special Tests

• Tissue diagnosis:
  • CT-guided percutaneous biopsy (peripheral lesions)
  • Bronchoscopy with biopsy/brushings/BAL (central lesions)
  • EBUS (endobronchial ultrasound): mediastinal lymph node sampling
  • Mediastinoscopy: if EBUS non-diagnostic
  • Pleural biopsy (if effusion)
• Molecular testing (NSCLC): EGFR mutations, ALK rearrangements, ROS1, PD-L1 expression, KRAS G12C - guide targeted therapy
• Pulmonary function tests: assess fitness for surgery (FEV₁, TLCO)
• Cardiopulmonary exercise testing (CPET): VO₂max assessment if borderline fitness

Non-pharmacological

• MDT discussion: all cases discussed at lung cancer MDT
• Smoking cessation
• Nutritional support
• Palliative care referral early in advanced disease
• Psychological support and lung cancer CNS involvement

Pharmacological

NSCLC:

• Stage I-II: surgical resection ± adjuvant chemotherapy (cisplatin-based doublet if stage IB-II)
• Stage IIIA: neoadjuvant/adjuvant chemo ± radiotherapy ± surgery (MDT decision)
• Stage IIIB-C (unresectable): concurrent chemoradiotherapy → durvalumab maintenance (PACIFIC trial; NICE TA578)
• Stage IV: systemic therapy based on molecular markers
  • PD-L1 ≥50%: pembrolizumab monotherapy first-line (KEYNOTE-024; NICE TA531)
  • PD-L1 <50% or irrespective: pembrolizumab + platinum-based chemo (KEYNOTE-189; NICE TA683)
  • EGFR mutation positive: osimertinib 80mg OD (FLAURA trial; NICE TA654)
  • ALK rearrangement: alectinib 600mg BD (ALEX trial; NICE TA670)
  • KRAS G12C: sotorasib (NICE TA)

SCLC:

• Limited disease: concurrent chemoradiotherapy (cisplatin + etoposide × 4-6 cycles + thoracic radiotherapy)
• Extensive disease: chemotherapy (carboplatin + etoposide) + atezolizumab (anti-PD-L1; IMpower133 trial; NICE TA803)
• Prophylactic cranial irradiation (PCI): if good response to first-line treatment

Surgical/Interventional

• Lobectomy: standard for stage I-II NSCLC
• VATS (video-assisted thoracoscopic surgery): preferred minimally invasive approach
• Pneumonectomy: if lobectomy insufficient
• Segmentectomy/wedge resection: if poor lung function
• SABR (stereotactic ablative radiotherapy): for early-stage NSCLC in patients unfit for surgery
• Radical radiotherapy: for unresectable locally advanced disease
• Stenting: SVC stent for SVC obstruction; endobronchial stent for airway obstruction
• Palliative radiotherapy: bone/brain metastases, SVC obstruction, haemoptysis

Referral Criteria

• Urgent 2WW referral (NICE NG12): CXR suspicious for lung cancer; unexplained haemoptysis >40 years
• All cases to lung cancer MDT
• Early palliative care referral for advanced disease (improves quality of life and survival - Temel 2010 NEJM)

• Overall 5-year survival: ~16%
• Stage IA: ~80% 5-year survival
• Stage IB: ~60%
• Stage II: ~40-50%
• Stage IIIA: ~25%
• Stage IIIB-C: ~10%
• Stage IV: ~5%
• SCLC limited: median survival ~15-20 months; 5-year ~10%
• SCLC extensive: median survival ~8-12 months; 5-year <5%
• Immunotherapy has improved advanced NSCLC median survival from ~12 months to ~20-24 months
• EGFR+ NSCLC with osimertinib: median PFS ~18 months
• UK lung cancer screening programme aims to improve stage-shift and survival

TNM Staging Summary (8th Edition)

Paraneoplastic Syndromes by Cell Type

Key Facts

Malignant pleural mesothelioma is an aggressive tumour arising from the mesothelial cells lining the pleural cavity. It is almost exclusively caused by asbestos exposure and is the most common primary malignancy of the pleura.

Epidemiology

• ~2,700 new cases per year in the UK (highest per capita worldwide)
• UK incidence peaked around 2018-2020; expected to decline slowly
• Male predominance (~4:1) reflecting occupational exposure patterns
• Median age at diagnosis: 70-75 years
• Latency period: 20-40 years from first asbestos exposure

Aetiology

• Asbestos exposure (>80%): occupational (construction, shipbuilding, insulation, plumbing); environmental; para-occupational (household contacts)
• Crocidolite (blue asbestos) > amosite (brown) > chrysotile (white) in carcinogenicity
• Non-asbestos causes: erionite (volcanic mineral), radiation, SV40 virus (debated)
• No dose threshold - even brief exposure can cause disease

Pathophysiology

• Asbestos fibres penetrate to pleural surface and cause chronic inflammation
• DNA damage from reactive oxygen species and frustrated phagocytosis
• Activation of oncogenic pathways (BAP1, NF2, CDKN2A loss)
• Tumour encases the lung (pleural rind), invading chest wall, diaphragm, and mediastinum
• Histological subtypes: epithelioid (60%, best prognosis), sarcomatoid (20%, worst prognosis), biphasic (20%)

Typical Presentation

• Progressive breathlessness (pleural effusion - 90% at presentation)
• Non-pleuritic chest wall pain (dull, persistent)
• Weight loss, fatigue, sweats
• Occupational asbestos exposure history (may be remote)

Clinical Signs

• Signs of pleural effusion: reduced expansion, stony dull percussion, reduced breath sounds
• Finger clubbing (~30%)
• Chest wall mass (advanced disease)
• Contralateral mediastinal shift (large effusion) or ipsilateral shift (trapped lung)

Advanced Disease

• Chest wall invasion: localised pain, palpable mass
• SVC obstruction
• Dysphagia (oesophageal compression)
• Pericardial involvement: effusion, tamponade
• Contralateral spread, peritoneal involvement

Red Flags

• Unilateral pleural effusion in patient with asbestos exposure history
• Non-resolving unilateral effusion
• Chest wall pain with effusion
• Pleural thickening >1cm on imaging

Bedside

• Pulse oximetry: baseline
• Occupational history: detailed asbestos exposure assessment

Bloods

• FBC, U&Es, LFTs: baseline
• CRP: elevated in some cases
• Mesothelin/fibulin-3: potential biomarkers (not yet routine)

Imaging

• CXR: unilateral pleural effusion ± pleural thickening; pleural plaques may be present
• CT chest (contrast-enhanced): nodular or circumferential pleural thickening, pleural effusion, mediastinal lymphadenopathy
• PET-CT: staging, assess metabolic activity, guide biopsy
• MRI chest: assess chest wall and diaphragmatic invasion (surgical planning)

