Interstitial lung disease Paul Swift

What the? 1.Extrinsic Allergic alveolitis 2.Idiopathic pulmonary fibrosis 3.Industrial dust disease 4.Organic dust disease 5.Sarcoidosis

What’s important Pathophysiology Pathophysiology Clinical features Clinical features Investigation Investigation Management Management Prognosis Prognosis

Expaaaaand Pathophysiology Pathophysiology Varies: inflammation  scarring  fibrosis Varies: inflammation  scarring  fibrosis Presentation Presentation Variation on a theme Variation on a theme SOBOE, lethargy, dry cough SOBOE, lethargy, dry cough SMOKING, PETS, OCCUPATION SMOKING, PETS, OCCUPATION O/E O/E Tachypnoea, clubbing Tachypnoea, clubbing Cyanosis Cyanosis Fine end inspiratory creps Fine end inspiratory creps

Investigation Investigations Investigations 1.Bedside  PEF (work v. home)  ABG  sats  RR 2.Blood  FBC, U&Es, LFTs, CRP, ESR  ANA and Rf in IPF sometimes 3.Imaging  CXR  HRCT

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Special tests Lung function tests Lung function tests Restrictive defect Restrictive defect FVC is reduced FVC is reduced FEV1 is reduced in proportion or slightly less FEV1 is reduced in proportion or slightly less FEV1:FVC ratio normal or raised FEV1:FVC ratio normal or raised TLCO the key! TLCO the key! Thickened fibrotic alveolar walls  shit for gas transfer Thickened fibrotic alveolar walls  shit for gas transfer Others: Bronchoscopy, bronchoalveolar lavage Others: Bronchoscopy, bronchoalveolar lavage

Lung function

Treatment Conservative Conservative Weight loss Weight loss Increased exercise Increased exercise Smoking cessation Smoking cessation Medical Medical Oxygen Oxygen Steroids Steroids Surgical Surgical Transplant Transplant

Extrinsic allergic alveolitis AKA- hypersensitivty penumonitis AKA- hypersensitivty penumonitis Type III hypersensitivity reaction Type III hypersensitivity reaction  Prior sensitisation to inhaled antigen Examples Examples 1.Mould hay (farmer’s lung) 2.Bird faeces (bird fancier’s lung) 3.Cotton fibres (byssionosis) 4.Sugar can fibres (bagassosis)

Famer’s lung

Bird fancier’s lung

EAA- why, why, why Non-caseating granulomas ResolveOrganise  pulmonary fibrosis Infiltration of small airways and alveolar walls Neutrophils 1 st Then lymphocytes/macrophages Antigen exposure Hypersensitivity reactionNeutrophil activation

Clinical features Standard stuff Standard stuff  Cough  SOB  Fever  Malaise Acute onset hours after exposure Acute onset hours after exposure  More insidious if long-term exposure to small amounts O/E: Coarse end inspiratory crackles- upper lung O/E: Coarse end inspiratory crackles- upper lung 

Investigations Bedside Bedside Bloods Bloods Neutrophil & leukocyte count Neutrophil & leukocyte count IgG antibody titres IgG antibody titres

Investigations Imaging Imaging CXR CXR Often normal in acute form Often normal in acute form Subacute- reticular nodular Subacute- reticular nodularShadowing Chronic- fibrosis with volume loss Chronic- fibrosis with volume loss HRCT HRCT Special Special Lung function Lung function Bronchoalveolar lavage Bronchoalveolar lavage Hisolopathological diagnosis Hisolopathological diagnosis

Treatment Conservative Conservative Antigen avoidance!!!! Antigen avoidance!!!! Medical: ?Corticosteroids Medical: ?Corticosteroids Yup, severe disease Yup, severe disease Speed initial recovery Speed initial recovery Prognosis Prognosis Variable, depends on antigen Variable, depends on antigenavoidance

