3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Clinical Case

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Female Caucasian 57 years old Retired (former teacher) Living in Braga (urban centre) Married Ex-smoker (<10 cig/day for 30 years) Medication: alprazolam 0.25mg, ocasionally Without known occupational or professional exposure Personal history unremarkable Mother with history of “pulmonary fibrosis”

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ February 2011 – 1st consult Major complaint of “dry”, persistent cough in the last 6 months Mild intermittent hand joint pain in the last 2 years Physical examination: Good performance status Weight: 74Kg Lung auscultation: velcro-like crackles in basal areas Skin and joints without significant changes

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung HRCT – February 2011

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung HRCT – February 2011

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung HRCT – February 2011

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung HRCT – February 2011

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung HRCT – February 2011

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Laboratory analysis: unremarkable except ANA 1/80. BAL fluid: Total cellular count: 247 cel/uL Differential count: lymphocytes 31% (CD4/CD8=2.0), neutrophils 13%, eosinophils 8%, macrophages 48% Evaluation from Rheumatology and Internal Medicine/Autoimmune diseases – no evidence of systemic/inflammatory disease

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Lung function (2011)

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ 6-minute walking test: 97>90%; 545m. Rest EKG and echocardiogram both normal.

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ March 2011 Case presented at interstitial lung disease multidisciplinary group in HSJ: Probable usual interstitial pneumonia Questions raised: IPF? Sub-clinical systemic disease related? Chronic hypersensitivity pneumonitis?

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ April 2011 – Surgical Lung Biopsy

Subpleural and paraseptal predominance Patchy parenchyma involvement

Subpleural and paraseptal predominance Patchy parenchyma involvement

Established fibrosis leading to loss of architecture (honeycombing)

Fibroblastic foci adjacent to the established fibrosis

Diagnosis: Usual interstitial pneumonia (UIP) Reactive smooth-muscle hyperplasia Subpleural fatty metaplasia Dilated lymphatics Distorted air spaces Hyperplastic bronchiolar epithelium Thickened blood vessel walls

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Definite (?) diagnosis: IPF Treatment options discussed with the patient Initiated deflazacort + azathioprine + N-acetylcysteine in June 2011. Transplant centre referral

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) Mild exertional dyspnea and chronic cough; stable until the last 3 months with slight deterioration Current treatment: deflazacort 6mg + azatioprine 150mg + N-acetylcysteine 1800mg /day Respiratory rehabilitation program Relevant events: Flu (2012) Herpes-zoster infection (2013)

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) Lung Function 2011 2012 2013 FVC (%) 102 101 92 FEV1 (%) 103 93.5 FEV1/FVC 85 84 TLC (%) 88 83 DLCO (%) 64 51 42 DLCO/VA (%) 75 68 47 6MWT (satO2) 97>90% 96>91% 98>90% 6MWT (dist) 545m 540m 500m

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) HRCT – 2011 HRCT – 2014

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) HRCT – 2011 HRCT – 2014

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) HRCT – 2011 HRCT – 2014

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) HRCT – 2011 HRCT – 2014

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) HRCT – 2011 HRCT – 2014

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) Echocardiogram (2013): abnormal left ventricular relaxation; mild tricuspid insufficiency (estimated pulmonary artery systolic pressure – 47 mmHg). Paranasal sinus CT scan: chronic rinitis Osteodensitometry: within normal range Abdominal echography: hepatic cyst

3º Curso de Doenças Pulmonares Difusas – FMUP/HSJ Evolution (2011-2014) Female patient, 60 years old, with chronic dry cough and exertional dyspnea since 2011, experiencing recent slight deterioration. Radiologic and pathologic UIP-pattern disease IPF with slowly progressive disease? Should we change pharmacological treatment?