Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1.

BACKGROUND: Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. OBJECTIVE: To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. METHODS: We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. RESULTS: Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV (1) (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01). CONCLUSION AND CLINICAL RELEVANCE: Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV (1) , which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.

Observational study of the natural history of eosinophilic bronchitis.

BACKGROUND: Eosinophilic bronchitis is an important cause of chronic cough. Treatment with inhaled corticosteroids is associated with a short-term improvement in cough and reduced sputum eosinophil count but the long-term outcome is uncertain. OBJECTIVE: To determine the long-term outcome in patients diagnosed with and treated for eosinophilic bronchitis. METHODS: We have performed a longitudinal study of symptoms, eosinophilic airway inflammation, spirometry and airway hyper-responsiveness in all patients diagnosed with eosinophilic bronchitis over 7 years. RESULTS: We identified 52 patients with eosinophilic bronchitis and longitudinal data of greater than 1 year (mean 3.1 years) was available in 32 patients, all of whom were treated with inhaled steroids. Three (9%) patients developed symptoms consistent with asthma and a methacholine PC20<8 mg/mL on one or more occasion. Five (16%) patients developed fixed airflow obstruction defined by a persistent post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity<70%. One (3%) patient had complete resolution of symptoms and eosinophilic airway inflammation off treatment. The remaining patients had ongoing eosinophilic airway inflammation and/or continuing symptoms. Multiple linear regression identified smoking, female gender and area under the curve of sputum eosinophil count over time as the most important predictors of decline in FEV1. CONCLUSIONS: The most common outcome in eosinophilic bronchitis is continuing disease and complete resolution is rare. Asthma and fixed airflow obstruction developed in relatively few patients. The most important factors associated with a more rapid decline in FEV1 were female gender, smoking and prolonged eosinophilic airway inflammation.

Airway function and markers of airway inflammation in patients with treated hypothyroidism.

BACKGROUND: There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. METHODS: Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. RESULTS: Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml: 38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). CONCLUSION: Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.