General Medicine

DEFINITION & DIAGNOSIS

COPD is a preventable, treatable chronic respiratory disease with persistent airflow limitation (post-BD FEV1/FVC < 0.70) caused by airway and alveolar abnormalities from prolonged noxious particle exposure.

NON-PHARMACOLOGICAL (Always First)

• Smoking cessation — single most effective intervention. Slows FEV1 decline from 50–60 to 25–30 mL/year. Offer NRT (nicotine patch/gum) or Varenicline 1 mg BD.
• Pulmonary rehabilitation — supervised exercise training + education; reduces dyspnoea, improves quality of life, decreases hospital admissions.
• Annual influenza vaccine + pneumococcal vaccine (PCV13 + PPSV23) — prevents exacerbations.

PHARMACOLOGICAL MANAGEMENT — GOLD ABE Groups

▶ Roflumilast 500 μg OD (PDE4 inhibitor) — add-on for FEV1 < 50% + chronic bronchitis phenotype + ≥ 2 exacerbations/year despite triple therapy.

LONG-TERM OXYGEN THERAPY (LTOT)

• Indications: PaO2 ≤ 55 mmHg (SpO2 ≤ 88%) at rest on room air; OR PaO2 56–60 mmHg with cor pulmonale or polycythaemia.
• Must use ≥ 15 hours/day including during sleep and exercise. With smoking cessation, LTOT is one of only two interventions proven to improve survival in COPD.

MANAGEMENT OF AECOPD

• Controlled O2: Venturi mask 28–35%; target SpO2 88–92%.
• Bronchodilators: Nebulised salbutamol 2.5–5 mg + ipratropium 0.5 mg q20–30 min.
• Steroids: Prednisolone 30–40 mg OD × 5 days oral.
• Antibiotics (purulent sputum/CRP > 20): Amoxicillin 500 mg TDS × 5 days; or doxycycline/azithromycin.
• NIV/BiPAP: If pH < 7.35 + PaCO2 > 45 mmHg. Settings: IPAP 12–20 / EPAP 4–8 cmH2O.

DEFINITION — Berlin Criteria 2012

ARDS = acute-onset (< 1 week of known insult) hypoxic respiratory failure with bilateral opacities on CXR/CT NOT fully explained by effusion/collapse/cardiac failure, with PaO2/FiO2 ≤ 300 mmHg on PEEP ≥ 5 cmH2O.

CAUSES

• Sepsis (#1 overall cause, ~40%) — gram-negative organisms most common.
• Direct: Pneumonia, aspiration, pulmonary contusion, near-drowning, inhalation injury.
• Indirect: Pancreatitis, massive transfusion (TRALI), burns, drug overdose (heroin, amiodarone, aspirin).

PATHOGENESIS

Insult → alveolar-capillary barrier damage → neutrophil/macrophage activation → proteases + ROS → protein-rich exudate floods alveoli → hyaline membrane formation → severe V/Q mismatch + intrapulmonary shunting → refractory hypoxia NOT corrected by supplemental O2 alone (shunted blood bypasses ventilated alveoli).

INVESTIGATIONS

• ABG — severe hypoxia; PaO2/FiO2 ratio determines severity; initial hypocapnia.
• CXR/CT — bilateral patchy infiltrates / ground-glass opacities; no cardiomegaly/effusions.
• BNP/NT-proBNP — normal/mildly elevated (excludes cardiogenic pulmonary oedema as primary cause).
• Echo — normal LV function; excludes cardiogenic cause; look for underlying aetiology.

MANAGEMENT

• Treat the underlying cause — antibiotics for sepsis; drain abscesses; stop offending drugs.
• Lung-Protective Ventilation (ARDSNet) :

• Tidal volume 6 mL/kg IBW (most critical setting; prevents volutrauma).
• Plateau pressure < 30 cmH2O — prevents barotrauma.
• PEEP 5–20 cmH2O — recruits collapsed alveoli.
• FiO2 titrated to SpO2 88–95%.

• Prone Positioning — ≥ 16 hrs/day (PROSEVA trial) — face down; redistributes ventilation; 16% mortality reduction; start when PaO2/FiO2 < 150 mmHg.
• Dexamethasone 6 mg IV OD × 10 days (RECOVERY trial) — anti-inflammatory.
• Conservative fluid strategy — avoid fluid overload after initial resuscitation.
• Neuromuscular blockade (cisatracurium infusion) — for ventilator dyssynchrony in severe ARDS.

DEFINITIONS

• Pneumothorax: Air in the pleural space.
• Hydropneumothorax: BOTH air AND fluid in the pleural space.
• Haemopneumothorax: Air + blood (trauma). Pyopneumothorax: Air + pus (TB cavity rupture).

CLINICAL SIGNS OF PNEUMOTHORAX

• Sudden sharp ipsilateral chest pain + dyspnoea (abrupt onset).
• Tracheal deviation AWAY from affected side (tension PTX) .
• Hyperresonance on percussion — air-filled pleural space (contrast with effusion = stony dull).
• Absent/reduced breath sounds on affected side.
• Absent tactile vocal fremitus on affected side.
• Reduced chest wall movement on affected side.

ADDITIONAL SIGNS IN HYDROPNEUMOTHORAX

• Succussion splash (PATHOGNOMONIC) — splashing sound heard when patient is shaken; occurs because both fluid AND air are present, causing fluid to slosh when shaken. Detected by placing stethoscope over lateral chest while shaking patient.
• CXR: Air-fluid level within pleural space — dark air above, fluid opacity below.
• Both stony-dullness (over fluid) and hyperresonance (over air) present in different areas.

TENSION PNEUMOTHORAX — EMERGENCY

One-way valve mechanism → progressive air accumulation → mediastinal shift AWAY → compresses heart + great vessels → obstructive shock → cardiac arrest. DO NOT wait for CXR .

MANAGEMENT

• Small PSP (< 2 cm, asymptomatic): Observation + high-flow O2 (accelerates reabsorption 4×).
• Large (≥ 2 cm) or symptomatic: Needle aspiration first (2nd ICS, MCL); ICD if aspiration fails.
• SSP (any size): Always ICD — less reserve, more dangerous even if small.
• Recurrent PSP: Surgical pleurodesis (VATS).

INTRODUCTION

Acute dyspnoea (sudden onset breathlessness) is a medical emergency requiring rapid systematic assessment. Causes span respiratory, cardiac, and systemic pathology.