Special Tests

• Pleural aspiration: exudative, often bloodstained; cytology sensitivity only ~30% (low sensitivity for mesothelioma)
• Thoracoscopic (VATS) pleural biopsy: gold standard for diagnosis - sensitivity >90%
• CT-guided percutaneous biopsy: alternative if VATS not possible
• Immunohistochemistry: calretinin+, WT1+, CK5/6+ (mesothelioma markers); CEA−, TTF-1− (excludes adenocarcinoma)
• BAP1 loss: supports mesothelioma diagnosis
• Pulmonary function tests: restrictive pattern if large effusion or trapped lung

Non-pharmacological

• MDT discussion: all cases at specialist mesothelioma MDT
• Compensation advice: refer for Industrial Injuries Disablement Benefit, civil litigation, and Diffuse Mesothelioma Payment Scheme
• Psychological support and palliative care early referral
• Smoking cessation (not causative but worsens lung function)

Pharmacological

First-line palliative chemotherapy:

• Pemetrexed 500mg/m² + cisplatin 75mg/m² every 21 days for up to 6 cycles (Vogelzang trial: improved median survival from 9 to 12 months)
• Pre-medicate with folic acid 400mcg daily and vitamin B12 1mg IM every 9 weeks to reduce pemetrexed toxicity
• Carboplatin substituted if cisplatin contraindicated

Immunotherapy:

• Nivolumab 360mg + ipilimumab 1mg/kg every 3 weeks for 4 cycles, then nivolumab 480mg every 4 weeks - first-line for non-epithelioid or PD-L1 ≥1% (CheckMate 743 trial; NICE TA781)

Symptom management:

• Pleural effusion: indwelling pleural catheter (IPC) or talc pleurodesis
• Pain: WHO analgesic ladder ± neuropathic agents (pregabalin, gabapentin)
• Palliative radiotherapy: prophylactic to biopsy/drain tract sites (debated)

Surgical/Interventional

• Pleurodesis (talc slurry via chest drain or thoracoscopic talc poudrage): for recurrent symptomatic effusion
• Indwelling pleural catheter (IPC): for trapped lung or recurrent effusion post-pleurodesis
• Extended pleurectomy/decortication (EPD): in highly selected patients; multimodal approach (MARS 2 trial ongoing)
• Extrapleural pneumonectomy: largely abandoned due to high morbidity/mortality (MARS trial)

Referral Criteria

• All suspected mesothelioma to specialist centre
• Early palliative care involvement
• Compensation/legal advice referral
• Specialist thoracic surgery opinion in selected early-stage disease

• Median overall survival: ~12 months from diagnosis
• Epithelioid: median ~18 months
• Sarcomatoid: median ~6-8 months
• Biphasic: median ~12 months
• Poor prognostic factors: sarcomatoid histology, advanced stage, poor performance status, raised WCC/platelet count, low Hb
• With pemetrexed/cisplatin: median survival ~12-14 months
• With nivolumab/ipilimumab (non-epithelioid): median survival ~18 months
• 5-year survival: <5% overall
• UK mesothelioma deaths expected to peak and then decline over coming decades as asbestos exposure diminishes

Asbestos-Related Conditions Spectrum

Mesothelioma Subtypes

Key Facts

A pleural effusion is an abnormal collection of fluid in the pleural space between the visceral and parietal pleura. It is classified as transudative or exudative based on the biochemical analysis of the pleural fluid.

Epidemiology

• ~1 million cases per year in the UK
• Heart failure is the commonest cause overall
• Parapneumonic effusion/empyema: ~65,000 cases per year in UK
• Malignant effusion: affects ~50% of patients with metastatic cancer

Aetiology

Transudative (protein <25 g/L):

• Heart failure (most common)
• Liver cirrhosis (hepatic hydrothorax)
• Nephrotic syndrome
• Hypothyroidism
• Meigs syndrome (ovarian fibroma + effusion + ascites)
• Peritoneal dialysis

Exudative (protein >35 g/L):

• Parapneumonic effusion/empyema
• Malignancy (lung, breast, lymphoma, mesothelioma)
• Tuberculosis
• Pulmonary embolism
• Autoimmune (RA, SLE)
• Pancreatitis (typically left-sided, high amylase)
• Drug-induced

Pathophysiology

• Normal pleural fluid: ~0.1-0.2 mL/kg, produced by systemic capillaries in parietal pleura, absorbed by parietal pleural lymphatics
• Transudates: imbalance of hydrostatic/oncotic pressures (elevated capillary hydrostatic pressure or reduced plasma oncotic pressure)
• Exudates: increased capillary permeability due to inflammation, infection, or malignancy; impaired lymphatic drainage

Typical Presentation

• Progressive breathlessness (proportional to effusion size)
• Pleuritic chest pain (if inflammatory cause)
• Dry cough
• Reduced exercise tolerance

Clinical Signs

• Reduced chest expansion on affected side
• Stony dull percussion note
• Reduced/absent breath sounds
• Reduced tactile vocal fremitus
• Mediastinal shift away from large effusion
• Tracheal deviation (towards in collapse, away in effusion)

Features Suggesting Cause

• Bilateral + oedema: heart failure
• Fever + pleuritic pain: infection (empyema)
• Weight loss + cachexia: malignancy
• Rheumatoid nodules + joint disease: RA
• Night sweats + weight loss: TB

Red Flags

• Rapidly accumulating effusion
• Bloodstained fluid on aspiration
• Loculated effusion with sepsis (empyema)
• Massive effusion causing mediastinal shift
• Non-resolving effusion despite treatment of presumed cause

Bedside

• Chest X-ray: blunting of costophrenic angle (>200mL on PA film), meniscus sign, opacification
• Thoracic USS: gold standard for detecting and guiding aspiration; identifies loculations, pleural thickening
• Pulse oximetry: baseline

Bloods

• FBC, CRP: infection markers
• U&Es: renal function
• LFTs, albumin: liver disease, protein status
• BNP/NT-proBNP: heart failure
• Coagulation: pre-aspiration

Pleural Fluid Analysis (BTS-recommended)

