INTERSTITIAL LUNG DISEASE. Radhika Reddy MD Pulmonary/Critical Care Long Beach VA Medical Center January 5, 2018

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1 INTERSTITIAL LUNG DISEASE Radhika Reddy MD Pulmonary/Critical Care Long Beach VA Medical Center January 5, 2018

2 Interstitial Lung Disease

3 Interstitial Lung Disease Prevalence by Diagnosis: Idiopathic Interstitial Pneumonia 30% Idiopathic pulmonary fibrosis 25% Sarcoidosis 20% CTD-associated 15% Exposure (drugs, XRT, pneumoconiosis) 10% Hypersensitivity pneumonitis 10% Smoking-related 5% Unclassified 5%

4 Interstitial Lung Disease A 75 year old male is evaluated for a 12 month history of cough and dyspnea. He reports no other symptoms or medical problems and takes no medications. He is a former smoker with a 40 pack-year history, and he is a retired carpenter. He has no pets and no known environmental exposures. On physical exam, BP 135/75, HR 88, RR 24, O2 Sat 88% on RA. Pulmonary exam discloses inspiratory crackles at the bases bilaterally. Digital clubbing is present. PFTs show decreased FEV1, FVC, normal FEV1/FVC, and decreased DLCO. CT scan of the chest is shown.

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6 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Respiratory Bronchiolitis Interstitial Lung Disease D. Nonspecific Interstitial Pneumonia

7 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Respiratory Bronchiolitis Interstitial Lung Disease D. Nonspecific Interstitial Pneumonia

8 Interstitial Lung Disease What is the next step in management of this patient? A. Bronchoscopy with BAL and transbronchial biopsies B. Surgical lung biopsy C. Treatment with anti-fibrotics D. Treatment with steroids

9 Interstitial Lung Disease What is the next step in management of this patient? A. Bronchoscopy with BAL and transbronchial biopsies B. Surgical lung biopsy C. Treatment with anti-fibrotics D. Treatment with steroids

10 Idiopathic Pulmonary Fibrosis Most common idiopathic interstitial pneumonia Prevalence in US cases per 100,000 Age of presentation age Very rare in patients < 50 Male-predominant Increased risk if significant history of smoking or GERD

11 Idiopathic Pulmonary Fibrosis Clinical Presentation - History Chronic cough and dyspnea Occurs over months to years Absent occupational/drug exposures, CTD, systemic disease Physical Exam Dry inspiratory crackles at the bases > 50% of patients have digital clubbing Severe disease PH (prominent P2), right heart failure Pulmonary Function Tests Restrictive ventilatory defect Decreased DLCO

12 Idiopathic Pulmonary Fibrosis High Resolution CT Scan

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14 Idiopathic Pulmonary Fibrosis

15 Idiopathic Pulmonary Fibrosis Treatment Refer early for lung transplant! Nintendanib Reduced decline in FVC slowed disease progression Side effects - diarrhea Pirfenidone Reduced decline in FVC slowed disease progression Side effects nausea, rash Treat associated conditions: GERD Smoking cessation

16 Idiopathic Pulmonary Fibrosis Recommend AGAINST use of: Prednisone Immunomodulators (azathioprine, cyclosporine) Combination of prednisone, azathioprine and N-acetylcysteine Medications for PH Phosphodiesterase inhibitors Endothelin receptor antagonists

17 Idiopathic Pulmonary Fibrosis

18 Idiopathic Pulmonary Fibrosis Acute Exacerbation Acute or sub-acute onset of worsening dyspnea Not explained by other causes (infection, heart failure, PE) HRCT ground glass opacities in addition to UIP pattern Biopsy diffuse alveolar damage pattern (like ARDS) Treatment steroids, supportive care

19 Idiopathic Pulmonary Fibrosis Prognosis Median survival is 3 years No curative treatment Anti-fibrotics only slow decline in lung function (do not improve lung function) Refer early for lung transplant Only therapy that increases survival in IPF

20 Interstitial Lung Disease A 50 year old woman presents with a six month history of dyspnea on exertion and dry cough. She also notes stiffness and mild pain in her joints, for which she takes NSAIDS as needed. She denies any environmental or occupational exposures. She does not take any other medications. On physical exam, vitals are normal. Oxygen saturation is 94% on room air. Lung exam reveals mild bibasilar crackles. CXR shows increased bibasilar markings. PFTs show mild restriction with moderately decreased DLCO. CT scan of the chest is shown.

