2. Idiopathic pulmonary fibrosis (IPF) – The need for early recognition and referral PRC-2128

3. It can be difficult to separate idiopathic pulmonary fibrosis (IPF) from other conditions IPF is a rare but fatal lung disease, with a lower survival rate than many common malignancies 1,2 Treatment is available, 3 and early diagnosis can make a difference It is important to identify patients presenting with the classical signs and symptoms so that they can be referred to a pulmonologist 1.Collard HR, et al. Am J Respir Crit Care Med 2003;168:538-42 2.Verdecchia A, et al. Lancet Oncol 2007;8:784-96 3.ATS/ERS/JRS/ALAT. Am J RespirCrit Care Med 2011;183:788-824

4. Overview These slides provide information about: –IPF pathophysiology, prevalence and prognosis –Clinical features and diagnosis of IPF –Recognising IPF in clinical practice –Patient management

5. Idiopathic pulmonary fibrosis (IPF): Pathophysiology, prevalence and prognosis

6. Idiopathic pulmonary fibrosis (IPF) IPF is a fatal lung disease characterised by an unpredictable decline of lung function due to lung fibrosis 1,2 Progressive decline in lung function restricts routine physical activity 1,2 Notable inter- and intra-patient variability in deterioration 3,4 Prognosis is extremely poor –Median survival 2–5 years 2-5 The cause of IPF is not known 1,2 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304 3.Collard HR, et al. Am J Respir Crit Care Med 2003;168:538-542 4.Kim DS, et al. Proc Am Thorac Soc. 2006;3:285-292 5.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8

7. Definition of idiopathic pulmonary fibrosis (IPF) A chronic, progressive, fibrosing type of pneumonia affecting the tissue and space around the air sacs of the lungs (the interstitium) Of unknown cause (‘idiopathic’) Occurring primarily in older adults (>45 years old) Associated with specific radiologic and/or histopathologic criteria 1 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824

8. Incidence and prevalence of idiopathic pulmonary fibrosis (IPF) IPF is an orphan disease Incidence ranges from 4.6 to 8.8 per 100,000 1-4 –Up to 30,000–35,000 patients diagnosed with IPF in Europe every year 5 Prevalence ranges from 14 to 28 per 100,000 3,4 –Up to 80,000–110,000 patients with IPF in Europe 5 Incidence and prevalence increase with age, and are higher in males than females 6 1.Gribbin J, et al. Thorax. 2006;61(11):980-985 2.Navaratnam V et al. Thorax. 2011;66(6):462-7 3.Raghu G et al. Am J Respir Crit Care Med. 2006;174(7):810-816 4.Fernández Pérez ER, et al. Chest. 2010;137(1):129-137 5.Eurostat data, January 2012 6.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8

9. Idiopathic pulmonary fibrosis (IPF) pathophysiology IPF is the result of an abnormal and persistent fibrotic response 1,2 The chronic fibrotic process in IPF ultimately converts the lungs into shrunken, firm, dense, and honeycombed structures 1.King TE Jr, et al. Lancet 2011;378:1949-1961 2.Selman M, et al. Ann Intern Med 2001;134:136-151

10. Prognosis Idiopathic pulmonary fibrosis (IPF) is an inevitably fatal disease, with a median survival of 2 to 5 years following diagnosis 1 IPF has a lower survival rate than many cancers 2-4 1.Costabel U. Eur Respir Rev 2012;21:140 2.Collard HR, et al. Am J Respir Crit Care Med 2003;168:538-542 3.Sørensen M, et al. Ann Oncol. 2010;21 Suppl 5:v120-125 4.Verdecchia A, et al. Lancet Oncol 2007;8:784-796

11. IPF disease progression is variable, irreversible, and inevitably fatal 1,2 At the time of diagnosis it is not possible to predict whether patients will have a slower or faster rate of decline 1 Clinical course of idiopathic pulmonary fibrosis (IPF) 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.Kim DS, et al. Proc Am Thorac Soc. 2006;3:285-292

12. The importance of early recognition and referral Early identification of idiopathic pulmonary fibrosis (IPF) is important: To confirm diagnosis and ensure timely referral 1 Because effective treatment to slow disease progression is available 2 –Early intervention may improve outcomes To list for lung transplant 2 Because there are several ongoing trials for potential new therapies 3 To give patients the opportunity to make the most of their remaining time 1.ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304 2.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 3.Available at www.clinicaltrials.gov [Accessed May 2013]

13. Clinical features and diagnosis of idiopathic pulmonary fibrosis (IPF)

14. Clinical features of idiopathic pulmonary fibrosis (IPF) Key presenting features include: 1-5 Increasing breathlessness on exertion Dry, non-productive cough Over 45 years old Basal inspiratory crackles on auscultation 1.ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304 2.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8 3.Kim DS, et al. Proc Am Thorac Soc. 2006;3:285-292 4.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 5.Cottin V, Cordier J-F. Eur Respir J. 2012;40:519-21

15. Bibasilar inspiratory crackles may indicate idiopathic pulmonary fibrosis (IPF) Fine crackles on inspiration are characteristic of IPF Similar to the sound heard when gently separating a strip of Velcro Predominantly located in the lower, posterior (basal) areas of the lung 1.Cottin V, Cordier J-F. Eur Respir J. 2012;40:519-21 Bilateral fine crackles should raise the suspicion of IPF and prompt referral for pulmonary function tests prior to a thin-slice HRCT scan without contrast agent

