Diffuse lung disease primarily affecting the interstitium, typically presents with progressive dyspnoea, hypoxaemia, restrictive lung function; but may be assymptomatic incidental. Chronic disease of >3 months. Most require histology for definitive diagnosis.

Predominant patterns include:

  • Nodules – sarcoidosis (spiculated but well defined), silicosis (well-defined punched out), HP (GG nodules), early LCH
  • Reticular predominant – fibrosis, UIP
  • Septal predominant – oedema, carcinomatosis
  • Consolidation – chronic eosinophilic pneumonia, COP, lymphoma/AIS
  • Cysts – LAM, UIP, late LCH

Idiopathic Interstitial Pneumonias (IIP)

Honeycombing may be microcystic or macrocystic (only UIP). New GGO may be infection or active disease.

Usual Interstitial Pneumonitis (UIP)

Radiological and histological pattern of fibrosis. Most common, likely from repetitive cycles of epithelial activation/injury by some known or unknown agent. Increased risk with smoking. Early proliferation of macrophages with thickening of interstitium by mononucelar cells, then fibrous tissue. Patchy, differing stages seen simultaneously in different portions of the lung (temporally heterogeneous). 40-70yo, M slightly > F. 30% associated with connective tissue disease (RA, SLE, scleroderma, dermatomyositis/polymyositis), chronic HP, asbestosis or drugs; most have no association and termed idiopathic pulmonary fibrosis (IPF, cryptogenic fibrosing alveolitis). Early fine bibasal reticulation, ground glass -> coarse reticular/reticulonodular, irregular septal/subpleural thickening -> honeycombing (destruction forming cystic spaces lined by hyperplastic type II pneumocytes), traction bronchiectasis, progressive loss of lung volume. Most severe peripherally and basally. Extensive fibrosis may cause PAH. Upper lobe bullae may cause spontaneous pneumothorax. Hilar lymphadenopathy and pleural effusions are rare. Mean survival <3yrs. Early active disease (GGO, reticulation) may benefit from immunosuppresants, corticosteroids and cyclophosphamides; end-stage fibrosis (honeycombing, traction bronchiectasis) will not. Increased risk of squamous metaplasia and bronchogenic carcinoma (esp adenocarcinoma).

Nonspecific Interstitial Pneumonitis (NSIP)

IIP that unable to be classified as UIP, AIP, COP, RB-ILD or DIP. Typically 45-55yo. Most have a history of connective tissue disease, HP or drug exposure. Temporally and geographically homogeneous. Usually less basal predominance and initial sparing of the immediate subpleural space cf UIP. Cellular NSIP has chronic inflammatory infiltrates with ground-glass and consolidation in peripheral and lower zone distribution; responsive to steroids. Fibrotic NSIP has bronchial dilatation, linear opacities, but honeycombing is rare. The degree of traction bronchiectasis may be predominate, extending to the subpleural region and mimicing honeycombing. Poor prognosis, but much better than UIP.

Acute Interstitial Pneumonia (AIP)

(Hamman-Rich syndrome, idiopathic ARDS). Acute, aggressive with cough, fever, dyspnoea, hypoxaemia, respiratory failure requiring mechanical ventilation. Commonly presents as a reaction after ‘binge’ smoking or new smokers. Diffuse alveolar damage with minimal mature collagen deposition. Diffuse ground glass and consolidation, increasing from anterior to posterior. Temporally homogeneous. Linear opacities, honeycombing and traction bronchiectasis uncommon. Fibrosis can develop, but tends to stabilise and not progress. Mortality 60-90%.

Organising Pneumonia (OP)

(previously bronchiolitis obliterans with organising pneumonia, BOOP). Most is secondary, from infection (influenza, adenovirus, measles, bacterial pneumonia), toxic fumes (sulfur dioxide, chlorine), connective tissue disease (RA, SLE), IBD, haematologic disease, organ transplant (chronic lung rejection of GVHD from BMT), drugs, radiotherapy, chronic aspiration. Idiopathic form is cryptogenic organising pneumonia (COP). Subacute illness over several months with cough, SOB, mild fever. Widespread deposition of plugs loose organising connective tissue within airways (Masson bodies of fibroblasts, collagen, capillaries), in the absence of parenchymal distortion and fibrosis. Patchy subpleural/peribronchial consolidation or randomly distributed GGO, ill-defined peribronchial nodules, bronchiectasis, bronchial wall thickening. Perilobular pattern with polygonal opacities bordering interlobular septa with central GGO (reverse halo, atoll sign; DDx sarcoid, Wegeners). Bronchial dilatation. Small effusions. Improves with corticosteroids, but requires a long course (months), may relapse if the course is too short, or if steroids are tapered too quickly. May result in NSIP.

