Hôpital Renée Sabran

Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze-omic datasets in rare genetic diseases as patient cohorts are inevitably small.

Exercise testing is part of the regular assessment of patients with cystic fibrosis (CF). We aimed to evaluate (1) the convergent validity of the 1-min sit-to-stand (STS) test in CF by investigating its relationships with peak oxygen uptake (peak V̇O2 ), quadriceps strength, and quality of life and (2) to compare these associations with those of the 6-min walk test (6MWT). Twenty-five adults with CF (FEV1 = 59 ± 24%) performed the STS test, the 6MWT, quadriceps strength assessment, and cardiopulmonary exercise test (CPET). Physical activity level, quality of life, and self-esteem were assessed by questionnaires. STS repetitions, 6-min walk distance, quadriceps strength, and peak V̇O2 were, respectively, 71 ± 12, 90 ± 10, 93 ± 29, and 62 ± 16% of predicted. The STS test had moderate associations with peak V̇O2 (r = 0.56, P = .004), quadriceps strength (r = 0.52, P = .008), and some questionnaire items (eg, perceived physical strength, r = 0.67, P < .001) only when repetitions were expressed as a product of body weight. Overall, these associations were weaker than those obtained from 6-min walk distance × weight. Oxygen desaturation during the STS test was strongly associated with oxygen desaturation during CPET (r = 0.80, P < .001). Peak heart rate was lower during the STS test as compared with CPET (P < .001) and the 6MWT (P = .009). The STS test cannot be used as a replacement for CPET to accurately assess peak exercise capacity in CF. The STS test may have utility in detecting patients with CF who may exhibit a high level of oxygen desaturation during heavy exercise. Further studies should identify the factors contributing to STS performance to confirm the potential interest of STS repetitions × body weight outcome as a useful submaximal exercise parameter in CF.

<b>Aims and objectives:</b> Recent discovery of cystic fibrosis transmembrane conductance regulator (CFTR) expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities which may lead to functional impairments. This study aimed to determine whether CF patients have altered resting muscle contractility and greater muscle fatigability compared to healthy controls matched for age, sex and physical activity levels. <b>Methods:</b> Fifteen CF and 15 controls performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations at rest, during and after an isometric intermittent fatiguing task (5-s on/5-s off knee extensions starting at 10% of maximal voluntary contraction (MVC) with 10%-MVC increment every 10 contractions until task failure). Quadriceps cross-sectional area (qCSA) was determined by nuclear magnetic resonance imaging. <b>Results:</b> MVC and some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (MVC: 197±76 Nm vs 245±101 Nm, <i>P</i> = 0.15; doublets 100Hz: 74±30 Nm <i>vs</i> 97±28 Nm, <i>P</i> = 0.06) but theses tendencies disappeared when expressed relative to qCSA. CF and controls had similar impairments in muscle contractility with fatigue, similar endurance and recovery. <b>Conclusions:</b> CF patients have slightly reduced muscle volume and strength and similar muscle endurance and fatigability compared to healthy controls. These results suggest quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF and further encourage the incorporation of strength rehabilitation programs aiming to increase skeletal muscle mass in these patients.