Dpld board reveiw 2019

for pulmonary fellow

1. Diffuse Parenchymal Lung Disease Dr Nahid Sherbini Internal Medicine & Pulmonary Consultant Certified from Harvard Medical School in Practice of clinical Research

2. Learning Targets -I- To elaborate the general diagnostic approach to ILDs and Classifications • To diagnose IPF and understand treatment options • To recognize forms of IIP and clinical relevance

3. DPLD I Idiopathic Interstitial Pneumonias (IIPs) • IPF • Other IIPs • Familial IP • IP with autoimmune features (IPAF) • Smoking-related ILDs

4. Learning Targets -II- To elaborate the diagnosis to other ILDs including clinical , radiological findings and management lines.

5. DPLD II • CTD-associated ILDs Diffuse Cystic Lung Diseases Lymphangioleiomyomatosis (LAM) Pulmonary Langerhans cell histiocytosis (PLCH) Others , Pulmonary alveolar proteinosis & DAD Radiation Iduced Lung Injury

6. Introduction (ILDs) are a heterogeneous group of disorders that are classified together because of similar clinical, radiographic, physiologic, or pathologic manifestations .

7. Pulmonary interstitium Alveolar lining cells (types 1 and 2) Thin elastin-rich connective component containing capillary blood vessels

8. What is the Pulmonary Interstitium? between the epithelial and endothelial basement membrane Expansion of the interstitial compartment by inflammation with or without fibrosis Necrosis Hyperplasia Collapse of basement membrane Inflammatory cells

9. Pathogenesis The pathogenesis of ILDs is unknown. But more and more facts have shown that immune cells and their cytokines play an important role in the course of ILDs .

10. Classification Divided into -Associated with known causes and -Idiopathic. The treatment choices and prognosis vary among the different causes and types of ILD

11. Classification

12. IPF: 47-64% NSIP: 14 to 36% RBILD/DIP: 10-17% COP: 4-12% AIP: 2% LIP: 2%

13. Incidence of ILD Coultas AJRCCM ; 150:967 (Incidence of IPF=26-31 per 100,000)

14. To Diagnose ILD 1- Clinical context (clinical features, labs, PFTs) 2- Disease nature: acute/subacute, chronic 3-Radiologic (HRCT) findings : Distribution • Pattern of opacities • Associated findings

15. Q What is the most important predictor for mortality in IPF patients? Male gender Age DLCO 6MWTS distance Low FVC

16. Age and Gender LAM Age Gender

17. 3. Subacute Diseases (weeks to months) HSP, Sarcoid , Cellular NSIP, Drug, “Chronic” EP __________________________________________________________________________________________________________________ 4. Chronic Diseases (months to years) UIP, Fibrotic NSIP, Pneumoconioses , CVD-related, Chronic HSP Smoking (RBILD and PLCH) 2. Acute Diseases (Days to weeks) DAD (AIP), EP, Vasculitis /DPH, Drug, CVD ________________________________________________________________________________________________________________ History: Duration of Illness

18. Modified Liebow classification of the idiopathic interstitial pneumonias ( Katzenstein ) Acute Acute interstitial pneumonia (AIP) Chronic Usual interstitial pneumonia /IPF (UIP) Subacute Nonspecific interstitial pneumonia (NSIP) Lymphocytic Interstitial Pneumonia (LIP) Cryptogenic Organizing Pneumonia (COP) Desquamative interstitial pneumonia (DIP) Respiratory bronchiolitis-associated interstitial lung disease (RBILD)

19. Revised Classification of IIPs -2013 Major IIPs • Idiopathic pulmonary fibrosis (idiopathic UIP) • Idiopathic nonspecific interstitial pneumonia ( iNSIP ) • Respiratory bronchiolitis-interstitial lung disease (RB-ILD) • Desquamative interstitial pneumonia (DIP) • Cryptogenic organizing pneumonia (COP) • Acute interstitial pneumonia (AIP) Rare IIPs • Idiopathic lymphoid interstitial pneumonia ( iLIP ) • Idiopathic pleuroparenchymal fibroelastosis ( iPPFE ) Unclassifiable IIP

20. Physical examinations Bilateral basilar, crepitant velcro -like rale wheezing, rhonchi and coarse rales are occasionally heard with advanced disease, patients may have tachypnea and tachycardia At last, pulmonary hypertention and cor pulmonale may be exist

21. Physical Findings Resting Tachypnea Shallow breathing Dry crackles Digital clubbing Pulmonary HTN Non-pulmonary findings

22. Radiological Findings -ILD

23. Q. 1 Classical HRCT findings for IPF , All true except : Traction Bronchiectasis Basal , Sub pleural , Central Honeycombing Reticular Pattern

24. Images courtesy of W. Richard Webb, MD. Basal and peripheral reticulation Reduced lung volume

25. nodular linear

26. nodular linear

27. Honeycomb

28. Classic IPF HRCT Image courtesy of W. Richard Webb, MD. Reticular opacities Traction bronchiectasis Honeycombing Basal and subpleural predominance

29. Radiological findings

30. NSIP >30% Sjogren’s Syndrome WITH LIP Am J Respir Crit Care Med. 2000;161:646-664. Slide courtesy of Ganesh Raghu, MD.

