Interstitial and Occupational Lung Disease Dr Robin Smith Dept of Respiratory Medicine

Interstitial Disease Any disease process affecting lung interstitium (ie alveoli, terminal bronchi). Interferes with gas transfer Restrictive lung pattern (may also have some airway obstruction if small airways involved) Symptoms: breathlessness, dry cough

Interstitial Lung Disease Classification Acute Episodic Chronic - part of systemic disease - exposure to agent (e.g. drug, dust etc) - idiopathic

Acute ILD Infection - usually viral Allergy - eg drug reaction Toxins - cytotoxic drugs, toxic fumes e.g. chlorine Vasculitis - eg Wegener’s granulomatosis, Churg-strauss, SLE, Goodpasture’s syndrome ARDS - trauma, sepsis

Episodic ILD Pulmonary eosinophilia Vasculitis (Churg-Strauss, Wegener’s, SLE) Extrinsic Allergic Alveolitis Cryptogenic Organising Pneumonia

Chronic ILD as part of systemic disease Connective Tissue Disease (eg Rheumatoid arthritis, SLE, Systemic Sclerosis, Ankylosing Spondylosis) Vasculitis (Churg-Strauss, Wegener’s, SLE) Sarcoidosis Cancer (lymphoma, lymphangitis carcinomatosis) Miscellaneous - tuberose sclerosis, lipid storage disorders, neurofibromatosis, amyloidosis, miliary TB, bone marrow transplant)

Chronic ILD - exposure to foreign agent Fibrogenic inorganic dusts - coal, silica, asbestos, aluminium, Non-fibrogenic dust - siderosis (iron), stannosis (tin), baritosis (barium) Granulomatous/fibrogenic - berylliosis Organic dusts - Farmer’s lung (Microsporylium), bagassosis (mouldy sugar cane), Bird fancier’s lung - (feather and dropping antigen)

Chronic ILD - idiopathic Idiopathic Pulmonary Fibrosis (IPF) – also known as Cryptogenic fibrosing alveolitis (CFA) Cryptogenic organising pneumonia (COP) Sarcoidosis Alveolar proteinosis Lymphangioleiomyomatosis (LAM) many other rarer causes

SARCOIDOSIS Multiple-system disease: common - lungs, lymph nodes, joints, liver, skin, eyes less common - kidneys, brain, nerves, heart non-caseating granuloma of unknown aetiology: probable infective agent in susceptible individual. Imbalance of immune system with type 4 (cell mediated) hypersensitivity Types Acute sarcoidosis: erythema nodosum, bilateral hilar lymphadenopathy, arthritis, uveitis, parotitis, fever. Chronic sarcoidosis: lung infiltrates (alveolitis), skin infiltrations, peripheral lymphadenopathy, myocardial, neurological, hepatitis, splenomegaly, hypercalcaemia.

SARCOIDOSIS Differential diagnosis = TB (tuberculin test -ve), Lymphoma, Carcinoma, fungal infection. Chest X-ray (BHL), CT scan of lungs (peripheral nodular infiltrate) Tissue biopsy (eg transbronchial, skin, lymph node)  non-caseating granuloma. Pulmonary function: Restrictive defect due to lung infiltrates. Blood test: - Angiotensin Converting Enzyme (ACE) levels as activity marker (NOT diagnostic test). - raised calcium - increased inflammitory markers Acute: self-limiting condition. Chronic: oral steroids if vital organ affected (eg lung, eyes, heart, brain).

SARCOIDOSIS Treatment Acute: self-limiting condition - usually no treatment Steroids if vital organ affected (eg impaired lung function, heart, eyes, brain, kidneys) Chronic: oral steroids usually needed Immunosuppression (eg azathioprine, methotrexate) monitor chest X-ray and pulmonary function for several years often relapses

Erythema Nodosum-Sarcoidosis

Iritis due to sarcoidosis

Bilateral hilar lymphadenopathy and lung infiltrares -Sarcoidosis

EXTRINSIC ALLERGIC ALVEOLITIS I Type III hypersensitivity (Immune complex deposition) reaction to antigen  lymphocytic alveolitis (hypersensitivity pneumonitis). Aetiology: Microsporylium (farmers lung, malt workers, mushroom workers), avian antigens (bird fanciers lung), drugs (gold, bleomycin, sulphasalazine) Can be ACUTE or CHRONIC ACUTE: cough, breathless, fever, myalgia - several hours after acute exposure (flu-like illness) Signs: +/- pyrexia, crackles (no wheeze!), hypoxia CxR: widespread pulmonary infiltrates Treatment: oxygen, steroid and antigen avoidance

EXTRINSIC ALLERGIC ALVEOLITIS II CHRONIC:  repeated low dose antigen exposure over time  progressive breathlessness and cough Signs: may be crackles, clubbing is unusual CxR pulmonary fibrosis - most commonly in the upper zones PFTs: restrictive defect (low FEV1 & FVC, high or normal ratio, low gas transfer - TLCO) Diagnosis: history of exposure, precipitins (IgG antibodies to guilty antigen), lung biopsy if in doubt. Treatment: remove antigen exposure, oral steroids if breathless or low gas transfer.

