Polymorphism in exercise genes and respiratory function in late-onset Pompe disease.

Genetic polymorphisms influencing muscle structure and metabolism may affect the phenotype of metabolic myopathies. We here analyze the possible influence of a wide panel of "exercise genes" on the severity and progression of respiratory dysfunction in late-onset Pompe disease (LOPD). We stratified patients with comparable age and disease duration according to the severity of their respiratory phenotype, assessed by both upright FVC% and postural drop in FVC%. We included 43 patients with LOPD (25 males, age 50.8 ± 13.6 yr) with a 2-yr follow-up since the beginning of enzyme replacement therapy (ERT). Twenty-two patients showed a postural drop >25% T0, seven other patients developed it during the follow-up. We analyzed the relationship between the progression of respiratory dysfunction and genetic polymorphisms affecting muscle function and structure [angiotensin converting enzyme (ACE), α-actinin 3 (ACTN3), peroxisome proliferator-activated receptor α (PPR-α), angiotensin (AGT)], glycogen metabolism [glycogen synthase (GYS), glycogen synthase kinase-3 isoform ß (GSK3ß)], and autophagy [sirtuin 1 (SIRT1), autophagy-related gene 7 (ATG7)]. Individuals carrying two copies of the ACE D-allele shared a 24-fold increase in the risk of severe respiratory dysfunction and progression during the 2-yr follow-up. ACTN3-XX polymorphism was also associated with worse respiratory outcome. The study of exercise genes is of particular interest in respiratory muscles, due to their peculiar features, that is, continuous, low-intensity contraction and prominent recruitment of type I fibers. In line with previous observations on skeletal muscles, ACE-DD and ACTN3-XX genotypes were associated with indirect evidence of more severe respiratory phenotypes. On the contrary, polymorphisms related to autophagy and glycogen metabolism did not seem to influence respiratory muscles.NEW & NOTEWORTHY Previous reports evaluated the role of exercise genes in influencing skeletal muscle phenotype and response to ERT in LOPD. Here, we investigate the role of polymorphisms in several exercise gene, focusing on respiratory muscles. ACE-DD and ACTN3-XX polymorphisms, possibly influencing muscle properties and fiber composition, were associated with more severe respiratory phenotypes.

Portable High-Flow Nasal Oxygen during Walking in Patients with Severe Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

BACKGROUND: High-flow nasal oxygen (HFNO) improves exercise capacity, oxygen saturation, and symptoms in patients with chronic obstructive pulmonary disease (COPD). Due to the need of electricity supply, HFNO has not been applied during free ambulation. OBJECTIVE: We evaluated whether HFNO delivered during walking by a battery-supplied portable device was more effective than usual portable oxygen in improving exercise capacity in patients with COPD and severe exercise limitation. The effects on 6-min walking tests (6MWTs) were the primary outcome. METHODS: After a baseline 6MWT, 20 stable patients requiring an oxygen inspiratory fraction (FiO2) <0.60 during exercise, randomly underwent 2 6MWT carrying a rollator, under either HFNO with a portable device (HFNO test) or oxygen supplementation by a Venturi mask (Control) at isoFiO2. Walked distance, perceived dyspnea, pulse oximetry, and inspiratory capacity at end of the tests as well as patients' comfort were compared between the tests. RESULTS: As compared to baseline, walked distance improved significantly more in HFNO than in the control test (by 61.1 ± 37.8 and 39.7 ± 43.8 m, respectively, p = 0.01). There were no significant differences between the tests in dyspnea, peripheral oxygen saturation, or inspiratory capacity, but HFNO test was appreciated as more comfortable. CONCLUSION: In patients with COPD and severe exercise limitation, HFNO delivered by a battery-supplied portable device was more effective in improving walking distance than usual oxygen supplementation.

Short-Term Effects of an Active Heat-and-Moisture Exchanger During Invasive Ventilation.

BACKGROUND: Humidification is a standard of care during invasive mechanical ventilation. Two types of devices are used for this purpose: heated humidifiers and heat-and-moisture exchangers (HME). AIM: To compare the short-term physiologic effects of an active HME, with those of heated humidifiers and HMEs in terms of respiratory effort, ventilatory pattern, and arterial blood gases during invasive mechanical ventilation. METHODS: We conducted a randomized crossover study with 3 different devices in 15 stable subjects who had a tracheostomy and were ventilator-dependent. Transdiaphragmatic pressure, ventilatory pattern, arterial blood gases, and dyspnea scale were recorded at baseline and at the end of a 20-min period with each device. RESULTS: Compared with heated humidifiers, the active HME was associated with higher diaphragmatic pressure-time product per minute (117.10 [interquartile range {IQR} 34.58-298.60]) versus 80.86 (IQR, 25.46-110.55) cm H2O×s/min, P = .01), higher PaCO2 (48.50 [IQR, 40.65-53.70] vs 39.60 [IQR, 37.50-49.95]) mm Hg, P = .02) and lower pH (7.41 [IQR, 7.36-7.49] vs 7.45 [IQR, 7.40-7.51], P = .030) without any significant difference in ventilatory pattern. A significantly worse dyspnea scale score (active HME, 3 (2-4) vs heated humidifiers: 4 (3-5); P = .009) was also observed. No significant differences were seen between active HME and HME. CONCLUSIONS: This study indicated that, compared with the heated humidifiers, the use of the active HME or the HME increased inspiratory effort, PaCO2 , pH, and dyspnea in stable subjects who were tracheostomized and ventilator-dependent. (ClinicalTrials.gov registration NCT02499796.).

Effects of heated and humidified high flow gases during high-intensity constant-load exercise on severe COPD patients with ventilatory limitation.

INTRODUCTION: High flow nasal cannula (HFNC) was shown to washout the anatomical dead space, permitting a higher fraction of minute ventilation to participate in gas pulmonary exchanges. Moreover, it is able to guarantee the desired inhaled oxygen fraction (FiO2) even at high level of patient's minute ventilation by minimizing the room air entrainment. The effect of HFNC has never been investigated on stable severe COPD patients in term of endurance capacity with standardised laboratory tests. METHOD/DESIGN: We performed, in a randomized crossover study, two constant load exercise tests at the 75% of maximum workload achieved at a previous incremental exercise test on cycle-ergometer: with (HFNC-test) and without HFNC (Control-test). Both constant load tests were fulfilled at the same inhaled oxygen fraction (isoFiO2). RESULTS: The endurance time significantly increased in the HFNC-test compared to the Control-test (the mean difference between the two groups was 109 ± 104 s, p < 0.015). At iso-time, HFNC-test showed a better oxygen saturation (95 ± 3% vs 89 ± 3%, respectively, p < 0.005) either in the subgroup of patients who used supplemental oxygen and in the subgroup who did not. Moreover, a significantly lower dyspnea (median of 5.5 vs 10, respectively, p = 0.002) and leg fatigue score (median of 5 vs 9.5, p = 0.002) was recorded at iso-time during HFNC-test. CONCLUSION: HFNC may improve the exercise performance in severe COPD patients with ventilatory limitation. This effect is associated to an improvement of SaO2 and perceived symptoms at iso-time. In a Pulmonary Rehabilitation program HFNC may allow a given high intensity load to be sustained for a longer time with less symptoms.