Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

Validation of Noninvasive Assessment of Pulmonary Gas Exchange in Patients with Chronic Obstructive Pulmonary Disease during Initial Exposure to High Altitude.

Investigation of pulmonary gas exchange efficacy usually requires arterial blood gas analysis (aBGA) to determine arterial partial pressure of oxygen (mPaO2) and compute the Riley alveolar-to-arterial oxygen difference (A-aDO2); that is a demanding and invasive procedure. A noninvasive approach (AGM100), allowing the calculation of PaO2 (cPaO2) derived from pulse oximetry (SpO2), has been developed, but this has not been validated in a large cohort of chronic obstructive pulmonary disease (COPD) patients. Our aim was to conduct a validation study of the AG100 in hypoxemic moderate-to-severe COPD. Concurrent measurements of cPaO2 (AGM100) and mPaO2 (EPOC, portable aBGA device) were performed in 131 moderate-to-severe COPD patients (mean ±SD FEV1: 60 ± 10% of predicted value) and low-altitude residents, becoming hypoxemic (i.e., SpO2 < 94%) during a short stay at 3100 m (Too-Ashu, Kyrgyzstan). Agreements between cPaO2 (AGM100) and mPaO2 (EPOC) and between the O2-deficit (calculated as the difference between end-tidal pressure of O2 and cPaO2 by the AGM100) and Riley A-aDO2 were assessed. Mean bias (±SD) between cPaO2 and mPaO2 was 2.0 ± 4.6 mmHg (95% Confidence Interval (CI): 1.2 to 2.8 mmHg) with 95% limits of agreement (LoA): -7.1 to 11.1 mmHg. In multivariable analysis, larger body mass index (p = 0.046), an increase in SpO2 (p < 0.001), and an increase in PaCO2-PETCO2 difference (p < 0.001) were associated with imprecision (i.e., the discrepancy between cPaO2 and mPaO2). The positive predictive value of cPaO2 to detect severe hypoxemia (i.e., PaO2 ≤ 55 mmHg) was 0.94 (95% CI: 0.87 to 0.98) with a positive likelihood ratio of 3.77 (95% CI: 1.71 to 8.33). The mean bias between O2-deficit and A-aDO2 was 6.2 ± 5.5 mmHg (95% CI: 5.3 to 7.2 mmHg; 95%LoA: -4.5 to 17.0 mmHg). AGM100 provided an accurate estimate of PaO2 in hypoxemic patients with COPD, but the precision for individual values was modest. This device is promising for noninvasive assessment of pulmonary gas exchange efficacy in COPD patients.

Features of Chronic Exertional Compartmental Syndrome of the Leg in Elite Nordic Skiers.

This study aimed to assess prevalence and incidence of chronic exertional compartmental syndrome as well as functional outcomes after surgery in elite Nordic skiers. An exhaustive list of 294 elite Nordic skiers from the French national teams between 1994 and 2014 was analyzed through their individual medical files in order to identify cases of chronic exertional compartmental syndrome. Eighteen athletes had confirmed diagnosis and performed a structured interview to identify factors associated with chronic exertional compartmental syndrome and surgery outcomes. The prevalence was 6.1% and the incidence 13 per 1000 skier-years. Biathletes had a higher prevalence than cross-country skiers (OR=0.40, p=0.08). Free-technique skiing and roller-skiing were the main conditions inducing symptoms. All injured athletes had bilateral surgery and 94% of them reported no more or sporadic leg pain after. Almost 90% resumed competition at the same or higher level than prior surgery. Compare to previous studies, the incidence rate of chronic exertional compartmental syndrome is higher in French elite Nordic skiers. The higher prevalence in biathletes and the trigger during free-technique skiing suggest a contribution of this technique to this disease. This study also confirmed that surgery was an efficient therapeutic solution without compromising athletes' career.

Peripheral muscle abnormalities in cystic fibrosis: Etiology, clinical implications and response to therapeutic interventions.