Extrinsic allergic alveolitis[Avian]

IDIOPATHIC PULMONARY FIBROSIS (also known as Cryptogenic Fibrosing Alveolitis) Most common interstitial lung disease Clinical presentation: progressive breathlessness, dry cough OE: clubbing, bilateral fine inspiratory crackles, Ix: restrictive defect (reduced FEV1 and FVC with normal or raised FEV1/FVC ratio, reduced lung volumes, low gas transfer CxR - bilateral infiltrates; CT scan - reticulonodular fibrotic change, worse at the lung bases. The presence of “ground-glass” suggests reversible alveolitis; fibrosis is irreversible. Causes: Primary (Idiopathic) Secondary (eg rheumatoid, SLE, systemic sclerosis, drugs - amiodarone, busulphan, bleomycin, penicillamine, nitrofurantoin, methotrexate).

IDIOPATHIC PULMONARY FIBROSIS II Differential diagnosis = exclude occupational disease (asbestosis, silicosis), mitral valve disease, left ventricular failure, sarcoidosis, extrinsic allergic alveolitis. Ask about occupation (in depth), pets and drugs Diagnosis: combination of history, examination and radiology tests If the presentation is atypical then lung biopsy (either transbronchial or thoracascopic) is needed Pathology: chronic inflammatory infiltrate (neutrophils and fibrosis in alveolar walls ± intra-alveolar macrophages.

IDIOPATHIC PULMONARY FIBROSIS III Treatment: not clear if influences course of disease oral steroids ± immunosuppressive drugs (eg azathioprine combined with N-acetyly cisteine) worth trying if patient is <75 years and evidence of acute inflammation on CT scan - some response in 30%. NB treatment is aimed as slowing future progression rather than reversing established fibrosis. Oxygen if hypoxic. Lung transplantation in young patients Future treatments: ?Anti-fibrotic agents ?anti-TNFα pulmonary artery vasodilators Prognosis: most patients progress into respiratory failure and are dead within 5 years

DIP-pre steroids Fibrosing Alveolitis

Lymphocytic alveolitis and intralumenal macrophages

COAL WORKERS PNEUMOCONIOSIS Simple pneumoconiosis - chest X-ray abnormality only (no impairment of lung function - often associated with chronic obstructive pulmonary disease). Complicated pneumoconiosis - progressive massive fibrosis  restrictive pattern with breathlessness. Chronic bronchitis (coal dust + smoking). Caplan’s syndrome - rheumatoid pneumoconiosis (pulmonary nodules).

SILICOSIS 15-20 years exposure to quartz (eg mining, foundry workers, glass workers, boiler workers). Simple pneumoconiosis - chest X-ray abnormality only (egg-shell calcification of hilar nodes). Chronic silicosis - restrictive pattern, pulmonary fibrosis.

Coal workers progressive massive fibrosis

Coal workers progressive massive fibrosis

Baritosis

ASBESTOS-related lung disorders Mining, construction, shipbuilding, boilers and piping, automotive components (eg brake linings). Pleural disease - 1- Benign pleural plaques - asymptomatic 2- Acute asbestos pleuritis - fever, pain, bloody pleural effusion 3- Pleural Effusion and Diffuse pleural thickening - restrictive impairment 4- Malignant Mesothelioma - incurable pleural cancer. Presents with chest pain and pleural effusion. No available treatment - fatal within two years. Pulmonary Fibrosis - “Asbestosis” - heavy prolonged exposure. Diffuse pulmonary fibrosis and restrictive defect. Asbestos bodies in sputum. Asbestos fibres in lung biopsy. Bronchial carcinoma - asbestos multiplies risk in smokers

Asbestosis

Asbestos pleural plaques and Bronchial Ca

Pleural effusion due to mesothelioma

OCCUPATIONAL ASTHMA Sensitising agents - high molecular weight (eg bakers, enzymes, gums, latex) - low molecular weight (eg isocyanates, wood dust, glutaraldehyde, solder, flux, dye, adhesives, drugs). Diagnosis: RAST test, provocation testing, PEFR at home/work. Reactive airway dysfunction syndrome - acute episode of toxic gas or fume inhalation (eg chlorine or sulphur dioxide)  followed by persistent bronchial hyperreactivity.

hhhttp://www.radiology.co.uk/srs-x/index.htm guidelines) Useful clinical & X-ray teaching sites hhhttp://www.radiology.co.uk/srs-x/index.htm guidelines) http://www.brit-thoracic.org.uk/clinical-information/interstitial-lung-disease-(dpld)/interstitial-lung-disease-(dpld)-guideline.aspx