Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: Results from a prospective longitudinal cohort study.

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents' education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales. CONCLUSION: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group. WHAT IS KNOWN: • Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being. • HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples. WHAT IS NEW: • Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. • Public health strategies to improve mental health may be effective in improving HRQOL in children.

Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students.

STUDY DESIGN: Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. BACKGROUND: Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. METHODS: On 7-8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from -1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating 'random guessing'-balanced 'active' and 'control' perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. RESULTS: 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, -0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (-0.12 to 0.30) and -0.10 (-0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. CONCLUSIONS: Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05822947 (retrospectively registered).

Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection.

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort (n = 2,917) and a cross-sectional cohort including children and adults (n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva (n = 4,993) and plasma (n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction (F ENO50 ).

BACKGROUND: Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s-1 (F ENO50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO50 . METHODS: Available individual F ENO50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of "healthy" were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. RESULTS: Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO50 (R2=0.12). F ENO device was neccessary as a predictor of F ENO50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. CONCLUSION: Available F ENO50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.

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.

Standards for the care of people with cystic fibrosis; establishing and maintaining health.

This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.

Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study "Ciao Corona", we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3-98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 .

Health-Related Quality of Life and Adherence to Physical Activity and Screen Time Recommendations in Schoolchildren: Longitudinal Cohort Ciao Corona.

Objectives: We investigated changes in adherence to physical activity (PA) and screen time (ST) recommendations of children and adolescents throughout the pandemic, and their association with health-related quality of life (HRQOL). Methods: 1,769 primary (PS, grades 1-6) and secondary (SS, 7-9) school children from Ciao Corona, a school-based cohort study in Zurich, Switzerland, with five questionnaires 2020-2022. HRQOL was assessed using the KINDL questionnaire. PA (≥60 min/day moderate-to-vigorous PA) and ST (≤2 h/day ST) recommendations followed WHO guidelines. Results: Adherence to PA recommendations dropped in 2020 (83%-59% PS, 77%-52% SS), but returned to pre-pandemic levels by 2022 (79%, 66%). Fewer children met ST recommendations in 2020 (74% PS, 29% SS) and 2021 (82%, 37%) than pre-pandemic (95%, 68%). HRQOL decreased 3 points between 2020 and 2022, and was 9.7 points higher (95% CI 3.0-16.3) in March 2021 in children who met both versus no recommendations. Conclusion: Adherence to WHO guidelines on PA and ST during the pandemic had a consistent association with HRQOL despite longitudinal changes in behavior.

Guidance and standard operating procedures for functional exercise testing in cystic fibrosis.

Regular exercise testing is recommended for all people with cystic fibrosis (PwCF). A range of validated tests, which integrate both strength and aerobic function, are available and increasingly being used. Together, these tests offer the ability for comprehensive exercise evaluation. Extensive research and expert consensus over recent years has enabled the adaptation and standardisation of a range of exercise tests to aid the understanding of the pathophysiology related to exercise limitation in PwCF and has led to the development of novel exercise tests which may be applied to PwCF. This article provides expert, opinion-based clinical practice guidance, along with test instructions, for a selection of commonly used valid tests which have documented clinimetric properties for PwCF. Importantly, this document also highlights previously used tests that are no longer suggested for PwCF and areas where research is mandated. This collaboration, on behalf of the European Cystic Fibrosis Society Exercise Working Group, represents expert consensus by a multidisciplinary panel of physiotherapists, exercise scientists and clinicians and aims to improve global standardisation of functional exercise testing of PwCF. In short, the standardised use of a small selection of tests performed to a high standard is advocated.

Heterogeneous evolution of SARS-CoV-2 seroprevalence in school-age children: Results from the school-based cohort study Ciao Corona in November-December 2021 in the canton of Zurich.