Smoking-Associated Interstitial Lung Disease

RB, RB-ILB and DIP thought to be on the spectrum of the same disease. Almost all only occur in smokers, M:F 2:1, peak age 40yo.

  • Respiratory bronchiolitis (RB) – assymptomatic.
  • Respiratory bronchiolitis-associated interstitial lung disease (RB-ILB) – Inflammation in and around respiratory bronchioles with aggregates of smokers’ macrophages (brown pigment). Diffuse linear and nodular opacities, bibasal atelecatsis, scattered ground-glass, small centrilobular nodules with upper lobe predominance. No progression to end-stage fibrosis, honeycombing not seen. Improves with smoking cessation and steroids.
  • Desquamative interstitial pneumonia (DIP) – Diffuse accumulation of smokers’ macrophages within alveolar spaces (DIP is a misnomer, originally thought to be desquamated pneumocytes). Bibasal reticulation, ground-glass opacity (33%). Temporally homogenous. Fibrosis is mild with rare honeycombing, traction bronchiectasis. Good response to steroids and smoking cessation.

Connective Tissue Disease

Immunologically mediated inflammation causing vasculitis, interstitial fibrosis.

Rheumatoid Lung Disease

Pulmonary involvement more common in men, in 30-40% of patients. Most tend to follow onset of joint disease, with high rhematoid factor titers and eosinophilia. UIP pattern. Alveolitis (reticulation, ground-glass) with lower zone predominance, progressing gradually to end-stage fibrosis with honeycombing. Rarely upper lobe predominence and cavity/bulla formation (DDx ankylosing spondylitis, TB). Necrobiotic (rheumatoid) nodules are peripheral, well-defined (DDx Caplan syndrome in pneumoconioses) similar to SC nodules, may evolve into thick-walled cavities, wax and wane with flares of arthritis. Associated with COP and bronchiolitis obliterans. Chronic pleuritis in 20% of patients, with male predilection, uni/bi-lateral pleural exudative pleural effusions with low glucose. May have tapered erosion of distal clavicles, rotator cuff atrophy with high-riding humeral head, bilateral symmetrical glenohumeral joint space narrowing ± DJD, superior rib notching/erosion.

Systemic Lupus Erythematosus (SLE)

Young/middle-aged women, common thoracic involvement which may be initial site. Often limited to pleura and pericardium with fibrinous serositis causing painful pleural and pericardial exudative effusions, pleural fibrosis when long-standing. Acute lupus pneumonitis has rapid onset of fever, dyspnoea, hypoxaemia, indistinguishable from ARDS with diffuse alveolar damage causing exudative intra-alveolar oedema with hyaline membrane formation, coalescening bilateral consolidation/ground-glass, improves with immunosuppression. Chronic interstitial disease is uncommonly seen radiographically, with bibasal reticulation. Severe fibrosis may represent overlap syndrome (mixed connective tissue disease) with rheumatoid lung disease and scleroderma. Bibasal linear atelectasis with volume loss, diaphragmatic elevation from primary myopathy (in 20%). Occasionally associated with COP (indistinguishable from lupus pneumonitis). May have superior rib erosions.


Inflammation and fibrosis of skin, oesophagus, MSK, heart, lungs and kidneys in middle-aged women, unknown aetiology. Lungs involved in 90%, but only 25% have symptoms or radiological evidence. NSIP pattern more common than UIP. Large 10-50mm subpleural lower lobe cysts may -> spontaneous pneumothorax. PAH in up to 50%, even in absence of interstitial fibrosis, from thickening and obliteration of small muscular arteries and arterioles. Pleural effusions less common than rheumatoid or SLE. May have eggshell calcification in mediastinal LN, dilated air-filled oesophagus (dysmotility from smooth muscle atrophy and fibrosis) ± air fluid level (stricture from chronic reflux oesophagitis) ± aspiration. Greater risk of bronchioalveolar carcinoma. Those with CREST syndrome (subcutaneous calcifications, Raynaud, oesophageal dysmotility, sclerodactyly, telangiectasia; variant of scleroderma) may have visiable SC calcifications. May see superior rib notching/erosion.