• Appearance: clear/straw (transudate), turbid (empyema), bloodstained (malignancy/trauma), milky (chylothorax)
• Protein: transudate <25 g/L, exudate >35 g/L; if 25-35 g/L use Light's criteria
• LDH: elevated in exudates
• pH: <7.2 suggests empyema (requires chest drain) or RA
• Glucose: low in empyema (<2.2), RA, TB, malignancy
• MC&S: bacterial infection
• Cytology: malignant cells (~60% sensitivity for malignancy)
• Cell differential: neutrophils (parapneumonic), lymphocytes (TB, malignancy, RA)
• Amylase: elevated in pancreatitis, oesophageal rupture
• Triglycerides: >1.24 mmol/L indicates chylothorax
• Adenosine deaminase (ADA): elevated >40 U/L supports TB

Imaging

• CT chest (contrast): pleural thickening, masses, lung parenchyma, lymphadenopathy
• PET-CT: if malignancy suspected

Special Tests

• Pleural biopsy: thoracoscopic (VATS) biopsy - gold standard for undiagnosed exudative effusions (sensitivity >90% for mesothelioma/TB)
• CT-guided biopsy: alternative
• Bronchoscopy: if endobronchial lesion suspected

Non-pharmacological

• Treat underlying cause (diuretics for heart failure, antibiotics for infection)
• USS-guided aspiration for symptomatic relief (drain max 1.5L at one time to avoid re-expansion pulmonary oedema)

Pharmacological

• Heart failure: diuretics (furosemide 40-80mg PO/IV), salt/fluid restriction
• Parapneumonic/empyema: antibiotics (co-amoxiclav/piperacillin-tazobactam) + chest drain if pH <7.2
• TB pleuritis: standard anti-TB therapy (RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol)
• Malignant effusion: talc pleurodesis or indwelling pleural catheter (IPC) for symptom control
• Intrapleural fibrinolytics: alteplase 10mg + DNase 5mg BD via chest drain for loculated empyema (MIST2 trial)

Surgical/Interventional

• Therapeutic aspiration: USS-guided; for symptom relief
• Intercostal chest drain: empyema (pH <7.2), large symptomatic effusion, haemothorax
• Talc pleurodesis: via chest drain (slurry) or thoracoscopy (poudrage) for recurrent malignant effusion
• Indwelling pleural catheter (IPC): for recurrent effusion, trapped lung, or failed pleurodesis
• VATS decortication: for chronic empyema or trapped lung
• Thoracotomy and decortication: if VATS fails

Referral Criteria

• Undiagnosed exudative effusion after initial aspiration: respiratory referral for thoracoscopy
• Suspected malignant effusion: urgent 2WW cancer pathway
• Empyema not responding to antibiotics/drain: thoracic surgery referral
• Recurrent effusion requiring intervention: IPC or pleurodesis

• Depends entirely on underlying cause
• Heart failure effusion: prognosis related to cardiac disease severity
• Parapneumonic effusion: good prognosis with appropriate antibiotics; empyema mortality ~15-20%
• Malignant effusion: median survival 3-12 months depending on primary tumour
• Lung cancer with malignant effusion: median survival ~4 months
• Breast cancer with malignant effusion: median survival ~12 months
• TB pleuritis: excellent prognosis with treatment (>95% cure)
• Talc pleurodesis success rate: ~70-80%
• IPC achieves spontaneous pleurodesis in ~40-60% over time

Light's Criteria (Exudative Effusion)

Pleural Fluid Appearance

Indications for Chest Drain in Pleural Effusion

Key Facts

A pneumothorax occurs when air enters the pleural space, disrupting the negative intrapleural pressure and causing partial or complete lung collapse. Management depends on the type (primary vs secondary), size, and clinical stability.

Epidemiology

• Primary spontaneous: incidence ~18-28 per 100,000 in males, ~1.2-6 per 100,000 in females
• Peak incidence: young men aged 20-30
• Secondary spontaneous: incidence increases with age and COPD severity
• Male:female ratio ~3:1 (primary); more equal in secondary

Aetiology

Primary spontaneous:

• Rupture of subpleural apical blebs/bullae
• Risk factors: tall thin body habitus, smoking, cannabis use, family history, Marfan syndrome, homocystinuria

Secondary spontaneous:

• COPD (most common)
• Asthma, cystic fibrosis, TB, Pneumocystis pneumonia
• Interstitial lung disease, LAM (lymphangioleiomyomatosis)
• Lung cancer, mesothelioma
• Catamenial pneumothorax (associated with endometriosis, right-sided, menstrual)

Traumatic:

• Penetrating/blunt chest trauma
• Iatrogenic: central line insertion, thoracentesis, lung biopsy, mechanical ventilation

Pathophysiology

• Air enters pleural space through visceral pleura defect (spontaneous) or chest wall breach (traumatic)
• Loss of negative intrapleural pressure → lung collapse
• Mediastinal shift occurs with large pneumothorax

Typical Presentation

• Sudden onset unilateral pleuritic chest pain
• Breathlessness (proportional to size and underlying lung function)
• May be relatively asymptomatic in small primary pneumothorax

Clinical Signs

• Reduced chest expansion on affected side
• Hyperresonant percussion
• Reduced or absent breath sounds
• Tracheal deviation away from affected side (large/tension)
• Tachycardia

Tension Pneumothorax

• Severe respiratory distress
• Tracheal deviation to contralateral side
• Distended neck veins
• Hypotension, tachycardia
• Cardiovascular collapse
• Absent breath sounds on affected side
• Clinical diagnosis - do not delay for CXR

Red Flags

• Haemodynamic compromise (tension pneumothorax)
• Bilateral pneumothorax
• Secondary pneumothorax in severe COPD
• Large pneumothorax (>2cm rim on CXR)
• Increasing breathlessness after initial management
• Pneumothorax on mechanical ventilation

Bedside

• CXR (PA, erect, in inspiration): visible visceral pleural line, absent lung markings peripherally
  • Size estimation: BTS uses distance from chest wall to lung edge at hilar level (>2cm = large)
• Pulse oximetry: SpO₂
• ABG: if secondary pneumothorax or SpO₂ <92%

Bloods

• FBC, U&Es: baseline (especially if intervention planned)
• Coagulation: pre-procedure

Imaging

• CT chest: if diagnostic uncertainty, suspected bullous disease, recurrent pneumothorax, pre-surgical planning
• USS (point-of-care): useful in trauma - absent lung sliding, absent comet tail artefacts, lung point sign

Special Tests

• Post-aspiration/drain CXR: confirm re-expansion
• Alpha-1 antitrypsin level: if bullous emphysema in young patient
• HRCT: assess for underlying cause in secondary pneumothorax

Non-pharmacological

• Conservative observation: primary spontaneous <2cm rim, minimal symptoms - observe 2-4 hours, repeat CXR, discharge with follow-up CXR
• High-flow oxygen 10L/min via non-rebreathe mask accelerates pneumothorax resolution (increases absorption rate 4-fold)
• Analgesia (paracetamol, NSAIDs)