31. DIP

32. RB-ILD

33. Peripheral Location COP IPF

34. Alveolar Infiltrates

35. DD W (Wegner’s) E (EP) B (BOOP) COP A (PAP, Aspiration) L (Lymphoma) L (Lipoid Pneumonia) S ( Sacroidosis )

36. Q. 2 55 year male with history of SOB and dry cough over 6 months. He smokes occasionally . PFT Restrictive pattern with reduced capacity . HIS HRCT show GGO with traction bronchiectasis . Which of the following is the most likely diagnosis? NSIP UIP RB-ILD LIP

37. Q.3 In interstitial lung diseases, lung function tests most often show: A. Reduced carbon monoxide diffusing capacity (DLCO) B. Increased total lung capacity (TLC) C. Airflow obstruction D. Elevated arterial PCO2

38. PFT A restrictive defect : (TLC), (FRC), (RV) ,(FVC) and (FEV1) but usually the changes are in proportion to the decreased lung volumes Low DLCO

39. PFT A reduction (DLCO) is a common, but nonspecific finding in ILD- , the severity of the DLCO reduction does not correlate well with disease prognosis, unless the DLCO is less than 35 %. Due to effacement of the alveolar capillary units but more importantly, to the extent of mismatching of ventilation and perfusion of the alveoli. In some ILDs, i.e sarcoidosis , there can be considerable reduction in lung volumes and/or severe hypoxemia but normal or only slightly reduced DLCO

40. Moderate to severe reduction of DLCO in the presence of normal lung volumes in a patient with ILD suggests one of the following: Combined emphysema and ILD Combined ILD and PVD Pulmonary Langerhans cell histiocytosis Pulmonary lymphangioleiomyomatosis All of the above Q.4

41. Q. 5 An interstitial pattern on CXR accompanied by obstructive airflow suggestive of : Sarcoidosis Diffuse alveolar hemorrhage Pulmonary lymphoangioliomatosis Combined COPD and ILD All of the above

42. An interstitial pattern on CXR accompanied by obstructive airflow suggestive of : Sarcoidosis Lymphangioleiomyomatosis HP PLCH Combined COPD and ILD

43. 6MWT 6MWT have correlated with prognosis in several studies of IPF Pulse oximetry desaturation to  88 during the 6MWT is associated with a median survival of 3.21 y compared with a median survival of 6.63 y in those who did not desaturate below 89%.

44. Q. 6 Which of the following is false regarding Pulmonary hypertension in ILDs ? A. The cause of PH in ILD is likely multifactorial. b. There is a linear correlation between PFT and PH in ILD. C. Genetic predisposition not play a role D. Proposed pathogenesis include presence of vaso -dilation ,angiopathy and PE E. All are False

45. The cause of PH in ILD is likely multifactorial The absence of a linear correlation between PFT PH in ILD suggests that other factors may play a role , These include the following: Vasoconstriction and vascular remodeling; Perivascular fibrosis and vascular destruction; Hypoxemia, both nocturnal and exertional ; Thrombotic angiopathy and pulmonary emboli; Elevated pulmonary capillary wedge pressure resulting from peripheral vascular occlusive disease, which has been described in both IPF and sarcoidosis and/or diastolic dysfunction; Microvascular inflammation and injury; Pathobiological process ( ie , vascular granulomas in sarcoidosis , PH of Langerhan's cell histiocytosis ); and Genetic predisposition and varying gene expression

46. Q. 7 Which is true about BAL in ILDs ? a. BAL is less likely to be helpful in patients with a radiographic pattern suggestive of IPF. b. BAL does not have an established role in the assessment of ILD progression or response to therapy c. Consist normally of macrophages >85%, lymphocytes 10-15%, neutrophils ≤3%, eosinophils ≤1%, epithelial ≤5% d. High CD4 /CD8 ratio in sarcoidosis and rheumatoid lung while reveals low ratio in HP . e. All are true

47. Q. Which of the following associated with neutrophilic Cellular pattern in BAL ? IPF HP COP Drug induced Pneumonitis Radiation Pneumonitis

48. ROLE OF BRONCHOALVEOLAR LAVAGE (BAL) The lavage fluid is sent for cell counts, cultures for mycobacterial, viral and fungal pathogens, and cytological analysis. Virtually all patients presenting with hemoptysis and radiographic ILD should undergo BAL  to confirm an alveolar source of bleeding and identify any infectious etiologies.

