Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external pathogens from airways. Impaired airway epithelium allows the pathogens to remain in the airway epithelium, which induces aberrant immunological reactions. Dysregulated functions of asthmatic airway epithelium have been reported in terms of impaired wound repair, fragile tight junctions, and excessive proliferation, leading to airway remodeling, which contributes to aberrant airway responses caused by external pathogens. To maintain airway epithelium integrity, a family of epidermal growth factor receptors (EGFR) have pivotal roles in mechanisms of cell growth, proliferation, and differentiation. There are extensive studies focusing on the relation between EGFR and asthma pathophysiology, which describe airway remodeling, airway hypermucus secretion, as well as immunological responses of airway inflammation. Furthermore, the second EGFR family member, erythroblastosis oncogene B2 (ErbB2), has been recognized to be involved with impaired wound recovery and epithelial differentiation in asthmatic airway epithelium. In this review, the roles of the EGFR family in asthmatic airway epithelium are focused on to elucidate the pathogenesis of airway epithelial dysfunction in asthma.

Gastroesophageal reflux disease (GERD) is known as a common comorbidity of asthma and chronic cough. The impact of GERD symptoms on cough-specific quality of life (QoL) in patients with asthmatic cough is poorly understood. The aim of this study is to determine the association of GERD symptoms with cough-specific quality of life in patients with cough variant asthma (CVA) using the Leicester Cough Questionnaire (LCQ). A total of 172 consecutive patients (121 females) with mean cough duration of 45.1 months (range 2-480 months) completed the Japanese version of the LCQ. The Frequency Scale for the Symptoms of Gastroesophageal reflux was administered to assess symptoms of acid-reflux and dysmotility. A range of clinical variables that may determine cough-specific QoL (LCQ) were estimated. The mean LCQ scores was 12.9 (SD 3.5), consistent with severe impairment in QoL. Female gender, symptoms of gastroesophageal dysmotility, sensitization to allergens (house dust and Japanese cedar pollen) and the number of sensitized allergens were associated with lower LCQ scores (i.e. impaired cough-specific QoL) in univariate regression analysis. Acid-reflux symptoms, airway hyperresponsiveness, fractional exhaled nitric oxide, and sensitization to molds were unrelated to the LCQ score. After adjustment for gender, symptoms of gastroesophageal dysmotility was the only significant determinant of impaired cough-specific QoL accounting for 23% of the variance. Cough-specific QoL is severely impaired in patients with CVA. Symptoms of gastroesophageal dysmotility are an independent predictor of cough-specific QoL of patients with CVA.