Clinical characteristics and cytokine profiles of adult obese asthma with type2 inflammation.

Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4-5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma.

First Report of Klebsiella subsp. Ozaenae Meningitis in Japan.

Although the frequency of community-acquired infections caused by Klebsiella pneumoniae subsp. ozaenae (K. ozaenae) is low, they are often detected in sputum specimens. In addition, lung abscesses, necrotizing pneumonia, and urinary tract infections caused by K. ozaenae have also been reported. We herein report the first detection of K. ozaenae as an etiological agent of bacterial meningitis in Japan. Cases of K. ozaenae meningitis complicated by diabetes mellitus and sinusitis have been reported elsewhere. When Klebsiella pneumoniae is detected in such cases, it is important to use other detection methods in addition to mass spectrometry for correct identification.

Persistent Asthma from Childhood to Adulthood Presents a Distinct Phenotype of Adult Asthma.

BACKGROUND: In approximately 30% of children with asthma, the condition persists into adulthood. The longer duration of asthma in these patients is a risk factor for poor asthma control. However, the characteristics of adult patients with asthma that has persisted since childhood are not well documented. OBJECTIVE: We sought to compare the clinical characteristics among patients with adult-onset asthma, patients who outgrew childhood asthma but relapsed, and patients with persistent asthma since childhood. METHODS: We conducted a cross-sectional study of adult patients with asthma who visited our hospital. We classified them into 3 groups: those with adult-onset asthma (adult-onset), those who had remitted childhood asthma that relapsed (relapsed), and those who had asthma that had persisted since childhood (persistent). The clinical characteristics of these groups were compared. RESULTS: A total of 1443 patients were enrolled. The persistent group was younger and included fewer patients with a smoking history. There were statistically significant differences among the 3 groups in the percentages of patients with a family history of asthma and comorbidities of allergic rhinitis and atopic dermatitis. The proportion of patients with severe asthma differed among the 3 groups (31% in the adult-onset group, 34% in the relapsed group, and 40% in the persistent group; P = .015). The values of forced expiratory flow at 75% of vital capacity were lower in the persistent group than the relapsed or adult-onset group. A multivariable logistic regression analysis (dependent variable: severe asthma) in each group revealed that the factors associated with severe asthma differed among the adult-onset, relapsed, and persistent groups. When we established an overall model that included interaction terms of cohort-by-other factors, there was a trend that comorbidity of allergic rhinitis affected the severity of asthma differently in the relapsed group compared with the other groups. CONCLUSION: The clinical phenotype of asthma that persists from childhood to adulthood seems to be a distinct phenotype of adult asthma.

Isolation of three distinct carbapenemase-producing Gram-negative bacteria from a Vietnamese medical tourist.

Carbapenem-resistant Klebsiella pneumoniae and Escherichia coli, multidrug-resistant Pseudomonas aeruginosa and vancomycin-resistant Enterococcus faecium were isolated from a single patient. The patient came to Japan for advanced medical treatment after having undergone laparoscopic cholecystectomy and hospitalization in Vietnam. Whole-genome sequence analysis revealed that K. pneumoniae harbored blaOXA-48 that was found on a Col156 -type small plasmid, E. coli harbored blaNDM-5 and P. aeruginosa harbored both blaNDM-1 and 16S rRNA methyltransferase (rmtB). To the best of our knowledge, this is the first report of detection of K. pneumoniae harboring blaOXA-48 on a Col156-type small plasmid in the world and P. aeruginosa coharboring genes encoding NDM-1 and RmtB in Japan.

Obesity-associated severe asthma in an adult Japanese population.

BACKGROUND: Severe asthma is increasingly being recognized as an important public health issue. Obesity has been identified as a risk factor for poor asthma control and for worsening of asthma severity. However, most studies investigating obese patients with asthma have been performed in Western countries. Reports on the characteristics of obese Japanese individuals with severe asthma are lacking. Herein, we investigated the clinical characteristics of patients with obesity-associated severe asthma in a Japanese population and the association between obesity and poor asthma control. METHODS: We conducted a retrospective observational study of adult patients with severe asthma. Patients were classified into two groups based on the definition of obesity recommended by the Japan Society for the Study of Obesity: obese (OB) group (body mass index [BMI] ≥25 kg/m2) and non-obese (NOB) group (BMI <25 kg/m2). The two groups were compared. The characteristics of obesity and the metabolic functions are known to differ between males and females; therefore, we analyzed male-only and female-only cohorts separately. RESULTS: A total of 492 patients were enrolled. Age, smoking history in terms of number of pack-years, daily controller medications use, and spirometric data were not significantly different between the OB and NOB groups in either cohort. In the female cohort, the annual exacerbation ratio and the percentage of frequent exacerbators were significantly higher in the OB group compared to the NOB group. A multivariate logistic regression analysis showed that obesity was independently associated with frequent asthma exacerbations in the female cohort. CONCLUSIONS: Our study revealed that obesity, defined as a BMI ≥25 kg/m2, was independently associated with poor asthma control (including acute exacerbations) in adult Japanese females with severe asthma.