Pharmacological

• Analgesia for procedural pain
• Antibiotics only if secondary infection

Surgical/Interventional

BTS Management Algorithm:

Primary spontaneous pneumothorax:

• <2cm rim + minimal symptoms → conservative + follow-up CXR

Secondary spontaneous pneumothorax:

• <1cm rim + minimal symptoms → observe with oxygen, admit

• 2cm rim or breathless → chest drain (small bore, Seldinger technique)

Chest drain management:

• Connect to underwater seal
• Never clamp a bubbling drain
• Remove when lung re-expanded and no air leak for >24 hours
• Post-removal CXR

Tension pneumothorax:

• Immediate needle decompression: 14G cannula, 2nd ICS MCL (or 4th/5th ICS mid-axillary line)
• Followed by chest drain insertion

Definitive (surgical):

• VATS pleurectomy/pleurodesis: after 2nd ipsilateral, 1st bilateral/contralateral, persistent air leak >5 days, or high-risk occupation (pilot, diver)
• Chemical pleurodesis (talc) via chest drain if surgery not possible

Referral Criteria

• All secondary pneumothoraces: respiratory admission
• Persistent air leak >48 hours: thoracic surgery referral
• Recurrent pneumothorax: surgical referral for VATS
• Bilateral pneumothorax: urgent referral
• Catamenial pneumothorax: gynaecology + respiratory

• Primary spontaneous: recurrence ~30% after first episode; ~50% after second; ~80% after third
• Secondary spontaneous: higher morbidity/mortality; in-hospital mortality ~10% for COPD patients
• VATS pleurectomy reduces recurrence to ~1-5%
• Chemical pleurodesis recurrence: ~10-20%
• Tension pneumothorax: fatal if untreated; excellent outcome if recognised and treated promptly
• Return to normal activities: 2-4 weeks after resolution
• Flying: avoid until confirmed CXR resolution + 1 week
• Diving: permanent contraindication unless bilateral surgical pleurectomy with normal CT

BTS Size Classification

Pneumothorax Management Summary (BTS)

Advice on Discharge

Key Facts

Tension pneumothorax is a medical emergency in which air progressively accumulates under pressure in the pleural space through a one-way valve mechanism, causing mediastinal shift, compression of the contralateral lung and great vessels, and ultimately cardiovascular collapse.

Epidemiology

• Most commonly occurs in trauma (penetrating and blunt chest injury)
• Iatrogenic: positive pressure ventilation, central line insertion, thoracentesis
• Can complicate any pneumothorax if inadequately managed
• Exact incidence difficult to quantify; occurs in ~2-5% of major trauma patients

Aetiology

• Traumatic: penetrating chest injury, blunt chest trauma with rib fractures
• Iatrogenic: positive pressure ventilation (especially high PEEP), central venous catheterisation (subclavian/internal jugular), thoracentesis, lung biopsy
• Spontaneous: complication of simple pneumothorax; underlying bullous emphysema, asthma (air trapping), cystic fibrosis
• Post-procedural: following chest drain removal, tracheostomy

Pathophysiology

• One-way valve: air enters pleural space during inspiration but cannot exit during expiration
• Progressive intrapleural pressure increase
• Ipsilateral lung complete collapse
• Mediastinal shift to contralateral side
• Compression of contralateral lung → bilateral ventilatory failure

• Cardiac arrest (pulseless electrical activity - PEA) if untreated

Clinical Features

• Severe respiratory distress
• Tachycardia
• Hypotension (late sign - indicates imminent arrest)
• Tracheal deviation away from affected side
• Distended neck veins (raised JVP)
• Absent breath sounds on affected side
• Hyperresonant percussion on affected side
• Cyanosis
• Subcutaneous emphysema (may be present)
• Cardiovascular collapse/cardiac arrest (PEA)

Context

• Trauma patient with deteriorating observations
• Ventilated patient with sudden increase in airway pressures and desaturation
• Post-procedure (central line, thoracentesis) with acute deterioration
• Worsening of known pneumothorax

Red Flags

• This entire condition is a red flag - immediate recognition and treatment is essential
• Any combination of: absent breath sounds + hypotension + tracheal deviation
• Cardiac arrest in trauma
• Sudden desaturation and rising airway pressures on ventilator

Bedside

• Clinical diagnosis: do NOT delay treatment for imaging
• Point-of-care USS (if available and experienced): absent lung sliding on affected side; can confirm diagnosis in seconds
• Post-decompression CXR: confirm position and resolution

Bloods

• ABG: post-decompression to assess gas exchange
• FBC, crossmatch: if traumatic (anticipate blood loss)
• Lactate: assess tissue perfusion

Imaging

• CXR: only AFTER decompression - large pneumothorax, mediastinal shift, flattened hemidiaphragm
• CT chest: after stabilisation if underlying pathology suspected

Special Tests

• Not applicable in acute setting - diagnosis is clinical and treatment is immediate

Non-pharmacological

• Immediate recognition: clinical diagnosis
• High-flow oxygen 15L/min
• Call for senior help/arrest team

Pharmacological

• Analgesia post-decompression
• Resuscitation drugs as per ACLS algorithm if cardiac arrest

Surgical/Interventional

Immediate decompression:

1. Needle decompression: insert 14G (orange) IV cannula into 2nd intercostal space, mid-clavicular line (or 4th-5th ICS, mid-axillary line - preferred in obese/muscular patients)

   • Insert perpendicular to chest wall, over superior border of rib (avoid neurovascular bundle)
   • Remove needle, leave cannula in situ
   • Hiss of air confirms tension pneumothorax
   • This is a temporising measure only

2. Chest drain insertion: definitive treatment

   • Insert Seldinger or surgical chest drain into safe triangle (4th-5th ICS, mid-axillary line, anterior border of latissimus dorsi, lateral border of pectoralis major)
   • Connect to underwater seal drain
   • CXR to confirm lung re-expansion

In cardiac arrest:

• Tension pneumothorax is a reversible cause (one of the 4 Ts)
• Perform bilateral needle decompression (or bilateral finger thoracostomies if in theatre/experienced)
• Follow ALS algorithm concurrently

Referral Criteria

• All tension pneumothoraces require hospital admission
• ICU if required mechanical ventilation
• Thoracic surgery if persistent air leak or underlying surgical pathology

• Untreated: near 100% mortality (cardiac arrest from obstructive shock)
• With prompt decompression: excellent survival if no significant underlying injury
• Needle decompression failure rate: ~10-40% (especially in obese patients - insufficient needle length)
• Outcome in trauma depends on associated injuries
• Iatrogenic tension pneumothorax: good prognosis with rapid recognition
• Delayed recognition is the primary cause of preventable death

Needle Decompression Technique

Reversible Causes of Cardiac Arrest (4 Hs and 4 Ts)

Key Facts

Empyema thoracis is the accumulation of pus within the pleural space. It most commonly develops as a complication of bacterial pneumonia (parapneumonic empyema) and requires prompt drainage alongside appropriate antibiotic therapy.

