Abstract
Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. ...However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of
MDC1
, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of
MDC1
rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
In this study, we proposed an autonomous motion planning method for improving passenger comfort while ensuring safety, particularly with respect to mobility scooters used by elderly people. We ...proposed a trajectory planner for restricting vehicle behaviors with large accelerations and jerks by selecting a safe trajectory from a set of preset trajectories. Then, based on this trajectory planner, we developed an autonomous motion planning method with four different driving modes, and evaluated the effectiveness of the method through a numerical simulation. The simulation results demonstrated that the proposed method increased comfort without compromising on safety.
Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity ...and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma.
This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA).
In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males.
Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.
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Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset ...asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population.
This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment.
Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly.
Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.
Abstract
Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, ...a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as “new-onset prolonged cough”. Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.
Bronchial thermoplasty (BT) is effective in some severe asthma patients; however, the specific asthma phenotypes that produce a good response to BT are not fully understood. Clinical data were ...retrospectively reviewed in severe asthma patients who underwent BT at a single institution in Japan. At the follow-up assessment, the Asthma Quality of Life Questionnaire (AQLQ) scores (P = 0.003), maintenance oral corticosteroid doses (P = 0.027), and exacerbation frequency (P = 0.017) were significantly improved, while prebronchodilator-forced expiratory volume in 1 second (% predicted) did not significantly change (P = 0.19). When we grouped the patients into 2 groups according to their body mass index levels, the AQLQ scores were more improved in patients with overweight/obesity than those with normal weight (P = 0.01). This study showed that patients with non-controlled severe asthma exhibiting overweight/obesity and low quality of life had potential benefits from BT.
Interstitial lung disease (ILD) has rarely been reported as a manifestation of giant cell arteritis (GCA). We herein report a unique case of GCA in a 76-year-old woman who presented with ILD as an ...initial manifestation of GCA. Ten years before admission, she had been diagnosed with granulomatous ILD of unknown etiology. Corticosteroid therapy induced remission. One year after the cessation of corticosteroid therapy, she was admitted with a persistent fever. After admission, she developed left oculomotor paralysis. Positron emission tomography with 2-deoxy-2-fluorine-18fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) proved extremely useful in establishing the diagnosis. Our case promotes awareness of GCA as a possible diagnosis for granulomatous ILD with unknown etiology.
Immune checkpoint inhibitors (ICIs) have been used to treat lung cancer. Several types of ICI-related interstitial lung diseases have been reported, including organizing pneumonia, non-specific ...interstitial pneumonia, and diffuse alveolar damage. However, pembrolizumab-associated bronchiolitis requiring treatment for persistent cough has not yet been reported. Here, we describe a patient who developed dry cough while being treated with pembrolizumab for lung adenocarcinoma. Radiography and lung biopsy findings indicated bronchiolitis. His cough improved after the discontinuation of pembrolizumab and treatment with erythromycin, an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2 agonist.
Background Asthma is a heterogeneous disease with variable response to treatment. Genetic backgrounds are involved in the severity of type 2 asthma, but their effects on responses to biologics remain ...unknown. This study aimed to clarify the role of genetic factors in response to biologics in patients with severe asthma. Methods Adults with severe asthma receiving biologics were enrolled in this multicenter, observational, real-world study. The responses to biologics were evaluated using Physicians’ Global Evaluation of Treatment Effectiveness (GETE). Optimal biologic for each patient was also determined based on the best GETE score for the biologic used or currently used biologic. Three single nucleotide polymorphisms ( IL1RL1 , rs1420101; IL4RA , rs8832; and TSLP , rs1837253) were examined. Results Among the 113 patients analysed, 53 (46.9%) had an excellent GETE score for at least one biologic. These patients with an excellent GETE score for at least one biologic, particularly for benralizumab, had the risk genotype of rs1420101 more frequently than the remaining patients, independent of the clinical demographics. Regarding the optimal biologic for each patient, anti-IL-5 drugs were optimal for patients with the rs1420101 TT or rs8832 GG genotype. Furthermore, dupilumab was similarly effective, regardless of the risk genotypes examined in this study. Conclusion IL1RL1 rs1420101 TT genotype and/or IL4RA rs8832 GG genotype may predict an excellent or optimal response to biologic therapy in each patient, particularly to anti-IL-5 targeted therapy. The elucidation of genetic predisposition may improve the management of severe asthma in the era of biologics.
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