BACKGROUND: Much remains unknown regarding the evolution of SARS-CoV-2 seroprevalence and variability in seropositive children in districts, schools and classes as only a few school-based cohort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to the understanding of how seroprevalence developed in the school aged population. AIM: We investigated the evolution of SARS-CoV-2 seroprevalence in children and its variability in districts, schools and classes in Switzerland from June/July 2020 to November/December 2021. METHODS: In this school-based cohort study, SARS-CoV-2 antibodies were measured in primary and secondary school children from randomly selected schools in the canton of Zurich in October/November 2020, March/April 2021 and November/December 2021. Seroprevalence was estimated using Bayesian logistic regression to adjust for test sensitivity and specificity. Variability of seroprevalence between school classes was expressed as maximum minus minimum seroprevalence in a class and summarised as median (interquartile range). RESULTS: 1875 children from 287 classes in 43 schools were tested, with median age 12 years (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% credible interval [CrI] 3.5-7.6%) to 31.1% (95% CrI 27.0-36.1%) in unvaccinated children, and 46.4% (95% CrI 42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (<5%) than those in secondary schools, but by late 2021, primary schools had 12.3% (44.3%) lower seroprevalence for unvaccinated (all) subjects. Variability in seroprevalence among districts and schools increased more than two-fold over time, and in classes from 11% (95% CrI 7-17%) to 40% (95% CrI 22-49%). CONCLUSIONS: Seroprevalence in children increased greatly, especially in 2021 following introduction of vaccines. Variability in seroprevalence was high and increased substantially over time, suggesting complex transmission chains.

Cystic fibrosis related diabetes is not associated with maximal aerobic exercise capacity in cystic fibrosis: a cross-sectional analysis of an international multicenter trial.

BACKGROUND: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO2peak), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO2peak. We investigated associations between CFRD and VO2peak following rigorous control for confounders including objectively measured physical activity. METHODS: Baseline data from the international multicenter trial ACTIVATE-CF with participants ≥12 years performing up to 4 h per week of vigorous physical activity were used for this project. Multivariable models were computed to study associations between CFRD and VO2peak (mL.min-1) adjusting for a set of pre-defined covariates: age, sex, weight, forced expiratory volume in 1 s (FEV1), breathing reserve index, Pseudomonas aeruginosa infection, and physical activity (aerobic step counts from pedometry). Variables were selected based on their potential confounding effect on the association between VO2peak and CFRD. RESULTS: Among 117 randomized individuals, 103 (52% female) had a maximal exercise test and were included in the analysis. Participants with (n = 19) and without (n = 84) CFRD did not differ in FEV1, physical activity, nutritional status, and other clinical characteristics. There were also no differences in VO2peak (mL.min-1 or mL.kg-1.min-1 or% predicted). In the final multivariable model, all pre-defined covariates were significant predictors of VO2peak (mL.min-1), however CFRD [coefficient 82.1, 95% CI -69.5 to 233.8, p = 0.28] was not. CONCLUSIONS: This study suggests no meaningful differences in VO2peak between people with and without CFRD given comparable levels of physical activity.

Low Cardiorespiratory Fitness Post-COVID-19: A Narrative Review.

Patients recovering from COVID-19 often report symptoms of exhaustion, fatigue and dyspnoea and present with exercise intolerance persisting for months post-infection. Numerous studies investigated these sequelae and their possible underlying mechanisms using cardiopulmonary exercise testing. We aimed to provide an in-depth discussion as well as an overview of the contribution of selected organ systems to exercise intolerance based on the Wasserman gears. The gears represent the pulmonary system, cardiovascular system, and periphery/musculature and mitochondria. Thirty-two studies that examined adult patients post-COVID-19 via cardiopulmonary exercise testing were included. In 22 of 26 studies reporting cardiorespiratory fitness (herein defined as peak oxygen uptake-VO2peak), VO2peak was < 90% of predicted value in patients. VO2peak was notably below normal even in the long-term. Given the available evidence, the contribution of respiratory function to low VO2peak seems to be only minor except for lung diffusion capacity. The prevalence of low lung diffusion capacity was high in the included studies. The cardiovascular system might contribute to low VO2peak via subnormal cardiac output due to chronotropic incompetence and reduced stroke volume, especially in the first months post-infection. Chronotropic incompetence was similarly present in the moderate- and long-term follow-up. However, contrary findings exist. Peripheral factors such as muscle mass, strength and perfusion, mitochondrial function, or arteriovenous oxygen difference may also contribute to low VO2peak. More data are required, however. The findings of this review do not support deconditioning as the primary mechanism of low VO2peak post-COVID-19. Post-COVID-19 sequelae are multifaceted and require individual diagnosis and treatment.

