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Background: Non-asthmatic eosinophilic bronchitis (NAEB) is one common cause of chronic cough which is characterized as airway eosinophilic inflammation like asthma but lack of airway hyper-responsiveness. Previous studies showed that Th2-pathway plays a role in NAEB, but the role of non-Th2 pathway in mechanism of NAEB remains unknown. Recently, IL-17A, a Th17-pathway cytokine, has been demonstrated to be involved in asthma development. However, the relationship between Th17-pathway and NAEB is unknown., Methods: We aim to assess the airway level of IL-17A in the subjects with NAEB. Relationships between the IL-17A level and airway function in NAEB or asthma are also observed. We measured IL-17A concentrations in the sputum supernatant from 12 subjects with EB, 16 subjects with asthma [9 eosinophilic asthmatic (EA) and 7 non-eosinophilic asthmatic (NEA) according to the sputum eosinophil ≥ 3%], and 9 healthy control subjects., Results: Increasing IL-17A level was found in NAEB group (29.65 ± 8.13 pg/ml), EA group (32.45 ± 3.22 pg/ml), and NEA group (29.62 ± 6.91 pg/ml) compared with the healthy control group (17.05 ± 10.30 pg/ml) (P < 0.05, P < 0.01, P < 0.05, respectively). The sputum IL-17A level was correlated with FENO (r = 0.44, P < 0.01), FEV1/FVC% (r = - 0.38, P < 0.05), MMEF%pred (r = - 0.34, P < 0.05), and sputum neutrophil% (r = 0.33, P < 0.05) in total., Conclusion: Th17-pathway may play a role not only in asthmatics, but also in subjects with NAEB, as reflected by increasing IL-17A concentrations in sputum supernatant.

Background: Several chemokines, notably eotaxin, mediate the recruitment of eosinophils into tissues via the CCR3 receptor., Objective: In this study, we investigated the role of CCR3 agonists in asthma by observing the effect of a small molecule antagonist of the CCR3 receptor (GW766994) on sputum eosinophil counts in patients with eosinophilic asthma., Methods: Clinical and physiological outcomes, the chemotactic activity of sputum supernatant for eosinophils and the presence of eosinophil progenitors in sputum and blood samples were also studied., Results: In a double-blind parallel group study, 60 patients with asthma were randomized to 300 mg of GW766994 twice daily or matching placebo for 10 days followed by prednisone 30 mg for 5 days. Of these patients, 53 had a sputum eosinophil count > 4.9% at baseline. Despite plasma concentrations of drug consistent with > 90% receptor occupancy during the dosing period, the CCR3 antagonist did not significantly reduce eosinophils or eosinophil progenitor cells (CD34(+) 45(+) IL-5Rα(+)) in sputum or in blood. The ex vivo chemotactic effect of sputum supernatants on eosinophils was attenuated by GW766944 compared to placebo. There was no improvement in FEV1 ; however, there was a modest but statistically significant improvement in PC20 methacholine (0.66 doubling dose) and ACQ scores, (0.43). Whilst the improvement in PC20 is statistically significant, it is not of clinical significance., Conclusions and Clinical Relevance: In conclusion, this study calls into question the role of CCR3 in airway eosinophilia in asthma and suggests that other cellular mechanisms mediated by the CCR3 receptor may contribute to airway hyperresponsiveness., (© 2013 John Wiley & Sons Ltd.)

Asthma and nonasthmatic eosinophilic bronchitis are among the most common causes of chronic cough, accounting for about 25 and 10% of cases, respectively. Chronic cough due to asthma may present in isolation in which case it is known as cough-variant asthma. Nonasthmatic eosinophilic bronchitis is characterized by the presence of eosinophilic airway inflammation in the absence of variable airflow obstruction or airway hyperresponsiveness. Both conditions share many immunopathological features with the exceptions to date of mast cell infiltration into the airway smooth muscle, increased IL-13 expression, and narrowing and thickening of the airway wall, which are features reserved to asthma. In most cases the trigger that causes the cough is uncertain. However, removal of potential triggers is important to consider, in particular with respect to occupational exposure to known sensitisers. In both conditions there is subjective and objective improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia. Whether eosinophilic inflammation is the cause of cough or an epiphenomenon is uncertain, but the failure of anti-IL-5 to modify cough in asthma has questioned a causal association. In asthma, beta-agonist theophylline, leukotriene receptor antagonist, and oral corticosteroid therapy improve cough. In noneosinophilic bronchitis, some patients require oral corticosteroids but the benefit of other additional therapies is unknown. In general, response to therapy in both conditions is very good and the limited long-term data available suggest that both usually have a benign course, although in some cases persistent airflow obstruction may occur.