Idiopathic pulmonary fibrosis AKA- Cryptogenic Fibrosing Alveolitis, Usual Intersitial Pneumonitis AKA- Cryptogenic Fibrosing Alveolitis, Usual Intersitial Pneumonitis Rare progressive chronic pulmonary fibrosis of unknown aetiology Rare progressive chronic pulmonary fibrosis of unknown aetiology 45-65yrs 45-65yrs

IPF- patho Alveolar walls thickened because of fibrosis Alveolar walls thickened because of fibrosis Predominantly lower lobes Predominantly lower lobes Number of chronic inflammatory cells in alveoli and interstitium Number of chronic inflammatory cells in alveoli and interstitium Usual interstitial pneumonitis Usual interstitial pneumonitis Other patterns: Other patterns: Desquamative interstitial pneumonitis Desquamative interstitial pneumonitis Bronchiolitis obliterans Bronchiolitis obliterans

Clinical features Same old Same old SOB SOB Dry cough Dry cough Fatigue Fatigue Can get considerable weight loss Can get considerable weight loss More chronic/late stage More chronic/late stage Cyanosis Cyanosis Pulmonary hypertension/cor pulmonale Pulmonary hypertension/cor pulmonale Resp failure Resp failure

Resp failure

On examination O/E O/E Clubbing Clubbing 2/3!! 2/3!! Chest expansion reduced Chest expansion reduced Fine-end inspiratory crackles Fine-end inspiratory crackles N/B. Associations N/B. Associations

Investigations Bedside Bedside ABG  resp failure ABG  resp failure Bloods Bloods Autoantibodies Autoantibodies ANA +ive in 1/3 ANA +ive in 1/3 Rf +ive in ½ Rf +ive in ½ Raised ESR Raised ESR

Investigations Imaging Imaging CXR CXR HRCT HRCT Special Special Lung function Lung function BAL BAL Neutrophils Neutrophils Transbronchial or open lung biopsy for histological diagnosis Transbronchial or open lung biopsy for histological diagnosis

Treatment Conservative Conservative Stop smoking Stop smoking Weight Exercise Weight Exercise Medical Medical 50% respond to immunosuppression with combo therapy recommended: 50% respond to immunosuppression with combo therapy recommended: Prednisolone 0.5mg/kg 1/12 Prednisolone 0.5mg/kg 1/12 Azathioprine 2-3mg/kg Azathioprine 2-3mg/kg (can sub in cyclophosphamide (can sub in cyclophosphamide for azathioprine) Oxygen Oxygen Surgical Surgical Transplant Transplant

Prognosis 50% 5 year survival 50% 5 year survival

More dust disease The pneumoconioses The pneumoconioses CABS CABS Coal Worker’s pneumoconiosis Coal Worker’s pneumoconiosis Asbestosis Asbestosis Berylliosis Berylliosis Silicosis Silicosis Group of disorders due to Group of disorders due to inhlation of mineral or biological dusts

Coal Worker’s pneumoconiosis Dose dependent Dose dependent Simple Simple Coal dust deposition in the lung Coal dust deposition in the lung Asymptomatic Asymptomatic Diagnosis made by several small round opacities on CXR Diagnosis made by several small round opacities on CXR Caplan’s Caplan’s Severe disease may progress to progressive massive fibrosis Severe disease may progress to progressive massive fibrosis

Progressive massive fibrosis Large round fibrotic nodules >10mm Large round fibrotic nodules >10mm Upper lobes Upper lobes Scarring Scarring Dyspnoea, cough, sputum Dyspnoea, cough, sputum May be black if cavitating lesions May be black if cavitating lesions

PMF

PMF treatment Progresses when exposure removed Progresses when exposure removed Unlike simple Unlike simple Prognosis is poor, no treatment Prognosis is poor, no treatment Coal Workers Pneumoconiosis Scheme Coal Workers Pneumoconiosis Scheme Pneumoconiosis Workers’ Compensation Act 1979 Pneumoconiosis Workers’ Compensation Act 1979 Lump sum compensation Lump sum compensation

Asbestosis Inhlation of asbestos Inhlation of asbestos Plumbers, electricians, builders Plumbers, electricians, builders Blue asbestos (crocidolite) Blue asbestos (crocidolite) Can’t be cleared by immune system Can’t be cleared by immune system Histology: asbestos bodies and features of pulmonary fibrosis, affecting lower lobes more Histology: asbestos bodies and features of pulmonary fibrosis, affecting lower lobes more

Rx No treatment No treatment Considerable time lag: years following exposure Considerable time lag: years following exposure Compensation Compensation Risk………. Risk……….