Monitoring practices of chronic lung allograft dysfunction in pediatric lung transplantation.

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) continues to negatively impact the survival of pediatric lung transplant (LTx) recipients. Current consensus guidelines are adult-focused. We sought to examine CLAD detection and monitoring practices at pediatric LTx programs. METHODS: We conducted a survey among the International Pediatric Lung Transplant Collaborative. Questions consisted of practitioner's experience, LTx program demographics, and querying tests used for CLAD surveillance and detection. Investigations queried included: chest x-ray (CXR), chest computed tomography (CT), lung magnetic resonance imaging (MRI), ventilation/perfusion scanning, conventional pulmonary function testing (PFT), multiple breath washout (MBW), infant/preschool PFT, bronchoalveolar lavage, transbronchial biopsies (TBBx), or other tissue sampling techniques. Preferences for certain modalities over others were questioned based on a five-point Likert scale. RESULTS: Twenty-four of 25 programs responded. Chest CT and CXR are used generally for both CLAD surveillance and detection. No programs use lung MRI clinically, it may have some utility in the future. While all centers use conventional PFT, MBW, and infant/preschool PFT are used in one-fifth and one-third of centers, respectively. While the majority of programs use TBBx, only 41.7% would obtain a diagnosis based on tissue histopathology over noninvasive techniques if CLAD is suspected. Utilization of biomarkers is still limited. CONCLUSIONS: Our results indicate continued use of conventional PFT along with chest CT and less so CXR for CLAD detection and monitoring in the large majority of centers. Infant/preschool PFT and novel methods such as MBW are used in a few centers only. Respondents agreed there is a timely need for pediatric consensus guidelines on CLAD detection and monitoring.

Lifestyle Behaviours of Children and Adolescents During the First Two Waves of the COVID-19 Pandemic in Switzerland and Their Relation to Well-Being: An Observational Study.

Objectives: To describe changes in adherence to recommendations for physical activity (PA), screen time (ST), and sleep duration over the first two waves of the pandemic in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health as well-being indicators. Methods: In this observational study, we included 2,534 participants (5-16 years) from four Swiss cantons. Participants, or their parents, completed repeated questionnaires and reported on their (child's) lifestyle and well-being, between June 2020 and April 2021. We used linear and logistic regression models to assess the associations between lifestyle and well-being. Results: The percentage of children meeting the recommendations for PA and ST decreased from the pre-pandemic period to the first wave, with a slight recovery during the second wave. Participants meeting all three recommendations during the second wave were more likely to report excellent health (OR: 1.65 [95% CI: 1.00-2.76]) and higher life satisfaction (ß: 0.46 [0.16-0.77]) in early 2021 than participants not meeting any recommendation. Conclusion: We showed a substantial impact of the COVID-19 pandemic on children's and adolescents' lifestyle, and a positive association between meeting lifestyle recommendations and well-being.

Parents' Working Conditions in the Early COVID-19 Pandemic and Children's Health-Related Quality of Life: The Ciao Corona Study.

Objective: To assess the associations between parents' working conditions during the lockdown period (March-May 2020) and children's health-related quality of life (HRQOL) over the first year of the COVID-19 pandemic in Zurich, Switzerland. Methods: We included 2211 children (6-16 years) and their parents from the prospective study Ciao Corona. Parents reported their employment status and working conditions during the lockdown. Children's HRQOL was assessed in June-July 2020, January and March 2021 using the parents-report of the KINDL®. We used mixed models to assess the associations between parents' working conditions and children's HRQOL at the three time points. Results: Children from families in which at least one parent changed their working conditions during the lockdown showed lower HRQOL in June-July 2020, than children from families in which neither parent experienced changes. Children from families in which at least one parent had to work remotely continued to show lower HRQOL in January and March 2021. Conclusion: Changes in parents' working conditions during lockdown were negatively associated with children's HRQOL. Public health policies aiming to support families susceptible to adverse changes are needed.