Epidemiology

• ~65,000 parapneumonic effusions per year in the UK; ~5% progress to empyema
• Incidence increasing, particularly in older adults
• Mortality: ~15-20% overall
• More common in males, elderly, immunocompromised, and those with comorbidities (diabetes, alcohol misuse)

Aetiology

Parapneumonic (most common):

• S. pneumoniae, S. milleri group, Staphylococcus aureus
• Anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus)
• Gram-negative bacilli (Klebsiella, E. coli - hospital-acquired)

Other causes:

• Post-surgical (thoracic, oesophageal surgery)
• Trauma
• Oesophageal rupture (Boerhaave syndrome)
• Subdiaphragmatic spread (hepatic abscess, subphrenic abscess)
• Haematogenous spread (rare)

Pathophysiology

Three stages:

1. Exudative stage (1-7 days): sterile parapneumonic effusion; free-flowing fluid; pH >7.2
2. Fibrinopurulent stage (7-14 days): bacterial invasion; fibrin deposition → loculations; pH <7.2, low glucose, high LDH
3. Organising stage (>14 days): fibroblast ingrowth → thick pleural peel (cortex) trapping the lung; requires surgical decortication

Typical Presentation

• Ongoing or recurrent fever despite antibiotics for pneumonia
• Persistent or worsening pleuritic chest pain
• Breathlessness
• Malaise, sweats, weight loss
• Failure to improve on appropriate pneumonia antibiotics

Clinical Signs

• Signs of pleural effusion: stony dull percussion, reduced breath sounds
• Pyrexia (may be swinging/spiking)
• Tachycardia
• Signs of sepsis in severe cases
• Reduced air entry at base

Red Flags

• Persistent fever >48-72 hours despite appropriate antibiotics
• Rapidly re-accumulating effusion
• Loculated effusion on USS/CT
• Sepsis (NEWS2 ≥5)
• Pleural fluid pH <7.2 with pneumonia

Bedside

• Thoracic USS: essential - identifies effusion, loculations, guides aspiration; more sensitive than CXR
• Pulse oximetry: baseline

Bloods

• FBC: leucocytosis
• CRP: markedly elevated
• U&Es: renal function
• Blood cultures x2: before antibiotics
• Albumin: nutritional status
• Lactate: if sepsis

Pleural Fluid Analysis

• Appearance: turbid/purulent (frank pus is diagnostic)
• pH: <7.2 mandates drainage (measure in blood gas analyser)
• Glucose: <2.2 mmol/L supports empyema
• LDH: markedly elevated (>1000 IU/L)
• Protein: exudative (>35 g/L)
• MC&S: identify causative organism (positive in ~60%)
• Gram stain: rapid identification

Imaging

• CXR: pleural effusion, consolidation, air-fluid level (if bronchopleural fistula)
• CT chest (contrast-enhanced): split pleura sign (enhancing visceral and parietal pleura separated by fluid), loculations, guide intervention
• Thoracic USS: loculations, septations, guide drain placement

Special Tests

• CT-guided drain placement: for complex/loculated collections
• Pleural fluid cytology: exclude malignancy if atypical

Non-pharmacological

• Nutritional support (often catabolic)
• Chest physiotherapy
• VTE prophylaxis

Pharmacological

Antibiotics:

• Co-amoxiclav 1.2g IV TDS (aerobic + anaerobic cover) - first-line
• Or piperacillin-tazobactam 4.5g IV TDS if severe/hospital-acquired
• If penicillin allergic: meropenem 1g IV TDS or clindamycin 600mg IV QDS + ciprofloxacin
• Duration: minimum 3 weeks (often 4-6 weeks); guided by clinical/radiological response
• Switch to oral when improving: co-amoxiclav 625mg TDS or clindamycin 300mg QDS

Intrapleural fibrinolytics (MIST2 trial):

• Alteplase (tPA) 10mg + DNase (dornase alfa) 5mg in 30mL saline via chest drain
• Instil BD for 3 days (6 doses total), clamp drain for 1 hour between doses
• Significantly improves drainage, reduces need for surgery, and reduces hospital stay

Surgical/Interventional

• Chest drain insertion: USS-guided, small bore (10-14Fr) Seldinger technique or large bore (24-28Fr) for thick pus
• Daily drain assessment: output, air leak, CXR
• VATS decortication: if failed medical/fibrinolytic management (persistent sepsis, loculated collection, organised empyema)
• Open thoracotomy and decortication: if VATS not possible
• Open window thoracostomy (Eloesser flap): for chronic empyema in patients unfit for decortication

Referral Criteria

• Early thoracic surgery referral if loculated empyema or failed drain/fibrinolytics
• Radiology for CT-guided drainage if complex collection
• Respiratory/infectious diseases for complex cases or unusual organisms

• Overall mortality: ~15-20%
• Higher in elderly, immunocompromised, hospital-acquired, and delayed treatment
• S. aureus and Gram-negative empyema carry higher mortality (~30%)
• Early drainage + antibiotics: good outcomes with complete resolution
• MIST2 fibrinolytic protocol reduces surgical referral from ~44% to ~16%
• VATS decortication success rate: ~80-90%
• Chronic empyema/trapped lung: may require prolonged treatment
• Full functional recovery expected in most patients with appropriate treatment

Empyema Staging (American Thoracic Society)

MIST2 Trial Summary

Pleural Fluid Analysis in Empyema

Key Facts

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. It remains a significant public health problem globally and in the UK, particularly among immigrant communities, the homeless, and immunosuppressed individuals.

