Interstitial lung disease

1. Interstitial lung disease Obeidahmasoudi. MD,FCCP. Pulmonary , critical care & sleep medicine American board –Brown university

2. 52 yr/ F patient otherwise healthy, presents with complains of Dry cough 6 months Increasing DOE , cardiac work up clear. Exam: RR 26 Sat 92% HR 114 Bibasilar Inspiratory Crackles Clubbing

3. ATS –ERS classification of IIPs (idiopathic interstitial pneumonia) • This is a clinical , radiological , pathological classification.

4. Hallmark of ILD • History : DOE, cough , chest pain. • Examination :- Tachypnea . Cyanosis , clubbing. Bibasilar Inspiratory crackles. Pul. HTN and cor pulmonale. • IMAGING : - Interstitial pattern. • PFT:- Restrictive pattern. • DLCO :- Reduced.

6. UIP or IPF • Prevelance 0.8- 64/100000 • Incidence 0.4 – 27/100000 • Increase with age • Median survival approximately 3 years, depending on stage at presentation. • B/L Reticular bibasilar and subpleural opacities. minimal ground-glass and variable honeycomb change.

7. Characteristic HRCT pattern ofUIP Subpleural Basal Honeycombing Tractionbronchiectasis “Propellerblade”cranio-caudaldistribution Absenceofatypicalfeatures: lobules of decreased attenuation in spared lung consolidation GGO nodules

8. Honeycombing HRCT showing subpleural broncheolectasis

9. UIP/IPF HISTOLOGIC PATTERN • CHARACTERISTICS • Temporal inhomogeneity • Dense fibrosis • Fibroblastic foci • Patchy lung involvement • Subpleural and basal

10. Radiological Features ofIPF ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis. Am J Respir Crit Care Med2011;183:788-824

13. Usual interstitial pneumonia. HRCT abnormalities predominate in the posterior, subpleural regions of the lower lobes and comprise honeycombing and traction bronchiectasis within the abnormal lung.

14. UIP PATTERN Coarse reticular opacities, subpleural honeycombing and traction bronchiectasis

15. IPF TreatmentGuideline “The majority of patients would want the intervention, but a significant minority would not.” StrongYES WeakYES “The majority of patients would not want the intervention, but a significant minoritywould.” WeakNO StrongNO Sildenafil NAC IPAHdrugs (forIPF-PH) Antacids Nintedanib Pirfenidone Warfarin Ambrisentan NAC+Aza+Pred Imatinib Prednisone Lung transplant Oxygen RaghuGetal.AmJRespirCritCareMed2015

16. Treatment • A)Nintedanib; TKI(VEGFR, FGFR,PDGFR) • 1) FVC (125ml) • 2)exacerbation

17. B) pirfenidone : antifibrotic agent , down regulate production of growth factor & procollagen I & II. • 1)FVC • 2)exercise tolerance • 3)progression – free survival • 4)fewer deaths.

18. Efficacy of nintedanib and pirfenidone over 1year ASCEND INPULSIS n=423 n=638 n=277 n=278 0 0 -50 -50 FVC change(ml/year) -100 -100 -150 -150 49.2% -200 -200 41.5% -250 -250 -300 -300 Placebo Nintedanib Placebo Pirfenidone Richeldi L et al. NEJM 2014 King TE Jr et al. NEJM2014

19. Pirfenidone andMortality Data from Capacity andASCEND Nathan SD et al. Lancet Respir Med2017

20. Time to first acute exacerbation (investigator-reported) pooled data from TOMORROW andINPULSIS Nintedanib 150 mgbid Placebo HR0.53 (95% CI: 0.34,0.83) p=0.0047 Richeldi L et al. Respir Med2016

21. Treatable or not treatable?

22. Thank you.