Upper-airway cough syndrome often coexists with other diseases that elicit chronic cough. However, the concomitant conditions are not always relevant to chronic cough, which complicates the cause diagnosis of chronic cough. The objective of this study was to explore the diagnosis and clinical implication of upper-airway cough syndrome with latent eosinophilic bronchitis. Eleven patients with upper-airway cough syndrome and latent eosinophilic bronchitis were retrospectively analyzed for their clinical manifestations, changes of eosinophilia in induced sputum, and cough threshold with capsaicin defined as capsaicin concentration that elicits two or more coughs (C2) and five or more coughs (C5) between pretreatment and post-treatment. All patients reported a history of allergic rhinitis, showed persistent dry cough or small amounts of viscid sputum with a time course of 2-60 months (median = 7 months), and presented with symptoms and signs of rhinitis, normal lung function, and airway responsiveness. Initial eosinophil percentage in induced sputum was 3.5-8.0%. Cough disappeared after 2-5 (3 +/- 1) weeks of only oral antihistamine. With successful treatment, cough threshold C2 increased from 1.73 +/- 1.45 to 4.43 +/- 4.50 micromol/L (t = 2.64, P = 0.025) and C5 increased from 2.79 +/- 2.16 to 10.10 +/- 8.22 micromol/L (t = 3.10, P = 0.011). However, there was no significant change of eosinophil percentage in induced sputum (4.8 +/- 1.5% vs. 4.4 +/- 1.4%, t = 0.84, P = 0.427). Upper-airway cough syndrome with latent eosinophilic bronchitis is a unique condition. The recognition of the entity may avoid unnecessary use of corticosteroids.

Eosinophilic bronchitis is a recently described condition in patients with chronic cough, sputum eosinophilia, normal spirometry and no evidence of bronchial hyperreactivity. The aim of the study was to assess the causes of chronic cough and to identify the prevalence of eosinophilic bronchitis as a cause of chronic cough. Thirty-six patients [mean age 45.4 +/- 14.3 years (range 16-69 years), M/F: 4/32] with an isolated chronic cough lasting for more than 4 weeks were recruited from the outpatient clinic. In all patients, after a full history and physical examination, blood eosinophil count, eosinophilic cationic protein (ECP), serum total and specific IgE levels were measured. Spirometry, methacholine provocation test, skin prick tests, ear, nose and throat examination, induction of sputum and esophageal pH testing were performed. The mean duration of cough was 31.3 +/- 52.3 months. Sputum eosinophilia greater than 3% was present in 12 (33.3%) patients and they were diagnosed as eosinophilic bronchitis. Their induced sputum had a mean eosinophil count of 8.3% and a mean ECP level of 98.5 mg x l(-1), which were higher than the others (P=0.003, both). The diagnosis of the remaining patients were postnasal drip syndrome in eight, gastroesophageal reflux disease in eight, post-infectious cough in two and cough-variant asthma in one patient. In conclusion, eosinophilic bronchitis is an important cause of chronic cough and should be considered in the assessment of patients before regarding them as having idiopathic chronic cough.

To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.

We have compared the inflammatory changes in the bronchial mucosa and the increase in the airway hyperresponsiveness in an asthmatic patient during the deterioration of symptoms. A striking increase in the number of bronchial epithelial eosinophils was associated with an increase in both airway hyperresponsiveness and asthma symptoms. During 16 wk of treatment with the inhaled corticosteroid, budesonide, the patient's clinical status and airway hyperresponsiveness improved. This was accompanied by an improvement in the ultrastructure of bronchial mucosa and a decrease in the number of epithelial eosinophils.

Sputum cell-counts were studied in 7 non-smokers with corticosteroid-responsive chronic cough productive of sputum and 8 smokers with a clinical diagnosis of chronic bronchitis, all of whom had normal lung function tests and methacholine airway responsiveness, and in 10 non-smokers with asthma, examined during an exacerbation. Sputum from asthmatic patients and subjects with corticosteroid-responsive cough contained eosinophils and metachromatic cells. Macrophages were by far the dominant cell type in sputum from subjects with chronic bronchitis. Airway inflammation with eosinophils and metachromatic cells is not always accompanied by increased airway responsiveness, and current definitions of obstructive airways disease may need to be revised.