Dermatomyositis and Polymyositis

Autoimmune inflammation/destruction of skeletal muscle with proximal pain/weakness (polymyositis) ± rash (dermatomyositis). UIP pattern in 5-10% of patients. Basal linear atelectasis from diaphragmatic and intercostal muscle involvement. Pharyngeal and upper oesophageal weakness predisposes to aspiration. Higher risk of bronchogenic carcinoma.

Sjogren Syndrome

Middle-aged women with sicca syndrome of dry eyes (keratoconjunctivitis), dry mouth (xerostomia) and dry nose (xerorhinia) from lymphocytic infiltration of glands. Most associated with other collagen vascular disease eg RA, scleroderma, SLE. Chest involved in 1/3. UIP pattern. Tracheobronchial mucous gland involvement causes thick sputum with mucous plugging, recurrent bronchitis, bronchiectasis, atelectasis, pneumonia, tree-in-bud. Higher risk of developing LIP and NHL.

Lymphocytic interstitial pneumonitis (LIP) – Proliferative disease, not a true IIP. Basal and perivacular predominate, coarse reticular/reticulonodular opacities indistinguishable from fibrosis. Associated with connective tissue disease, esp Sjogren syndrome. Ground-glass, scattered thin-walled cysts. Rarely associated with lymphoma.

Follicular bronchioitis is thought to be a mildler form on the same spectrum as LIP which just involves the distal airways.

Ankylosing Spondylitis

1-2% develop upper lobe pulmonary fibrosis, may be associated with bullae, cavities prone to mycetoma (Aspergillus).

Overlap Syndrome

Mixed connective tissue disease with clinical features or SLE, scleroderma and polymyositis. UIP pattern, PAH from arteriopathy, pleural effusion and thickening from fibrinous pleuritis (SLE).

Inhalational Diseases


Inhalation of inorganic and organic particles causing fibrosis (focal nodular or diffuse reticular) and aggregation of particle-laded macrophages. Increased risk with smoking which impairs mucociliary clearance and predisposes accumulation of the dust. Most dangerous particle size is 1-5μm, as the particles may reach the terminal airways and air sacs. Diseases include asbestosis, silicosis, CWP; less commonly aluminium (coarse reticular/reticulonodular, reduced lung volumes, marked pleural thickening, apical bullae), hard metal pneumoconiosis from cobalt and tungsten (previously giant cell interstitial pneumonitis, coarse retulonodular ± small cystic shadows, LN).

Progressive massive fibrosis (PMF) – In complicated pneumoconiosis esp silicosis and CWP. Nodular/masslike >20-30mm irregular fibrosis, most common peripheral upper and midzones, may cross interlobar fissures, may involve entire lobe. Starts peripherally and slowly ‘migrates’ to hilum creating peripheral emphysema. Central cavitation common, from infarction (obliteration of vessels by fibrosis), occasionally superinfection (TB, fungus, anaerobic bacteria). PMF may progress in absence of further exposure.

Caplan syndrome (rheumatoid pneumoconiosis) – Pneumoconiosis with RA causing 5-50mm nodules developing rapidly in crops, sharply defined, more peripheral than PMF.


Asbestos is resistant to heat and chemical insults, divided into serpentine (chrysotile, >90%; curly, flexible, smooth) and amphibole (crocidolite, amosite; straight, needle-like) types, with amphiboles greater fibrogenic and carcinogenic potential. Pleural disease includes parietal pleural plaques, pleural effusion, localised pleural fibrosis/plaque, diffuse pleural fibrosis, mesothelioma (1000x increased risk, not increasd with smoking). Parenchymal disease includes asbestosis (interstitial fibrosis), round atelectasis and bronchogenic carcinoma (5x increased risk, greatly increased with smoking). There is also incresed risk of laryngeal and other extrapulmonary neoplasms including colon cancer, peritoneal mesothelioma.

