Determinants of physical activity in newly diagnosed obstructive sleep apnea patients: testing the health action process approach.

This study aims to identify the determinants associated with physical activity (PA) behavior in newly diagnosed obstructive sleep apnea (OSA) patients by applying the Health Action Process Approach (HAPA) with a longitudinal design. Anthropometric and clinical (OSA severity, subjective somnolence, use of continuous positive airway pressure (CPAP)) variables, the determinants of physical activity specified in the HAPA (motivational self-efficacy, outcome expectancies, risk perception, intention, maintenance self-efficacy, action planning, coping planning, social support), as well as physical activity behavior were assessed using a longitudinal (T1 and T2) design in a sample of 57 OSA patients in routine care. Applying regression analyses, regarding the motivation phase, the amount of explained variance in intention was 77% and 39% of the variance in physical activity. In the motivational phase, motivational self-efficacy, risk perception and outcome expectancies were associated with intention. In the volitional phase, physical activity at T1 and social support (family) were related with physical activity at T2. In conclusion, the assumptions of HAPA were partially found in the context of newly diagnosed OSA patients. This study provided additional evidence regarding the role of motivational self-efficacy, outcome expectancies and risk perception during motivational phase, and highlighted the important role of social support from the family in the PA in this population.

Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting.

Chronic obstructive pulmonary disease (COPD) is a worldwide prevalent respiratory disease mainly caused by tobacco smoke exposure. COPD is now considered as a systemic disease with several comorbidities. Among them, skeletal muscle dysfunction affects around 20% of COPD patients and is associated with higher morbidity and mortality. Although the histological alterations are well characterized, including myofiber atrophy, a decreased proportion of slow-twitch myofibers, and a decreased capillarization and oxidative phosphorylation capacity, the molecular basis for muscle atrophy is complex and remains partly unknown. Major difficulties lie in patient heterogeneity, accessing patients' samples, and complex multifactorial process including extrinsic mechanisms, such as tobacco smoke or disuse, and intrinsic mechanisms, such as oxidative stress, hypoxia, or systemic inflammation. Muscle wasting is also a highly dynamic process whose investigation is hampered by the differential protein regulation according to the stage of atrophy. In this review, we report and discuss recent data regarding the molecular alterations in COPD leading to impaired muscle mass, including inflammation, hypoxia and hypercapnia, mitochondrial dysfunction, diverse metabolic changes such as oxidative and nitrosative stress and genetic and epigenetic modifications, all leading to an impaired anabolic/catabolic balance in the myocyte. We recapitulate data concerning skeletal muscle dysfunction obtained in the different rodent models of COPD. Finally, we propose several pathways that should be investigated in COPD skeletal muscle dysfunction in the future.

Standardization of the assessment process within telerehabilitation in chronic diseases: a scoping meta-review.

BACKGROUND: Telerehabilitation (TR) interventions are receiving increasing attention. They have been evaluated in various scientific areas through systematic reviews. However, there is a lack of data on how to standardize assessment and report on their domains to guide researchers across studies and bring together the best evidence to assess TR for chronic diseases. AIMS AND OBJECTIVES: The aim of this study was to identify domains of assessment in TR and to qualitatively and quantitatively analyze how and when they are examined to gain an overview of assessment in chronic disease. METHODS: A scoping meta-review was carried out on 9 databases and gray literature from 2009 to 2019. The keyword search strategy was based on "telerehabilitation", "evaluation", "chronic disease" and their synonyms. All articles were subjected to qualitative analysis using the Health Technology Assessment (HTA) Core Model prior to further analysis and narrative synthesis. RESULTS: Among the 7412 identified articles, 80 studies met the inclusion criteria and addressed at least one of the noncommunicable diseases (NCD) categories of cardiovascular disease (cardiovascular accidents), cancer, chronic respiratory disease, diabetes, and obesity. Regarding the domains of assessment, the most frequently occurring were "social aspect" (n = 63, 79%) (e.g., effects on behavioral changes) and "clinical efficacy" (n = 53, 66%), and the least frequently occurring was "safety aspects" (n = 2, 3%). We also identified the phases of TR in which the assessment was conducted and found that it most commonly occurred in the pilot study and randomized trial phases and least commonly occurred in the design, pretest, and post-implementation phases. CONCLUSIONS: Through the HTA model, this scoping meta-review highlighted 10 assessment domains which have not been studied with the same degree of interest in the recent literature. We showed that each of these assessment domains could appear at different phases of TR development and proposed a new cross-disciplinary and comprehensive method for assessing TR interventions. Future studies will benefit from approaches that leverage the best evidence regarding the assessment of TR, and it will be interesting to extend this assessment framework to other chronic diseases.