The impact of seat height on 1-min sit-to-stand test performance in COPD: a randomised crossover trial.

Study question: Is there a difference in the number of repetitions in the 1-minute sit-to-stand (1MSTS) test using an individually adapted seat height to 90° knee flexion (1MSTSIND), compared with the commonly used standard chair seat height of 46 cm (1MSTSSTD), in people with COPD? Methods: We conducted a single-centre, single-blinded, randomised crossover trial in people with COPD between August 2020 and March 2021 at a specialised rehabilitation clinic in Switzerland. After a learning 1MSTS test, all participants performed two 1MSTS tests in random order on consecutive days. Participants were blinded, as they did not receive detailed information on the testing protocols. Results: 49 individuals with COPD (47% female) participated. In a regression model adjusted for sequence period and subject, 1MSTS test performance was lower on 1MSTSIND compared to 1MSTSSTD (-0.78 repetitions, 95% CI -1.47 to -0.11). In a second regression model additionally including the knee angle and an interaction term (1MSTSIND×knee angle), the interaction term was significant: 0.18 (95% CI 0.05 to 0.30). The limits of agreement were between -5.5 and 4 repetitions. Conclusion: Although we observed a statistically significant difference between 1MSTSIND and 1MSTSSTD on a population level, the difference is negligible. Further studies may be needed to determine whether individual adaptation of seat height is needed for very tall or short people to ensure a valid assessment of 1MSTS test performance in COPD.

Effectiveness of a Long-term Home-Based Exercise Training Program in Patients With COPD After Pulmonary Rehabilitation: A Multicenter Randomized Controlled Trial.

BACKGROUND: Most patients with COPD do not maintain exercise training after pulmonary rehabilitation (PR). RESEARCH QUESTION: Does a 12-month home-based, minimal-equipment strength training program after PR have an effect on dyspnea, exercise capacity, and patient-reported outcomes in patients with COPD? STUDY DESIGN AND METHODS: In a parallel-arm multicenter study across four Swiss PR clinics, patients with COPD were allocated randomly (1:1 ratio) into an intervention group (IG; home-based strength training program) or control group (CG; usual care). The primary outcome was change in Chronic Respiratory Questionnaire (CRQ) dyspnea scale score from baseline to 12 months. Secondary outcomes were change in exercise capacity (1-min sit-to-stand-test [1MSTST], 6-min walk test [6MWT]), health-related quality of life, exacerbations, and symptoms. We assessed the IG's experience by interviews at study end. Main analyses were based on the intention-to-treat approach, and adjusted linear regression models were used. RESULTS: One hundred twenty-three patients with COPD (IG, n = 61; CG, n = 62) were randomized, 61 of whom were women and whose mean ± SD age was 66.8 ± 8.1 years and mean ± SD FEV1 was 39.3 ± 15.3% predicted. One hundred four participants completed 12 months of follow-up (IG, n= 53; CG, n= 51). Of the 53 IG participants, 37 participants (70%) conducted the training until study end. We found no difference in change in CRQ dyspnea scale score over 12 months (adjusted mean difference, 0.28; 95% CI, -0.23 to 0.80; P = .27). We found moderate evidence for a difference in 1MSTST repetitions favoring the IG (adjusted mean difference, 2.6; 95% CI, 0.22-5.03; P = .033), but no evidence for an effect in other outcomes. Seventy-nine percent of the IG reported positive effects that they attributed to the training. INTERPRETATION: The home exercise program had no effect on dyspnea, but improved 1MSTST performance and patient-perceived fitness. The supported program was well accepted by patients with COPD and may facilitate continued exercise training at home. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03461887; URL: www. CLINICALTRIALS: gov.

Physical activity and exercise training in cystic fibrosis.

