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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.

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.

Background: This systematic review assesses the current available evidence across the WHO European region on the effectiveness and cost-effectiveness of the different approaches used for TB screening and also explores the facilitators and barriers that migrants face during screening programmes.

Methods: We conducted an extensive, comprehensive, and systematic literature search across multiple databases, including MEDLINE, Cochrane, Scopus, and ISI Web of Knowledge, without any restrictions on publication date or language. In addition, we reviewed grey literature and reports. The data were meticulously analysed with a focus on screening of TB active disease and infection effectiveness indicators, and cost-effectiveness economic analyses as a primary objective and the comprehension of barriers and facilitators of screening as a secondary objective.

Findings: Our review included 43 studies covering over 8 million migrants from 11 countries. The findings demonstrate that while screening uptake was high, coverage varied, and completion rates for preventive treatments were low. Economic analyses supported the high cost-effectiveness of the screening programmes, particularly when integrating both active TB and TBI screening strategies.

Interpretation: This review underscores the cost-effectiveness and public health importance of TB screening in migrant populations within Europe. However, the disparities in screening practices highlight the urgent need for standardisation at the European level.