A 58-year-old post menopausal nonsmoker Caucasian female was evaluated for chronic cough of 13 months duration. The patient has a past medical history significant for hyperlipidemia, and obstructive sleep apnea. The cough was described as a dry cough and was severe enough to cause her to gag and vomit. She reported frequent nighttime awakenings due to cough. Initial work-up at another facility was reported as normal pulmonary function tests, negative methacholine challenge test, normal chest radiogram, normal chest and sinus CT scans, and a normal inspection of vocal cords, trachea, and bronchi by flexible bronchoscopy. A bronchial biopsy was performed during the bronchoscopy and results are reviewed below. She was prescribed an empiric one-week trial of prednisone which resulted in near resolution of her cough. The patient was then started on inhaled fluticasone and tiotropium without a clear diagnosis given. As a consequence, she was uncertain about the use of the inhalers and was noncompliant. The cough came back prompting another evaluation. The cough was not associated with rhinorrhea, sneezing, wheezing, dyspnea, postnasal drip, heartburn, chest pain, fever, sputum production, hemoptysis, weight loss, or night sweats. She denied ever having had exposure to immigrants or any travel outside her home state. No history of ACE inhibitors intake was noted. The patient worked with Christmas trees helping to shear, bale, and make wreaths. She has a dog at home but no other pets. She has no prior history of allergies or allergy testing. The patient did not have a history of childhood asthma, sinusitis, GERD, hayfever or tuberculosis, and no history of indoor hot tub. In addition, the patient complained of bilateral sharp chest discomfort for about 10 months, associated with the cough episodes, nonradiating and not associated with exercise, nausea, or diaphoresis.
Physical examination showed normal vital signs. There was a perforated right tympanic membrane. Oropharynx showed no exudates or lesions, and normal nasal mucosa with no polyps. Lung auscultation showed normal breath sounds, and no wheezing or crackles. The heart rhythm was regular and auscultation evidenced no murmurs, rub, or gallop; her abdomen was soft with no organomegaly, extremities with no peripheral edema, and the skin showed no cyanosis or rash. Finally, no clubbing was observed. Diagnostic work up included a spirometry with FEV1 112% of predicted, FVC 111% of predicted, and an FEV1/FVC ratio of 81. The shape of the inspiratory and expiratory flow-volume curves was unremarkable. The diffusing capacity showed a DLCO of 97% of predicted. The methacholine challenge test showed that the PC20 was >16 mg/dL (normal bronchial responsiveness). Chest CT showed no infiltrates or pleural effusions, and no abnormal hilar or mediastinal lymphadenopathy. CT scan of the sinuses showed normal mucosal thickening and no air-fluid levels. A 24-hour esophageal pH probe of proton pump inhibitor excluded gastroesophageal reflux disease. CBC showed hemoglobin of 13.6 g/dL (normal range 12-15.5 g/dL), the WBC was 9.2 x 109/L (normal range 3.5-10.5 x 109/L), and differential evidenced 60% Neutrophils, 1% eosinophils, 35% lymphocytes, and 4% monocytes. Electrolytes including sodium, potassium, chloride, calcium, magnesium, and phosphorus were within normal limits. Serum creatinine and BUN were 0.8 mg/dL (normal range 0.6-1.1 mg/dL), and 12 mg/dL (normal range 6-21 mg/dL) respectively. Serology for Bordetella pertussis and Respiratory Syncytial virus (RSV) were negative. Her oral exhaled nitric oxide was elevated to 158 parts/billion (upper limit of normal <30 parts/billion). The biopsy of the left main bronchus was reviewed and revealed peribronchiolar chronic inflammation with eosinophils and thickened basement membrane (Figure 1). Sputum examination for eosinophil was not performed. Based on the normal spirometry, negative methacholine challenge test, the elevated oral exhaled nitric oxide that correlates with eosinophilic airway inflammation and bronchial biopsy, a diagnosis of chronic cough due to eosinophilic bronchitis was made. To exclude the possibility of a cardiac cause of her chest discomfort, the patient underwent an adenosine sestamibi study. During this test, she developed sudden onset of dyspnea, flushing, and bilateral wheezing (confirmed by two different clinicians) during the adenosine infusion and required hospitalization in the intensive care unit, where she was successfully treated with intravenous aminophylline.