A 38-year-old man presented with an 8-day history of fever, myalgia, dry cough, dyspnea, and fatigue. He was a current smoker (10 cigarettes a day) and reported no occupational exposure. His medical history was unremarkable. Symptoms persisted despite antibiotic therapy with amoxicillin/clavulanic acid and roxithromycin. At admission, temperature was 38.5 C, respiratory rate was 24/minute, auscultation was normal and no extrathoracic signs were present. Chest X-ray showed diffuse micronodular opacities (Fig. 1A). High-resolution computed tomography (CT) demonstrated a profusion of well-delimited centrilobular micronodules, 2 mm in diameter, with subpleural sparing and a "bud in tree" pattern in some areas (Fig. 1B). Interbronchial lymph nodes were present (Fig. 1C). Arterial blood gases at 21% FiO2 showed PaO2 66 mm Hg, PaCO2 35 mm Hg, pH 7.44. Laboratory parameters were as follows: leukocyte count: 19.8 x 109/L (85% polymorphonuclear cells), C-reactive protein: 305 mg/L and fibrinogen: 12 g/L. Serum electrolytes, and renal and liver function tests were normal, as well as serological tests for Legionella pneumonia, Mycoplasma, Chlamydia, Coxiella psittaci, hepatitis C and B viruses, and HIV. Antinuclear antibody, perinuclear antineutrophil cytoplasmic antibody (P-ANCA), cytoplasmic-ANCA, and cyclic citrullinated protein antibody tests were negative. Urine cocaine test was negative. Bronchoalveolar lavage (BAL) showed 400 x 103 cells/mL, comprising 73% macrophages, 18% lymphocytes, 5% neutrophils, and 4% eosinophils. Golde score was normal (40). Testing for Pneumocystis jiroveci, Mycobacterium tuberculosis, and yeasts remained negative. Transbronchial biopsies were not contributive.
Pulmonary function test results were as follows: FEV1: 1.34 L (34%), FVC: 1.94 L (40%), FEV1/VC: 69%, TLC: 4.24 L (61%), DLCO: 11.59 mL min-1 mm Hg-1 (42%) and KCO: 3.83 mL min-1 mm Hg-1 (97%).
To rule out an infectious disease, lung biopsies were performed under video-assisted thoracoscopy (VATS). Gross examination of slides disclosed a patchy nodular pattern. On microscopic examination, lung architecture was preserved. Nodules consisted in buds of granulation tissue fulfilling distal airspaces and extending from one alveolus to the next one, mimicking in some areas a butterfly pattern. Fibrotic buds disclosed bronchiolocentric predominance and in some areas extended into bronchiolar lumen. No granuloma was seen in lung parenchyma or in peribronchiolar areas. Mild inflammatory infiltrates was seen around fibrotic areas but interstitial inflammation was not present at distance of fibrotic plugs (Fig. 2). No pathogen was identified on Grocott and PAS staining and on biopsy cultures. This histological pattern was consistent with OP. The lack of marked interstitial inflammation and absence of granuloma ruled out other diagnoses such as sarcoidosis or hypersensitivity pneumonia.
Oral corticosteroid therapy was started at 1 mg/kg/day. Improvement of dyspnea was observed after 1 month of treatment, and CT micronodules had dramatically decreased (Fig. 1D). Steroids were tapered over 6 months and lung CT scan returned to normal with no signs of relapse at 5-year follow-up.
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(B) HRCT scan showing diffuse small centrilobular nodules.