49. BAL Normal : macrophages >85%, lymphocytes 10-15%, neutrophils ≤3%, eosinophils ≤1%, epithelial ≤5% Lymphocytic (>15%): sarcoidosis, NSIP, HP, druginduced , CTDs, radiation, COP, lymphoproliferative disorders Eosinophilic (>1%): eosinophilic pneumonias, druginduced , BM transplant, asthma, ABPA, infections, Hodgkin Neutrophilic (>3%): CTDs, IPF, aspiration, infections, bronchitis, asbestosis, ARDS/DAD Bronchoalveolar Lavage (BAL): Cell Patterns ATS Guideline. AJRCCM 2012

50. ILD BAL CD4 CD8 T Lymphocyte

51. Q. 8 Which is true regarding VATS use for diagnosing ILDs ? A. Low diagnostic accuracy B. More morbidity and mortality than open lung biopsy C. Role of BAL and TBBx is highly diagnostic in all IIP D. Ideal biopsy include two or more surgical wedge biopsies with areas of normal lung and samples should measure 3-5 cm in length and 2-3 cm in depth E. None of the above

52. Video Assisted Thoracic Surgery (VATS) Chang AC, et al. Ann Thorac Surg . 2002.74;1942-1946. Rena O, et al. Eur J Cardiothorac Surg . 1999;16:624-627. VATS is the preferred procedure for obtaining a lung biopsy High diagnostic accuracy Less morbidity and mortality than open lung biopsy BAL and TBBx limited to excluding other IPF mimickers Ideal biopsy Two or more surgical wedge biopsies with areas of normal lung Samples should measure 3  5 cm in length and 2  3 cm in depth Outpatient thoracoscopic lung biopsy can be a safe and effective procedure for patients with interstitial or focal lung disease Diagnosis obtained in 61/62 patients 72.5 % discharged home within 8 hours 22.5% discharged home within 23 hours ATS/ERS Consensus Statement. Am J Respir Crit Care Med . 2000;161:646-664.

53. Probability of Histologic Diagnosis of Diffuse Diseases Surgical Biopsy 1. Granulomatous diseases 2. Malignant tumors/lymphangitic 3. DAD (any cause) 4. Certain infections 5. Alveolar proteinosis 6. Eosinophilic pneumonia 7. Vasculitis 8. Amyloidosis 9. EG/HX/PLCH 10. LAM 11. RB/RBILD/DIP 12. UIP/NSIP/LIP COP 13. Small airways disease 14. PHT and PVOD Often Sometimes Rare Transbronchial Biopsy Courtesy of Kevin O. Leslie, MD.

54. Some Pathology Slides

55. More Slides

56. Q. 9 55 y old , 30 y pack history Progressive dyspnea and cough Was working in plastic factory for the last 30 y Bilateral infiltrate in chest radiograph and cyst Surgical biopsy shown What is true about the nature of the disease ? a. This stage carry good prognosis b. Respond to Steroids c. Changing his work will be beneficial d. Poor Prognosis

57. Q. 55 y old , 30 y pack history Progressive dyspnea and cough Was working in plastic factory for the last 30 y Bilateral infiltrate in chest radiograph and cyst Surgical biopsy shown What is true about the nature of the disease ? a. This stage carry good prognosis b. Respond to Steroids c. Changing his work will be beneficial d. Poor Prognosis Fibrosis with honeycombing Architectural destruction Peripheral and basal distribution Patchy ( i.e. normal and abnormal lung ) Fibroblastic foci UIP

58. IPF

59. Average survival diagnosis of IPF is approximately 2.5–3.5 years 1 from diagnosis Onset of symptoms Initial visit Kaplan-Meier plot of the survival probability in IPF patients (n=238) 2 Ley B et al. Am J Respir Crit Care Med 2010 October 8 2. King TE et al. Am J Respir Crit Care Med 2001; 164: 1171-1181

60. Prevalence IN ME

61. Q .10 Which of the following conditions cause UIP pattern in HRCT ? IPF Chronic HP Drug Induced Infections e.g TB All of the above

62. Establish Diagnosis Multi-Disciplinary Team (MDT) Discussion Clinical Symptoms Smoking history Exposures Features of CTD Examination Investigations CXR CT Thorax Blood tests Lung Function Pathology Bronchoalveolar lavage Surgical lung biopsy

63. Q.11 A confident diagnosis of idiopathic pulmonary fibrosis (IPF) requires which one of the following? A. Surgical lung biopsy B. Usual interstitial pneumonia (UIP) pattern on lung biopsy or HRCT. C. Failure to respond to corticosteroid therapy D. Evidence of disease progression

64. To Diagnose 1. Exclude identifiable causes of ILD (e.g., occupational or environmental exposures, drugs &radiation, CTDs) 2. UIP pattern shown by: a) HRCT or b) Surgical lung biopsy, in the absence of HRCT features inconsistent with UIP Diagnostic Criteria for IPF (ATS/ERS/JRS/ALAT statement. AJRCCM 2011)

