堀口 高彦

INTRODUCTION: Screening for ω-5 gliadin specific IgE antibody (sIgE) has high diagnostic utility in cases of suspected wheat-dependent exercise-induced anaphylaxis (WDEIA); however, negative cases may require confirmatory tests, such as the oral challenge test. Thus, newly identified allergens that can be used for the serological diagnosis of WDEIA are needed. This study aimed to identify additional sIgE biomarkers of WDEIA. METHODS: Forty-two patients with WDEIA (5 negative/37 positive for ω-5 gliadin sIgE) were enrolled. For comparison, 8 patients with immediate-type wheat allergy without WDEIA and 20 healthy controls without wheat allergy were also enrolled. Extracted wheat proteins were separated by 2D-PAGE. Proteins that reacted with serum IgE antibody in 2D Western blotting (2D-WB) were identified using mass spectrometry. Recombinant proteins were synthesized in Escherichia coli, and the antigenicity was tested using ELISA and the basophil activation test. RESULTS: In 2D-WB, nine proteins reacted with the serum IgE antibody from at least 60% of patients with WDEIA (n ≥ 25/42). ELISA revealed that alpha/beta gliadin MM1 exhibited the highest positive immunoreactivity in 23 of 26 patients who were positive for ω-5 gliadin sIgE (88%) and in 5 of 5 patients who were negative for ω-5 gliadin sIgE (100%). Alpha/beta gliadin MM1 exhibited significantly higher basophil activation in 14 patients with WDEIA when compared to 5 individuals without a wheat allergy. CONCLUSIONS: Alpha/beta gliadin MM1 sIgE exhibited the highest seropositivity, even among patients who were negative for ω-5 gliadin sIgE. The inclusion of alpha/beta gliadin MM1 in allergen-sIgE tests may improve the sensitivity for diagnosing WDEIA.

RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.

There is a concern that persons with underlying respiratory disease may have increased susceptibility to COVID-19 and/or increased severity/mortality if infected. However, information regarding such patients during the first wave of the epidemic is lacking in Japan. We surveyed chest physicians nationwide, and collected anonymous data concerning 1444 patients. Among COVID-19 patients, the prevalence of asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD) was 3.4%, 4.8%, and 1.5%, respectively. Among COVID-19 patients with these 3 comorbidities, exacerbation of the comorbidity occurred in 12.2%, 18.8%, and 36.4%, respectively, and mortality (6.2% overall) was 4.1%, 13.0%, and 31.8%, respectively. The prevalence of asthma among COVID-19 patients was not higher than that for the general population, and mortality in COVID-19 patients with asthma was not higher than mortality in COVID-19 patients without underlying respiratory disease. COVID-19 patients having COPD or ILD had relatively high mortality, especially for ILD.