BACKGROUND: Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review. OBJECTIVES: To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV1), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The most recent search was on 3 March 2022. We also searched two ongoing trials registers: clinicaltrials.gov, most recently on 4 March 2022; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), most recently on 16 March 2022.  SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs comparing physical activity interventions of any type and a minimum intervention duration of two weeks with conventional care (no physical activity intervention) in people with CF. DATA COLLECTION AND ANALYSIS: Two review authors independently selected RCTs for inclusion, assessed methodological quality and extracted data. We assessed the certainty of the evidence using GRADE.  MAIN RESULTS: We included 24 parallel RCTs (875 participants). The number of participants in the studies ranged from nine to 117, with a wide range of disease severity. The studies' age demographics varied: in two studies, all participants were adults; in 13 studies, participants were 18 years and younger; in one study, participants were 15 years and older; in one study, participants were 12 years and older; and seven studies included all age ranges. The active training programme lasted up to and including six months in 14 studies, and longer than six months in the remaining 10 studies. Of the 24 included studies, seven implemented a follow-up period (when supervision was withdrawn, but participants were still allowed to exercise) ranging from one to 12 months. Studies employed differing levels of supervision: in 12 studies, training was supervised; in 11 studies, it was partially supervised; and in one study, training was unsupervised. The quality of the included studies varied widely. This Cochrane Review shows that, in studies with an active training programme lasting over six months in people with CF, physical activity probably has a positive effect on exercise capacity when compared to no physical activity (usual care) (mean difference (MD) 1.60, 95% confidence interval (CI) 0.16 to 3.05; 6 RCTs, 348 participants; moderate-certainty evidence). The magnitude of improvement in exercise capacity is interpreted as small, although study results were heterogeneous. Physical activity interventions may have no effect on lung function (forced expiratory volume in one second (FEV1) % predicted) (MD 2.41, 95% CI ‒0.49 to 5.31; 6 RCTs, 367 participants), HRQoL physical functioning (MD 2.19, 95% CI ‒3.42 to 7.80; 4 RCTs, 247 participants) and HRQoL respiratory domain (MD ‒0.05, 95% CI ‒3.61 to 3.51; 4 RCTs, 251 participants) at six months and longer (low-certainty evidence). One study (117 participants) reported no differences between the physical activity and control groups in the number of participants experiencing a pulmonary exacerbation by six months (incidence rate ratio 1.28, 95% CI 0.85 to 1.94) or in the time to first exacerbation over 12 months (hazard ratio 1.34, 95% CI 0.65 to 2.80) (both high-certainty evidence); and no effects of physical activity on diabetic control (after 1 hour: MD ‒0.04 mmol/L, 95% CI ‒1.11 to 1.03; 67 participants; after 2 hours: MD ‒0.44 mmol/L, 95% CI ‒1.43 to 0.55; 81 participants; moderate-certainty evidence). We found no difference between groups in the number of adverse events over six months (odds ratio 6.22, 95% CI 0.72 to 53.40; 2 RCTs, 156 participants; low-certainty evidence). For other time points (up to and including six months and during a follow-up period with no active intervention), the effects of physical activity versus control were similar to those reported for the outcomes above. However, only three out of seven studies adding a follow-up period with no active intervention (ranging between one and 12 months) reported on the primary outcomes of changes in exercise capacity and lung function, and one on HRQoL. These data must be interpreted with caution. Altogether, given the heterogeneity of effects across studies, the wide variation in study quality and lack of information on clinically meaningful changes for several outcome measures, we consider the overall certainty of evidence on the effects of physical activity interventions on exercise capacity, lung function and HRQoL to be low to moderate. AUTHORS' CONCLUSIONS: Physical activity interventions for six months and longer likely improve exercise capacity when compared to no training (moderate-certainty evidence). Current evidence shows little or no effect on lung function and HRQoL (low-certainty evidence). Over recent decades, physical activity has gained increasing interest and is already part of multidisciplinary care offered to most people with CF. Adverse effects of physical activity appear rare and there is no reason to actively discourage regular physical activity and exercise. The benefits of including physical activity in an individual's regular care may be influenced by the type and duration of the activity programme as well as individual preferences for and barriers to physical activity. Further high-quality and sufficiently-sized studies are needed to comprehensively assess the benefits of physical activity and exercise in people with CF, particularly in the new era of CF medicine.