RESPIRATORY CAUSES

• Tension pneumothorax — most acute; immediate life threat; tracheal deviation.
• Pulmonary embolism — sudden onset with pleuritic pain; normal CXR; ↑ A-a gradient.
• Acute severe asthma / Status asthmaticus — wheeze; PEFR < 33% best.
• AECOPD — in known COPD patient; purulent sputum; ↑ PaCO2.
• Pneumonia — fever, cough, consolidation on CXR.
• ARDS — bilateral infiltrates; severe hypoxia; PaO2/FiO2 < 300 mmHg.
• Large pleural effusion; upper airway obstruction (inhaled FB, anaphylaxis, croup).

CARDIAC CAUSES

• Acute left ventricular failure / Pulmonary oedema — #1 cardiac cause; orthopnoea; PND; pink frothy sputum; basal creps; ↑ BNP.
• Acute MI / ACS — chest pain radiation; ECG changes; ↑ troponin.
• Cardiac tamponade — Beck's triad: hypotension + ↑ JVP + muffled heart sounds.
• Arrhythmias — AF with rapid ventricular rate; SVT.

OTHER SYSTEMIC CAUSES

• Anaphylaxis — allergen exposure; urticaria; stridor; hypotension.
• Severe anaemia — pallor; tachycardia; high-output dyspnoea; Hb < 7 g/dL.
• Metabolic acidosis (DKA, uraemia, lactic acidosis) — Kussmaul breathing (deep, sighing respirations compensating for acidosis).
• Anxiety / Panic attack — hyperventilation; perioral/fingertip tingling; normal SpO2.

APPROACH TO ACUTE DYSPNOEA

• BNP/NT-proBNP — distinguishes cardiac (↑ BNP) from respiratory cause.
• POCUS (bedside echo) — most rapid diagnostic tool; assess LV function, RV strain (PE), pneumothorax (absent lung sliding), effusion.

DEFINITION

Acute Severe Asthma / Status Asthmaticus = severe acute asthma NOT responding to initial bronchodilator therapy (> 3 SABA doses in 1 hour), requiring hospitalisation and urgent escalation.

ASSESSMENT OF ACUTE SEVERITY

STEP-WISE MANAGEMENT — MNEMONIC

INDICATIONS FOR INTUBATION / ICU

• Silent chest — most ominous sign; no wheeze despite severe dyspnoea.
• Normal or rising PaCO2 — severe asthmatics should HYPERVENTILATE → low CO2. Normalisation = tiring.
• SpO2 < 88% despite high-flow O2; exhaustion; GCS < 15.
• Near-fatal asthma or previous intubation history.

ABG INTERPRETATION IN ASTHMA

• Mild: PaO2 normal, PaCO2 low (hyperventilation), respiratory alkalosis.
• Moderate: PaO2 slightly low, PaCO2 still low.
• Severe: PaO2 < 60 mmHg, PaCO2 still normal or low.
• Life-threatening: PaO2 < 60 mmHg, PaCO2 > 45 mmHg — exhaustion; impending arrest.

CLASSIFICATION OF PNEUMONIA — 3 Systems

System 1 — By Acquisition Site:

• CAP (Community-Acquired) — outside hospital or < 48 hrs of admission.
• HAP (Hospital-Acquired / Nosocomial) — onset ≥ 48 hrs after admission. GNB dominate (Pseudomonas, Klebsiella, Acinetobacter).
• VAP (Ventilator-Associated) — HAP occurring > 48 hrs after endotracheal intubation.
• HCAP (Healthcare-Associated) — nursing home, dialysis, recent hospitalisation.

System 2 — By Aetiology:

• Bacterial (Typical): S. pneumoniae (#1 CAP); H. influenzae; Klebsiella (alcoholics).
• Bacterial (Atypical): Mycoplasma (young adults); Legionella (hyponatraemia); Chlamydophila.
• Viral: Influenza (commonest viral CAP); SARS-CoV-2; Varicella.
• Fungal: PCP (HIV with CD4 < 200); Aspergillus (immunocompromised).
• Aspiration: Anaerobes (alcoholics, epileptics, stroke); right lower lobe.

System 3 — By Radiological Pattern:

• Lobar — typical (S. pneumoniae): entire lobe consolidated; rusty sputum.
• Bronchopneumonia — patchy bilateral; Staphylococcal, H. influenzae.
• Interstitial — atypical pattern (Mycoplasma, Legionella): bilateral perihilar haze.

CURB-65 SCORE

ANTIBIOTIC SELECTION

▶ CURB 0–1 (outpatient typical): Amoxicillin 500 mg–1 g TDS × 5 days.

▶ CURB 0–1 (atypical): Doxycycline 100 mg BD × 7 days OR Azithromycin 500 mg OD × 5 days.

▶ CURB 2 (hospitalised): Ceftriaxone 1 g IV OD + Azithromycin 500 mg IV OD.

▶ CURB 3–5 (severe/ICU): Ceftriaxone 2 g IV OD + Azithromycin 500 mg IV OD (or levofloxacin). Antipseudomonal cover if risk factors.

DEFINITION

Hypereosinophilic syndrome (HES) is persistent peripheral blood eosinophilia > 1500 cells/μL for > 6 months with eosinophil-mediated end-organ damage, in the absence of secondary causes.

SECONDARY CAUSES (Exclude First)

• Parasitic infections — Toxocara, Ascaris, Strongyloides, filariasis, trichinosis (most common worldwide).
• Drugs: penicillin, phenytoin, allopurinol, NSAIDs.
• Atopic diseases: asthma, eczema, allergic rhinitis.
• Malignancy: Hodgkin's lymphoma, T-cell lymphoma, adenocarcinoma (paraneoplastic).
• Autoimmune: IBD, vasculitis, EGPA (formerly Churg-Strauss).

CLINICAL FEATURES — ORGAN INVOLVEMENT

INVESTIGATIONS

• CBC: Absolute eosinophil count > 1500/μL (may be > 10,000 in severe).
• Bone marrow biopsy — eosinophil precursor infiltration; exclude haematological malignancy.
• FISH for FIP1L1-PDGFRA fusion — myeloproliferative variant; imatinib-responsive.
• Troponin/BNP + Echo — assess cardiac involvement; Löffler's endocarditis.
• Serum tryptase — elevated in systemic mastocytosis (differential diagnosis).

TREATMENT

▶ Prednisolone 40–60 mg/day — first-line for ALL variants. Reduces eosinophils rapidly.

▶ Imatinib 100–400 mg/day — for FIP1L1-PDGFRA fusion-positive variant; dramatically effective. First-line in myeloproliferative variant.

▶ Mepolizumab (anti-IL-5 biologic) — for steroid-dependent HES without PDGFRA mutation.

▶ Hydroxyurea — for cytoreduction in refractory cases.

INTRODUCTION

PFTs objectively measure lung volumes and airflow to classify respiratory disease as obstructive or restrictive and monitor progression/treatment response. Spirometry is the cornerstone.

