Bronchiolitis is a fibrotic lung disease involving the small airways characterized by cough, dyspnea and irreversible airflow obstruction. Idiopathic bronchiolitis is frequently confused for common conditions as asthma or chronic obstructive pulmonary disease. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare cause of bronchiolitis. We describe a male with asthma subsequently diagnosed with bronchiolitis due to diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.
A 42-year-old male with asthma was referred for evaluation of cough and exertional dyspnea. He developed a nonproductive cough 10 years prior to referral and had been treated with bronchodilators and corticosteroids without improvement. The cough was paroxysmal, aggravated by fumes and physical activity, but not relieved with antihistamines, antacids or corticosteroids. He smoked tobacco and quit 8 years ago. He denied prior respiratory infections, inhalational injury, substance abuse, aspirin sensitivity, or heartburn. Medications included amilodipine, theophyline, albuterol and fluticasone. Physical examination revealed a healthy appearing male with a respiratory rate 20 min-1 and SpO2 98%. Neck was supple without stridor. Lung fields were clear. Heart examination did not reveal murmurs or extra heart sounds. Peripheral edema was absent. Chest radiography revealed peribronchial thickening. Pulmonary function tests demonstrated airway obstruction with a normal inspiratory flow-volume loop. Review of past pulmonary function studies demonstrated progressive airway obstruction (table). A high resolution chest CT to evaluate for small airway disease revealed bronchial wall thickening and focal areas of ground glass opacities. A bronchoscopy revealed no evidence of vocal chord dysfunction and the transbronchial biopsies were nondiagnostic. Subsequently, an open lung biopsy revealed neuroendocrine cell proliferation in the epithelium as well as submucosal and peribronchial fibrosis with little active inflammation indicative of obliterative bronchiolitis. Immunostains confirmed the presence of neuroendocrine cell hyperplasia. Other etiologies for obliterative bronchiolitis were excluded, leading to the diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. He received a 6 week course of steroids that failed to improve symptoms and pulmonary function testing continued to demonstrate a decline. A six-minute walk demonstrated new onset exercise-induced hypoxemia. Oxygen was prescribed and a lung transplantation evaluation initiated.
Bronchiolitis is frequently overlooked as a cause for chronic cough and dyspnea. Classification of bronchiolitis has been based on clinical history, radiology and histopathology. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is a rare cause of bronchiolitis characterized by cough, longstanding dyspnea and an unrevealing chest radiograph. High resolution chest CT may demonstrate nodules or patchy areas of hyperlucency indicative of air trapping. Pulmonary function studies reveal irreversible airflow obstruction. Open lung biopsy is required to confirm the diagnosis and the histopathologic findings include submucosal bronchial fibrosis with diffuse hyperplasia of neuroendocrine cells in the bronchioles. Neuroendocrine cell hyperplasia is postulated to be a tissue response to hypoxemia. Neuroendocrine release of bombesin, serotonin and calcitonin-related gene protein leads to airway injury and fibrosis and may have a role in the development of chronic obstructive lung disease (1).
Obliterative bronchiolitis may produce persistent cough and dyspnea that may be mistaken for asthma or chronic obstructive pulmonary disease. Neuroendocrine cell hyperplasia is a rare form of bronchiolitis that responds poorly to conventional therapies and progresses to worsening airflow obstruction.
Test dateFEV1 (L)FVC (L)FEF 25-75(L/s)DLCO19992.623.951.3529.9420042.153.400.9127.3420051.742.510.9120.14
Luigi Terminella, None.