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Sarcoidosis A 25-year old afro-Caribbean woman presents with SOB and bilateral leg lesions…… A 25-year old afro-Caribbean woman presents with SOB and bilateral leg lesions…… Multisystem granulomatous disorder of unknown aetiology Multisystem granulomatous disorder of unknown aetiology Commonly effects the lungs Commonly effects the lungs Non-caseating granulomas Non-caseating granulomas Rare (19/ in UK) Rare (19/ in UK) Peak 20-40yrs Peak 20-40yrs

Sarcoid path Non-caseating granulomas Non-caseating granulomas (Infiltrated by Th1 lymphocytes and macrophages) (Infiltrated by Th1 lymphocytes and macrophages) (Fuse to multinucleated epithelioid cells) (Fuse to multinucleated epithelioid cells) Resolution of granulomas Resolution of granulomas 10-20% persistent  interstitial fibrosis 10-20% persistent  interstitial fibrosis

Clinical features 90% have pulmonary involvement 90% have pulmonary involvement SOB SOB Chest pain Chest pain Cough Cough Non-specific features Non-specific features Lymphadeopathy Lymphadeopathy Weight loss Weight loss Fever Fever Fatigue Fatigue

Extrapulmonary features

Inv Bedside Bedside The usual The usual Bloods Bloods FBC (normochronic normocyctic anaemia) FBC (normochronic normocyctic anaemia) ESR ESR Serum Ca2+ Serum Ca2+ Serum ACE Serum ACE Can be 2x normal levels Can be 2x normal levels Used to monitor progression Used to monitor progression Imaging- CXR Imaging- CXR

More inv

Expensive stuff HRCT HRCT Staging Staging Identifying pulmonary fibrosis Identifying pulmonary fibrosis Biopsy Biopsy GOLD standard for diagnosis GOLD standard for diagnosis

Rx Hilar lymphadenopathy and no pulmonary involvement = no treatment Hilar lymphadenopathy and no pulmonary involvement = no treatment Medical Medical Infiltration > 6weeks = steroids Infiltration > 6weeks = steroids Prognosis Prognosis Depends on stage Depends on stage Mortality < 5% UK Mortality < 5% UK Shadowing on CXR >2 years  risk pulm fibrosis Shadowing on CXR >2 years  risk pulm fibrosis

Summary Pathogenesis Pathogenesis Varied but endstage is fibrosis and inflammation of the alveoli and interstitium Varied but endstage is fibrosis and inflammation of the alveoli and interstitium Presentation Presentation Cough, SOB, fine end inspiratory crackles Cough, SOB, fine end inspiratory crackles Smoking, occupation, pets Smoking, occupation, pets Investigations Investigations Bed, blood, imaging, special Bed, blood, imaging, special Lung function- restrictive Lung function- restrictive CT- honeycombing, groundglass CT- honeycombing, groundglass Treatment Treatment Steroids, transplant, avoid exposure Steroids, transplant, avoid exposure

Case study A 64 year old gentleman presents to his GP with increasing SOB over the last 6 months. His exercise tolerance has reduced to the point where walking to the corner shop makes him out of breath. He also complains of a dry cough. He has a past medical history of high blood pressure which is managed with Ramipril. He has never smoked and works as an office manager. On examination he is slightly short of breath with O2 sats 93% on air and he has clubbing. Auscultation reveals bilateral basal fine end inspiratory crepitations and no wheeze.

???? What are your main differential diagnoses for this gentleman? (make sure these include all important differentials that must be ruled out) How would you investigate this gentleman? What is your management plan? Will anything help? Can you tell me about the pathophysiology of ILD? Can you tell me some causative organisms for EAA?

Any questions