RESUMEN
Environmental air pollution presents a considerable risk to global respiratory health. If critical levels are exceeded, inhaled pollutants can lead to the development of respiratory dysfunction and provoke exacerbation in those with pre-existing chronic respiratory disease. Over 90% of the global population currently reside in areas where environmental air pollution is considered excessive-with adverse effects ranging from acute airway irritation to complex immunomodulatory alterations. This narrative review provides an up-to-date perspective concerning the impact of environmental air pollution on respiratory health and function and describes the underpinning mechanisms that contribute to the development and progression of chronic respiratory disease.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminación del Aire/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/toxicidad , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/inducido químicamente , Enfermedades Respiratorias/fisiopatología , Animales , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
OBJECTIVE: Elexacaftor/Tezacaftor/Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator with the potential to improve exercise capacity. This case series of three adolescents with CF aimed to investigate whether 6 weeks treatment with Elexacaftor/Tezacaftor/Ivacaftor could improve exercise capacity in CFTR modulator naive adolescents with CF. METHODS: Three adolescents (14.0 ± 1.4 years) with CF (FEV1 % predicted: 62.5 ± 17.1; F508del/F508del genotype) completed an exhaustive maximal cardiopulmonary exercise test on a cycle ergometer to determine peak oxygen uptake ( V Ì $\dot{{\rm{V}}}$ O2peak ) and measure changes in gas exchange and ventilation during exercise at 6 weeks. We also analyzed wrist-worn device-based physical activity (PA) data in two of the three cases. Validated acceleration thresholds were used to quantify time spent in each PA intensity category. RESULTS: Clinically meaningful improvements in V Ì $\dot{{\rm{V}}}$ O2peak were observed in all three cases (+17.6%, +52.4%, and +32.9%, respectively), with improvements greatest in those with more severe lung disease and lower fitness at baseline. Although lung function increased in all cases, inconsistent changes in markers of ventilatory and peripheral muscle efficiency likely suggest different mechanisms of improvement in this case group of adolescents with CF. Device-based analysis of PA was variable, with one case increasing and one case decreasing. CONCLUSION: In this case series, we have observed, for the first time, improvements in exercise capacity following 6 weeks of treatment with Elexacaftor/Tezacaftor/Ivacaftor. Improvements were greatest in the presence of more severe CF lung disease and lower aerobic fitness at baseline. The mechanism(s) responsible for these changes warrant further investigation in larger trials.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Adolescente , Aminofenoles/uso terapéutico , Benzodioxoles/uso terapéutico , Agonistas de los Canales de Cloruro , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Combinación de Medicamentos , Tolerancia al Ejercicio , Humanos , Indoles , Mutación , Oxígeno , Pirazoles , Piridinas , Pirrolidinas , QuinolonasRESUMEN
BACKGROUND: The development of cystic fibrosis (CF)-related diabetes (CFRD) in paediatric groups is associated with a reduced aerobic fitness. However, this has yet to be investigated in adults with more severe lung disease. METHODS: Cardiopulmonary exercise and glycaemic control tests were retrospectively analysed in 46 adults with CF (age: 26.9 y [range: 16.3-66.5 y]; forced expiratory volume in 1s: 65.3% [range: 26.8-105.7%]; 26 males), diagnosed with CFRD (nâ¯=â¯19), impaired glucose tolerance (IGT; nâ¯=â¯8) or normal glucose tolerance (NGT; nâ¯=â¯19). RESULTS: Maximal oxygen uptake (VËO2max) was reduced in adults with IGT and CFRD compared to their age- and gender-matched counterparts with NGT (p < 0.05); however, there was no difference when lung function was included as a covariate (all p > 0.05). VËO2max was greater in adults who experienced post-reactive hypoglycaemia vs. NGT without hypoglycaemia (p < 0.05). The frequency of ventilatory limitation (84%, 63% and 37%, respectively; p < 0.05) but not ventilation-perfusion mismatch (42%, 38% and 16%, respectively; p > 0.05), was greater with CFRD and IGT vs. NGT. There was also no difference in arterial oxygen saturation changes between groups (p > 0.05). Gender and body mass index were significant predictors of VËO2max (adjusted R2â¯=â¯0.37, p < 0.01), but glycaemic control did not explain additional variance (p > 0.05). CONCLUSIONS: Adults with CF-related dysglycaemia had a reduced VËO2max compared to age- and gender-matched counterparts, due to a greater degree of CF lung disease in these populations.