KEY PARAMETERS AND NORMAL VALUES

OBSTRUCTIVE vs RESTRICTIVE — COMPARISON

SPECIAL TESTS

• Bronchodilator reversibility test — administer SABA → repeat spirometry after 15–20 min. FEV1 ↑ ≥ 12% AND ≥ 200 mL = reversible obstruction (asthma). If < 12% improvement = fixed obstruction (COPD).
• Bronchoprovocation test (methacholine challenge) — used when spirometry is normal but asthma suspected. PC20 < 8 mg/mL = positive (hyperresponsiveness).
• Flow-volume loop — obstructive: scooped-out expiratory curve (concave). Fixed upper airway obstruction: flattening of both inspiratory and expiratory limbs.
• 6-Minute Walk Test — functional capacity assessment; useful in fibrosis, pulmonary hypertension.

AETIOLOGY

Caused by *Mycobacterium tuberculosis* — aerobic, acid-fast bacillus (AFB) , slow-growing (doubling time 15–20 hrs), obligate intracellular pathogen. India = 28% of global burden (WHO 2023). Transmission by droplet nuclei (1–5 μm).

PATHOGENESIS — GHON COMPLEX

• Inhaled bacilli → alveolar macrophages → phagosome-lysosome fusion blocked (via ESAT-6) → intracellular multiplication.
• At 2–8 weeks: CD4+ Th1 → IFN-γ → epithelioid + Langerhans giant cells → caseating granuloma (tubercle).
• Primary granuloma = Ghon focus; + hilar nodes = Ghon complex ; calcified = Ranke complex.
• In immunocompromised: caseous necrosis liquefies → CAVITY (hallmark of post-primary TB).

CLINICAL FEATURES

DIAGNOSIS — NTEP 2022

• CBNAAT (GeneXpert MTB/RIF) — FIRST test recommended. Detects MTB DNA + rifampicin resistance in 2 hours. Sensitivity ~89%.
• ZN Smear Microscopy — AFB = red rods on blue background. Sensitivity 40–60%. Needs ≥ 10,000 bacilli/mL.
• Culture (Gold Standard) — LJ medium (6–8 weeks); MGIT liquid culture (10–14 days).
• TST (Mantoux) — intradermal PPD; Type IV hypersensitivity; read induration at 48–72 hrs.
• CXR — Ghon focus (primary); upper lobe consolidation + cavitation (post-primary) ; miliary (millet-seed) pattern.

TREATMENT

• New DS-TB: 2 months HRZE (Intensive) + 4 months HR (Continuation) = 6 months total .
• All under NTEP DOT (Directly Observed Therapy) — daily fixed-dose combination tablets.
• Key side effects: H → peripheral neuropathy (give B6); R → orange urine; Z → hyperuricaemia; E → optic neuritis .

PRINCIPLES OF ANTI-TB THERAPY

• Combination therapy — prevents resistance selection; each drug targets different mechanism.
• Fixed-dose combinations (FDC) — improves compliance; prevents selective drug intake.
• Directly Observed Therapy (DOT) — healthcare worker witnesses each dose; cornerstone of NTEP.
• Adequate duration — short treatment → relapse + resistance.

TREATMENT REGIMENS — NTEP 2022

DRUG SIDE EFFECTS — FREQUENTLY ASKED

MDR-TB

• MDR-TB = resistance to BOTH isoniazid AND rifampicin (minimum); diagnosed by CBNAAT/DST.
• Pre-XDR-TB (WHO 2021) = MDR-TB + any fluoroquinolone resistance.
• XDR-TB = MDR-TB + fluoroquinolone + bedaquiline or linezolid resistance.

▶ Bedaquiline 400 mg OD × 2 weeks, then 200 mg 3×/week × 22 weeks — blocks ATP synthase; QTc monitoring monthly.

▶ Pretomanid 200 mg OD × 26 weeks — kills replicating + non-replicating MTB.

▶ Linezolid 600 mg OD × 26 weeks — protein synthesis inhibitor; monitor optic neuropathy (monthly visual acuity) and myelosuppression (monthly CBC).

DEFINITION

Respiratory failure = failure of the respiratory system to maintain adequate gas exchange: PaO2 < 60 mmHg AND/OR PaCO2 > 50 mmHg on room air at sea level.

TYPE I vs TYPE II — KEY COMPARISON

CAUSES — SYSTEMATIC

Type I (Hypoxaemic) — Five mechanisms:

• V/Q mismatch — commonest: pneumonia (↓ V, normal Q), COPD, PE (normal V, ↓ Q).
• Shunt — blood bypasses ventilated lung (consolidation, atelectasis, ARDS, pulmonary AVM).
• Diffusion defect — pulmonary fibrosis, emphysema.
• Low FiO2 — high altitude.
• Low mixed venous O2 — severe anaemia, circulatory shock.

Type II (Hypercapnic) — Four mechanisms:

• Reduced central drive — opioids, sedatives, brainstem injury.
• Chest wall/Diaphragm failure — kyphoscoliosis, flail chest.
• Neuromuscular disease — GBS , MND, myasthenia gravis, polio.
• COPD — increased WOB + gas trapping + ↓ chemoreceptor response.

MANAGEMENT

• Secure airway — maintain patent airway; position (semi-recumbent); suction.
• Oxygen therapy:

• Type I: High-flow O2; HFNC; target SpO2 94–98%.
• Type II: Controlled O2 via Venturi mask 24–35%; target SpO2 88–92%. Never uncontrolled high-flow O2 in COPD.

• Treat the underlying cause — antibiotics (pneumonia), bronchodilators (COPD/asthma), anticoagulation (PE), diuretics (LVF).
• NIV/BiPAP — first-line for Type II (COPD exacerbation with pH < 7.35 + ↑ PaCO2). IPAP 12–20 / EPAP 4–8 cmH2O.
• Invasive Mechanical Ventilation — NIV failure, contraindications, or life-threatening.

DEFINITION

Pleural effusion = abnormal accumulation of fluid in the pleural space (normal 10–20 mL). Detectable on CXR when > 300 mL (blunts costophrenic angle); USS detects ≥ 50 mL.

TRANSUDATE vs EXUDATE — Classification

LIGHT'S CRITERIA — Identify EXUDATE

CLINICAL SIGNS

• Dyspnoea (proportional to size); reduced chest expansion ipsilaterally.
• STONY DULL percussion — most specific sign of pleural effusion (flat, dense dullness).
• Absent breath sounds + absent vocal resonance over effusion.
• Tracheal deviation AWAY from side of large effusion (> 1 litre).
• Bronchial breathing ABOVE effusion — lung compressed above fluid line.