Epidemiology

• Global: ~10 million new cases and ~1.5 million deaths per year (leading infectious disease killer)
• UK: ~5,000 cases per year; incidence declining since 2011
• ~60-70% of UK cases are in non-UK born individuals
• London accounts for ~40% of UK cases
• Risk groups: migrants from high-prevalence countries, homeless, IV drug users, HIV-positive, immunosuppressed, prisoners

Aetiology

• Mycobacterium tuberculosis: obligate aerobe, acid-fast bacillus, slow-growing (doubling time ~24 hours)
• Transmitted by airborne droplet nuclei (coughing, sneezing)
• Inhaled bacilli reach alveoli → primary infection
• Granuloma formation (caseating granulomas) contains but may not eliminate infection
• Latent TB: 5-10% lifetime risk of reactivation; higher if immunosuppressed

Pathophysiology

• Primary TB: initial infection, usually lower/middle lobes; Ghon focus (primary lesion) + hilar lymphadenopathy = Ghon complex
• Latent TB: contained by cell-mediated immunity within granulomas; no symptoms; positive IGRA/tuberculin skin test
• Post-primary (reactivation) TB: typically upper lobe cavitating disease; occurs with waning immunity
• Miliary TB: haematogenous dissemination; multiple organ involvement; millet seed pattern on CXR
• Extrapulmonary TB (~40% of UK cases): lymph nodes, pleura, bone/spine (Pott disease), CNS (TB meningitis), genitourinary, peritoneal

Pulmonary TB

• Chronic cough >3 weeks (most common symptom)
• Haemoptysis
• Weight loss, anorexia
• Night sweats
• Low-grade fever
• Malaise, fatigue

Extrapulmonary TB

• Lymph node TB (most common extrapulmonary): painless cervical lymphadenopathy ("cold abscess")
• Pleural TB: unilateral pleural effusion, pleuritic pain
• Bone/joint: Pott disease (spinal TB), chronic joint swelling
• TB meningitis: headache, neck stiffness, cranial nerve palsies, altered consciousness
• Miliary TB: fever, weight loss, hepatosplenomegaly, pancytopenia, millet seed CXR pattern
• Genitourinary: sterile pyuria, frequency, haematuria

Red Flags

• TB meningitis (medical emergency)
• Miliary TB (systemic, multi-organ)
• Massive haemoptysis (Rasmussen aneurysm)
• Spinal TB with neurological deficit
• TB in HIV-positive (atypical presentations)

Bedside

• Sputum samples: 3 early morning sputum for AFB smear and culture
• Pulse oximetry: baseline

Bloods

• FBC: anaemia of chronic disease; pancytopenia in miliary TB
• CRP/ESR: elevated
• U&Es, LFTs: baseline before treatment (hepatotoxic drugs)
• HIV test: all TB patients must be offered HIV testing (NICE)
• HbA1c: diabetes increases TB risk
• Hepatitis B and C serology: if abnormal LFTs

Imaging

• CXR: upper lobe consolidation/cavitation (reactivation), miliary pattern, hilar lymphadenopathy, pleural effusion
• CT chest: better delineation of cavitation, lymphadenopathy, miliary disease
• CT/MRI spine: if spinal TB suspected
• MRI brain: TB meningitis (basal meningeal enhancement, hydrocephalus, tuberculomas)

Special Tests

• Sputum AFB smear (Ziehl-Neelsen or auramine stain): positive in ~50-80% of cavitatory pulmonary TB
• TB culture (Lowenstein-Jensen or BACTEC): gold standard; takes 2-8 weeks; drug sensitivity testing
• GeneXpert MTB/RIF: rapid PCR (results in 2 hours); detects MTB and rifampicin resistance
• IGRA (interferon-gamma release assay): QuantiFERON-TB Gold or T-SPOT.TB; detects latent TB (does not distinguish latent from active)
• Mantoux/tuberculin skin test: intradermal injection of PPD; induration ≥6mm at 48-72 hours positive (less specific than IGRA due to BCG cross-reactivity)
• Bronchoscopy with BAL: if sputum smear-negative but high clinical suspicion
• Tissue biopsy: lymph node, pleural, bone - caseating granulomas on histology; send for culture

Non-pharmacological

• Notification: statutory notification to Public Health England (all cases)
• Contact tracing: screen close contacts (household, workplace) with IGRA and CXR
• Isolation: respiratory isolation until 2 weeks of effective treatment (smear-positive patients)
• DOT (directly observed therapy): for homeless, drug users, prisoners, previous non-adherence
• Nutrition: high-calorie, high-protein diet

Pharmacological

NICE NG33 - Standard treatment for drug-sensitive pulmonary TB:

Intensive phase (2 months):

• Rifampicin 600mg OD (or 450mg if <50kg)
• Isoniazid 300mg OD (+ pyridoxine 10mg OD to prevent peripheral neuropathy)
• Pyrazinamide 2g OD (or 1.5g if <50kg)
• Ethambutol 15mg/kg OD

Continuation phase (4 months):

• Rifampicin + isoniazid (+ pyridoxine)

Total duration: 6 months (9-12 months for CNS TB, bone/joint TB)

Side effects to monitor:

• Rifampicin: orange discolouration of secretions, hepatotoxicity, enzyme inducer (reduces efficacy of OCP, warfarin)
• Isoniazid: peripheral neuropathy (give pyridoxine), hepatotoxicity, SLE-like syndrome
• Pyrazinamide: hepatotoxicity (most hepatotoxic), hyperuricaemia, arthralgia
• Ethambutol: optic neuritis (visual acuity and colour vision testing before and during)

MDR-TB (resistant to rifampicin + isoniazid):

• Specialist management; 18-24 months of second-line agents (fluoroquinolones, aminoglycosides, bedaquiline, linezolid)

Latent TB treatment:

• 3 months isoniazid + rifampicin, OR 6 months isoniazid alone

Surgical/Interventional

• Rarely needed: lobectomy for destroyed lung/aspergilloma in old TB cavity
• Drainage of psoas/spinal abscess
• VP shunt for TB hydrocephalus

Referral Criteria

• All TB cases managed by TB specialist team
• MDR-TB: refer to national MDR-TB service
• Complex extrapulmonary TB: specialist input
• HIV co-infection: joint HIV-TB management
• Contact tracing: public health team

• Drug-sensitive pulmonary TB: cure rate >95% with completed treatment
• MDR-TB: cure rate ~50-80% (improving with newer agents - bedaquiline, pretomanid)
• TB meningitis: mortality ~20-30%; survivors may have neurological sequelae
• Miliary TB: mortality ~15-20% with treatment
• Non-adherence to treatment leads to relapse (~10-20%) and drug resistance
• HIV co-infection increases TB mortality 2-4 fold
• Global: TB responsible for ~1.5 million deaths per year

Anti-TB Drug Side Effects

TB Treatment Duration Summary

Mnemonic: RIPE

Key Facts

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause pulmonary disease mimicking TB, particularly in patients with pre-existing lung disease or immunodeficiency. Unlike TB, NTM infections are not transmitted between humans.