Peripheral muscle dysfunction is an important systemic consequence of cystic fibrosis (CF) with major clinical implications, such as exercise intolerance and reduced quality of life. Evidence is now accumulating that lack of physical activity is unlikely to be the sole explanation for peripheral muscle dysfunction of patients with CF. Particularly, the demonstration of CFTR expression in both murine and human skeletal muscle suggests the potential implication of intrinsic CF-related factors. By combining data from both human and animal models, this review describes CF peripheral muscle abnormalities and critically reviews the advances in understanding the impact of the underlying mechanisms. We also describe how peripheral muscles respond to intervention in this population. Methodological concerns and directions for future research are also considered. Peripheral muscle atrophy and weakness is prevalent in patients with CF and associated with reduced aerobic and anaerobic performances. Further investigations are however needed to confirm alterations in peripheral muscle endurance and fatigability. Physical inactivity is probably the major contributor of peripheral muscle abnormalities in patients with CF with mild-to-moderate phenotypes. However, the relative influence of additional factors (e.g. inflammation, metabolic abnormalities) probably increases with disease severity making specific and individualized interventions necessary in severe patients. Exercise training is the most effective intervention to address peripheral muscle dysfunction but other strategies, such as neuromuscular electrical stimulation and nutritional or hormonal supplementation may be of interest in some patients. Investigations are needed to determine whether pharmacological interventions such as CFTR modulators are effective to address this condition. To better elucidate the etiology of peripheral muscle dysfunction in CF, future studies should combine measurements at the cellular level with indices of muscle function and monitor physical activity levels to account for its potential effects on muscle function.

Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: A randomized controlled trial.

BACKGROUND: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-based exercise training program on fitness, muscle, and motor function in FSHD patients. METHODS: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n = 8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35 minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention. RESULTS: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P = 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P = 0.008) and 46% (P = 0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG. CONCLUSIONS: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.

Skeletal muscle contractility and fatigability in adults with cystic fibrosis.

BACKGROUND: Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. METHODS: Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. RESULTS: Some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (e.g., mechanical response to doublets stimulation at 100 Hz: 74±30 Nm vs. 97±28 Nm, P=0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P>0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. CONCLUSIONS: We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease.

Neuromuscular fatigue and exercise capacity in fibromyalgia syndrome.

OBJECTIVE: To assess quadriceps strength and fatigability by using femoral nerve magnetic stimulation (FNMS) and their relationship to exercise capacity in patients with fibromyalgia syndrome (FMS) and healthy controls. METHODS: Twenty-two women (11 with FMS, 11 controls) performed a maximal incremental cycling test and a quadriceps fatigue test on 2 separate visits. For quadriceps assessment, we used FNMS during and after maximum voluntary contraction (MVC) to evaluate central and peripheral factors of neuromuscular fatigue. Subjects performed sets of 10 intermittent (5 seconds on/5 seconds off) isometric contractions starting at 10% MVC, in 10% MVC increments from one set to another until exhaustion. Neuromuscular fatigue was assessed with FNMS after each set. RESULTS: FMS patients had reduced initial MVC compared to controls (mean ± SD 102 ± 18 versus 120 ± 24 Nm; P < 0.05) without significant impairment of voluntary activation (mean ± SD 93.5% ± 3.0% versus 93.1% ± 3.4%; P = 0.74). During the fatigue task, FMS patients exhibited a greater fall in evoked muscular responses (mean ± SD -26% ± 6% versus -16% ± 8% at set 50% MVC; P < 0.05), but not in MVC (mean ± SD -24% ± 7% versus -19% ± 4% at set 50% MVC; P = 0.12). During the cycling test, FMS patients had lowered maximal exercise capacity and an enhanced rate of perceived exertion (RPE) compared to controls. The percent reduction in evoked muscular responses during the quadriceps fatigue test correlated with maximum oxygen consumption (r = 0.56, P < 0.05) and RPE at submaximal intensity (r = 0.84, P < 0.05) during cycling. CONCLUSION: Greater impairment in muscle contractility is associated with enhanced perception of exertion and reduced maximal exercise capacity in FMS patients. Neuromuscular impairments should be considered as an important factor underlying functional limitations in FMS patients.