INVESTIGATIONS

• CXR PA: Blunted costophrenic angle (> 300 mL); meniscus sign (concave upper border); homogeneous opacity.
• USS — most sensitive (≥ 50 mL); guides diagnostic thoracocentesis.
• Diagnostic Thoracocentesis: Protein, LDH, glucose, pH, Gram stain, culture, cytology, ADA (TB), triglycerides (chylothorax).
• CT chest — identifies septations, loculations, underlying malignancy, lymph nodes.

MANAGEMENT

• Treat the underlying cause — diuretics for CCF; anti-TB for TB; oncology for malignancy.
• Therapeutic thoracocentesis — if large/symptomatic; drain ≤ 1.5 L per session to prevent re-expansion pulmonary oedema.

▶ Empyema (pH < 7.2 OR glucose < 2.2 mmol/L OR frank pus): Intercostal drain (ICD) + IV antibiotics.

▶ Recurrent malignant effusion: Talc pleurodesis (instill 4 g talc slurry via ICD) — chemical pleurodesis prevents re-accumulation.

• Surgical options — VATS (video-assisted thoracoscopic surgery) pleurodesis for failed chemical pleurodesis.

OVERVIEW

PE = obstruction of pulmonary artery/ies by thrombus (usually from DVT of lower limbs). Sudden dyspnoea (80%) and tachycardia (90%) are the most common symptom and sign respectively.

INVESTIGATIONS

DIAGNOSTIC PATHWAY

• Haemodynamically STABLE: Calculate Wells score → if ≤ 4: D-dimer (if negative, PE excluded; if positive, CTPA) → if > 4: CTPA directly.
• Haemodynamically UNSTABLE: Cannot go to CT → bedside echo → if RV strain → empirical thrombolysis → CTPA after stabilisation.

MANAGEMENT

▶ UFH IV — preferred if thrombolysis planned or severe renal failure. Loading 80 IU/kg → maintenance 18 IU/kg/hr; target aPTT 60–100 sec.

HYPERSENSITIVITY PNEUMONITIS (HP) — Extrinsic Allergic Alveolitis

HP = immune-mediated interstitial lung disease from repeated inhalation of organic antigens. Type III (immune complex) + Type IV (CMI) hypersensitivity .

Clinical Forms:

• Acute HP: Fever, chills, myalgia, dyspnoea, cough 4–8 hours after antigen exposure . Resolves 24–72 hrs after removal.
• Subacute HP: Insidious cough and dyspnoea; bilateral crackles.
• Chronic HP: Progressive fibrosis — eventual respiratory failure.

ABPA — Allergic Bronchopulmonary Aspergillosis

ABPA = hypersensitivity to *Aspergillus fumigatus* colonising airways in patients with asthma or cystic fibrosis .

Diagnosis — 3 Major Criteria (all required):

• Total serum IgE > 1000 IU/mL (dramatically elevated).
• Positive Aspergillus-specific IgE (skin prick test or serum IgE to Af).
• Central bronchiectasis on HRCT (proximal, central — unlike distal bronchiectasis in other causes).

Other features: Peripheral eosinophilia; expectoration of brown mucus plugs ; serum precipitins (IgG) against Aspergillus; positive IgG to Aspergillus; fleeting infiltrates on CXR.

▶ Prednisolone 0.5 mg/kg/day × 2 weeks, taper over several months — reduces inflammation; essential for acute flares.

▶ Itraconazole 200 mg BD × 16 weeks — reduces Aspergillus antigen load; steroid-sparing.

▶ Omalizumab (anti-IgE) — for severe steroid-dependent ABPA; reduces exacerbations.

DEFINITION & PATHOGENESIS

Bronchiectasis = permanent, irreversible abnormal dilation of bronchi/bronchioles due to destruction of the bronchial wall (cartilage, muscle, elastic tissue). Vicious cycle: infection → inflammation → destruction → re-infection .

CAUSES

• Post-infective — TB (#1 in India), measles, pertussis (whooping cough), severe pneumonia.
• Cystic Fibrosis (#1 in Western countries) — CFTR mutation → thick secretions → obstruction → infection → bronchiectasis.
• Immunodeficiency — hypogammaglobulinaemia, HIV; recurrent infections.
• ABPA — central bronchiectasis; Aspergillus hypersensitivity.
• Kartagener's Syndrome — Primary ciliary dyskinesia: Situs inversus + Bronchiectasis + Sinusitis (immotile cilia → poor mucociliary clearance → recurrent infections).
• Foreign body / Endobronchial obstruction (carcinoma) — post-obstructive bronchiectasis.

CLINICAL FEATURES

• Copious purulent sputum — especially in mornings (postural drainage while lying overnight); 3-layer sputum (frothy top + mucopurulent middle + sediment bottom on standing).
• Recurrent respiratory infections; haemoptysis (erosion of bronchial arteries — can be massive).
• Coarse crackles at lung bases (bilateral); clubbing; wheeze.
• HRCT: Signet ring sign — dilated bronchus (ring) appears larger than adjacent pulmonary artery (stone) — diagnostic.

MANAGEMENT

Non-pharmacological:

• Chest physiotherapy + postural drainage — cornerstone of management. Twice daily minimum. The single most important long-term management step.
• Active Cycle of Breathing Technique (ACBT) — controlled breathing + huffing; mobilises secretions.
• Mucolytics — nebulised hypertonic saline (7%) loosens secretions.

Pharmacological:

▶ Acute exacerbation: Amoxicillin 500 mg TDS × 14 days; OR Ciprofloxacin 500 mg BD × 14 days (if Pseudomonas risk or previous isolation).

▶ Prophylactic azithromycin 250–500 mg 3×/week — for ≥ 3 exacerbations/year; reduces frequency. Monitor for QTc and macrolide resistance.

▶ Nebulised colistin or gentamicin — for chronic Pseudomonas infection.

Surgical:

• Lobectomy — for localised, severe, refractory bronchiectasis; massive haemoptysis uncontrolled by BAE.
• Bronchial artery embolisation (BAE) — first choice for massive haemoptysis; interventional radiology.

AETIOLOGY & EPIDEMIOLOGY

MERS-CoV is a beta-coronavirus causing severe respiratory illness. First identified in Saudi Arabia, 2012 . Zoonotic reservoir = dromedary camels (#1 animal reservoir). Person-to-person transmission occurs predominantly in healthcare settings (nosocomial amplification) .

VIROLOGY

• RNA virus; genus Betacoronavirus; enters cells via DPP4 (dipeptidyl peptidase-4) receptor on Type II pneumocytes and renal tubular cells — explains renal involvement unique to MERS.
• Compared to SARS-CoV: MERS-CoV has higher CFR (~35%) but lower human-to-human transmissibility.

