1. Clinical Tools for the Primary Care Physician

2. Objectives Raise the clinical index of suspicion for ILD in patients presenting with the hallmark signs and symptoms Identify the importance of early referrals to pulmonologists for potential IPF patients

3. Current Definition of IPF A distinct type of chronic fibrosing interstitial pneumonia of unknown cause, limited to the lungs, and associated with a surgical lung biopsy showing a histologic pattern of UIP ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

4. US Demographics Incidence: > 30,000 patients/year Prevalence: > 80,000 current patients Age of onset: 40 to 70 years Two-thirds > 60 years old at presentation Males > females Caucasians > minorities ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. Weycker D, et al. Paper presented at: CHEST 2002, November 2-7, 2002; San Diego, California.

5. IPF Prognosis Median length of survival from diagnosis: 2.5 to 5 years 5-year survival rate from diagnosis: 30% to 50% Factors associated with increased survival – Younger age – Female gender – Milder dyspnea (less functional impairment) – Response to therapy – Cigarette smoking at time of diagnosis (unexplained result) ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664.

6. IPF Prognosis: A Comparative Analysis Disease 5-Year Survival Lung Cancer(all)15% IPF30–50% CHF50% Colorectal Cancer62% Breast Cancer87% Prostate Cancer98% ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. American Lung Association. Lung Disease Data 2003. Available at: www.lungusa.org/dta/s2s03/ldd03.pdf. National Institutes of Health. Congestive Heart Failure Data Fact Sheet. Available at: www.nhlbi.gov/health/public/heart/other/CHF.htm.

7. Potential Risk Factors Familial (genetic) Smoking Environmental factors (eg, occupational exposure to wood dust or metal dust) Chronic aspiration associated with gastroesophageal reflux disease (GERD) Infectious agents ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664.

8. Diseases That Mimic IPF IPF is often misdiagnosed or diagnosed at an advanced stage of the disease Symptoms of other diseases that mimic IPF: – COPD – CHF – Connective tissue diseases (eg, RA, Sjögren’s, SLE) – Other lung diseases (asbestosis, hypersensitivity pneumonitis) ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

9. Clinical Evaluation Patient History Comorbid diseases Environmental exposures (tobacco, alcohol, recreational drugs) Medications (eg, antibiotics, chemotherapeutic agents, radiation) Occupational exposures (dates, duration, detailed description of work activities) Pets Previous malignancy and treatment Family history ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

10. Clinical Evaluation Physical Exam Age > 50 years Gradual onset of symptoms Progressive dyspnea on exertion – Usually present 6 months Nonproductive paroxysmal cough – Usually unresponsive to antitussives Bibasilar “Velcro-like” crackles on auscultation Digital clubbing (25% to 50% of patients) ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

11. Referring Patients to a Pulmonologist Consider referring if the following are noted: Progressive dyspnea on exertion  3 months Unexplained dry cough  3 months Desaturation occurs on oximetry testing – Drop in saturation Chest radiograph is abnormal – Inflammation – Fibrosis – Lower-lobe predominance ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002;165:277-304.

12. 6-Minute Walk Test for Interstitial Lung Disease Baseline blood pressure, pulse, O 2 saturation Timed walk at any pace As many stops as necessary If oxygen saturation persistently less than 88%, repeat test with supplemental oxygen Primary endpoint is walk distance Enright PL. Respir Care. 2003;48:783-785 ATS. Am J Respir Crit Care Med. 2002;166:111-117.

13. Normal CXR Abnormal CXR Typical Features of IPF on Chest X-Ray Slide courtesy of Ganesh Raghu, MD.

14. Terms in Radiology Reports That Should Get Your Attention Chronic changes Increased interstitial markings Prominent interstitial changes Fibrosis Abnormal CXR CXR courtesy of Ganesh Raghu, MD.

15. Radiographic Features Slide courtesy of W. Richard Webb, MD.

16. Multidisciplinary Approach to IPF Pulmonologists PCPs Radiologists Pathologists Serologies PFTs History PE CXR HRCT Biopsy

17. Reasons for Early Referral Confirm Dx (some ILDs treatable) List for lung transplant Recent data suggests early intervention may improve outcomes Several on-going trials for potential new therapies

18. Idiopathic Pulmonary Fibrosis: Ongoing Clinical Trials MedicationStudy PhaseDesignPatients (N) Primary Endpoints IFN gamma (INSPIRE) Phase IIIRandomized 2:1, double- blind, placebo-controlled 600Survival time Bosentan (BUILD 1)Phase II/IIIRandomized, double-blind, placebo-controlled, parallel assignment N/AChange in 6-minute walk distance at 1 year PirfenidonePhase II/IIIPending study designN/ASafety and efficacy EtanerceptPhase IIRandomized, double-blind, placebo-controlled, parallel assignment 100Safety and efficacy Imatinib MesylatePhase IIRandomized, double-blind, placebo-controlled 100Disease progression FG-3019Phase INonrandomized, open- label, uncontrolled, single group assignment 18–27Safety and tolerability N/A = not available

19. Additional Management Issues Patients should enroll in a pulmonary physical rehabilitation program Supplemental oxygen Lung transplant Patient education and support is imperative ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664. Gold Scientific Committee. Am J Respir Crit Care Med. 2001;163:1256-1276.