16. Diagnostic criteria for idiopathic pulmonary fibrosis (IPF) The diagnosis requires exclusion of known causes, plus radiological and/or histological criteria 1 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824

17. Diagnosis of IPF is based on high-resolution computed tomography (HRCT) and, when needed, histopathologic criteria, requiring a multi-disciplinary approach 1 Multi-disciplinary discussion increases the accuracy of diagnosis 1,2 The need for a multi-disciplinary approach in idiopathic pulmonary fibrosis (IPF) 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.Flaherty KR, et al. Am J Respir Crit Care Med. 2004;170:904-910

18. HRCT has a critical role in the diagnosis of idiopathic pulmonary fibrosis (IPF) A pulmonary function test may warrant further investigation to analyse lung structure High-resolution computed tomography (HRCT) is an essential component of the diagnostic pathway in IPF 1 HRCT has greatly increased the accuracy of IPF diagnosis 1 –The positive predictive value of a HRCT diagnosis is 90 to 100% A thin slice HRCT scan without contrast agent is required 2 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.ACR practice guideline for HRCT in adults 2009. Available at www.acr.org HRCT scan of lungs with UIP pattern

19. A normal chest x-ray cannot exclude idiopathic pulmonary fibrosis (IPF) Terms in radiology reports that warrant attention: Interstitial markings/changes Fibrosis Lower lobe predominance 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 Abnormal chest x-ray

20. Recognising idiopathic pulmonary fibrosis (IPF) in clinical practice

21. The typical IPF patient Over 45 years old Smoker or ex-smoker Male > female Exertional dyspnoea usually present for more than 6 months Dry, non-productive cough Comorbidities 1,2 –May include Pulmonary hypertension Gastro-oesophageal reflux Emphysema –These may be sub-clinical (asymptomatic) 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8 3.Kim DS, et al. Proc Am Thorac Soc. 2006;3:285-292 4.ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304

22. Bibasilar inspiratory crackles may indicate idiopathic pulmonary fibrosis (IPF) Fine crackles on inspiration are characteristic of IPF Similar to the sound heard when gently separating a strip of Velcro Predominantly located in the lower, posterior (basal) areas of the lung Best detected during slow, deep breaths Present throughout the inspiratory time 1.Cottin V, Cordier J-F. Eur Respir J. 2012;40:519-21 Bilateral fine crackles should raise the suspicion of IPF and prompt referral for pulmonary function tests prior to a thin-slice HRCT scan without contrast agent

23. When and where to refer The patient should be referred to a pulmonologist if the following are noted: Progressive breathlessness on exertion ≥3 months Dry cough ≥3 months Basal inspiratory crackles on auscultation Over 45 years old 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824

24. Idiopathic pulmonary fibrosis (IPF) patient management

25. Pharmacological therapy for idiopathic pulmonary fibrosis (IPF) Approved There is approved pharmacological therapy for the treatment of IPF available 1 Under investigation A number of therapies are in clinical trials for the treatment of IPF 2 1.ATS/ERS/JRS/ALAT. Am J RespirCrit Care Med 2011;183:788-824 2.Available at www.clinicaltrials.gov [Accessed May 2013]

26. Non-pharmacological therapy for idiopathic pulmonary fibrosis (IPF) Oxygen therapy –Recommended for patients with IPF and clinically significant resting hypoxaemia 1 Lung transplantation –Only available for a small number of patients with IPF 1,2 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824 2.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8

27. Providing additional support Pulmonary rehabilitation –Pulmonary rehabilitation programs involve aerobic conditioning, strength and flexibility training, educational lectures, nutritional interventions and psychosocial support, and may provide benefits to the majority of patients with IPF 1 Education and support –Patients and caregivers should be provided with appropriate information and support –Specific goals for palliative care include relief from physical and emotional suffering and consideration for psychological and spiritual support 1 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824

28. Summary IPF is a progressive, irreversible and ultimately fatal fibrotic lung disease with a lower survival rate than many common cancers 1-3 Key presenting clinical features include: 1 –Increasing breathlessness on exertion –Dry, non-productive cough –Over 45 years old –Basal inspiratory crackles on auscultation Timely diagnosis and referral to a pulmonologist is key to prompt initiation of treatment, which may improve outcomes 1.ATS/ERS/JRS/ALAT. Am J RespirCrit Care Med 2011;183:788-824 2.Collard HR, et al. Am J Respir Crit Care Med 2003;168:538-42 3.Verdecchia A, et al. Lancet Oncol 2007;8:784-96

29. Back-up slides

30. IPF is the most common type of idiopathic interstitial pneumonia 1.ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304

31. Common IPF misdiagnoses IPF is often diagnosed at an advanced stage of the disease 1,2 It is commonly misdiagnosed as other conditions which have some symptoms that mimic IPF 1,2 –Chronic obstructive pulmonary disease (COPD) –Congestive heart failure (CHF) –Other lung diseases –Connective tissue diseases 1.Meltzer EB, Noble PW. Orphanet J Rare Dis. 2008;3:8 2.Collard HR, et al. Respir Med. 2007;101(6):1350-4

32. Taking a patient history A thorough history should aim to eliminate other causes of ILDs, including medication and environmental exposures 1 Assess:  Onset of symptoms  Family history  Smoking  Comorbidities  Occupational/environmental exposures  Allergies  Pets  Medications  Previous malignancy and treatment 1.ATS/ERS/JRS/ALAT. Am J Respir Crit Care Med 2011;183:788-824