VI-45. A 56-year-old woman presents for evaluation of dyspnea and cough for 2 months. During this time, she has also had intermittent fevers, malaise, and a 5.5-kg (12- lb) weight loss. She denies having any ill contacts and has not recently traveled. She works as a nurse, and a yearly purified protein derivative test performed 3 months ago was negative. She denies any exposure to organic dusts and does not have any birds as pets. She has no other exposures and no autoimmune symptoms. She takes no medications regularly. On physical examination, diffuse inspiratory crackles and squeaks are heard. A CT scan of the chest reveals patchy alveolar infiltrates and bronchial wall thickening. Pulmonary function testing reveals mild restriction. She undergoes a surgical lung biopsy. The pathology shows granulation tissue filling the small airways, alveolar ducts, and alveoli. The alveolar interstitium has chronic inflammation and organizing pneumonia. What is the most appropriate therapy for this patient? 

A. Azathioprine 100 mg daily 

B. Nintedanib 150 mg twice daily 

C. Pirfenidone 2403 mg daily 

D. Prednisone 1 mg/kg daily 

E. Referral for lung transplantation 

VI-45. The answer is D. (See Harrison’s 19th edition, Chap. 315) This patient is presenting with subacute pulmonary symptoms, intermittent fevers, myalgias, and malaise. The biopsy shows a pattern of cryptogenic organizing pneumonia (COP). COP (formerly bronchiolitis obliterans organizing pneumonia) usually presents in the fifth or sixth decades with a flulike illness. Symptoms include fevers, malaise, weight loss, cough, and dyspnea. Inspiratory crackles are common, and late inspiratory squeaks may also be heard. Pulmonary function testing reveals restrictive lung disease. The typical pattern on chest HRCT is patchy areas of airspace consolidation, nodular opacities, and ground-glass opacities that occur more frequently in the lower lung zones. Pathology shows the presence of granulation tissue plugging airways, alveolar ducts, and alveoli. There is frequently chronic inflammation in the alveolar interstitium. Treatment with high-dose steroids is effective in two-thirds of individuals, with most individuals being able to be tapered to lower doses over the first year. Azathioprine is an immunosuppressive therapy that is commonly used in interstitial lung disease due to usual interstitial pneumonitis. While it may be considered in COP unresponsive to glucocorticoids, it would not be a first-line agent used without concomitant steroid therapy. Because most patients with COP respond to corticosteroids, referral for lung transplantation is not required unless there is a failure to respond to therapy. Nintedanib and pirfenidone are treatments for idiopathic pulmonary fibrosis.