Pulmonary Fibrosis. Dr Paul Beirne

Size: px

Start display at page:

Download "Pulmonary Fibrosis. Dr Paul Beirne"

Sharyl Short
7 years ago
Views:

1 Pulmonary Fibrosis Dr Paul Beirne

2 Pulmonary Fibrosis What is pulmonary fibrosis? Idiopathic Pulmonary Fibrosis (IPF) Non-IPF How does it present? How is it diagnosed? How is it treated? Active management Supportive management

3 What is pulmonary fibrosis? Pulmonary fibrosis is the common final pathway of a NUMBER of DIFFERENT interstitial lung diseases

4 Interstitial Lung Diseases Known cause e.g. drugs OR Known association e.g. CTDs Idiopathic interstitial pneumonia Granulomatous e.g. Sarcoid, EAA Others (Eosinophilic pneumonia, LAM, Histiocytosis X, Alveolar proteinosis, Cancer) IPF Other COP NSIP DIP/RBILD LIP AIP IPF = Idiopathic Pulmonary Fibrosis (Cryptogenic Fibrosing Alveolitis (CFA))

5 Symptoms Shortness of breath Dry cough Constitutional weight loss, anorexia and fevers - unusual None

6 Signs Digital clubbing 25-50% Bibasilar fine late inspiratory crackles ( Velcro crackles) Look for: Cyanosis Cor pulmonale (loud P2, raised JVP, peripheral oedema) Rheumatological signs Evidence of malignancy

7 Screening Tests Spirometry CXR Proceed to HRCT chest

8 Spirometry in Pulmonary Fibrosis Restrictive FVC greatly reduced FEV1 reduced FEV1/FVC ratio increased to > 80% Pitfalls Smokers Co-existent COPD

10 Diagnosing the ILD Patient History Occupational Drugs Smoking Connective tissue disease Precipitants of Hypersensitivity Pneumonitis birds, damp/mould Examination: Digital clubbing Fine late-inspiratory Velcro crackles SpO 2 and pulmonary hypertension

11 Investigation of the ILD Patient HRCT chest Full lung function Bloods Routine haematology and biochemistry Autoantibodies (ANA, ENA, RF, ANCA) and CK ECG and echocardiogram If necessary, proceed to invasive tests: Bronchoscopy - principally to exclude infection (TB) Consider lung biopsy???

12 IPF or Non-IPF All cases of pulmonary fibrosis should be discussed at an ILD multidisciplinary team meeting in order to establish a clinicalradiological-pathological diagnosis In older patients, the principal decision will usually be between IPF and Non-IPF

13 Definition (ATS): IPF A distinctive type of chronic fibrosing interstitial pneumonia of unknown cause limited to the lungs and associated with a surgical biopsy showing a Usual Interstitial Pneumonitis (UIP) pattern The histological correlate of IPF is UIP - architectural destruction by fibrosis, often with honeycombing, with fibroblastic foci and patchy distribution including some areas of normal lung and some areas of mild to moderate inflammation Epidemiology 5000 cases per year in UK Death certification rates suggest is becoming more common Median age of onset 70, range Male: female ratio 1.5 2:1 Median survival from diagnosis is 3 years

15 IPF HRCT Features Reticular opacities with traction bronchiectasis and honeycombing in a predominantly basal and peripheral distribution Ground glass not a prominent feature Pleural involvement may suggest asbestosis or connective tissue disease NB Sarcoidosis and hypersensitivity pneumonitis can both present with this HRCT appearance

16 IPF Prognosis Clinical course is unpredictable: Gradual steady deterioration Periods of stability possible often prolonged Periods of accelerated decline may occur and can be rapidly fatal IPF is associated with markedly increased risk of lung cancer (10-fold) which interacts multiplicatively with smoking Median survival from diagnosis is 3 years New treatments have emerged in last 2 years

17 IPF - NICE CG163 and QS79 Accurate diagnosis by MDT approach Information and education Patient Healthcare professionals Treatment Pharmacological Non-pharmacological Pulmonary rehabilitation Ambulatory and long term oxygen Consider lung transplant Support Palliative care

18 Oxygen Short-burst IPF Best Supportive Care For relief of breathlessness associated with hypoxia not requiring LTOT of ambulatory oxygen Long-term (LTOT) Via concentrator for patients with PaO2 < 7.3 kpa on air at rest, or < 8 kpa with evidence of pulmonary hypertension Ambulatory For patients who desaturate on exercise by 4% or more to SaO2 < 90%, and in whom reduced breathlessness or improved exercise tolerance can be demonstrated on retesting with supplemental oxygen Pulmonary Rehabilitation Antireflux therapy Cough suppressants Oral codeine or opiates Diuretics for cor pulmonale Palliative Opiates Benzodiazepines End of life decisions