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22 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Sarcoidosis D. Nonspecific Interstitial Pneumonia

23 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Sarcoidosis D. Nonspecific Interstitial Pneumonia

24 Interstitial Lung Disease Which of the following is the most appropriate next step in the management of this patient s lung disease? A. Bronchoalveolar lavage B. Connective tissue disease testing C. Open lung biopsy D. Clinical observation

25 Interstitial Lung Disease Which of the following is the most appropriate next step in the management of this patient s lung disease? A. Bronchoalveolar lavage B. Connective tissue disease testing C. Open lung biopsy D. Clinical observation

26 Nonspecific Interstitial Pneumonia Strongly associated with connective tissue disease Most common scleroderma Also seen in RA, SLE, MCTD, and polymyositis/dermatomyositis Can often be the first presentation of a connective tissue disease, which may develop months to years later Can be idiopathic as well

27 Nonspecific Interstitial Pneumonia High resolution CT chest Ground glass and reticular opacities Usually bilateral and symmetrical Sub-pleural predominance Honeycombing not common Lung Biopsy Chronic inflammation and fibrosis that appear uniform

28 Nonspecific Interstitial Pneumonia Treatment Depends on clinical context If associated with CTD, treat the underlying CTD Steroids Steroid sparing agents Referral for lung transplant if not responding to treatment Prognosis variable If biopsy is more fibrotic, prognosis is poor Regardless of biopsy, prognosis is better than IPF

29 Interstitial Lung Disease A 67 year old male presents with 3 months of cough, dyspnea on exertion, and occasional low-grade fevers. He had gone to the ER several times in the last 3 months and was treated with multiple courses of antibiotics for presumed pneumonia. His symptoms initially improved with antibiotics, but then recurred. On exam, vital signs are stable. Lung exam reveals mild diffuse inspiratory crackles. Chest x-ray shows patchy areas of consolidation bilaterally. CT scan of the chest is shown.

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31 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Acute Interstitial Pneumonia C. Cryptogenic Organizing Pneumonia D. Sarcoidosis

32 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Acute Interstitial Pneumonia C. Cryptogenic Organizing Pneumonia D. Sarcoidosis

33 Interstitial Lung Disease What is your next step in management of this patient? A. Bronchoscopy with BAL and trans-bronchial biopsies B. Surgical lung biopsy C. Broader spectrum antibiotics D. Treatment with steroids

34 Interstitial Lung Disease What is your next step in management of this patient? A. Bronchoscopy with BAL and trans-bronchial biopsies B. Surgical lung biopsy C. Broader spectrum antibiotics D. Treatment with steroids

35 Cryptogenic Organizing Pneumonia Clinical Presentation Symptoms: cough, dyspnea, constitutional symptoms Symptoms usually develop over the course of 6-8 weeks Typically occurs in middle-aged adults Often misdiagnosed as community acquired pneumonia Pulmonary function tests Restrictive ventilatory defect Decreased DLCO

36 Cryptogenic Organizing Pneumonia High resolution CT Chest Patchy areas of consolidation and ground glass opacities Distribution along bronchovascular bundles and subpleural areas Pathology Plugs of loose organizing connective tissue (Masson bodies) within the bronchioles and alveolar ducts

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38 Cryptogenic Organizing Pneumonia

39 Cryptogenic Organizing Pneumonia Treatment Steroids usually 6-12 months If cannot tolerate steroids, can use steroid sparing agents Prognosis Usually good prognosis Most patients have some remaining disease seen on follow up CT chest Can recur especially if steroids are tapered too quickly

40 Interstitial Lung Disease A 40 year old male with 20 pack-year history of smoking presents to the ER with a 2 week history of severe dyspnea, productive cough, and fever. In the ER, HR 120, BP 110/70, RR 35, O2 Saturation 85% on 100% NRB FM. Physical exam reveals diffuse bilateral crackles. Labs including CBC, BMP, LFTs, BNP are unremarkable. The patient rapidly develops worsening respiratory distress and is emergently intubated in the ER. CT scan of the chest is shown.

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42 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Acute Interstitial Pneumonia C. Cryptogenic Organizing Pneumonia D. Acute Eosinophilic Pneumonia

43 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Acute Interstitial Pneumonia C. Cryptogenic Organizing Pneumonia D. Acute Eosinophilic Pneumonia

44 Acute Interstitial Pneumonia Rapidly progressive interstitial lung disease that often results in hypoxic respiratory failure Develops over 1-3 weeks Need for mechanical ventilation in the majority of patients History of viral prodrome is commonly seen Clinical presentation is similar to ARDS Differentiation between ARDS and AIP - no identifiable etiology in cases of AIP after clinical evaluation Usually affects middle-aged adults

45 Acute Interstitial Pneumonia High resolution CT Chest Similar findings to ARDS Diffuse patchy areas of consolidation and ground glass opacities Absence of traction bronchiectasis, architectural distortion, or cystic lesions Pathology Diffuse alveolar damage (similar to ARDS)

46 Acute Interstitial Pneumonia Treatment Supportive care mechanical ventilation with use of low TV, high PEEP Steroids Prognosis Very poor 6-month mortality of patients with AIP is > 50% Patients who recover can relapse or develop chronic lung disease

47 Interstitial Lung Disease A 50 year old female presents with a 1 year history of progressive dyspnea on exertion and dry cough. She has no other medical problems and denies any exposures. Physical exam reveals inspiratory crackles at the bases. EKG shows evidence of 1 st degree heart block. PFTs show a mixed restrictive and obstructive ventilatory defect with decreased DLCO. CT scan of the chest is shown.