65. Q. 12 73-year-old retired insulating engineer presents with a 6-m history of increasing dyspnoea. He worked with asbestos for 2 years, 35 years ago. He has seronegative rheumatoid arthritis, clubbing and basal crackles on chest examination. The CT scan is shown below. Which one of the following is the most likely diagnosis? a. Idiopathic pulmonary fibrosis B. Asbestosis c. Rheumatoid lung d. Lung adenocarcinoma e. Bronchiectasis

66. A. Idiopathic pulmonary fibrosis Asbestosis is unlikely because the patient’s asbestos exposure was only 2 years in duration and his disease began more than 20 years later. The absence of pleural plaques is evidence against asbestosis, in which more than 95% of patients have pleural plaques demonstrable on chest CT. Rheumatoid lung with interstitial fibrosis is unlikely in seronegative disease , and clubbing is uncommon in rheumatoid pulmonary fibrosis. Lung adenocarcinoma remains a possible diagnosis but in this case is less likely than IPF and the CT does not suggest the presence of a cancer. Bronchiectasis is unlikely in the absence of cough and sputum production and clubbing seldom occurs nowadays except in patients with cystic. Bronchiectasis is not a prominent feature in the presented CT.

67. Q 13 70 year-old never-smoking man, who is former office worker, complains of a dry cough and progressive sob (NYHA class III) for 6 m. He takes 20 mg enalapril daily for hypertension. He has no other diseases. He has not kept animals, or been exposed to dust or fumes. Auscultation reveals Velcro rales over both lung bases. There is no clubbing. Pulmonary function tests cannot be performed because of impressive, possibly psychogenic, hyperventilation. While breathing room air, ABG shows PaO2 72 mmHg, PaCO2 41 mmHg, pH 7.36 and SaO2 94%. His chest CT image is shown below.

68. Q13 What is the initial diagnostic test ? Serology for CTD VATS BAL TBB Serum precipitating Ab

69. Q 14 In patients with suspected idiopathic pulmonary fibrosis, the most valuable measure is: A. Bronchoscopy B. ESR C. Trial of steroids D. Video-assisted thorascopic surgery (VATS) E. None of the above

70. Q 15 75-year-old female is referred for dyspnoea on exertion and chronic cough that have worsened progressively over the past 12 months. Pulmonary function testing reveals an FVC of 72% predicted, FEV1 of 80% predicted and TLCO of 38% predicted. The chest radiograph shows bilateral interstitial basal infiltrates. On HRCT, bilateral reticular opacities and clustered basal honeycombing are found. Open-lung biopsy reveals randomly distributed foci of usual interstitial pneumonia surrounded by normal lung parenchyma. What is the most appropriate therapy for this patient? a. Pirfenidone b. Bosentan C. Acetylcysteine d. Prednisolone/azathioprine e. Supportive care

71. The recommendation against the use of the following agents for the treatment of IPF • Anticoagulation • Imatinib • Combination prednisone, azathioprine, and N-acetylcysteine • Selective endothelin receptor antagonist ( ambrisentan • Phosphodiesterase-5 inhibitor (sildenafil) • Dual endothelin receptor antagonists ( macitentan , bosentan ) (ATS/ERS/JRS/ALAT Guideline. AJRCCM 2015)

72. Q. In Ascend and CAPACITY Trial , What is most common reported side effect of Perfinidone compared to placebo? Vomiting Insomnia Rash Headache Nausea

73. Q Pooling the results of Ascend , Capacity 1 and Capacity 2 , Which is false ? Improve dyspnoea Reduce mortality Reduce decline in 6 MWT Decrease all cause mortality Reduce decline in FVC

74. Pirfenidone

75. ASCEND: Key inclusion criteria 40–80 years of age Definite UIP on HRCT, or possible UIP on HRCT plus definite or probable UIP on surgical lung biopsy Extent of fibrotic changes greater than extent of emphysema on HRCT scan FVC ≥50% and ≤90% predicted DL CO ≥30% and ≤90% predicted FEV 1 /FVC ratio ≥0.8 6MWT distance ≥150 m King TE Jr, et al. N Engl J Med 2014;370:2083-2092.

76. ASCEND Trial

77. ASCEND Trial

78. TOMORROW: Annual rate of decline in FVC Difference between nintedanib 150 mg bid and placebo: p=0.064 vs placebo (pre-specified primary multiplicity-corrected analysis [closed testing procedure]); p=0.014 vs placebo (pre-specified hierarchical testing procedure). Richeldi L, et al. N Engl J Med 2011;365:1079–1087.

79. TOMORROW: Preservation of health-related quality of life * *p=0.007 vs placebo. SGRQ, St George’s Respiratory Questionnaire. Richeldi L, et al. N Engl J Med 2011;365:1079–1087.

