Dataset Information

Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation.

ABSTRACT: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx). In this prospective cohort study, we consecutively recruited patients with asthma (n = 334), classified as the SMM Normal group (n = 223), SMM Low group (n = 88), and SMM High group (n = 23). We investigated the association between SMM and clinical asthma characteristics and explored the association between SMM and asthma control and AEx within a 12-month follow-up period. Based on SMM, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort (n = 157). Compared with the SMM Normal group, SMM Low group exhibited more airway obstruction and worse asthma control, while SMM High group had a reduced eosinophil percentage in induced sputum. Furthermore, SMM Low group was at a significantly increased risk of moderate-to-severe exacerbation compared with the SMM Normal group (relative risk adjusted 2.02 [95% confidence interval (CI), 1.35-2.68]; p = 0.002). In addition, a model involving SMM was developed which predicted AEx (area under the curve: 0.750, 95% CI: 0.691-0.810). Low SMM was an independent risk factor for future AEx. Furthermore, a model involving SMM for predicting the risk of AEx in patients with asthma indicated that assessment of SMM has potential clinical implications for asthma management.

SUBMITTER: Zhang S

PROVIDER: S-EPMC9738130 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation.

Zhang Shuwen S Zhang Xin X Deng Ke K Wang Changyong C Wood Lisa G LG Wan Huajing H Liu Lei L Wang Ji J Zhang Li L Liu Ying Y Cheng Gaiping G Gibson Peter G PG Oliver Brian G BG Luo Fengming F McDonald Vanessa M VM Li Weimin W Wang Gang G

Journal of clinical medicine 20221206 23

<h4>Background</h4>Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored.<h4>Objective</h4>To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx).<h4>Methods</h4>In this prospective cohort study, we consecutively recruited pati ...[more]

PMID: 36498815

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Project description:BackgroundSevere asthma exacerbation reduces patients' quality of life, results in visits to the emergency department (ED) and hospitalization, and incurs additional medical costs. Antipsychotics block receptors with bronchodilation function; however, the association between antipsychotic use and severe asthma exacerbation is unknown. This study aimed to investigate the effects of antipsychotics on asthma-related ED visits and hospitalizations.MethodsA case-crossover design was used in this study. Using the 2003-2017 Taiwan National Health Insurance Reimbursement Database, we established a cohort of 18,657 adults with asthma exacerbation leading to ED visits or hospitalization. Univariate and multivariate conditional logistic regressions were conducted to explore the association between antipsychotic use and severe asthma exacerbation. Subgroup analyses of different classes, doses, receptor functions of antipsychotics, different psychiatric disease, and sensitivity analyses of excluding patients with schizophrenia were also performed.ResultsAntipsychotic use was associated with a higher risk of severe asthma exacerbation (adjusted odds ratio [OR]: 1.27; 95% confidence interval [CI] 1.05-1.54; P = 0.013) compared with no use of antipsychotics. The use of typical antipsychotics increased the risk of severe asthma exacerbation (adjusted OR: 1.40, 95% CI 1.10-1.79, P = 0.007), whereas the use of atypical antipsychotics did not. These results did not change after the exclusion of patients with schizophrenia. There was a dose-dependent effect of antipsychotics (trend test, P = 0.025). Antipsychotics that block the M2 muscarinic or D2 dopaminergic receptors were associated with an increased risk of severe asthma exacerbation (adjusted OR: 1.39, 95% CI 1.10-1.76, P = 0.007 and adjusted OR: 1.33, 95% CI 1.08-1.63, P = 0.008, respectively). However, use of antipsychotics did not increase risk of severe asthma exacerbation in patients with psychiatric disorder.ConclusionsThe use of typical antipsychotics is associated with a dose-dependent increased risk of severe asthma exacerbation, especially for patients without psychiatric disorders. Further research on the impact of typical antipsychotics on asthma exacerbation is warranted.

Project description:A prominent feature of striated muscle is the regular lateral alignment of adjacent sarcomeres. An important intermyofibrillar linking protein is the intermediate filament protein desmin, and based on biochemical and structural studies in primary cultures of myocytes it has been proposed that desmin interacts with the sarcomeric protein nebulin. Here we tested whether nebulin is part of a novel biomechanical linker complex, by using a recently developed nebulin knockout (KO) mouse model and measuring Z-disk displacement in adjacent myofibrils of both extensor digitorum longus (EDL) and soleus muscle. Z-disk displacement increased as sarcomere length (SL) was increased and the increase was significantly larger in KO fibers than in wild-type (WT) fibers; results in 3-day-old and 10-day-old mice were similar. Immunoelectron microscopy revealed reduced levels of desmin in intermyofibrillar spaces adjacent to Z-disks in KO fibers compared with WT fibers. We also performed siRNA knockdown of nebulin and expressed modules within the Z-disk portion of nebulin (M160-M170) in quail myotubes and found that this prevented the mature Z-disk localization of desmin filaments. Combined, these data suggest a model in which desmin attaches to the Z-disk through an interaction with nebulin. Finally, because nebulin has been proposed to play a role in specifying Z-disk width, we also measured Z-disk width in nebulin KO mice. Results show that most Z-disks of KO mice were modestly increased in width (approximately 80 nm in soleus and approximately 40 nm in EDL fibers) whereas a small subset had severely increased widths (up to approximately 1 microm) and resembled nemaline rod bodies. In summary, structural studies on a nebulin KO mouse show that in the absence of nebulin, Z-disks are significantly wider and that myofibrils are misaligned. Thus the functional roles of nebulin extend beyond thin filament length regulation and include roles in maintaining physiological Z-disk widths and myofibrillar connectivity.