Epidemiology

• Incidence increasing worldwide (~5-10 per 100,000 in the UK)
• More common in elderly, COPD, bronchiectasis, cystic fibrosis, and post-menopausal women
• HIV with CD4 <50: disseminated MAC is an AIDS-defining illness
• Geography: M. kansasii more common in urban areas; M. xenopi in Southern England

Aetiology

• Environmental organisms found in soil, water (including domestic water supplies), and biofilms
• Slow-growing: MAC (M. avium, M. intracellulare), M. kansasii, M. xenopi, M. malmoense
• Rapid-growing: M. abscessus complex, M. chelonae, M. fortuitum
• Not transmitted person-to-person (except possibly M. abscessus in CF patients)

Pathophysiology

• Inhalation of environmental NTM or aspiration from colonised water sources
• Host susceptibility is key - NTM is rarely pathogenic in healthy lungs
• Pre-existing structural lung disease (bronchiectasis, cavities, bullae) provides environment for colonisation
• Impaired mucociliary clearance and immune dysfunction allow progressive infection
• Granuloma formation similar to TB but often non-caseating

Pulmonary NTM Disease

Cavitatory form (fibrocavitatory):

• Predominantly in older men with COPD/smoking history
• Upper lobe cavitation mimicking TB
• Cough, haemoptysis, weight loss

Nodular/bronchiectatic form (Lady Windermere syndrome):

• Predominantly in elderly women without traditional risk factors
• Middle lobe/lingula bronchiectasis with centrilobular nodules
• Chronic cough, often attributed to bronchiectasis

Disseminated NTM (HIV/AIDS)

• CD4 <50 cells/µL
• Fever, weight loss, night sweats
• Hepatosplenomegaly, lymphadenopathy
• Pancytopenia, markedly raised ALP

Other NTM Manifestations

• Skin/soft tissue: M. marinum (swimming pool/fish tank granuloma), M. chelonae, M. abscessus
• Lymphadenitis: typically cervical, children (MAC)

Red Flags

• Positive AFB smear in non-TB patient
• Persistent cavitation despite TB treatment
• Worsening bronchiectasis despite standard management
• M. abscessus in CF patient (may preclude transplant)

Bedside

• Sputum samples: 3 early morning sputum for AFB smear and mycobacterial culture

Bloods

• FBC: anaemia, lymphopenia (HIV)
• LFTs: baseline before treatment
• HIV test: all patients with NTM
• ESR/CRP: inflammatory markers

Imaging

• HRCT: cavitation (fibrocavitatory), middle lobe/lingula bronchiectasis with centrilobular nodules (nodular-bronchiectatic), tree-in-bud pattern
• CXR: may show cavitation, infiltrates, nodules

Special Tests

• Mycobacterial culture (Lowenstein-Jensen/BACTEC): gold standard; species identification; takes 2-8 weeks
• ATS/IDSA diagnostic criteria (all 3 required):
  1. Clinical: compatible symptoms + exclusion of other diagnoses
  2. Radiological: nodular/cavitatory opacities on CXR OR HRCT showing bronchiectasis + nodules
  3. Microbiological: ≥2 positive sputum cultures, OR 1 positive BAL culture, OR biopsy with granulomas + positive culture
• Drug susceptibility testing: essential, especially for M. abscessus (clarithromycin resistance)
• Bronchoscopy with BAL: if unable to produce sputum
• CT-guided biopsy: if tissue diagnosis needed

Non-pharmacological

• Specialist decision to treat: not all NTM isolates require treatment; weigh risks vs benefits
• Address underlying conditions (optimise bronchiectasis, COPD, CF management)
• Airway clearance techniques
• Nutritional support

Pharmacological

BTS Guidelines - species-specific:

MAC (M. avium complex):

• Rifampicin 600mg OD + ethambutol 15mg/kg OD + clarithromycin 500mg BD (or azithromycin 250mg OD)
• Treat for 12 months after sputum culture conversion
• Severe/cavitatory: consider adding amikacin IV/nebulised for initial 1-3 months

M. kansasii:

• Rifampicin 600mg OD + ethambutol 15mg/kg OD + isoniazid 300mg OD (+ pyridoxine)
• Duration: 12 months after culture conversion

M. abscessus complex:

• Most challenging to treat; often requires IV induction + oral maintenance
• IV induction (~1-3 months): amikacin 15mg/kg OD + tigecycline 50mg BD + imipenem 1g BD (or cefoxitin)
• Oral maintenance: clarithromycin 500mg BD (if susceptible) + 1-2 additional agents (clofazimine, linezolid)
• Duration: prolonged (12-24 months); often incurable

M. malmoense:

• Rifampicin + ethambutol + clarithromycin for ≥12 months after conversion

M. xenopi:

• Rifampicin + ethambutol + clarithromycin ± isoniazid or fluoroquinolone for ≥12 months after conversion

Surgical/Interventional

• Surgical resection (lobectomy): considered for localised disease, particularly M. abscessus, if medical therapy failing
• Adjunctive to medical therapy rather than standalone

Referral Criteria

• All suspected NTM disease should be managed by or in consultation with a specialist in NTM/mycobacterial disease
• CF patients with NTM: joint respiratory/CF/ID management
• Pre-transplant M. abscessus: specialist transplant centre assessment

• MAC pulmonary disease: culture conversion achieved in ~50-70% with appropriate therapy
• M. kansasii: best outcomes; cure rate ~90% with rifampicin-based regimen
• M. abscessus: worst prognosis; cure rates <50%; often chronic/suppressive therapy
• Cavitatory disease has worse outcomes than nodular-bronchiectatic
• Relapse rate: ~10-20% after treatment completion
• Disseminated MAC in HIV: excellent response to ART + antimycobacterial therapy
• NTM pulmonary disease associated with increased all-cause mortality vs matched controls

NTM Treatment Summary

ATS/IDSA Diagnostic Criteria

Key Facts

Bronchiectasis is characterised by permanent dilatation and thickening of the bronchial walls, resulting from a vicious cycle of infection, inflammation, and impaired mucociliary clearance. It is increasingly recognised as a common and debilitating chronic respiratory disease.