80. OR 0.52 (95% CI: 0.36, 0.76) p=0.0007 OR 0.78 (95% CI: 0.54, 1.13) p=0.1833 OR 0.63 (95% CI: 0.49, 0.82) p=0.0007 INPULSIS ® -1 INPULSIS ® -2 Pooled data n=309 n=204 Nintedanib 150 mg bid Placebo n=329 n=219 n=638 n=423 Logistic regression including age, sex, height and baseline FVC % predicted as covariates (with addition of trial as a covariate for pooled analysis). Patients with missing data at week 52 (including those with missing data due to death) were considered to have had an absolute decline of >10%. Cottin V, et al. Presented at European Respiratory Society International Congress, Munich, Germany, 6–10 September 2014. Patients with an absolute decline in FVC % predicted of >10% at week 52 Progresses (%)

81. All-cause mortality over 52 weeks: Pooled data from INPULSIS ® Placebo Nintedanib 150 mg bid HR 0.70 (95% CI; 0.43, 1.12) p=0.1399 Richeldi L, et al. N Engl J Med 2014;370:2071–2082.

82. Pirfenidone Experience in Saudi

83. Q 16 About GERD in patients with IPF ,Which of the following statement correct ? a. GERD is common (60-90%) in IPF b. Majority (50-75%) asymptomatic. c. May contribute to fibrosis progression, AE. d. Some studies suggest use of GERD medications to be an independent predictor of longer survival time in IPF, associated with slower decline in FVC, decreased AE. e. All are true

84. Treatment of IPF • “ We suggest that clinicians use regular antacid treatment for patients with IPF.” “ lung transplantation in patients with IPF.” • “The committee did not make a recommendation regarding treatment of PH in patients with IPF.” (ATS/ERS/JRS/ALAT Guideline. AJRCCM 2015)

85. Q 17 Which of the following is true regarding NSIP? NSIP is a specific disease entity. Prognosis associated with NSIP and UIP are similar. NSIP is commonly associated with connective tissue diseases. NSIP commonly manifests cystic lung lesions on HRCT.

86. NSIP EITHER Idiopathic iNSIP OR Identifiable cause • Connective tissue diseases • Drugs • Environmental/occupational exposures • Immunocompromised hosts • Infections • Resolving acute lung injury

87. Q 18.

88. LIP idiopathic LIP Identifiable cause or underlying disease Connective tissue disorders – esp. Sjögren Immunodeficiency Infections Drugs/toxins -Radiologically with GGO ,Cysts

89. Q 19 A 50-year-old man, current smoker and HIV with CD4 500, has been complaining of shortness of breath and non-productive cough for 5 months. He is previously treated with antibiotics but his symptoms have failed to improve. In the emergency department, he is noted to be hypoxic on room air and crackles on auscultation of his lungs. His WBC 16,000; Hgb 14; Plt 300; LDH 500.He had a chest CT which showed below The cell count from the bronchial alveolar lavage reveals eosinophils 5%, lymphocytes 15%, neutrophils 15%. The transbronchial biopsy shows inflammatory intraluminal plugs consisting of granulation tissue with fibroblasts and myofibroblasts in connective matrix, in small airway, ducts and alveoli with mild interstitial inflammation. There is preservation of architecture and uniform appearance. What is your presumptive diagnosis? a. Chronic eosinophilic pneumonia b. Cryptogenic organizing pneumonia c. Desquamative interstitial pneumonia d. Pulmonary Oedema e. Acute eosinophilic pneumonia

90. OP Idiopathic = cryptogenic OP= (idiopathic BOOP) OR Identifiable cause • Connective tissue diseases/ vasculitides • Drugs , toxins, radiation • Infections • Hypersensitivity pneumonitis • Aspiration • Chronic eosinophilic pneumonia • Diffuse alveolar damage • Hematologic diseases, allograft transplants

91. Q 20. The patient has been discharged on prednisone 20 mg PO daily for 4 weeks. He has not been compliance to his medications and he comes in complaining of fatigue and shortness of breath. He is noted to have oxygen saturation of 95% on room air and afebrile. Repeat radiographs show new central sparing infiltrates on the left lung. Cultures have been obtained which has been negative. What would be the next appropriate step? Prednisone 20 mg PO daily Solumedrol 1 g IV daily for 3 days Piperacillin– Tazobactam 3.375 mg IV every 6 hours with vancomycin 1 g IV every 12 hours Cellcept 1,000 mg PO every 12 hours Amphotericin B

92. A. Answer: A. Prednisone 20 mg PO daily The patient appears to have a relapse, which manifests as worsening symptoms with reoccurrence of prior or new infiltrates. They are common during steroid taper. Predictors of relapse include delayed treatment and mild increases with alkaline phosphatase and gammaglutamyltransferase . Proposed taper of medications include prednisone 0.75 mg/kg/day for 4 weeks; followed by 0.5 mg/kg/day for 4 weeks, and then 20 mg daily for 4 weeks, 10 mg for 6 weeks, and 5 mg daily for 6 weeks. If relapse occur while dose <20 mg daily, increase dose to 20 mg daily and slowly taper accordingly. Treatment of COP includes steroids from 0.75 to 1.5 mg/kg/day with usual duration of up to 1 year.