Project description:BackgroundChronic kidney disease (CKD) is commonly associated with multifactorial neuromuscular impairments. Few studies have investigated CKD-induced changes in maximal voluntary force (MVF), and even fewer have longitudinal follow-up. The aim of this study is to investigate whether CKD progression modifies the relationship between skeletal muscle mass and force, and the prevalence of sarcopaenia and sarcopenic obesity.MethodsThe data used were prospectively collected during routine check-ups in a network of nutritional centres in Mexico and retrospectively analysed. From a dataset of 5430 patients, we selected 1098 patients with available anthropometric, kidney function, handgrip and bioimpedance data. The relationship between appendicular skeletal muscle mass (ASM) and MVF was investigated using mixed models and adjusted for age, sex, body mass index, physical activity level and CKD aetiology. Sarcopaenia prevalence were tested across period of follow-up using the Cochran-Mantel-Haenzen for repeated measures and across CKD stages using the Chi-2 test.ResultsAfter normalization with ASM, MVF was higher in CKD G1-G3 compared with G4 and G5 (P ≤ .001, Cohen's d = 0.270-0.576). Slopes between MVF and ASM were lower in CKD G3, G4 and G5 than in CKD G1-G2 [-2.268 (-3.927, -0.609), P = .008; -2.694 (-4.593, -0.794), P = .006; -3.675 (-5.326, -1.725), P < .001, respectively]. The prevalence of sarcopaenia and sarcopaenic obesity did not differ across CKD stages, but recovery was most commonly observed in CKD G1-G2. Slope analysis showed an independent interaction between the slopes of kidney function and ASM on MVF evolution over time.ConclusionsCKD negatively, progressively and independently affects the neuromuscular system, and force production is reduced for any given muscle mass as CKD progresses. While no association was found between CKD stage and prevalence of sarcopaenia, recovery was more frequent in the early CKD stages. These results suggest the importance of early rehabilitation programs to improve musculoskeletal health, quality of life and survival in CKD patients.

Project description:ObjectivesIncreased air pollutant concentrations have been linked to several asthma-related outcomes in children, including respiratory symptoms, medication use, and hospital visits. However, few studies have examined effects of ultrafine particles in a pediatric population. Our primary objective was to examine the effects of ambient concentrations of ultrafine particles on asthma exacerbation among urban children and determine whether consistent treatment with inhaled corticosteroids could attenuate these effects. We also explored the relationship between asthma exacerbation and ambient concentrations of accumulation mode particles, fine particles (≤2.5 micrograms [μm]; PM2.5), carbon monoxide, sulfur dioxide, and ozone. We hypothesized that increased 1-7 day concentrations of ultrafine particles and other pollutants would be associated with increases in the relative odds of an asthma exacerbation, but that this increase in risk would be attenuated among children receiving school-based corticosteroid therapy.MethodsWe conducted a pilot study using data from 3 to 10 year-old children participating in the School-Based Asthma Therapy trial. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of a pediatric asthma visit treated with prednisone (n=96 visits among 74 children) associated with increased pollutant concentrations in the previous 7 days. We re-ran these analyses separately for children receiving medications through the school-based intervention and children in a usual care control group.ResultsInterquartile range increases in ultrafine particles and carbon monoxide concentrations in the previous 7 days were associated with increases in the relative odds of a pediatric asthma visit, with the largest increases observed for 4-day mean ultrafine particles (interquartile range=2088p/cm(3); OR=1.27; 95% CI=0.90-1.79) and 7-day mean carbon monoxide (interquartile range=0.17ppm; OR=1.63; 95% CI=1.03-2.59). Relative odds estimates were larger among children receiving school-based inhaled corticosteroid treatment. We observed no such associations with accumulation mode particles, black carbon, fine particles (≤2.5μm), or sulfur dioxide. Ozone concentrations were inversely associated with the relative odds of a pediatric asthma visit.ConclusionsThese findings suggest a response to markers of traffic pollution among urban asthmatic children. Effects were strongest among children receiving preventive medications through school, suggesting that this group of children was particularly sensitive to environmental triggers. Medication adherence alone may be insufficient to protect the most vulnerable from environmental asthma triggers. However, further research is necessary to confirm this finding.

Dataset Information

Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation.

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Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation.

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