  • Asbestosis – May be delayed 20-40y, most mild and asymptomatic. Numerous asbestos bodies consisting of core transparent asbestos fibre surrounded by thick iron and protein. May be within interstitial fibrous tissue, airspace, rarely in pleural plaques. Number of bodies is proportional to occupational exposure and severity of fibrosis. UIP pattern of fibrosis.
  • Pleural plaques – Well circumscribed dense collagen, often calcified. Most anterior, posterolateral and diaphragmatic parietal pleura. Size and number do not correlated with exposure, do not contain asbestos bodies.


Most common, elderly males. Silica (crystalline silicon dioxide) exposure in mining, quarrying, foundry work, ceramic work, sandblasting). After exposure over 10-20yrs. Increased risk of TB.

  • Silicotic nodules – After 10-20 years. Centrilobular and peribronchiolar nodules of connective tissue surrounded by macrophages containing silica (birefringent crystals). Numerous tiny nodules (reticular pattern) coalesce into 1-20mm well-defined punched-out nodules with lamellated collagen esp upper lobes and parahilar regions (simple silicosis), diffusely calcify/ossify in 20%. May have central cavitation ?superimposed TB or ischaemia. Further exposure and coalescence of lesions produces PMF in complicated silicosis. Hilar lymphadenopathy at any stage, may have peripheral eggshell calcification.
  • Silicoproteinosis (acute silicosis) – Very high exposure over months-years (usually sandblasting) with filling of alveolar spaces with lipoproteinaceous material, indistinguishable from idiopathic alveolar proteinosis. Predisposed to superinfection with nocardia (masslike consolidation and chest wall involvement).

Coal Worker’s Pneumoconiosis (CWP)

  • Anthracosis – Asymptomatic, in coal miners, urban residents and smokers with carbon pigments engulfed by alveolar or intesrtitial macrophages which accumulate along lymphatics.
  • Simple CWP – Coal dust macules (1-2mm) and larger coal nodules, consisting of carbon-laden macrophages with minimal collagen. Scattered throught the lung, more in the upper and lower zones, in peribronchiolar interstitium. Central calcification in 10%. May lead to centrilobular emphysema.
  • Complicated CWP (<10%) – Associated with pigmented PMF after many years.


Uncommon, noncaseating granulomas primarily lung but also multiple other organs, from exposure to berillium (mining, fluorescent light bulbs). Radiographically indistinguishable from sarcoidosis with hilar/mediastinal LN, bilateral reticulonodular opacities, progression to end-stage fibrosis with honeycombing ± upper lobe bullae.

Hypersensitivity Pneumonitis (HP)

(Extrinsic allergic alveolitis, EAA). From inhalation of antigenic organic dusts penetrating alveolar spaces. Include thermophilic bacteria (humidifier lung, hot tub lung), true fungi (farmer’s lung from moldy hay, animal proteins), bird-fancier’s lung from avian proteins in feathers/droppings. Uncommon in smokers ?due to inhibition of granulomatous inflammation.

  • Acute/subacute disease – In 4-6hrs from type 3 (immune complex) reaction. Capillary congestion and granulomatous inflammation within alveolar septae, later bronchiolitis and alveolitis with granulomas. Airsapce opacity, patchy ground-glass and ill-defined centrilobular nodules mostly in mid and lower zones. Obliterative with air trapping, mosaic attenuation on expiration. These develop in 4-6hrs, persisting for ~12hrs before resolving, with normal CXR between exposures.
  • Chronic disease – Insidious from type 4 (cell-mediated) immune reaction resulting in noncaseating granulomas and interstitial pulmonary fibrosis. With repeditive exposure there is progressive interstitial fibrosis, patchy then diffuse with interlobular and intralobular interstitial thickening, honeycombing, traction briochiectasis, relative sparing of costophrenic angles (cf UIP). LN enlargement and pleural effusions uncommon.

