Cryptogenic Adult Bronchiolitis is a rare clinicopathologic syndrome that represents a diagnostic challenge to clinicians. The pathologic findings are typical for cellular obliterative bronchiolitis, with acute and chronic inflammatory infiltrates in the bronchioles while the alveolar parenchyma is spared. Cases are labeled cryptogenic when cultures and serology for infectious sources are negative and no etiology is elicited. The incidence and pathogenesis are unknown, though the disease tends to occur in middle-aged women who present with non-productive cough for several months. Patients usually have a progressive course and there are no proven therapies.  Macrolide antibiotics have been shown to have dramatic effects on survival when used to treat patients with Diffuse Panbronchiolitis (DPB). Given the current lack of effective therapy for Cryptogenic Adult Bronchiolitis, it seems reasonable to try long-term macrolide therapy in this unique patient population.
A 46 year-old woman was evaluated in October 2003 for chronic cough of three months duration, without any apparent precipitating event, that did not respond to conventional therapies, including cough suppressants, short course antibiotics (azithromycin for five days), reflux medications and asthma inhalers. She had no significant past medical history and was otherwise in good health. Her clinical exam was normal except for diffuse, end-inspiratory squeaks. Pulmonary Function Tests revealed a restrictive pattern (Fig. 1). Initial chest CT showed increased interstitial markings, peripheral bronchiectasis and a mosaic pattern seen only on expiratory views. Laboratory testing was significant for negative ANA and RF. A bronchoscopy with lavage was performed and all subsequent cultures were negative, including viral, legionella, mycoplasma and mycobacterial. The patient was empirically started on prednisone 40mg qd, but after one month of therapy, she denied any symptomatic improvement and her pulmonary function tests were unchanged (Fig. 1). In addition, she developed an elevated fasting glucose and the steroids were discontinued. The patient underwent a surgical lung biopsy that revealed a patchy bronchiolocentric inflammatory process with minimally involved alveolar parenchyma. Airway lumens were distorted and narrowed by lymphoplasmacytic and neutrophilic infiltrates. (Fig 2) The clinical and pathologic diagnoses were consistent with Cryptogenic Adult Bronchiolitis. The patient recovered quickly from surgery, but still complained of chronic cough and limited exercise tolerance. She was empirically started on Clarithromycin 250mg bid. After one month of treatment, she stated that her cough had diminished and her dyspnea was improved. Pulmonary function tests were repeated and demonstrated improvement in FEV1, FVC, FEF 25-75%, and TLC (Fig. 1).
The cryptogenic presentation of bronchiolitis remains a diagnostic and therapeutic mystery. The pathologic findings, as well as the response to long-term macrolides in the case described, raises the suspicion that Cryptogenic Adult Bronchiolitis may have an unidentified infectious etiology or an undefined immune mechanism. The immunomodulatory activity of macrolides has been demonstrated in several pulmonary disorders, including Cystic fibrosis, Asthma, and DPB. DPB, which had a 26% five year survival rate in 1984 before the use of macrolides, now has a 10 year survival rate of 94%. Most patients experience a clinical and physiologic improvement within the first month of treatment.
We believe this case is the first report using long-term macrolide therapy in patients with Cryptogenic Adult Bronchiolitis. The mechanism of disease and therapy are unknown, but may be related to DPB given the similarity in response. Further studies are warranted.
B.D. Gelbman, None.