93. Q 21. 40 y old female , progressive dyspnea for 5 m Abnormal CT Fig 1 TBB reveals adenocarcinoma received cisplatin and gemcitabine EGFR mutation positive , so started gefitinib . Her symptoms improve CT repeated after 2 m of treatment with no new symptoms except sob Fig 2 Bronchoscopy done and reveals lymphocytes 30 % CD4/CD8 3/3 TBB Fig 3 ,Based on results what do you suggest ? Begin Ganciclovir Start radiation Start Antibiotics Stop gefitinib

94. Fig 1 Fig 2

95. Fig 3

96. Q 22 40 y old female , progressive dyspnea for 5 m Abnormal CT Fig 1 TBB reveals adenocarcinoma received cisplatin and gemcitabine EGFR mutation positive , so started gefitinib . Her symptoms improve CT repeated after 2 m of treatment Fig 2 Bronchoscopy done and reveals lymphocytes 30 % CD4/CD8 3/3 TBB Fig 3 ,Based on results what do you suggest ? Begin Ganciclovir Start radiation Start Antibiotics Stop gefitinib

97. Q. 25 y old lady not known to have any medical illness , history of recurrent abortions, presented with dyspnea , admitted to ICU CT shown - Bronchoscopy done Which is true about this condition? Good prognosis Bronchoscopy will not help in diagnosis Need high dose steroids Complements will be normal

98. DAD Histologic pattern of ALI characterized by diffuse involvement with edema, hyaline membranes, and acute interstitial inflammation (exudative phase) evolving to loose organizing fibrosis and type II pneumocyte hyperplasia (organizing phase). • HRCT: Diffuse ground-glass and/or consolidative opacities • Management: depends on the clinical context, corticosteroids commonly used when non-infectious • Prognosis: high short-term mortality

99. Acute Interstitial Pneumonia Idiopathic (“Hamman Rich syndrome”) Identifiable cause or underlying disease: • Infections • Toxic inhalants • Drugs • CTDs/ vasculitides /alveolar hemorrhage • Acute radiation reaction • Acute exacerbation in ILDs Histo – Septal thickening and proliferation of spindle cells

100. Q 23 40 y old female teacher , Hypothyroidism and hypoadrenalism on treatment, presented with shortness of breath ,cough a typical chest pain and haemoptysis- minimal amount. History of Raynaud's and generalized fatigability .No fever . No other systemic symptoms Looks Sick , Fully Oriented , BP 90/60 P130 Afebrile Spo2 90 % CVS S1, loud S2 with pansystolic murmur , Chest bilateral crackle and L L oedema Leukopenia ,Mild elevation of transaminase CXR show Cardiomegaly and bilateral lung infiltrate Previous CT one y back :Interstitial lower lobes infiltrates with traction bronchiectasis Echo Severe Pulmonary HTN 90 and dilated RA ,RV normal LV RHC ,ANA Positive ,all other autoimmune profile were negative

101. Q 23. What is suggested treatment ? A. Sildenafil ,Bosentan and Pirfenidone B. illoprost , Bosentan and steroids C. Lasix , Steroids ,Sildenafil and illoprost D. Bosentan , illoprost ,Lasix and Steroids E. Steroids only

102. Autoimmune-features ILD (Interstitial Pneumonia with Autoimmune Features (IPAF) ) . Classification criteria: • Presence of an interstitial pneumonia (by HRCT or SLBx ) • Exclusion of alternative etiologies and, • Does not meet criteria of a defined connective tissue and, disease and, • At least one feature from at least 2/3 domains: clinical (e.g., Raynaud’s), serologic, morphologic (HRCT or SLBx features) ERS/ATS statement. ERJ 2015

103. Rare ilds

104. PPFE Idiopathic PPFE OR with Chemotherapy • Hematopoietic stem cell transplant • Recurrent infections • Familial interstitial pneumonia Pleural and subpleural fibrosis with septal elastosis, predominantly upper lobes HRCT: bilateral irregular pleuroparenchymal thickening, more marked in upper and middle Spontaneous pneumomediastinum or pneumothorax common no effective treatment identified generally poor, most progress

105. Q. 24 Which is true about Familial Interstitial Pneumonia/ Familial Pulmonary Fibrosis? a. >20 % relatives b. ~40% of interstitial pneumonia / pulmonary fibrosis c. ~25% of these familial cases have identifiable mutations d. Spescific HRCT and histopathologic pattern e. None of the above