Granulomatous Diseases


Multisystem granulomatous disease of unknown aetiology (?mycobacterium, Yersinia, virus) with hard noncaseating granulomas in perilymphatic disribution, which may lead to fibrosis. Blacks > whites, rare in asians, F>M, most 20-40yo, asymptomatic in 75%. Extrapulmonary findings include uveitis, erythema nodosum, uncommonly liver, heart, kdineys, CNS. Hypercalcaemia, hypergammaglobulinaemia, elevated serum ACE. Tissue diagnosis by transbronchial biopsy (positive in 90%), FNA/biopsy of liver, scalene LN or masslike lung lesions. Gallium scintigraphy shows increased uptake in hilar nodes, lung, salivary glands, useful to assess degree of disease activity. Activated pulmonary macrophages recruit mononuclear cells into interstitium forming granulomas, proliferation of T-helper cells, overactivity of B lymphocytes (hypergammaglobulinaemia). Noncaseating granulomas of palisading epithelioid histiocytes and multinucleated giant cells (containing asteroid and dark-staining Schaumann bodies in cytoplasm, characteristic but not specific). Most commonly in peribronchovascular and peripheral/subpleural interstitium, may involve parenchymal/alveolar interstitium. The small granulomas usually resolve after months-years.

LNs architecture replaced with granulomas which may regress, coalesce or fibrose. Enlargement in 80% (of which >50% have normal lungs), esp right paratracheal (left obscured by vessels), bilateral symmetric hilar nodes; mediastinal/paratracheal alone (suggests lymphoma, mets) or unilateral (in 5%, suggests TB, mets) is uncommon. Lobulated contour (individual nodes remain dicrete), may enhance, 75% regress in 2yrs, calcification in 20% (peripheral ‘eggshell’).

Lungs involved radiographically in 40-50%.

  • Interstitial fibrosis in 20% (long-standing parenchymal involvement) – Nodularity along lymphatic pathways. Scarring migrating toward hilum with broad bands of tissue, causing hilar elevation, distortion of vessels esp perihilar upper lobes, scalloping of lung-mediastinal interface, septal thickening, honeycombing, may occasionally be conglomerate masses (simulating PMF) with crowded ectatic bronchi, contains air bronchograms with traction bronchiectasis. No significant tree-in-bud opacities.
  • Reticulonodular – 3-10mm interstitial nodules in mid and upper zones (granulomas and fibrosis) predominantly peribronchovascular and subpleural, never preceding LN enlargement. Spiculated well-defined nodules. Patchy ground-glass correlates with active alveolitis. Rarely diffuse micronodular (similar to miliary TB) which may precede LN enlargement. May have coalescent nodules surrounded by multiple satellite nodules (galaxy sign) mimicing TB.
  • ‘Alveolar’ sarcoidosis in 10% – Granulomas coalesce and contain air bronchograms simulating consolidation, esp parahilar or peripheral midzone (simulating eosinophilic pneumonia); usually active disease resolving with corticosteroids.
  • Nodular/masslike sarcoidosis – Similar to alveolar, can be large, typically sharply defined, often air bronchograms, rarely cavitates.
  • Bullous sarcoidosis – Peripheral emphysema/cysts/bullae from obstruction of airways, may have increased lung volume, predisposed to pneumothorax, mycetoma and massive haemoptysis from erosion into bronchial aa.
  • Pleural thickening or effusion in 7% – Granulomatous inflammation of visceral and parietal pleura.
  • Endobronchial granulomas may cause fibrosis of the wall and bronchostenosis.
  • PAH is uncommon, from long-standing fibrosis.

Staging of sarcoidosis based on chest radiograph.

  • Stage 0 – Normal CXR
  • Stage 1 – Bilateral hilar LN, 75% resolve.
  • Stage 2 – Bilateral hilar LN and parenchymal disease, 30% resolve.
  • Stage 3 – Parenchymal disease only, 10% resolve.
  • Stage 4 – Pulmonary fibrosis.

Pulmonary Langerhan’s Cell Histiocytosis (PLCH)

>90% smokers. Peribronchiolar granulomas composed of Langerhans cells (previously histocytosis X cells) with eosinophilic cytoplasm, normally found in skin acting as antigen-processing cells; these proliferate in response to an unidentified antigen. PLCH is a polyclonal  proliferation of Langerhans histiocytes, whereas the childhood systemic form of LCH is a monoclonal (more neoplastic) proliferation of Langerhans cells. The lesions are in an upper zone distribution, with a reduction in number inferiorly. The only treatment is to quit smoking, which which most cases will improve (leaving permanent cystic spaces).