Epidemiology

• Prevalence: ~500-600 per 100,000 in the UK (increasing due to improved diagnosis with HRCT)
• More common in women and increasing with age
• Peak prevalence >70 years
• Significant burden on healthcare: frequent GP visits, antibiotic courses, hospital admissions

Aetiology

• Idiopathic (~50%): no identifiable cause after investigation
• Post-infective: childhood pneumonia, TB, whooping cough, measles, aspergillus
• Immunodeficiency: common variable immunodeficiency (CVID), IgA deficiency, HIV
• Cystic fibrosis: most common inherited cause
• ABPA: allergic bronchopulmonary aspergillosis (central bronchiectasis)
• Primary ciliary dyskinesia: Kartagener syndrome (situs inversus + bronchiectasis + sinusitis)
• Connective tissue disease: RA, Sjögren syndrome
• Inflammatory bowel disease: UC > Crohn
• Yellow nail syndrome: yellow nails + lymphoedema + pleural effusion + bronchiectasis
• Alpha-1 antitrypsin deficiency

Pathophysiology

Vicious cycle hypothesis (Cole):

• Initial insult (infection/inflammation) damages airways
• Impaired mucociliary clearance → mucus retention
• Bacterial colonisation and biofilm formation
• Chronic neutrophilic inflammation → further structural damage
• Progressive bronchial dilatation, destruction, and fibrosis
• Bronchial artery hypertrophy (risk of haemoptysis)

Typical Presentation

• Chronic productive cough with copious mucopurulent sputum (often daily)
• Recurrent chest infections (≥3/year)
• Breathlessness (progressive)
• Haemoptysis (mild to massive)
• Fatigue, reduced exercise tolerance

Clinical Signs

• Coarse inspiratory crackles (bilateral, lower zones often)
• Wheeze
• Finger clubbing (~3%)
• Sputum pot at bedside

Exacerbation Features

• Increased sputum volume and purulence
• Worsening breathlessness
• New or worsening cough
• Fever
• Deterioration in lung function

Red Flags

• Massive haemoptysis (bronchial artery erosion)
• Rapid decline in lung function
• New Pseudomonas isolation (associated with worse outcomes)
• Recurrent exacerbations (≥3/year)
• Progressive respiratory failure

Bedside

• Sputum MC&S: identify colonising organisms and guide antibiotic therapy
• Pulse oximetry: baseline

Bloods

• FBC: raised WCC (infection), eosinophilia (ABPA)
• CRP: elevated during exacerbations
• Immunoglobulins (IgG, IgA, IgM, IgE): screen for immunodeficiency
• Total IgE + Aspergillus-specific IgE and IgG: ABPA screen
• Alpha-1 antitrypsin level: if not previously tested
• Autoimmune screen: RF, anti-CCP, ANA (if rheumatological features)
• HIV test: if risk factors

Imaging

• HRCT chest: gold standard - bronchial dilatation (internal diameter > accompanying artery = signet ring sign), bronchial wall thickening, mucus plugging, tree-in-bud pattern, varicose/cystic changes
• CXR: tramlines, ring shadows; less sensitive than CT

Special Tests

• Spirometry: obstructive pattern (FEV₁/FVC <0.7); mixed in advanced disease
• Sputum mycobacterial culture: NTM screen
• Sweat test / CFTR genotyping: if CF suspected (<40 years, bilateral upper lobe, nasal polyps, male infertility)
• Nasal NO / ciliary biopsy: primary ciliary dyskinesia screen
• Bronchoscopy: if focal bronchiectasis (exclude foreign body, obstruction)
• CT sinuses: if PCD or ABPA suspected

Non-pharmacological

• Airway clearance techniques: physiotherapy-led; active cycle of breathing technique (ACBT), oscillatory PEP devices (Acapella, Flutter), postural drainage
• Pulmonary rehabilitation: for MRC dyspnoea ≥3 or functional limitation
• Annual influenza and pneumococcal vaccination
• Patient education and self-management plan

Pharmacological

Acute exacerbations:

• Empirical antibiotics guided by previous sputum cultures (14 days)
• First-line: amoxicillin 500mg TDS (or co-amoxiclav 625mg TDS if recurrent)
• Pseudomonas: ciprofloxacin 500-750mg BD PO or IV anti-pseudomonal (piperacillin-tazobactam)

Long-term management (BTS guideline):

• Mucolytics: carbocisteine 750mg TDS (or hypertonic saline nebulised 6-7%) to aid sputum clearance
• Long-term macrolide prophylaxis: azithromycin 250mg 3×/week or 500mg 3×/week (if ≥3 exacerbations/year)
  • Check baseline ECG (QTc prolongation risk), LFTs, NTM sputum culture
  • EMBRACE, BAT, BLESS trials: reduced exacerbation frequency by 40-50%
• Pseudomonas eradication: first isolation - ciprofloxacin 500-750mg BD for 2 weeks ± nebulised colistin/gentamicin for 3 months
• Long-term nebulised antibiotics: colistin 1-2 MU BD or gentamicin 80mg BD (chronic Pseudomonas with frequent exacerbations)
• Inhaled bronchodilators: if airflow obstruction

Surgical/Interventional

• Bronchial artery embolisation: for massive/recurrent haemoptysis
• Surgical resection (lobectomy): localised disease with recurrent severe infections, refractory to medical therapy
• Lung transplantation: end-stage bilateral bronchiectasis (particularly CF-related)

Referral Criteria

• Respiratory specialist referral for all new diagnoses of bronchiectasis
• Specialist input for Pseudomonas colonisation, frequent exacerbations, or diagnostic uncertainty
• Immunology referral if immunodeficiency confirmed
• Thoracic surgery for consideration of resection in localised disease

• Variable depending on aetiology, microbiology, and exacerbation frequency
• Pseudomonas colonisation: 3-fold increased mortality and accelerated lung function decline
• Frequent exacerbations (≥3/year): associated with worse QoL and survival
• BSI (Bronchiectasis Severity Index) predicts 4-year mortality: mild 5.3%, moderate 9.9%, severe 29.3%
• Long-term macrolide prophylaxis reduces exacerbation frequency by 40-50%
• CF bronchiectasis: median survival now ~50+ years with modern therapies
• Non-CF bronchiectasis: life expectancy generally good with appropriate management

Bronchiectasis Severity Index (BSI)

Aetiology Investigation Checklist

Key Facts

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians, caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. It results in defective chloride and bicarbonate transport, leading to thick, viscid secretions affecting multiple organs.

Epidemiology

• Incidence: ~1 in 2,500 live births in the UK (~800 new diagnoses/year)
• Prevalence: ~10,800 people living with CF in the UK
• Carrier frequency: ~1 in 25
• Median predicted survival: >50 years (improving dramatically with CFTR modulators)
• Equal sex distribution

Aetiology

• Mutations in CFTR gene (chromosome 7q31)

• 2,000 known mutations; ΔF508 accounts for ~70% of UK alleles

• CFTR mutations classified I-VI based on mechanism of protein defect
• ΔF508 is a class II mutation (defective protein processing)

Pathophysiology

• CFTR is a chloride and bicarbonate channel on epithelial cell surfaces
• Defective CFTR → reduced chloride secretion and increased sodium/water absorption
• Thick, dehydrated mucus in airways, pancreatic ducts, bile ducts, intestine, and vas deferens