19 IPF Active Treatment Corticosteroids as monotherapy are now considered CONTRA- INDICATED: NO MORE TRIAL OF STEROIDS IN DEFINITE IPF Pirfenidone Nintedanib

20 Pirfenidone evidence Japanese study (2010) 275 patients reduction in lung function decline and increased chance of stability after 52 weeks CAPACITY 004 and 006 (2011) 779 patients one of these 2 trials showed a reduction in lung function decline at week 72 ASCEND (2014) 555 patients convincing evidence that pirfenidone is an effective treatment

21 %FVC Decline 10% or Death No Decline in %FVC Relative Difference 47.9%* 31.8 Relative Difference 132.5%* * Rank ANCOVA p-value < Death or all-cause mortality

22 Pirfenidone (N=278) Mean change in FVC (ml) Placebo (N=277)

23 Pirfenidone evidence On pirfenidone, lung function declines by approximately half as much as on placebo On pirfenidone, the risk of IPF progression is reduced and the chances of having stable disease are increased.

24 Pirfenidone The only NHS funded treatment for IPF Slows the rate of decline Does not reverse the fibrosis the patient will not feel any better Up to 9 tablets per day 3 tablets with each meal Significant incidence of side effects NICE have recommended NHSE funding through recognised specialist centres for patients with FVC 50 80% only

25 Pirfenidone Side-effects Gastro-intestinal Nausea Cramps Loose stools Loss of appetite Weight loss Skin Photosensitive skin rash Liver function test abnormalities Monthly LFT for 6/12, then 3/12ly Others Dizziness Fatigue

27 Nintedanib evidence INPULSIS 1 and 2 (2014) 1061 patients Nintedanib demonstrated a slower disease progression in IPF by significantly reducing the annual decline in lung function by approximately 50% Mild to moderate diarrhoea is the most frequent side-effect, affecting ~60% of patients. Less than 5% of patients stopped nintedanib due to diarrhoea

Adjusted annual rate of decline in FVC (ml/year) 109.

28 Adjusted annual rate of decline in FVC (ml/year) ml/year (95% CI: 75.9, 144.0) p<0.001 Nintedanib 150 mg bid (n=638) Placebo (n=423)

29 Mean (SE) observed change from baseline in FVC (ml) Nintedanib 150 mg bid Placebo ml (95% CI: 83.2, 137.9) p< Week

30 Nintedanib NICE TA published 27 th January 2016 recommends that nintedanib is funded for the treatment of IPF Drug is licensed for mild to moderate IPF (defined as FVC >50% predicted) NICE have restricted funding to patients with FVC 50 80% predicted 30% of IPF patients have FVC > 80% and are therefore excluded from treatment UK/RESP a Date of Preparation: June 2014

31 Drug Reaction: Non-IPF Stop any pneumotoxic drugs: Consider 3-6 months of corticosteroids Hypersensitivity Pneumonitis Suspect especially if exposure to birds or damp/mould May have squawks audible in chest (element of bronchiolitis) HRCT appearances often characteristic Remove trigger and consider corticosteroids

35 Non-IPF Non-specific Interstitial Pneumonitis (NSIP) Younger age of onset than IPF Often a better prognosis Often respond better to treatment Not all pulmonary fibrosis is IPF If case not clinically and radiologically consistent with IPF then alternative diagnoses, causes and treatments should be considered

36 Summary Pulmonary fibrosis thickens the alveolar wall and impairs gas exchange Presents with dyspnoea and cough Commonest signs are clubbing and crackles Spirometry often restrictive and CXR usually abnormal In older people, the commonest diagnosis is IPF IPF is a clearly defined specific disease with characteristic clinical, radiological and histological features IPF has a poor prognosis but new treatment options are emerging Other diagnoses are possible ( non-ipf ) and a careful occupational, environmental and drug history is essential; HRCT findings not typical of IPF should prompt further investigation to ensure that a treatable condition is not missed

Defending the Rest Basics on Lung Cancer, Other Cancers and Asbestosis: Review of the B-Read and Pulmonary Function Testing

Defending the Rest Basics on Lung Cancer, Other Cancers and Asbestosis: Review of the B-Read and Pulmonary Function Testing ASBESTOSIS November 2013 Bruce T. Bishop Lucy L. Brandon Willcox & Savage 440