106. Familial Interstitial Pneumonia/ Familial Pulmonary Fibrosis Evolving recommendations regarding genetic testing for those with early onset (<50 yr ), positive family history, suspicious extrapulmonary features Borie et al. Eur Respir Rev 2017

107. Q 25 Which one of the following interstitial lung diseases is related to smoking? LAM Desquamative interstitial pneumonia UIP NSIP DAD

108. Q Which one of the following interstitial lung diseases is NOT related to smoking? Acute eosinophilic pneumonia Desquamative interstitial pneumonia Respiratory bronchiolitis –ILD Hypersensitivity Pneumonitis IPF

109. Smoking-related ILDs Respiratory bronchiolitis-associated ILD (RB-ILD) Desquamative interstitial pneumonia (DIP) Pulmonary Langerhans cell histiocytosis (PLCH) Acute eosinophilic pneumonia (AEP) Combined pulmonary fibrosis and emphysema (CPFE) ( Vassallo et al. Clin Chest Med 2012)

110. Q. 26 40 y old ,nurse ,15y pack history Progressive SOB No fever or haemoptysis RR 27 SPO2 93%RA Chest bilateral crepitation Normal Labs including ESR & ANA CT Shown Best treatment Observation & Stop Smoking Stop Smoking & Steriods Steriods and azathioprin Perfinedone

111. RB-ILD numerous pigmented macrophages Relatively uniform appearance Most are smoking-related HRCT: GGOs ± reticular opacities; sometimes cysts, or and vague nodules Management: smoking cessation, corticosteroids Prognosis: generally good, up to 30% mortality

112. Q 27 44 y old came with dyspnea on exertion and cough. Has been told she has emphysema. Attempt of tobacco cessation failed. Physical examination reveals crackles Her radiographic ,pathology shown Which of the following is most likely ? COPD Goodpasture Syndrome with diffuse pulmonary haemorrhage Pulmonary Langerhans histiocytosis DIP

113. Q.

114. Q.

115. Combined Pulmonary Fibrosis and Emphysema (CPFE) Upper lung emphysema and lower lung fibrosis Typically male smokers Relatively preserved spirometry and lung volumes with low DLCO Increased incidence of pulmonary hypertension – associated with increased mortality “Pulmonary fibrosis” includes UIP, NSIP, RB-ILD, DIP, etc.

116. DPLD II

117. Learning Targets -II- To elaborate the diagnosis to other ILDs including clinical , radiological findings and management lines.

118. DPLD II • CTD-associated ILDs Diffuse Cystic Lung Diseases Others

119. Q 28 Respiratory manifestations in CTD is characterized by which one of the following? Obstructive lung disease is not seen. Lung biopsy is usually needed. SLE involves the lung more often than other CTDs. Acute exacerbation can occur in patients with CTD-ILDs .

120. Rheumatic Disease ILD RA 20 - 30 % PM/DM 20 - 50 % More common with anti- synthetase antibodies Systemic sclerosis 45 % (“clinically significant”) More common in diffuse disease; topoisomerase-1 antibodies SLE 2 - 8 % Usually in patients with multisystem disease MCTD 20 – 60 % Sjögren to 25 % ( Castelino et al. Arthritis Res Ther 2010)

121. Q 29 45 year old man known case of PM/DM , presented with three weeks history of dyspnea on exertion ,progressive and associated with dry cough ,weight loss and loss of appetite He has a history of Raynaud’s. Physical Examination show ankle joint swelling, HRCT show bilateral interstitial infiltrate diffuse predominantly upper lobes with traction bronchiectasis ILD. What is true about this disease? a. 2-5 % of PM\DM patients will have it b. UIP pattern is the commonest to be found in HRCT c. Anti –jo antibodies positive d. Obstructive ventilatory defect in PFT e. None of the above

122. AntiSythestase Syndrome Subset (16-30%) of patients with PM/DM Characterized by relatively acute onset, constitutional symptoms, Raynaud’s, “mechanic’s hands”, arthritis, ILD. anti-Jo-1 (anti- histidyl – tRNA synthetase ) Associated with ↑ risk of ILD Usually NSIP > UIP > OP; sometimes LIP, DAD, etc Can be more refractory to treat than other PM/DM-associated ILD

123. Q 30 30 y lady with SLE , C\o progressive SOB 3 m , no other respiratory symptoms . On Warfarin for previous DVT. Examination is normal PFT FEV1 55% ,FVC 58% FEV1\FVC 0.78 TLC 68% RV 100% DLCO 77% adjusted to alveolar volume 100% CXR small lung volume without lung infiltrates or effusion What is the next to do ? Echo VQ scan Maximum Inspiratory and Expiratory Pressure Bronchoscopy

