1. Clinical Case 11 th February 2015 4 th Course of Diffuse Parenchymal Lung Diseases

2. Presentation Identification Male gender Caucasian 39 years-old Born and resident in Bragança Occupation: car collision repair and painting

3. First visit at 27/10/2014 Main complaints Chronic (2 years) non-productive cough Dyspnea on exertion

4. First visit at 27/10/2014 Past medical history Thrombocytopenia of unknown etiology Gastroesophageal reflux disease Allergies: dust mites and grasses Smoker since 16 years (23 pack-year) Environmental exposures: occupational, neighbour with birds Medication: salmeterol/fluticasone inhaler was recently prescribed

5. First visit at 27/10/2014 Physical examination Good performance status Without respiratory discomfort Neck reveals no significant JVD Heart: S1 and S2 present. No murmurs. Lungs: bilateral basal inspiratory crackles Extremities showed no edema

6. High-resolution CT scan

32. UIP UIP Pattern Subpleural, basal predominance Reticular abnormality Honeycombing with traction bronchiectasis

33. UIP UIP Pattern Inconsistent with UIP Pattern Subpleural, basal predominance Reticular abnormality Honeycombing with traction bronchiectasis Profuse micronodules

35. Lung function tests % predicted FVC4.20 L92.3 % FEV13.81 L93.8 % FEV1/FVC90.7 % RV1.96 L104.3 % TLC6.42 L96.4 % RV/TLC30.5 % DLCO40.4 % DLCO/VA57.7 % Arterial blood gases (fiO 2 21%) pH 7.42, pO 2 81.5 mmHg, pCO 2 37.9 mmHg, HCO 3 - 24.8 mmol/L, SO 2 96.2% 6 minute walk test Distance 420 meters, with 3% desaturation (baseline SpO 2 93%, minimum 90%) Initial Borg dyspnea scale 0  final Borg 0

36. Blood analysis Ref. values Hemoglobin RBC 15.6 g/dL 45.5 % 13.0-18.0 43-55 WBC Neutrophils Eosinophils Basophils Lymphocytes Monocytes 6.81 x10 9 /L 44.7 % / 3.04 x10 9 /L 1.9 % / 0.13 x10 9 /L 0.1 % / 0.01 x10 9 /L 44.8 % / 3.05 x10 9 /L 8.2 % / 0.56 x10 9 /L 4.0-11.0 53.8-69.8 0.6-4.6 0.0-1.5 22.6-36.6 4.7-8.7 Platelets73 x10 9 /L150-400 Sedimentation rate33 mm/1 st h0-22

37. Blood analysis Ref. values Glucose87 mg/dL75-110 AST32 U/L10-40 ALT36 U/L7-56 Urea28 mg/dL10-50 Creatinine0.69 mg/dL0.67-1.17 Na138 mEq/L135-147 K3.9 mEq/L3.5-5.1 Cl100 mEq/L101-109 C-reactive protein6.5 mg/L< 3.0

38. Blood analysis Ref. values AbHCVNegative AgHBs, AbHBs and AbHBcNegative AbHIVNegative Serum protein electrophoresisNormal Total IgE (high specific IgE to tree, dust mite, grass, weed) 1497 UI/mL150-1000

39. Blood analysis ImmunologyRef. values Anti-nuclear antibodies (ANA)Negative< 1/100 Anti-Ds DNA antibodies< 10.0 UI/mL< 100 Anti-CCP< 0.4 U/mL< 7 Rheumatoid factor< 10.0 UI/mL< 30 Anti-ENA antibodies anti-Jo 1 anti-RNP anti-SCL70 anti-Sm anti-SSa anti- SSb Negative

40. Flexible bronchoscopy and middle lobe BAL Bronchoalveolar lavage analysis Total celularity 2.56 x10 5 /mL Lymphocytes 6% Neutrophils 4% Eosinophils 2%

41. Additional diagnostic tests Upper digestive endoscopy erosions in the distal third of esophagus gastric hiatal hernia duodenum exhibited no remarkable alteration Conclusion: peptic esophagitis grade 2

42. 39 yo caucasian male, works in car collision repair and painting Multiple allergies, Gastroesophageal reflux disease and Thrombocytopenia of unknown etiology Smoker. No drugs CT: Reticular abnormality and honeycombing of subpleural basal predominance + micronodules Lung function tests: decreased diffusion capacity of the lung Blood tests: small increase of ESR and CRP; Autoimmune screening blood tests were normal BAL: normal celularity, with a mild increase in the neutrophil and eosinophil count

43. Definitive diagnosis can be established? Additional diagnostic tests required? Which tests? 39 yo caucasian male, works in car collision repair and painting Multiple allergies, Gastroesophageal reflux disease and Thrombocytopenia of unknown etiology Smoker. No drugs CT: Reticular abnormality and honeycombing of subpleural basal predominance + micronodules Lung function tests: decreased diffusion capacity of the lung Blood tests: small increase of ESR and CRP; Autoimmune Screening Blood Tests were normal BAL: normal celularity, with a mild increase in the neutrophil and eosinophil count

44. Transbronchial cryobiopsy -Peribronchiolar fibrosis, associated to the presence of inflammatory cells infiltration, mostly lymphoplasmacytic and some aggregates of neutrophils -Focal subepitelial loose fibrosis (fibroblastic foci?) Inconclusive

45. Surgical lung biopsy

47. Conclusion: UIP pattern, most probable secondary to HP with chronic bronchiolitis and bronchiolar fibrosis. Due to isocyanate inhalation? The case was therefore sent to Prof. Helmut Popper.

48. fibroblastic foci cystic degeneration of primary lobules (honeycombing) timely heterogeneity (fibroblastic foci and fibrosis) geographic variation (fibrosis and uninvolved lung lobules) UIP

49. Not IPF Secondary UIP fibrosis of pleura chronic inflammation changes at bronchioles (fibrosis, occlusion) fibroblastic foci cystic degeneration of primary lobules (honeycombing) timely heterogeneity (fibroblastic foci and fibrosis) geographic variation (fibrosis and uninvolved lung lobules) UIP

50. Helmut Popper Institute of Pathology | Medical University of Graz Chronic Hypersensitivity Pneumonia Autoimmune disease Isocyanate toxicity Most often present with DAD or organizing pneumonia Systemic sclerosis? (grade 4 sclerosis of pulmonary arteries) Sjögren’s syndrome, Rheumatoid Arthritis and SLE not likely changes at bronchioles (fibrosis, occlusion) … but no granulomas, low lymphocytes on BAL

51. What’s the most probable diagnosis? Which treatment is indicated? Should he be advised to change job?