Efficacy of a long-term pulmonary rehabilitation maintenance program for COPD patients in a real-life setting: a 5-year cohort study.

BACKGROUND: Pulmonary rehabilitation (PR) improves exercise capacity, health-related quality of life (HRQoL) and dyspnea in chronic obstructive pulmonary disease (COPD) patients. Maintenance programs can sustain the benefits for 12 to 24 months. Yet, the long-term effects (> 12 months) of pragmatic maintenance programs in real-life settings remain unknown. This prospective cohort study assessed the yearly evolution in the outcomes [6-min walking distance (6MWD), HRQoL, dyspnea] of a supervised self-help PR maintenance program for COPD patients followed for 5 years. The aim was to assess the change in the outcomes and survival probability for 1 to 5 years after PR program discharge in COPD patients following a PR maintenance program supported by supervised self-help associations. METHODS: Data were prospectively collected from 144 COPD patients who followed a pragmatic multidisciplinary PR maintenance program for 1 to 5 years. They were assessed yearly for 6MWD, HRQol (VQ11) and dyspnea (MRC). The 5-year survival probability was compared to that of a control PR group without a maintenance program. A trajectory-based cluster analysis identified the determinants of long-term response. RESULTS: Maintenance program patients showed significant PR benefits at 4 years for 6MWD and VQ11 and 5 years for MRC. The 5-year survival probability was higher than for PR patients without PR maintenance. Two clusters of response to long-term PR were identified, with responders being the less severe COPD patients. CONCLUSIONS: This study provides evidence of the efficacy of a pragmatic PR maintenance program in a real-life setting for more than 3 years. In contrast to short-term PR, long-term PR maintenance appeared more beneficial in less severe COPD patients.

Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

BACKGROUND: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. METHODS: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). RESULTS: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]. CONCLUSIONS: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries.

Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Nav), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Nav in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent INa current. Various Nav genes, encoding α-subunit isoforms sensitive (Nav 1.2; 1.3; 1.7) and resistant (Nav 1.5) to TTX, were detected both in arterial tissue and in SMCs. Nav channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Nav channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na+/Ca2+ exchanger, Na+/K+-ATPase and the cardiac Nav channel. These results highlight the role of Nav as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Nav channels involved in the initiation of rhythmic oscillatory contractile activity.

COPD is deleterious for pericytes: implications during training-induced angiogenesis in skeletal muscle.

Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%V̇o2: COPD-RI) or absolute (mL·min-1·kg-1: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2+ pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (V̇o2VT) than both patients with COPD-RI and patients with COPD-AI (Group × Time: P = 0.004). Despite a preserved increase in the C/F ratio, NG2+ pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time: P = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology (P < 0.001) and drastically reduced MSC differentiation into pericytes (P < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.NEW & NOTEWORTHY This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.

Effects of a human microenvironment on the differentiation of human myoblasts.

Myogenic differentiation mechanisms are generally assessed using a murine cell line placed in low concentrations of an animal-derived serum. To more closely approximate in vivo pathophysiological conditions, recent studies have combined the use of human muscle cells with human serum. Nevertheless, the in vitro studies of the effects of a human microenvironment on the differentiation process of human myoblasts require the identification of the culture conditions that would provide an optimal and reproducible differentiation process of human muscle cells. We assessed the differentiation variability resulting from the use of human myoblasts and serums from healthy subjects by measuring the myotube diameter, fusion index and surface covered by myotubes. We showed the preserved cell-dependent variability of the differentiation response of myoblasts cultured in human serums compared to FBS. We found that using a pool of serums reduced the serum-dependent variability of the myogenic response compared to individual serums. We validated our methodology by showing the atrophying effect of pooled serums from COPD patients on healthy human myotubes. By replacing animal-derived tissues with human myoblasts and serums, and by validating the sensitivity of cultured human muscle cells to a pathological microenvironment, this human cell culture model offers a valuable tool for studying the role of the microenvironment in chronic disease.