124. A. MIP ,MEP To assess muscle weakness ?myositis or phrenic n palsy Dx shrinking lung syndrome Tx steroid , theophylline , beta agonist and immunosuppression

125. Q 31 66 y old lady with Systemic sclerosis , Raynaud's Never smoker , work as a secretary Examination reveals Spo2 93% , diffuse skin thickening and telangactasia upper limb digitals FVC 60% HRCT bilateral basal ground glass opacities What is the best treatment ? Cyclophosamide Cyclosporine Steroids Azathioprine

126. A. B. RCT 49% improved with cyclophosphamide Vs 26% Clin Rheumatol . 2006 Mar;25(2):205-12. Epub 2005 Oct 14. A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis. Nadashkevich O1, Davis P, Fritzler M, Kovalenko W

127. What is the Diagnosis? LAM Bronchiectasis E EG

128. Diffuse Cystic Lung Disease Cyst = a round parenchymal lucency with a well defined thin-wall (<2 mm), usually contain air • Focal/multifocal vs diffuse Cavity = a lucency within pulmonary consolidation, a mass, or a nodule. (thick wall) Emphysema = focal areas of low attenuation without visible walls Fleischner Society, 2008

129. Mechanism of Cyst Formation Elastolysis mediated by matrix metalloproteinases MMPs) – LAM, PLCH • Destruction of the bronchial wall and progressive luminal dilatation – PLCH Airway narrowing and check valve mechanism – LIP, amyloidosis • Hamartoma-like cystic alveolar formation – BHD • Cavitation of nodule (inflammatory/infectious, neoplastic)

130. Q 32 Which of the following radiographic features is least likely to be found in Langerhans’ cell histiocytosis of the lung? a.Nodules ranging in size up to 10 mm b.Bilateral reticulonodular opacities c.Pneumothorax d.Pleural effusion e.Honeycomb lung

131. Langerhans’ cell histiocytosis (LCH) d. Pleural effusion Early , Centrilobular nodules (2–10 mm in size) and Reticular and nodular opacities with a predominantly bilateral symmetric upper- to mid-lung distribution. Late , Cysts develop and become the dominant imaging finding. Cysts vary in size but usually are smaller than 1 cm  may result in bullous formation, which then predisposes the patient to recurrent spontaneous pneumothorax. In advanced LCH, honeycomb changes can occur. Pleural effusions are rare. Zaveri et al. 2014

132. Pulmonary Langerhans cell Histiocytosis Diagnosis • BAL: ³5% CD1a cells • Lung biopsy: bronchoscopic or VATS Management • Stop smoking • Sometimes, 2-chlorodeoxyadenosine (2-CdA, cladribine ) • B- raf inhibitors (e.g., vemurafenib )? • Pulmonary hypertension • Prognosis Variable, risk of malignancy

133. Q 33 56 y F , smoker Secretary Progressive SOB for last 2 y Childhood asthma with FH of asthma Not on any medications Chest examination  reduced breath sounds -No skin lesions Previous- 1 y - CXR reported as increase lung volume. FVC 79% FEV1 46% DLCO 60 What is the most likely diagnosis? a.LAM b.PLCH c. Birt -Hogg-Dude syndrome d.LIP

134. LAM Proliferation of abnormal smooth muscle cells (LAM cells – HMB-45+) Sporadic and TSC-related forms; caused by mutation in the TSC genes Mostly women High risk of pneumothorax: 60-80% PFT: Typically obstructive

135. Diagnosis and Management - LAM CT chest findings plus any one or more of the following: • Biopsy of lung or extrapulmonary LAM • Renal angiomyolipomas • Chylothorax (seen in 20-40% during course) • Tuberous sclerosis complex (TSC) • High serum VEGF-D level, >800 pg /mL Management

136. What is the name of this radiological findings?

137. PAP Most are 20-60 y of age (median ~40) Nonspecific presentation: insidious onset DOE, cough - sometimes asymptomatic Fever, fatigue, weight loss, chest pain, haemoptysis Inspiratory crackles in 20- 50% Serum LDH, surfactant A and D, KL-6 (mucinlike glycoprotein) - common, nonspecific Anti-GM-CSF antibodies detectable in serum & BAL fluid in most cases of acquired PAP PFTs: a restrictive defect, reduced DLCO Whole Lung Lavage

138. What is the diagnosis?

139. Radiation-induced Lung Injury After radiation therapy in patients with lung cancer and mediastinal lymphoma, radiologic abnormalities occur in 60-90%; 5-15% symptomatic. Radiation pneumonitis - symptoms 4-12 weeks after irradiation Radiation fibrosis - 6-12 months after irradiation • Imaging: radiographic abnormalities confined to radiation field with “straight line” effect • Management: symptomatic pneumonitis, prednisone 40-60 mg/d x 2 wk , then taper over 4-12 wk

140. Thank you