Mechanism of Airway Remodeling Induced by Repeated Inhalation of Methacholine in a Mouse Model of Asthma

Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p<0.01)after 15 challenges, but not in the Mch group. Significant increase in thickness of airway smooth muscle layer and the number of goblet cells were revealed in both the OVA and Mch group after 10(p<0.05 and p<0.01, p<0.01 and p<0.05, respectively, for the comparison of the two challenge groups with the control group)and 15 challenges(p<0.05 and p<0.01, both p< 0.01, respectively, for the comparison with control), further, all these measurements were greater in the OVA group than in the Mch group after both 10 and 15 challenges(both p<0.05 and p<0.01, respectively). An increase in mast cell counts within the airway wall was shown in the OVA group after 10 challenges (p<0.01 compared with control), not in the Mch group at all. Epithelia expression of transforming growthfactor b (TGF-b)increased in both challenge groups after 15 challenges(both p<0.05 compared with control), and was higher than in Mch(p<0.05).Conclusion:Repeated Mch inhalation may induce airway remodeling, while comparatively mild, potentially resulting in progressive severity of asthma. The results implicate that the potential risk associated with Mch challenge should be considered

Analysis of the Characteristics of Patients Presenting with Exacerbation of Asthma to Emergency Care Units

Background:Fatal asthma remains a serious problem, and patient self-management of asthma is important to prevent exacerbation. To reduce the asthma mortality rate, we analyzed the characteristics of patients who visited an emergency care unit with exacerbation of asthma.Methods:Subjects were 317 patients(135 men, 182 women;mean age, 47.0 years)who visited the emergency room at Dokkyo Medical University Hospital or Dokkyo Medical University Koshigaya Hospital for exacerbation of asthma between April 2010 and March 2011. When categorized by severity, 41.3% ofpatients were step 1, 8.2% were step 2, 18.9% were step 3, 30.9% were step 4, and 0.6% were unknown. When categorized by primary care physician, 60.3% of patients had a primary care physician at Dokkyo Medical University, 13.6% had one at another hospital, and 26.2% had no primary care physician. When categorized by recovery from exacerbation, control was achieved within 1 day in 63.1% of cases, after more than 1 day in 30.6% of cases, and required admission in 6.3% of cases.Results:The rate of admissions was highest for cases with step 1 severity(step 1, 55.0%;step 2, 20.0%;step 3, 0.0%;and step 4, 25.0%). The rate of admissions did not differ significantly by age(age 15-39 years, 40.0%;40-65 years, 25.0%;>65 years, 35.0%). Initial value of oxyhemoglobin saturation(SpO_2) measured by pulse oximetry was significantly lower in the admission group(SpO_2 92.4%)than in the nonadmissiongroup(SpO_2 95.2%, p<0.01).Conclusion:Patients with step 1 severity who visit an emergency unit with exacerbation of asthma may need regular treatment for asthma. When initial SpO_2 is less than 92%, we should consider hospitalization for treatment of asthma