全部最新文献

Introduction and objectives: The human congenital central hypoventilation syndrome (CCHS) is caused by mutations in the PHOX2B (paired-like homeobox 2B) gene. Genetically engineered PHOX2B rodents exhibit defective development of the brainstem retrotrapezoid nucleus (RTN), a carbon dioxide sensitive structure that critically controls expiratory muscle recruitment. This has been linked to a blunted exercise ventilatory response. Whether this can be extrapolated to human CCHS is unknown and represents the objective of this study.

Materials and methods: Thirteen adult CCHS patients and 13 healthy participants performed an incremental symptom-limited cycle cardiopulmonary exercise test. Responses were analyzed using guideline approaches (ventilation V'_E, tidal volume V_T, breathing frequency, oxygen consumption, carbon dioxide production) complemented by a breathing pattern analysis (i.e. expiratory and inspiratory reserve volume, ERV and IRV).

Results: A ventilatory response occurred in both study groups, as follows: V'_E and V_T increased in CCHS patients until 40 W and then decreased, which was not observed in the healthy participants (p<0.001). In the latter, exercise-related ERV and IRV decreases attested to concomitant expiratory and inspiratory recruitment. In the CCHS patients, inspiratory recruitment occurred but there was no evidence of expiratory recruitment (absence of any ERV decrease, p<0.001).

Conclusions: Assuming a similar organization of respiratory rhythmogenesis in humans and rodents, the lack of exercise-related expiratory recruitment observed in our CCHS patients is compatible with a PHOX2B-related defect of a neural structure that would be analogous to the rodents' RTN. Provided corroboration, ERV recruitment could serve as a physiological outcome in studies aiming at correcting breathing control in CCHS.

Approximately 400 million people live at high altitudes worldwide, yet reference equations for spirometry in these populations are inadequately documented. This study aims to develop reference equations for spirometry and assess their applicability to residents at altitudes ranging from 2,100 to 4,700 metres above sea level. This extensive cross-sectional study encompassed healthy non-smokers aged 15 years or older living at Xinjiang and Tibet autonomous region, which covered eight high-altitude areas by a multistage stratified sampling procedure. All individuals underwent pre- and post-bronchodilator measurement. We used the Lambda-Mu-Sigma (LMS) method to establish reference equations for various spirometry parameters. We assessed model fit using mean absolute error (MAE), mean absolute percentage error (MAPE), and residual values (standard deviation), relative to established benchmarks such as GLI, ECSC, and NHANES III, to evaluate the applicability of our equations to high-altitude residents. Between June 2015 and August 2016, 3174 healthy subjects were included. The reference equations utilise age and height as independent variables, with improved accuracy achieved through spline functions. Our spirometry reference equations demonstrate minimal MAE, MAPE, and residual values (standard deviation) for most of the analysed spirometry parameters, stratified by gender. Our spirometry reference equations are more applicable to residents of high-altitude regions.

There are approximately 220 million (about 12% regional prevalence) adults living with diabetes mellitus (DM) with its related complications, and morbidity knowingly or unconsciously in the Western Pacific Region (WP). The estimated healthcare cost in the WP and Malaysia was 240 billion USD and 1.0 billion USD in 2021 and 2017, respectively, with unmeasurable suffering and loss of health quality and economic productivity. This urgently calls for nothing less than concerted and preventive efforts from all stakeholders to invest in transforming healthcare professionals and reforming the healthcare system that prioritizes primary medical care setting, empowering allied health professionals, improvising health organization for the healthcare providers, improving health facilities and non-medical support for the people with DM. This article alludes to challenges in optimal diabetes care and proposes evidence-based initiatives over a 5-year period in a detailed roadmap to bring about dynamic and efficient healthcare services that are effective in managing people with DM using Malaysia as a case study for reference of other countries with similar backgrounds and issues. This includes a scanning on the landscape of clinical research in DM, dimensions and spectrum of research misconducts, possible common biases along the whole research process, key preventive strategies, implementation and limitations toward high-quality research. Lastly, digital medicine and how artificial intelligence could contribute to diabetes care and open science practices in research are also discussed.

Introduction: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA.

Materials and methods: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day.

Results: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001).

Conclusions: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Air pollution is a major global environment and health concern. Recent studies have suggested an association between air pollution and COVID-19 mortality and morbidity. In this context, a close association between increased levels of air pollutants such as particulate matter ≤2.5 to 10 µM, ozone and nitrogen dioxide and SARS-CoV-2 infection, hospital admissions and mortality due to COVID 19 has been reported. Air pollutants can make individuals more susceptible to SARS-CoV-2 infection by inducing the expression of proteins such as angiotensin converting enzyme (ACE)2 and transmembrane protease, serine 2 (TMPRSS2) that are required for viral entry into the host cell, while causing impairment in the host defence system by damaging the epithelial barrier, muco-ciliary clearance, inhibiting the antiviral response and causing immune dysregulation. The aim of this review is to report the epidemiological evidence on impact of air pollutants on COVID 19 in an up-to-date manner, as well as to provide insights on in vivo and in vitro mechanisms.