Akihiro Tagawa

Pseudomonas aeruginosa-Induced Neutrophilic Lung Inflammation Is Attenuated by Adenovirus-Mediated Transfer of the Heme Oxygenase 1 cDNA in Mice

Heme oxygenase (HO) is well known as the rate-limiting enzyme in the oxidative degradation of heme to biliverdin, carbon monoxide (CO), and iron. Based on recent evidence that overexpression of HO-1 confers protection against various types of cell and tissue injury by regulating apoptotic cell death or cytokine expression profiles, the present study was performed to examine whether the transfer of exogenous HO-1 cDNA in the lung would provide therapeutic effect in a murine model of lung inflammation induced by Pseudomonas aeruginosa. HO-1 overexpression clearly attenuated neutrophil influx and decreased numbers of apoptotic bronchial epithelial cells. Interestingly, the overexpression of Bcl-2, a known antiapoptotic factor, was observed and thought to be the mechanism that inhibits bronchial epithelial cellular apoptosis. It is thus suggested that HO-1 overexpression is useful for treating P. aeruginosa-associated lung inflammation by attenuating neutrophil influx and apoptotic cell death.

Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal mucosal permeability in guinea pigs in vivo

Abstract.Objective: To examine whether heme oxygenase (HO)-1 inhibits cigarette smoke (CS)-induced increase in the airway mucosal permeability.Methods: Mucosal permeability was quantified by monitoring the rate of appearance in the circulation of horseradish peroxidase that had been instilled into the isolated tracheal segment in guinea pigs in vivo, after exposure to CS or room air.Results: Exposure to 10 puffs of CS did not increase the tracheal mucosal permeability but did increase the permeability after pretreatment with zinc protoporphyrin, a competitive inhibitor of HO-1. Moreover, pretreatment with hemin, a potent inducer of HO-1, inhibited the increase in the permeability of the tracheal mucosa induced by 20 puffs of CS exposure.Conclusion: It is concluded that HO-1 has an important role in suppressing the increase in the mucosal permeability induced by CS in guinea pig trachea.

314 GERD Screening by the Use of F-Scale and Allergy Screening for Diagnosis and Treatment of Chronic Cough.

Background Allergy and gastro-esophageal reflux (GERD) are main causes of chronic cough, and simple, easy and rapid screening is desired for diagnosis of these symptoms. We used F-scale (Frequency Scale for Symptoms of GERD: FSSG) for GERD screening, developed by Japanese gastro-enterologist, did general allergy screenings, and investigated clinical outcome after treatment retrospectively. Methods GERD was screened by F-scale questionnaire, composed in twelve questions concerned with reflux symptoms, and scored 5 grades in each symptom. General allergy screening was defined as asking history of allergy, serum immnogloblin E (IgE) test (total, fourteen kinds of specific allergens) and measuring fraction of exhaled nitric oxide (FeNO),its positive range was greater than or equal to 20 ppb. Allergy positive was defined as at least one positive finding of allergy screening test. GERD was treated with proton pump inhibitor (PPI), and allergy was treated with inhaled corticosteroid or histamine H1 receptor blocker or leukotriene receptor antagonist. Results Fifty-four consecutive chronic cough patients were screened in GERD and general allergy screening. Thirty-seven patients (69%) were F-scale positive and 43 patients (80%) were positive in general allergy screening. Thirty patients (56%) were positive in both F-scale and general allergy screening. All patients were treated with allergy medicine or PPI, or both medicines. In all patients screened and treated with both GERD and allergy concurrently, cough improved within 2 weeks, and in patients whose positive finding was either GERD or allergy, cough improved by treatment with PPI or allergy drugs similarly. Delayed screening or treatment of either GERD or allergy was related to delayed improvement of cough. Cough finally improved in all patients in visit within 3 times. Conclusions In examination of chronic cough, adding GERD screening by use of F-scale to general allergy screening is beneficial to proper diagnosis, treatment and rapid improvement of symptom.