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49 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Sarcoidosis D. Nonspecific Interstitial Pneumonia

50 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Idiopathic Pulmonary Fibrosis C. Sarcoidosis D. Nonspecific Interstitial Pneumonia

51 Sarcoidosis Multisystem disorder of unknown cause characterized by the presence of non-caseating epithelioid cell granulomas No other identifiable disease that causes granulomas Infections mycobacteria, fungi, others Environmental/occupational exposures HP Drugs Aspiration Autoimmune disorders PBC, Crohn s Sarcoid-like reactions to neoplasms Represents ~ 20-30% of ILDs Increased incidence in African Americans Women > men

52 Sarcoidosis Clinical presentation Lungs involved in > 90% cases Extra-pulmonary manifestations skin, lymph nodes, eye, liver, spleen, nervous system, heart conduction system abnormalities, hypercalcemia Pulmonary Function Tests Restrictive, obstructive, or mixed picture High Resolution CT Chest Hilar and mediastinal lymphadenopathy Nodules along bronchovasacular bundles/fissures Upper/mid lung predominance Reticulation/fibrosis

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55 Sarcoidosis Treatment If early stage, minimal symptoms clinical observation Steroids usually require 6-12 month course Alternative immunosuppressive agents Methotrexate Azathioprine Leflunomide TNF antagonists Lung Transplantation Monitoring Yearly EKG and eye exam

56 Interstitial Lung Disease A 70 year old male is evaluated for a 1 year history of cough and dyspnea. He reports no other symptoms or medical problems and takes no medications. He is an active smoker with a 40 pack year history. He has no pets and no known environmental exposures. On physical exam, BP 130/80, HR 80, RR 16, O2 Sat 95% on RA. Pulmonary exam is normal. CT scan of the chest is shown.

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58 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Nonspecific Interstitial Pneumonia C. Respiratory Bronchiolitis Interstitial Lung Disease D. Desquamative Interstitial Pneumonia

59 Interstitial Lung Disease Which of the following is the most likely diagnosis? A. Hypersensitivity Pneumonitis B. Nonspecific Interstitial Pneumonia C. Respiratory Bronchiolitis Interstitial Lung Disease D. Desquamative Interstitial Pneumonia

60 Interstitial Lung Disease What would be the next step in management of this patient? A. Bronchoscopy with BAL B. Surgical lung biopsy C. Treatment with steroids D. Smoking cessation

61 Interstitial Lung Disease What would be the next step in management of this patient? A. Bronchoscopy with BAL B. Surgical lung biopsy C. Treatment with steroids D. Smoking cessation

62 Respiratory Bronchiolitis - ILD Nearly all cases are related to smoking Imaging Centrilobular, vague micronodules Ground glass BAL pigmented macrophages Histology - pigmented macrophages and mild interstitial inflammatory changes centering on respiratory bronchioles and neighboring alveoli

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64 Desquamative Interstitial Pneumonia Nearly all cases are related to smoking Imaging Ground glass opacities + reticular opacities Occasionally cysts, honeycombing BAL pigmented macrophages Histology - presence of numerous pigmented macrophages within affected airspaces

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66 Smoking-Associated ILD Treatment Smoking cessation May need steroids/steroid-sparing agents if no improvement with smoking cessation Prognosis RB-ILD very good DIP Good but worse than RB-ILD Up to 30% mortality

67 Interstitial Lung Disease

68 References Attili AK. Smoking-related Interstitial Lung Disease: Radiologic-Clinical- Pathologic Correlation. RadioGraphics 2008; 28: Bouros D. Acute Interstitial Pneumonia. Eur Respir J 2000; 15: Criado E. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High-Resolution CT with Pathologic Correlation. RadioGraphics 2010; 30: Gotway M. Challenges in pulmonary fibrosis. 1: Use of high resolution CT scanning of the lung for the evaluation of patients with idiopathic interstitial pneumonias. Thorax 2007;62: Hyzy R. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. CHEST 2007; 132: Lee JW. Cryptogenic Organizing Pneumonia: Serial High-Resolution CT Findings in 22 Patients. AJR 2010; 195: MKSAP 16 Pulmonary and Critical Care Medicine. Raghu G. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med Vol 183. pp , 2011.

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