  • Exudative phase – Filling of spaces with exudate including Langerhans cells, but radiographic consolidation uncommon.
  • Nodular phase – Multiple small nodules (granulomas) predominantely axial interstitium/peribronchial mid and upper zones. May coalesce into large nodules that may cavitate or infiltrate alveolar septa inducing interstitial inflammation. Nodules may resolve completely or be replaced by fibrosis.
  • Late fibrotic phase – Most nodules fibrose centrally causing stellate lesions, coarse reticular pattern; later larger cysts and honeycombing. Cysts likely arise from cavitation of nodules (thick -> thin-walled cysts), many are irregularly shaped. Larger peripheral cysts/bullae in apices from bronchiolar obstruction by fibrosis. Relative preservation of lung volume (due to cysts). LN enlargement uncommon. Pneumothorax in 25%. Pleural effusion without pneumothorax is rare. DDx emphysema, LAM. Tx corticosteroids, but >50% stablisize or improve spontaneously.

Wegener Granulomatosis

Autoimmune necrotising granulomas of upper respiratory (almost always, Sx usually dominated by chronic sinusitis) and lower (90%) respiratory tracts, necrotizing granulomatous small vessel vasculitis (esp lungs, upper airways), glomerulonephritis (80%). Middle-aged, M>F. 70% have discrete nodules/masses (usually <10, single in 1/3) with no zonal predominance and randomly distributed with central necrosis/cavitation in 50% (esp if >20mm), may have radiating spiculations, typically irregular thick-walled, may have halo or reverse halo with GGO (haemorrhage, acute exacerbation or superimposed infection). Progressively increase in size and number. Localised or diffuse consolidation represents haemorrhage or pneumonia (often S aureus). Pleural effusion in 10%, pneumothorax from ruptured cavity. No LN enlargement. High PR3-ANCA. Diagnosis by biopsy of nasal mucosa or lung, renal biopsy often nonspecific. Tx cyclophosphamide, co-trimoxazole.

Mucosal and submucosal lesions in tracheobronchial tree almost exclusive in women, as calcified deposits with irregular narrowing, usually not associated with parenchymal disease, may cause atelectasis.

Lymphangioleiomyomatosis (LAM)

Uncommon, occurring almost exclusively in women or  tuberous sclerosis. Mean age 43yo, not inherited, associated with uterine leiomyomas. Now throught to be a neoplasm with smooth muscle proliferation (TS gene). Replacement of normal lung with 2-20mm cysts with smooth muscle proliferation in intervening interstitium (thickened), veins, bronchioles, lymphatics (may cause obstruction, dilatation and chylothorax/chyloperitoneum/chylopericardium), nodes. Symmetric bilateral fine reticular/reticulonodular, normal/increased lung volumes, evenly distributed thin-walled cysts, large recurrent chylous pleural effusion(s), spontaneous pneumothorax, less severe areas of intervening lung normal. Prognosis 30% at 5yr.

Alveolar Septal Amyloidosis

Amyloidosis is extracellular deposition of the polypeptide forming beta-pleated sheets; types include primary (no chronic disease, or plasma cell disorder), secondary (chronic disease eg TB), familial (uncommon, usually localised to CNS), and senile (>70yo). Amyloid L (AL) is in plasma cell dyscrasias with deposition of immunoglobulin light chains. Amyloid A (AA) in patients with chronic inflammatory diseases eg HL, familial Mediteranean fever. Amyloid deposition in lungs including tracheobronchial, nodular parenchymal and diffuse parenchymal (alveolar septa between capillary endothelium and alveolar epithelium), usually independently. May cause medial dissection of PAs. Interlobular septal thickening, reticulation, micronodules. Fibrosis and LN enlargement uncommon. DDx silicosis, sarcoidosis.

Chronic Aspiration Pneumonia

Recurrent aspiration over months-years causes peribronchial scarring, granulomas around food particles. Irregular reticular/reticulonodular pattern between acute episodes of aspiration pneumonitis.

Diffuse Pulmonary Ossification

Uncommon, formation of bone within parenchyma. Nodular (mitral stenosis) or irregular (chronic inflammation eg amyloidosis, UIP) forms.

Chronic Interstitial Pulmonary Oedema

Chronic elevation of pulmonary venous pressure with distention of pulmonary lymphatics and interstitial oedema may lead to fibrosis. Most common in long-standing mitral stenosis or LVF. Peribronchial cuffing, tram tracking, ill-defined vascular markings, linear or reticular opacities. No honeycombing.

