桑原 和伸

BACKGROUND: The genetic factors contributing to exacerbations in type 2-low asthma are not well understood. OBJECTIVE: We sought to clarify the association between variants in gasdermin B/orosomucoid-like 3 (GSDMB/ORMDL3) on 17q21 and exacerbations in type 2-low asthma. METHODS: This follow-up study of the multicenter Kinki Hokuriku Airway disease Conference (KiHAC) enrolled adults with asthma who were receiving inhaled corticosteroids. It examined associations between asthma exacerbations requiring systemic corticosteroids over 2 years and clinical and genetic factors in patients with the type 2-low endo-genotype, defined by serum periostin levels lower than 95 ng/mL and the IL4RA rs8832 A allele. Exacerbation risks were also evaluated in patients with the type 2-low genotype, defined by both the POSTN rs3829365 C allele and the IL4RA rs8832 A allele, using the KiHAC and replication cohorts. The genetic variant rs7216389 in GSDMB was the primary focus for assessing genetic risk. RESULTS: A total of 115 patients with the type 2-low endo-genotype were analyzed (mean age, 62 years; 76.5% female). During the 2-year follow-up, 32 patients experienced 1 or more exacerbation. Multivariate analysis identified the rs7216389 TT genotype, recent exacerbations, female sex, and higher body mass index as independent risk factors for asthma exacerbations in patients with the type 2-low endo-genotype. The association between the rs7216389 TT genotype and exacerbations was confirmed in patients with the type 2-low genotype in the KiHAC (n = 89) and replication (n = 125) cohorts. CONCLUSIONS: The rs7216389 TT variant on 17q21 may be an independent risk factor for exacerbations in adults with type 2-low asthma, highlighting the role of GSDMB in its pathophysiology.

OBJECTIVES: To examine the differences in antimicrobial selection outcomes in nursing and healthcare-associated pneumonia (NHCAP) patients with and without risk factors for drug-resistant pathogen (RDRP) infection, and to identify the cause of in-hospital death after improvement of NHCAP. METHODS: We conducted a retrospective analysis of the medical records of hospitalized adult patients with NHCAP. NHCAP patients were divided into the RDRP and non-RDRP groups. The RDRP group was further classified into the narrow and broad subgroups according to the type of empirical antimicrobial agent selected. The difference in mortality between these subgroups was then examined. The cause of all in-hospital deaths was also evaluated. RESULTS: e evaluated 220 patients with NHCAP. There was no difference in mortality between the narrow and broad subgroups (11.8% vs. 15.4%, p=0.655). Among the group with improved NHCAP, 11.3% (n=23/203) died in hospital before discharge. Although the causes of death in patients who improved after NHCAP were diverse, the most common was recurrence of pneumonia. CONCLUSIONS: Empirical antimicrobial therapy for NHCAP may not always require selection of broad-spectrum antimicrobial agents, as has been previously reported. Patients with NHCAP may die from other causes, even after NHCAP has improved.

OBJECTIVES: To determine whether the prevalence of gram-negative bacilli (GNB; Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli) in sputum and urine specimens from outpatients and inpatients differed by season and according to temperature and humidity changes. METHODS: In this retrospective study, microbiologic data for adult patients from 2008 to 2019 were retrieved from the electronic database of a hospital in Japan. Data were categorized by specimen type (sputum and urine) and specimen collection (outpatient and inpatient). Associations between variables were assessed using Spearman's rank correlation coefficients. Differences between groups were assessed using Pearson's chi-square test and analysis of discrete variance. RESULTS: Among inpatients, the frequencies of P. aeruginosa and K. pneumoniae isolation from sputum specimens were higher in summer and autumn. The frequency of P. aeruginosa isolation from urine specimens was higher in autumn. These seasonal trends were observed in specimens from both outpatients and inpatients. No seasonal trend was observed in the frequency of E. coli isolation. Mean monthly temperature was positively correlated with the frequency of isolating P. aeruginosa (r=0.2198, p=0.0081) and K. pneumoniae (r=0.3443, p=0.00002) from sputum as well as with the frequency of isolating K. pneumoniae (r=0.1905, p=0.0222) from urine. Mean monthly humidity was positively correlated with the frequency of isolating K. pneumoniae (r=0.2602, p=0.0016) from sputum. CONCLUSIONS: GNB were isolated more frequently in summer and autumn than in other seasons. These seasonal trends were observed for both outpatient and inpatient specimens. Seasonality should be considered for optimal infection control of GNB in hospitals.

OBJECTIVE: This study aimed to evaluate the predictors of response to benralizumab therapy in patients with refractory bronchial asthma. METHODS: After 16 weeks of benralizumab therapy, 32 patients with refractory bronchial asthma were assigned to two groups based on the response to treatment as indicated by changes in the asthma control test score (responders and non-responders) and evaluated for clinical characteristics. RESULTS: Overall, 25 responders and 7 non-responders were identified at week 16. Logistic regression analysis identified a peripheral eosinophil count of >300/μL during benralizumab treatment and a maximal peripheral eosinophil count of >300/μL in the past year as predictors of response. CONCLUSIONS: The predictors of response to benralizumab included a peripheral eosinophil count of >300/μL during treatment and a maximal peripheral eosinophil count of >300/μL in the past year. These findings could improve patient selection and reduce medical costs in the future.