Eosinophil Progenitors in Patients With Non-Asthmatic Eosinophilic Bronchitis, Eosinophilic Asthma, and Normal Controls.

Objective: This study aims to explore the potential of in situ airway differentiation of eosinophil progenitors (EoPs) and hematopoietic progenitor cells (HPCs) in sputum and peripheral blood from patients with non-asthmatic eosinophilic bronchitis (NAEB), eosinophilic asthma (EA), and healthy controls (HC). Methods: Using flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 µg, bid) or budesonide and formoterol (200/6 µg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated. Results: At baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (p<0.05) compared to HC. There were no differences between NAEB and EA. After 1 month of inhaled corticosteroid (ICS) treatment, NAEB patients showed a significant improvement in cough symptoms, but the attenuation of sputum HPC and EoP levels was not significant. Conclusions: NAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling in situ airway differentiation of EoPs may control airway eosinophilia and provide long-term resolution of symptoms in NAEB.

Elevated Circulating CD4+CD25+CD127-/low Regulatory T Cells in Patients with Non-asthmatic Eosinophilic Bronchitis.

PURPOSE: Non-asthmatic eosinophilic bronchitis (NAEB) is a common cause of chronic cough. It is characterized by sputum eosinophilia like asthma but lacks airway hyperresponsiveness. Regulatory T cells (Tregs) are recognized as immune suppressors and are involved in the pathogenesis of asthma. However, the relationship between Tregs and NAEB remains unknown. This study aimed to preliminarily explore the role of Tregs in NAEB by comparing circulating Tregs levels to asthma and healthy controls. METHODS: Fractional exhaled nitric oxide (FeNO), spirometry with bronchial provocation test, sputum induction and blood routine test were performed in all subjects. Peripheral blood mononuclear cells were used to detect the Tregs (CD4+CD25+CD127-/low) by flow cytometry. Relationship between the levels of circulating Tregs and clinical indexes was also observed. RESULTS: A total of 15 patients with NAEB, 20 patients with asthma and 11 healthy controls were included. The absolute numbers of circulating Tregs in the NAEB group (49.8 ± 18.9 × 103 cells/ml) and asthma group (53.3 ± 18.7 × 103 cells/ml) were higher than that in healthy control group (32.7 ± 11.6 × 103 cells/ml) (both P < 0.01). In total, the level of circulating Tregs showed positive correlation with FeNO (r = 0.30, P < 0.05). CONCLUSION: Tregs may play a key role not only in asthmatic patients, but also in patients with NAEB, as reflected by the elevated Tregs in peripheral blood.

Arnold Nerve Reflex: Vagal Hypersensitivity in Chronic Cough With Various Causes.

BACKGROUND: A higher incidence of Arnold nerve reflex (ANR) has been observed in patients with chronic cough. However, the different ANR response in various causes of chronic cough remains unclear. Furthermore, it is unknown whether ANR will change after effective treatment. METHODS: Patients with chronic cough were enrolled in the Guangzhou Institute of Respiratory Health. The causes of chronic cough were diagnosed via a validated management algorithm. Patients underwent an assessment of ANR response before and after 1 month of etiologic treatment. RESULTS: A total of 127 patients with chronic cough and 55 healthy control subjects were enrolled. The positive response, defined as cough-only ANR or urge-to-cough (UTC), was present in 14.8% of patients with cough variant asthma (CVA), 11.1% of patients with upper airway cough syndrome, 15.4% of patients with gastroesophageal reflex related cough (GERC), 4.8% of patients with eosinophilic bronchitis, and 26.9% of patients with unexplained cough (UC). No ANR or UTC was found in the healthy control subjects. The incidence of the positive response was higher in subjects with CVA, GERC, and UC compared with healthy control subjects (all P < .05). No difference was observed among the different causes of chronic cough (all P > .05). After 1 month of treatment, 87.5% of patients identified with a positive response changed to a negative response. In a subgroup analysis, an increased cough sensitivity to capsaicin was found in the patients with a positive response compared with the patients with a negative response (P < .05). CONCLUSIONS: A positive ANR appears to be a sign of vagal hypersensitivity and can be reversed after effective treatment of chronic cough. However, although various causes of chronic cough share a similar feature of an elevated ANR response in a minority of patients, there appears to be limited usefulness in assessing ANR because it does not appear to be a valid predictor of etiology of chronic cough or outcome of treatment.