Drug Reactions

Acute pulmonary reactions include:

  • Hypersensitivity to drug metabolite (combined with endogenous protein, esp penicillin, sulfonamide) with ABs against hapten-protein complex, causing bronchospasm or eosinophilic pneumonia. Fleeting peripheral patchy airspace opacity in hours-days. Often responds to corticosteroids.
  • Diffuse alveolar damage, esp opiates (heroin, crack cocaine, chemotherapy agents). Acute interstitial or airpsace opacity, identical to early ARDS. Typically clears as rapidly as it appears.
  • Vasculitis causing haemorrhage and infarction.
  • Diffuse haemorrhage from anticoagulation (warfarin), thrombocytopaemia (intense chemotherapy, bone marow transplant), penicillamine in RA (unknown mechanism). Usually resolves completely without scarring.

Chronic reactions occur after weeks-months-years, include:

  • Chronic interstitial pneumonitis (most common) causing fibrosis in the healing phase (esp amiodarone, nitrofurantoin, cyclophosphamide, bleomycin, methotrexate) with lower lobe reticulation. Diagnosis of exclusion with DDx lymphangitic carcinomatosis, pulmonary haemorrhage, opportunistic infection, oedema.
  • Pulmonary nodules (uncommon) from bleomycin or cyclophosphamide.
  • Lupus-like syndrome (often indistinguishable from SLE) from procainamide, hydralazine, isoniazid.
  • Pleural and pericardial effusions common.
  • Bronchiolitis obliterans from granulation in bronchioles, from aspiration, organ transplant, virus, collagen vascular disease or drugs (esp penicillamine in RA).
  • Chronic granulomatous vasculitis from particulates (talc, starch in IV drug abuse) may obliterate vasculature causing PAH/RVF with enlarged central PAs, interstitial pattern, rarely central conglomerate masses (similar to progressive massive fibrosis).
  • Enlarged LN uncommon (usually part of hypersensitivity), in phenytoin, methotrexate.

Specific drug reactions:

  • Nitrofurantoin – Acute form in 90% is likely hypersensitivity with interstital ± alveolar infiltrates, basal predominance, small pleural effusions. Chronic form (weeks-years of continuous therapy) is likely toxic damage with interstitial pneumonitis and fibrosis.
  • Bleomycin (cytotoxic antibiotic in lymphoma, SCC, testicular cancer) injury proportional to dose with bilateral lower lobe reticulation. Minority have acute patchy/confluent consolidation from hypersensitivity or DAD. Pulmonary nodule(s) uncommon, usually resolve with cessation.
  • Alkylating agents (busulfan in myoproliferative disorders, cyclophosphamide in malignancy and autoimmunity) causes lung toxicity in 1-4% with organising alveolar exudate, fibrosis, large atypical type 2 pneumocytes. Diffuse reticular, basal predominance, consolidation.
  • Cytosine arabinoside (Ara-C, antimetabolic for acute leukaemia) causes toxicity in 15-30% with interstitial and airspace permeability oedema.
  • Methotrexate (antimetabolite for malignancy and autoimmunity eg RA, psoriasis) causes reversible hypersensitivity, but DAD leads to restrictive lung disease in 10%.
  • Amiodarone (antiarrhytmic) causes toxicity in 5% (chronic therapy) after months-years, drug concentrates in lung with long tissue half-life (~90 days). Unknown mechanism with accumulation of phospholipids, inflammation, fibrosis of alveolar septae, lipid-laded macrophages, hyperplasia of type 2 pneumocytes. Airspace and reticular opacity (similiar to oedema), fibrosis and high attenuation within parenchymal abnormality. Drug should be stopped at earliest sign due to long half-life.

Radiation-Induced Lung Disease

Most involves radiation field, but may extend to other areas.

  • Acute radiation pneumonitis (1-6/12) – Lymphocytic alveolitis, hypersensitivity pneumonitis in 10-20%.
  • Chronic radiation pneumonitis – Pulmonary fibrosis as a consequence of rapair of endothelial and epithelial injry. DAD with atypical hyperplastic type II pneumocytes and fibroblasts.