Impaired training-induced angiogenesis process with loss of pericyte-endothelium interactions is associated with an abnormal capillary remodelling in the skeletal muscle of COPD patients.

Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = - 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients. TRIAL REGISTRATION: NCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

Interactive whiteboard use in clinical reasoning sessions to teach diagnostic test ordering and interpretation to undergraduate medical students.

BACKGROUND: Over-testing of patients is a significant problem in clinical medicine that can be tackled by education. Clinical reasoning learning (CRL) is a potentially relevant method for teaching test ordering and interpretation. The feasibility might be improved by using an interactive whiteboard (IWB) during the CRL sessions to enhance student perceptions and behaviours around diagnostic tests. Overall, IWB/CRL could improve their skills. METHODS: Third-year undergraduate medical students enrolled in a vertically integrated curriculum were randomized into two groups before clinical placement in either a respiratory disease or respiratory physiology unit: IWB-based CRL plus clinical mentoring (IWB/CRL + CM: n = 40) or clinical mentoring only (CM-only: n = 40). Feasibility and learning outcomes were assessed. In addition, feedback via questionnaire of the IWB students and their classmates (n = 233) was compared. RESULTS: Analyses of the IWB/CRL sessions (n = 40, 27 paperboards) revealed that they met validated learning objectives. Students perceived IWB as useful and easy to use. After the IWB/CRL + CM sessions, students mentioned more hypothesis-based indications in a test ordering file (p <  0.001) and looked for more nonclinical signs directly on raw data tests (p <  0.01) compared with students in the CM-only group. Last, among students who attended pre- and post-assessments (n = 23), the number of diagnostic tests ordered did not change in the IWB/CRL + CM group (+ 7%; p = N.S), whereas it increased among CM-only students (+ 30%; p <  0.001). Test interpretability increased significantly in the IWB/CRL + CM group (from 4.7 to 37.2%; p <  0.01) but not significantly in the CM-only group (from 2.4 to 9.8%; p = 0.36). CONCLUSIONS: Integrating IWB into CRL sessions is feasible to teach test ordering and interpretation to undergraduate students. Moreover, student feedback and prospective assessment suggested a positive impact of IWB/CRL sessions on students' learning.

Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease.

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3-methyladenine (3-MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.

Standardized Method to Measure Muscle Force at the Bedside in Hemodialysis Patients.

OBJECTIVES: In hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients. DESIGN: Repeated-measures cross-sectional study. SETTING: Clinical and academic hospital. PARTICIPANTS: Fifty-three healthy adult subjects (23 males, 36.5 + 12.5 y.o.) and 21 hemodialysis patients (14 males, 72.4 + 13.3 y.o., dialysis vintage 30 + 75.1 months). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: MVF measurements were assessed with belt-stabilized HHD and dynamometer chair, by two independent investigators. The agreement between the two devices would be quantified using the Bland-Altman 95% limits of agreement (LOA) method and the Spearman correlation. RESULTS: For healthy subjects and hemodialysis patients, Spearman coefficients between belt-stabilized HHD and dynamometer chair were 0.63 and 0.75, respectively (P < .05). In hemodialysis group, reliability was excellent for both the intratester and intertester reliability R2 = 0.85 (P < .01) and R2 = 0.90 (P < .01), respectively. In all individuals, the mean difference between the dynamometer chair and the belt-stabilized HHD was -13.07 ± 21.77 N.m. (P < .001). The LOA for the upper and the lower was 29.59 and -55.73 N.m., respectively. CONCLUSION: In healthy subjects and in hemodialysis patients, the belt-stabilized HHD dynamometer appears as a valid and reliable method to measure in clinical practice isometric MVF of quadriceps in hemodialysis patients. Therefore, the belt-stabilized HHD appears as a suitable and a relevant diagnostic tool for the identification of muscle dysfunction in hemodialysis patients.

An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. METHODS: Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified. RESULTS: Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. CONCLUSIONS: Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.

Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients.

The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes.

An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.