CLINICAL FEATURES

• Incubation period: 2–14 days (median 5–6 days in healthcare clusters).
• Fever, cough, dyspnoea → pneumonia → ARDS in severe cases.
• Acute renal failure — distinguishing feature of MERS (unlike SARS or COVID-19); renal tubular injury from DPP4 receptor binding.
• GI symptoms — diarrhoea, vomiting, abdominal pain.
• Haemoptysis; multiorgan failure in severe cases.
• Risk factors for severe disease: Diabetes , CKD, immunosuppression, older age.

DIAGNOSIS

• RT-PCR — of lower respiratory tract specimens (BAL/tracheal aspirate preferred over nasopharyngeal swab, as viral load is higher).
• Serology (ELISA/IFA) for retrospective confirmation or seroprevalence studies.
• WHO case definition: Fever + LRTI + epidemiological link (travel to Middle East/dromedary contact).

TREATMENT & INFECTION CONTROL

• Treatment: Supportive only — no proven specific antiviral. ICU care for ARDS; renal replacement for AKF.
• Combination ribavirin + IFN-α2b studied but no clinical benefit in RCTs.
• Infection control : Contact + droplet precautions; N95 respirators for aerosol-generating procedures; isolation in single room.
• No approved vaccine in humans (as of 2024); camel vaccines being developed.

PARANEOPLASTIC SYNDROMES — Definition

Systemic effects of malignancy at distant sites NOT caused by direct tumour invasion or metastasis, but by ectopic hormone secretion or immune-mediated mechanisms (tumour antigens cross-react with normal tissues).

PARANEOPLASTIC SYNDROMES — CELL TYPE & MECHANISM

SUPERIOR VENA CAVA SYNDROME (SVCS)

SVC syndrome = obstruction of superior vena cava (SVC) impairing venous drainage from head, neck, and upper limbs. #1 cause: Malignancy (lung cancer ~80% — SCLC or squamous cell; mediastinal lymphoma ~15%).

Clinical Features — SVCS triad:

• Facial oedema + periorbital puffiness — worst in morning on waking; eyes swollen shut.
• Distended non-pulsatile neck veins — unlike cardiac causes (where veins are pulsatile and JVP fluctuates with breathing).
• Dilated chest wall collateral veins — blood bypasses obstructed SVC via chest wall collaterals (visible on inspection).
• Headache (worse on bending forward); plethoric face; arm oedema; dyspnoea; Pemberton's sign.

▶ Immediate: Dexamethasone 8 mg TDS → reduces peritumour oedema within hours.

▶ SVC stenting (fastest definitive relief ) — interventional radiology; recommended for NSCLC.

▶ Chemotherapy — SCLC responds dramatically (within days); systemic treatment of choice for SCLC-SVCS.

▶ Radiotherapy — for NSCLC SVCS not amenable to stenting.

DEFINITION

Lung abscess = localised area of suppurative necrosis within lung parenchyma producing a pus-filled cavity. Acute (< 4–6 weeks) vs Chronic (> 6 weeks) with surrounding fibrosis and clubbing.

CAUSES

• Aspiration (#1 cause) — altered consciousness (alcoholics , epileptics, stroke, GA, opioids) → aspiration of oral/oropharyngeal contents → anaerobic bacteria (Bacteroides fragilis, Fusobacterium, Peptostreptococcus).
• Right side (especially right lower lobe posterior segment, RLL apical segment in recumbent patients) — due to anatomy of right main bronchus (more vertical).
• Pneumonia — Klebsiella (alcoholics; 'currant jelly' sputum; upper lobe; excavates rapidly), S. aureus (post-influenza; multiple cavities), P. aeruginosa (hospital-acquired).
• Septic emboli from infective endocarditis (right-sided, IV drug users) → multiple peripheral abscesses.
• Obstructive — bronchogenic carcinoma (obstruct→ stasis → infection); bronchial adenoma; FB.

CLINICAL FEATURES

• Foul-smelling, foul-tasting purulent sputum — hallmark of anaerobic infection; pathognomonic.
• High spiking fever with chills; chest pain; weight loss and malaise.
• Clubbing in chronic abscess > 6 weeks (periosteal changes).
• CXR/CT: Thick-walled cavity with air-fluid level — key radiological finding. Round opacity that excavates to form cavity.

INVESTIGATIONS

• CXR — thick-walled cavity with air-fluid level; usually in dependent segments (right lower lobe posterior/apical segment).
• CT chest — differentiates abscess from empyema (lung abscess: cavity within lung, acute angle with chest wall; empyema: lenticular fluid, obtuse angle).
• Sputum — Gram stain, culture, AFB (exclude TB cavity); cytology (exclude squamous cell CA — cavitating tumour mimics abscess ).
• Bronchoscopy — if obstruction suspected; obtain protected brush specimen; exclude tumour.

MANAGEMENT

▶ Amoxicillin-clavulanate 1.2 g IV TDS (or 625 mg TDS oral) — first-line for community-acquired anaerobic lung abscess. Duration: 6–8 weeks (longer than standard CAP).

▶ IV Metronidazole 500 mg TDS — excellent anaerobic coverage; combined with penicillin for synergy.

▶ Piperacillin-tazobactam 4.5 g IV TDS — for hospital-acquired or Pseudomonas risk.

• Postural drainage — twice daily; facilitates sputum clearance.
• CT-guided percutaneous drainage — for large (> 4 cm) abscesses not responding to 4–6 weeks antibiotics.
• Surgery (lobectomy) — rarely needed; for massive haemoptysis, very large refractory abscess, or underlying malignancy.

AETIOLOGY

*Streptococcus pneumoniae* (Pneumococcus) = #1 cause of CAP worldwide . Gram-positive diplococcus, lancet-shaped; encapsulated — capsule is the main virulence factor (87+ serotypes). Pneumolysin causes RBC haemolysis (rusty sputum).

CLINICAL FEATURES

• Sudden onset with severe rigors — classically single rigors at onset; subsequent fever without rigors.
• Rusty/blood-tinged sputum — due to pneumolysin-induced haemolysis within alveoli (hepatisation phase).
• Pleuritic chest pain — sharp, worsens on inspiration and coughing; indicates pleural involvement.
• Herpes labialis — HSV-1 reactivation triggered by fever and immune stress; appears on lips day 2–3. Classic association with pneumococcal pneumonia.
• High fever (39–40°C); dyspnoea proportional to consolidation extent.

Physical signs of consolidation:

• Reduced expansion over affected lobe; dull percussion ; bronchial breathing (high-pitched, tubular sound); coarse crackles.
• ↑ vocal resonance; aegophony (E→A change); whispering pectoriloquy .
• CXR: Lobar consolidation — entire lobe uniformly opacified (white-out); air bronchogram .

COMPLICATIONS

• Parapneumonic effusion → Empyema — most common complication; pH < 7.2 = empyema = ICD needed.
• Pneumococcal bacteraemia → sepsis, meningitis, endocarditis, septic arthritis (haematogenous spread).
• Organising pneumonia — slow resolution; fibrosis; rare.
• ARDS (severe bilateral spread); lung abscess (uncommon with pneumococcal).

MANAGEMENT

▶ Outpatient (mild, CURB 0–1): Amoxicillin 500 mg–1 g TDS × 5 days.

▶ Inpatient (CURB 2–3): Ceftriaxone 1–2 g IV OD (± azithromycin 500 mg IV OD for atypical coverage).

▶ Severe (ICU/CURB 4–5): Ceftriaxone 2 g IV OD + Azithromycin 500 mg IV OD; macrolides reduce mortality.

Prevention — Vaccines:

• PCV13 (Prevenar 13) + PPSV23 (Pneumovax 23) — indicated for all > 65 years, COPD, immunocompromised, asplenic patients, CKD, diabetes, smokers.
• Children: PCV13 at 6, 10, 14 weeks + booster under NIP.

NOSOCOMIAL (HOSPITAL-ACQUIRED) PNEUMONIA — HAP/VAP

HAP (Hospital-Acquired Pneumonia) = pneumonia developing ≥ 48 hours after hospital admission in a patient NOT intubated at admission. VAP (Ventilator-Associated Pneumonia) = HAP in intubated patients, occurring > 48 hours after intubation .

• Pathogens — Gram-negative bacilli dominate: Pseudomonas aeruginosa (most common VAP pathogen), Klebsiella pneumoniae (extended-spectrum beta-lactamase — ESBL), Acinetobacter baumannii (ICU), E. coli.
• Gram-positive: MRSA (especially post-influenza, in ICU).

Risk factors for HAP/VAP:

• Intubation/mechanical ventilation (#1 risk — microaspiration around ETT cuff).
• Prolonged ICU stay; immunosuppression; prior antibiotics; nasogastric tube; Trendelenburg position.

Diagnosis: New infiltrate on CXR + ≥ 2 of: fever > 38°C, leucocytosis/leucopenia, purulent secretions (CPIS score — Clinical Pulmonary Infection Score).

▶ No MDR risk factors (early HAP): Piperacillin-tazobactam 4.5 g IV TDS × 7 days OR Amoxicillin-clavulanate IV.

▶ MDR risk / ICU / Late VAP: Carbapenem (meropenem 1 g IV TDS) + Colistin (for pan-resistant Acinetobacter); add Vancomycin/Linezolid if MRSA risk.

MYCOPLASMA PNEUMONIA — Atypical Pneumonia

Caused by *Mycoplasma pneumoniae* — smallest free-living organism ; no cell wall (inherently resistant to beta-lactams). Most common atypical CAP in young adults . Spreads by respiratory droplets.

• Gradual onset (unlike pneumococcal sudden onset); prodrome of malaise, headache, myalgia.
• Dry/non-productive cough (most common symptom); low-grade fever.
• CXR worse than clinical findings — bilateral patchy interstitial infiltrates despite patient appearing 'well'.

Extra-pulmonary features (commonly asked):

• Haemolytic anaemia — cold agglutinins (IgM anti-I antibodies; in 50–75% of patients; titre ≥ 1:64 significant).
• Skin: Erythema multiforme → Stevens-Johnson syndrome (in severe cases).
• Neurological: Encephalitis, meningitis, transverse myelitis, Guillain-Barré syndrome.
• GI: Nausea, diarrhoea; hepatitis; pancreatitis.

▶ Azithromycin 500 mg OD × 5 days — first-line (macrolide); excellent tissue penetration; no cell wall target.

▶ Doxycycline 200 mg loading → 100 mg BD × 7–14 days — alternative; equally effective.

▶ Levofloxacin 500 mg OD × 5 days — for macrolide-resistant or severe Mycoplasma.

DEFINITION

Haemoptysis = expectoration of blood from the respiratory tract below the glottis (below vocal cords). Massive haemoptysis = > 200–600 mL/24 hrs (various definitions; clinically = any amount threatening airway).

CAUSES — SYSTEMATIC

APPROACH TO DIAGNOSIS

• ABC assessment + airway protection — position patient bleeding-side DOWN (to protect good lung from aspiration of blood).
• History: Quantity; character (frothy = pulmonary; coffee-ground = upper GI); associated symptoms (fever for TB/pneumonia; dyspnoea for PE; cardiac history for MS).
• Investigations: CXR → CT chest (localise source) → bronchoscopy (identify exact bleeding site; apply tamponade).
• Specific: Sputum AFB/culture/CBNAAT (TB); echo (MS/LVF); CTPA (PE); anti-GBM antibody (Goodpasture's).

MANAGEMENT

• Minor haemoptysis: Treat underlying cause; antitussive (codeine 30 mg TDS) to reduce cough-induced bleeding.

▶ Massive haemoptysis — Bronchial Artery Embolisation (BAE) — FIRST-CHOICE treatment; interventional radiology; embolises hypertrophied bronchial arteries supplying bleeding; 85–90% initial success rate.

• Rigid bronchoscopy — therapeutic (endobronchial tamponade, balloon blocking, adrenaline instillation); localises site.
• ICU + intubation — protect airway; selective intubation of non-bleeding bronchus (double-lumen ETT) to isolate.
• Surgical (lobectomy) — definitive if BAE fails and localised source; only for fit patients.
• Treat underlying cause — anti-TB therapy; antibiotics for abscess; diuretics + valvuloplasty for MS.

HIGH ALTITUDE PULMONARY OEDEMA (HAPE)

HAPE = non-cardiogenic pulmonary oedema occurring at altitudes > 3000 m in unacclimatised individuals. One of the commonest causes of death from high altitude illness.

Pathogenesis:

• Rapid ascent → hypobaric hypoxia → patchy hypoxic pulmonary vasoconstriction (HPVC) → uneven distribution of elevated pulmonary vascular pressure → regions with less HPVC (more blood flow) → high-pressure leak from over-perfused capillaries → protein-rich fluid floods alveoli.
• Contributory: sympathetic activation; Na-K-ATPase dysfunction (reduced alveolar fluid clearance).

Clinical Features:

• Progressive dyspnoea at rest + dry cough → pink frothy cough (capillary fluid in alveoli).
• Central cyanosis; bilateral crackles; NO raised JVP / cardiomegaly (distinguishes from cardiogenic oedema).
• CXR: bilateral patchy infiltrates (asymmetric); normal cardiac silhouette.

▶ IMMEDIATE DESCENT — single most important treatment; even 1000 m descent can be life-saving.

▶ High-flow O2 — reverses hypoxia; reduces HPVC.

▶ Nifedipine 10 mg stat → 30 mg SR BD — pulmonary vasodilator; reduces pulmonary artery pressure.

▶ Sildenafil 50 mg BD or Tadalafil 10 mg BD — PDE5 inhibitors; alternative pulmonary vasodilators.

▶ Portable hyperbaric chamber (Gamow bag) — simulates descent by increasing ambient pressure.

▶ Prophylaxis : Acetazolamide 125–250 mg BD (carbonic anhydrase inhibitor) starting 1–2 days before ascent. Gradual ascent ≤ 500 m/day above 3000 m.

PULMONARY OEDEMA IN ACUTE PE

Acute PE → occlusion of pulmonary artery → right ventricle (RV) must work against sudden increase in afterload → acute RV dilation → interventricular septum shifts leftward (D-shaped septum ) → impairs LV filling (reduced LV preload) → ↓ cardiac output → systemic hypotension. Simultaneously: RV failure → blood backs up → raised pulmonary venous pressure → pulmonary oedema.

• Echo: McConnell's sign — RV free-wall akinesia with preserved apical contraction.
• Treatment: Alteplase 100 mg IV over 2 hours (massive PE with haemodynamic compromise) + O2 + ICU monitoring.

INTERSTITIAL LUNG DISEASE (ILD)

ILD (also called Diffuse Parenchymal Lung Disease) encompasses > 200 heterogeneous disorders characterised by inflammation and/or fibrosis of the pulmonary interstitium (alveolar walls, peribronchiolar tissue, alveolar septa). Most important: Idiopathic Pulmonary Fibrosis (IPF) .

Pathogenesis (IPF):

• Repeated alveolar epithelial injury (trigger unknown in IPF) → dysregulated repair → TGF-β and fibroblast growth factors released → myofibroblast activation → abnormal collagen deposition → progressive fibrosis → honeycombing.
• Usual Interstitial Pneumonia (UIP) pattern on HRCT: basilar + peripheral GGO + traction bronchiectasis + honeycombing (late).
• Features: Progressive exertional dyspnoea; dry cough; bilateral fine 'Velcro' crackles at bases; clubbing; eventual respiratory failure.

▶ IPF Treatment: Nintedanib 150 mg BD OR Pirfenidone 801 mg TDS — antifibrotics that slow decline (don't reverse fibrosis). Lung transplant for eligible patients. Avoid corticosteroids (↑ mortality in IPF).

CHYLOTHORAX — Pathogenesis

Chylothorax = accumulation of chyle (lymph fluid rich in chylomicrons and triglycerides) in the pleural space.

Causes:

• Malignancy (#1 cause) — lymphoma (most common), lung cancer, metastatic disease → thoracic duct obstruction/invasion.
• Trauma/Surgery — thoracic surgery (oesophageal, cardiac), subclavian catheter, blunt trauma → thoracic duct laceration.
• Idiopathic — in neonates and adults; lymphangiomyomatosis (LAM).

Pathogenesis: Damage or obstruction to thoracic duct (which drains into left subclavian vein) → chyle (absorbed dietary fat in triglyceride/chylomicron form) leaks from lymphatics into pleural space.

• Diagnosis: Pleural fluid milky/turbid appearance ; Triglycerides > 110 mg/dL ; chylomicrons on lipoprotein electrophoresis.

▶ Treatment: Dietary fat restriction (medium-chain triglycerides only) + Octreotide 100–200 μg SC TDS; ICD for drainage; thoracic duct ligation/embolisation if persistent (interventional radiology).

WHEEZE

Musical, continuous, adventitious sounds produced by turbulent airflow through narrowed airways (bronchi/bronchioles). Heard mainly on expiration (airways narrow further during expiration — like collapsing straws).

• Polyphonic wheeze (multiple tones simultaneously) = widespread airway narrowing → asthma, COPD .
• Monophonic wheeze (single fixed tone) = localised obstruction → bronchogenic carcinoma, FB , extrinsic compression.
• Expiratory wheeze = below glottis (intrathoracic airways — asthma, COPD, bronchiectasis).

STRIDOR

Loud, harsh, high-pitched sound from extrathoracic or upper airway obstruction . Always suggests a potentially life-threatening obstruction — treat as emergency.

• Inspiratory stridor = supraglottic or glottic obstruction (larynx + above) — croup , epiglottitis , anaphylaxis , laryngeal carcinoma.
• Expiratory stridor = subglottic/tracheal obstruction.
• Biphasic stridor = severe/fixed obstruction at glottis or trachea.
• Causes: Croup (parainfluenza virus, children), epiglottitis (H. influenzae, vaccinated children), inhaled FB (right main bronchus), laryngeal CA, anaphylaxis, post-extubation oedema.

EGOPHONY (AE-to-E Sign)

When patient says 'E', it is heard through stethoscope as 'A' (like 'aaa') . Present over consolidated lung (solid lung transmits and modifies high-frequency sound, changing vowel quality). Also called 'goat sound ' or 'AE-to-E change'.

• Positive in: consolidation (pneumonia, collapse); above pleural effusion (compressed lung).
• Absent in: normal lung, emphysema, pneumothorax.

WHISPERED PECTORILOQUY

When patient whispers, the whispered words are heard CLEARLY through the stethoscope — as if the patient is whispering directly into the ear. Normally, whispered sounds are too faint and high-pitched to conduct through lung tissue.

• Mechanism: Over consolidated lung (pneumonia), solid parenchyma transmits high-frequency whispered sounds better than air-filled lung → whispered words clearly audible.
• Compare: Bronchophony = patient says '99' — heard louder and clearer over consolidation.
• Both whispered pectoriloquy and bronchophony = signs of lung consolidation.

BARREL CHEST

Increased anteroposterior (AP) diameter of the chest — AP ≈ transverse diameter (normally AP < transverse); chest appears round like a barrel. Most common cause: Emphysema / COPD .

• Mechanism: Chronic hyperinflation in COPD/emphysema → air trapping → lungs permanently overinflated → chest wall held in inspiratory position → AP diameter increases → ribs become horizontal + intercostal spaces widen.
• Inspection: Chest appears round and full; ribs horizontal; intercostal spaces widened.
• Percussion: Hyperresonant throughout (unlike normal dull percussion).
• Auscultation: Breath sounds distant and decreased; prolonged expiration.
• Other causes: Severe asthma (during acute attack); kyphoscoliosis.

DEFINITION & CLINICAL ASSESSMENT

Clubbing = painless enlargement/bulbous swelling of the distal phalanges of fingers/toes with obliteration of the nail-fold angle (Lovibond angle > 180°) and bogginess of the nail bed.

Clinical tests:

• Schamroth's sign — when dorsal surfaces of terminal phalanges of both index fingers are apposed (back-to-back), the normal diamond-shaped window is lost (obliterated) in clubbing.
• Fluctuation test — nail bed feels spongy/fluctuant when pressed — due to subperiosteal oedema.
• Profile sign — lateral view: Lovibond angle (nail + dorsal skin) > 180° (normal < 160°).

CAUSES OF CLUBBING — TABULAR

PATHOGENESIS OF CLUBBING

The most widely accepted theory involves megakaryocyte/platelet-derived growth factors:

• In pulmonary and cardiac diseases: Megakaryocytes (platelet precursors) and platelet clumps are normally fragmented in the pulmonary circulation. In disease (pulmonary AV shunts, cyanotic CHD, pulmonary tumours), intact megakaryocytes and platelet clumps bypass the pulmonary filtration → reach systemic fingertip capillaries intact.
• These release VEGF (Vascular Endothelial Growth Factor) and PDGF (Platelet-Derived Growth Factor) locally → fingertip capillary dilation + endothelial proliferation + connective tissue hypertrophy.
• Result: Increased blood flow to fingertips + local soft tissue + periosteal proliferation → characteristic clubbing appearance.

• Grading: Grade I - softening of nail bed; Grade II - obliteration of Lovibond angle; Grade III - drumstick appearance with increased nail curvature; Grade IV - hypertrophic pulmonary osteoarthropathy (periosteal reaction, bone pain).
• Causes not to miss: congenital cyanotic heart disease (all types - clubbing in a child suggests this); infective endocarditis (bacterial seeding); Crohn disease and UC (IBD); hepatic cirrhosis; mesothelioma (must exclude with asbestos exposure history).
• Unilateral clubbing: suggests a local vascular lesion - aneurysm of the ipsilateral subclavian artery, arteriovenous fistula for haemodialysis, or Pancoast tumour compressing subclavian vessels.
• Grading in practice: Grade I and II are detected by clinical examination (softening and loss of Lovibond angle); Grade III (drumstick appearance) is visible on inspection; Grade IV (HPOA - hypertrophic pulmonary osteoarthropathy) causes periosteal new bone formation and painful joints, most commonly in lung cancer.
• Management: treat the underlying cause; HPOA pain responds to NSAIDs; clubbing itself is not reversible in short-term but may regress with treatment of the underlying condition (e.g., after lung transplant for cystic fibrosis).

DEFINITION & EPIDEMIOLOGY

Primary malignant tumour arising from bronchial epithelium. Lung cancer is the #1 cause of cancer death worldwide in both males and females.

RISK FACTORS

• Cigarette smoking (#1 risk factor — 90%) — 20-fold relative risk vs non-smokers. Risk proportional to pack-years and depth of inhalation.
• Asbestos — mesothelioma (#1 association) + adenocarcinoma; synergistic with smoking (50× risk combined).
• Radon gas — radioactive; in basements/mines; 2nd leading cause of lung CA in non-smokers.
• Occupational: arsenic, chromium, silica, polycyclic aromatic hydrocarbons.
• COPD — independent risk factor (2–3× risk even after controlling for smoking).
• Family history; prior lung cancer; previous radiation to chest.

TYPES OF LUNG CANCER — CELL TYPES

CLINICAL FEATURES

Pulmonary (local):

• Persistent cough (often blood-streaked); haemoptysis ; dyspnoea; chest pain; recurrent pneumonia (post-obstructive — same lobe, same organism).

Local invasion (common exam questions):

• Hoarseness — recurrent laryngeal nerve palsy (left RLN loops under aorta; compression by left hilar tumour/AP window nodes).
• Horner's syndrome — ptosis + miosis + enophthalmos + anhidrosis — sympathetic chain (T1 ganglion) compression by apical tumour.
• Pancoast (Superior Sulcus) Tumour — apex tumour; shoulder + arm pain (C8, T1, T2 brachial plexus); Horner's syndrome; wasting of hand muscles (T1 motor root).
• SVCS — SVC compression → facial oedema + collar stud neck vein distension.
• Dysphagia (oesophageal compression); phrenic nerve palsy (elevated hemidiaphragm).

Paraneoplastic (see SN17): SIADH (SCLC), Cushing's (SCLC), LEMS (SCLC), hypercalcaemia (squamous), HPOA (adeno).

Metastatic: Brain (headache, seizures); bone (pain, pathological fractures); liver (↑ ALP); adrenals; lymph nodes (scalene, axillary).

INVESTIGATIONS

• CXR (initial) → CT chest + abdomen + pelvis (staging) → PET-CT (N/M staging).
• Bronchoscopy + biopsy — central tumours; allows direct visualisation + EBUS (endobronchial USS) for lymph node sampling.
• CT-guided biopsy — peripheral tumours.
• Molecular testing on biopsy — EGFR mutation, ALK rearrangement, ROS1, KRAS, PD-L1 expression — guides targeted therapy.
• Sputum cytology (low sensitivity ~50%); pleural fluid cytology (malignant effusion).

MANAGEMENT

NSCLC (Non-Small Cell — adenocarcinoma, squamous, large cell):

• Stage I–II: Surgical resection (lobectomy/pneumonectomy) — curative intent. Followed by adjuvant chemotherapy (Stage II).
• Stage III: Concurrent chemoradiotherapy (cisplatin + etoposide + radiotherapy) ± durvalumab (immunotherapy consolidation).
• Stage IV (Metastatic): Based on molecular profile:

• Molecular targeted therapy — EGFR+ → Osimertinib 80 mg OD; ALK+ → Alectinib 600 mg BD.
• Immunotherapy — PD-L1 ≥ 50% → Pembrolizumab monotherapy (first-line, no chemo); PD-L1 1–49% → Pembrolizumab + platinum doublet.
• No driver mutation: Carboplatin/Cisplatin + Paclitaxel + Bevacizumab.

SCLC (Small Cell):

• Limited disease (one hemithorax + same ipsilateral nodes — can be covered in one RT field): Concurrent chemoradiotherapy — Cisplatin + Etoposide + thoracic RT. Prophylactic cranial irradiation (PCI) for responders.
• Extensive disease (beyond limited): Carboplatin + Etoposide + Atezolizumab (immunotherapy) — 1st line. No surgical role.