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

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

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

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

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.

Characteristic HRCT pattern of UIP Subpleural Basal Honeycombing Traction bronchiectasis “Propeller blade” cranio-caudal distribution Absence of atypical features: lobules of decreased attenuation in spared lung consolidation GGO nodules

Honeycombing HRCT showing subpleural broncheolectasis

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

Radiological Features of IPF UIP pattern (all four features) Possible UIP pattern (all three features) Inconsistent with UIP pattern (any one of seven features) Subpleural basal predominance Upper or mid lung predominance Peribronchovascular predominance Reticular abnormality Extensive ground glass abnormality (extent > reticular abnormality) Profuse micronodules (bilateral, predominantly upper lobes) Honeycombing with or without traction bronchiectasis Discrete cysts (multiple bilateral, away from areas of honeycombing) Diffuse mosaic attenuation/air trapping (bilateral in three or more lobes) Absence of features listed as inconsistent with UIP pattern Absence of features listed as inconsistent with UIP pattern Consolidation in broncho- pulmonary segment(s)/lobe(s) ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;183:788-824

Usual interstitial pneumonia 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.

UIP PATTERN Coarse reticular opacities, subpleural honeycombing and traction bronchiectasis

IPF Treatment Guideline “The majority of patients would want the intervention, but a significant minority would not.” Strong YES Weak YES “The majority of patients would not want the intervention, but a significant minority would.” Weak NO Strong NO Lung transplant Oxygen Antacids Nintedanib Pirfenidone Sildenafil NAC IPAH drugs (for IPF-PH) Warfarin Ambrisentan NAC+Aza+Pred Imatinib Prednisone Raghu G et al. Am J Respir Crit Care Med 2015

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

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.

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

Pirfenidone and Mortality Data from Capacity and ASCEND Nathan SD et al. Lancet Respir Med 2017

Time to first acute exacerbation (investigator-reported) pooled data from TOMORROW and INPULSIS Nintedanib 150 mg bid Placebo HR 0.53 (95% CI: 0.34, 0.83) p=0.0047 Richeldi L et al. Respir Med 2016

Treatable or not treatable?

Thank you.