Health-related quality of life in children and adolescents born very preterm and its correlates: a cross-sectional study.

OBJECTIVE: We aimed to assess health-related quality of life (HRQOL) in a cohort of very preterm born children and adolescents (aged 5-16), and to compare it with their fullterm born siblings and the general population. We also explored correlates of HRQOL among the very preterm born. DESIGN: Cross-sectional survey. PATIENTS: Children born <32 weeks gestation (N=442) as well as their fullterm born siblings (N=145). MAIN OUTCOME MEASURES: Primary outcome was KINDL total score (0 worst to 100 best), a validated multidimensional measure of HRQOL in children and adolescents. METHODS: Linear mixed models accounted for family unit. Secondary analysis compared very preterm born children to another cohort of healthy children from the same time period. A classification tree analysis explored potential correlates of HRQOL. RESULTS: On average, preterm children, both <28 and 28-31 weeks gestational age, had similar KINDL total score to fullterm sibling controls (-2.3, 95% CI -3.6 to -0.6), and to population controls (+1.4, 95% CI 0.2 to 2.5). Chronic non-respiratory health conditions (such as attention deficit hyperactivity disorder or heart conditions, but not including cerebral palsy), age and respiratory symptoms affecting daily life were key correlates of HRQOL among very preterm born children. CONCLUSIONS: Very preterm birth in children and adolescents was not associated with a relevant reduction in HRQOL compared with their fullterm born peers. However, lower HRQOL was explained by other factors, such as older age, and the presence of chronic non-respiratory health conditions, but also by possibly modifiable current respiratory symptoms. The influence of respiratory symptom amelioration and its potential influence on HRQOL needs to be investigated further. TRIAL REGISTRATION NUMBER: NCT04448717.

Exploring immediate cardiorespiratory responses: low-intensity blood flow restricted cycling vs. moderate-intensity traditional exercise in a randomized crossover trial.

PURPOSE: Blood-flow restriction (BFR) endurance training may increase endurance performance and muscle strength similar to traditional endurance training while requiring a lower training intensity. We aimed to compare acute cardiorespiratory responses to low-intensity interval exercise under BFR with moderate-intensity traditional interval exercise (TRA). METHODS: We conducted a randomized crossover study. The protocol involved three cycling intervals interspersed with 1 min resting periods. With a 48-h washout period, individuals performed the protocol twice in random order: once as BFR-50 (i.e., 50% incremental peak power output [IPPO] and 50% limb occlusion pressure [LOP]) and once as TRA-65 (65% IPPO without occlusion). TRA-65 intervals lasted 2 min, and time-matched BFR-50 lasted 2 min and 18 s. Respiratory parameters were collected by breath-by-breath analysis. The ratings of perceived breathing and leg exertion (RPE, 0 to 10) were assessed. Linear mixed models were used for analysis. RESULTS: Out of the 28 participants initially enrolled in the study, 24 healthy individuals (18 males and 6 females) completed both measurements. Compared with TRA-65, BFR-50 elicited lower minute ventilation (VE, primary outcome) (-3.1 l/min [-4.4 to -1.7]), oxygen consumption (-0.22 l/min [-0.28 to -0.16]), carbon dioxide production (-0.25 l/min [-0.29 to -0.20]) and RPE breathing (-0.9 [-1.2 to -0.6]). RPE leg was significantly greater in the BFR-50 group (1.3 [1.0 to 1.7]). CONCLUSION: BFR endurance exercise at 50% IPPO and 50% LOP resulted in lower cardiorespiratory work and perceived breathing effort compared to TRA at 65% IPPO. BFR-50 could be an attractive alternative for TRA-65, eliciting less respiratory work and perceived breathing effort while augmenting perceived leg muscle effort. TRIAL REGISTRATION: NCT05163600; December 20, 2021.

Effects of Pycnogenol® in people with post-COVID-19 condition (PYCNOVID): study protocol for a single-center, placebo controlled, quadruple-blind, randomized trial.

BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study. DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.

Evidence-based coaching of core competencies in epidemiology, using the framework of randomized controlled trials: the Zurich approach.

Teaching epidemiological concepts in academic settings poses a challenge due to the intricate nature of the discipline as both a science and a practice. Whereas traditional classroom-based teaching methods are commonly employed, evidence suggests they may not be the most effective approach for fostering core competencies and skills required in real-life scientific work. In this article, we describe our process of transitioning from traditional classroom teaching of epidemiology towards practice-based coaching to convey epidemiological concepts to bachelor's and master's students in Biomedicine. We chose the framework of randomized controlled trials (RCT) since they offer a great opportunity to teach epidemiological concepts in a hands-on course. This practice-based course encompasses the entire life cycle of a study, allowing students to design and conduct a short-term experiment, analyse its data and prepare a scientific paper. We provide a comprehensive overview of the course structure, content, learning objectives and course evaluation, while also discussing the advantages and disadvantages of this innovative format. Our approach offers a promising alternative to classroom teaching by incorporating practical, hands-on experiences offering students a high level of independence and self-determination, as well as facilitation and coaching by faculty. It has the potential to be applied across diverse academic settings, providing students with valuable skills and competencies in epidemiology.

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.

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.

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.

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.