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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.

Background: Home-based pulmonary rehabilitation (PR) can enhance accessibility to PR, but no at-home field exercise test has been validated for individualized endurance training prescriptions.

Research question: What is the accuracy of the six-minute stepper test (6MST) in estimating endurance training intensity as determined during cardiopulmonary exercise testing (CPET)?

Study design and method: This multicenter (N = 3) cross-sectional study included individuals with COPD. Participants performed CPET and two 6MSTs to evaluate the 6MST's ability to estimate endurance training intensity based on CPET-derived heart rate at the first ventilatory threshold (HRvt₁), the corresponding power output (Pvt₁), and peak power output (Ppeak). Predictive equations were tested for external validity using data from two prior studies.

Results: 105 patients were included (mean age 61 (SD 9) years; mean FEV1 61 (SD 21) %). Predictive equations moderately predicted HRvt₁ (r² = 0.38), strongly predicted Pvt₁ (r² = 0.63) and very strongly predicted Ppeak (r² = 0.75). External validity was small to moderate for HRvt₁ and Pvt₁ but was strong for 60% of Ppeak (mean absolute difference: 10W, 95% CI 5 to 10). Passing and Bablok regression confirmed interchangeability for Pvt₁ and 60% of Ppeak.

Interpretation: The 6MST offers a reliable method to set initial training intensity when CPET is unavailable.

Clinical trial registration: NCT02842463.

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.