A case of falciparum malaria: Acute hearing loss as the initial symptom.

A 49-year-old healthy woman, who returned from Burkina Faso, visited an ear, nose, and throat clinic with complaints of left hearing loss, tinnitus, and dizziness. Pure tone audiometry demonstrated bilateral mild sensorineural hearing loss. Three days later, she was transported in an ambulance to a general hospital due to high fever and disturbance of consciousness. Plasmodium falciparum was found in the peripheral blood smear. After diagnosing severe falciparum malaria with cerebral involvement, quinine hydrochloride, clindamycin, and artemether/lumefantrine were administered. After recovery of consciousness, she was followed up at our department with bilateral hearing loss. After taking prednisolone for 10 days, there was improvement to normal hearing level. Furthermore, no neurologic sequelae were observed. In this case, acute sensorineural hearing loss occurred before administration of the antimalarial drug. Therefore, hearing loss was not drug-induced, but was caused by the malaria itself. In patients with acute hearing loss and who have history of travel to tropical regions, physicians should include malaria and other causes of acute deafness in the differential diagnoses.

Diagnostic usefulness of ribosomal protein l7/l12 for pneumococcal pneumonia in a mouse model.

The capsular antigen detection (CAD) kit is widely used in clinics to detect Streptococcus pneumoniae infection from urine, because it is rapid, convenient, and effective. However, there are several disadvantages, including false-positive results in children colonized with S. pneumoniae and prolonged positive readings even after the bacteria have been cleared. RP-L7/L12 is a component of the 50S ribosome that is abundant in all bacteria and is specific for each bacterial species. We investigated whether RP-L7/L12 could be used to accurately diagnose pneumococcal pneumonia infection in mouse models of pneumonia and colonization generated by infecting CBA/JN or CBA/N mice, respectively, with S. pneumoniae strain 741. RP-L7/L12 detection by enzyme-linked immunosorbent assay accurately assessed active lung infection, as RP-L7/L12 levels decreased simultaneously with the bacterial lung burden after imipenem administration in the pneumonia mouse model. Based on the data, antibodies detecting RP-L7/L12 were applied to rapid immunochromatographic strips (ICS) for urine sample testing. When we compared the ICS test with the CAD kit in the pneumonia model, the results correlated well. Interestingly, however, when the lung bacterial burden became undetectable after antibiotic treatment, the ICS test was correspondingly negative, even though the same samples tested by the CAD kit remained positive. Similarly, while the ICS test exhibited negative results in the nasal colonization model, the CAD kit demonstrated positive results. Bacterial RP-L7/L12 may be a promising target for the development of new methods to diagnose infectious disease. Further studies are warranted to determine whether such a test could be useful in children.

Roles of Pseudomonas aeruginosa autoinducers and their degradation products, tetramic acids, in bacterial survival and behavior in ecological niches.

Pseudomonas aeruginosa, an opportunistic pathogen, is known to mainly use N-acylhomoserine lactones (AHLs) as autoinducers. Recent progress in this field demonstrated that not only AHLs, but also their degradation products, tetramic acids, may have some biological activities. The present study examined the roles of Pseudomonas autoinducers and tetramic acids in bacterial survival and behavior in ecological niches. P. aeruginosa autoinducers and the tetramic acid derivatives were chemically synthesized, and the structure-activity correlation was investigated. Some tetramic acids derived from AHLs caused a significant reduction in the viability of P. aeruginosa in a concentration dependent manner (30-300 µM). The smaller the inoculum of bacteria, the stronger the bactericidal activity that was observed. The data from tetramic acid derivatives indicated the keto-enol structure of tetramic acid to be critical for the antibacterial activity. Exogenous tetramic acid did not induce significant changes in the formation of biofilm or production of exoproducts such as pyocyanin and elastase. Tetramic acid and disinfectants acted synergistically to kill P. aeruginosa. These results suggest the AHL-degradation product tetramic acid to be useful for bacterial control.