BACKGROUND: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. PURPOSE: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. METHODS: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. RESULTS: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. CONCLUSIONS: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An official European Respiratory Society statement on physical activity in COPD.

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 "Rehabilitation and Chronic Care" determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5-8 years).

Relationship between CT air trapping criteria and lung function in small airway impairment quantification.

BACKGROUND: Small airways are regarded as the elective anatomic site of obstruction in most chronic airway diseases. Expiratory computed tomography (CT) is increasingly used to assess obstruction at this level but there is no consensus regarding the best quantification method. We aimed to evaluate software-assisted CT quantification of air trapping for assessing small airway obstruction and determine which CT criteria better predict small airway obstruction on single breath nitrogen test (SBNT). METHODS: Eighty-nine healthy volunteers age from 60 to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day. Air trapping was estimated using dedicated software measuring on inspiratory and expiratory CT low attenuation area (LAA) lung proportion and mean lung density (MLD). CT indexes were compared to SBNT results using the Spearman correlation coefficient and hierarchical dendrogram analysis. In addition, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal CT air-trapping criterion. RESULTS: 43 of 89 subjects (48,3%) had dN2 value above the threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to inspiratory MLD ratio (r = 0.40) and LAA for the range -850 -1024 HU (r = 0.29) and for the range -850 -910 HU (r = 0.37) were positively correlated with SBNT results. E/I MLD was the most suitable criterion for its expression. Expiratory to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small airway obstruction assessment. CONCLUSION: Among all CT criteria, all correlating with small airway obstruction on SBNT, E/I MLD was the most suitable criterion for its expression in asymptomatic subjects with mild small airway obstruction TRIAL REGISTRATION: Registered at Clinicaltrials.gov, identifier: NCT01230879.

Quality Assessment of Smartphone Medication Management Apps in France: Systematic Search.

BACKGROUND: Adherence to medication is estimated to be around 50% for chronically ill patients in high-income countries. Improving the effectiveness of adherence interventions could have a far greater impact on population health than any improvement in specific medical treatments. Mobile health (mHealth) is one of the most effective solutions for helping patients improve their medication intake, notably through the use of mobile apps with reminder systems. With more than 327,000 apps available in the mHealth field, it is difficult for health care professionals and patients alike to choose which apps to recommend and use. OBJECTIVE: We aim to carry out a systematic search of medication management smartphone apps available in France that send reminders to patients and assess their quality using a validated scale. METHODS: Mobile apps were identified in October and November 2022 after a systematic keyword search on the 2 main app download platforms: App Store (Apple Inc) and Google Play Store. Inclusion criteria were free availability, date of last update, and availability in French. Next, 2 health care professionals independently evaluated the included apps using the French version of the Mobile App Rating Scale (MARS-F), an objective scoring system validated for assessing the overall quality of apps in the mHealth field. An intraclass correlation coefficient was calculated to determine interrater reliability. RESULTS: In total, 960 apps were identified and 49 were selected (25 from the App Store and 24 from the Google Play Store). Interrater reliability was excellent (intraclass correlation coefficient 0.92; 95% CI 0.87-0.95; P<.001). The average MARS-F score was 3.56 (SD 0.49) for apps on the App Store and 3.51 (SD 0.46) for those on the Google Play Store, with 10 apps scoring above 4 out of 5. Further, 2 apps were tested in at least one randomized controlled trial and showed positive results. The 2 apps with the highest ratings were Mediteo rappel de médicaments (Mediteo GmbH) and TOM rappel medicaments, pilule (Innovation6 GmbH), available on both platforms. Each app's MARS-F score was weakly correlated with user ratings on the App Store and moderately correlated on the Google Play Store. CONCLUSIONS: To our knowledge, this is the first study that used a validated scoring system to evaluate medication management apps that send medication reminders. The quality of the apps was heterogeneous, with only 2 having been studied in a randomized controlled trial with positive results. The evaluation of apps in real-life conditions by patients is necessary to determine their acceptability and effectiveness. Certification of apps is also essential to help health care professionals and patients identify validated apps.

Altered skeletal muscle function and beneficial effects of exercise training in a rat model of induced pulmonary emphysema.

AIM: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits. METHODS: We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long-term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross-sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed. RESULTS: An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats. CONCLUSION: Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients.