Clinical recommendations for cardiopulmonary exercise testing in children with respiratory diseases

Introduction: Cardiopulmonary exercise testing (CPET) quantitates and qualitates the integrated physiological response of a person to incremental exercise and provides additional information compared to static lung function tests alone.Areas covered: This review covers rationale for the use of CPET parameters beyond the usual parameters like peak oxygen uptake and peak minute ventilation in children with respiratory disease.Expert opinion: CPET provides a wealth of data from rest, submaximal and maximal exercise and data during recovery from exercise. In this review an interpretative approach is described for analyzing CPET data in children with respiratory disease

Coping with paediatric illness: Child's play? Exploring the effectiveness of a play- and sports-based cognitive behavioural programme for children with chronic health conditions

Little is known about how play affects the development of children with a chronic condition. Studying play poses major methodological challenges in measuring differences in play behaviour, which results in a relative scarcity of research on this subject. This pilot study seeks to provide novel directions for research in this area. The effectiveness of a play- and sports-based cognitive behavioural programme for children (8-12 years) with a chronic condition was studied. The children and parents completed a battery of measurement tools before and after the programme. Moreover, the application of automated computer analyses of behaviour was piloted. Behaviour (Child Behavior Checklist) seemed to be positively affected by the programme. An increase in psychological well-being was observed (KIDSCREEN). Perceived competence (Self-Perception Profile for Children) and actual motor competence (Canadian Agility and Movement Skill Assessment) did not show any positive trends. These results of 13 participants suggest that children might learn to better cope with their illness by stimulating play behaviour. For the analysis of the effectiveness of programmes like this, we therefore propose to focus on measuring behaviour and quality of life. In addition, pilot measurements showed that automated analysis of play can provide important insights into the participation of children

Short-term effect of air stacking and mechanical insufflation-exsufflation on lung function in patients with neuromuscular diseases

Air stacking (AS) and mechanical insufflation-exsufflation (MI-E) aim to increase cough efficacy by augmenting inspiratory lung volumes in patients with neuromuscular diseases (NMDs). We studied the short-term effect of AS and MI-E on lung function. We prospectively included NMD patients familiar with daily AS or MI-E use. Studied outcomes were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) prior to, immediately after, and up to 2 h after treatment. Paired sample T-test and Wilcoxon signed-rank test was used. Sixty-seven patients participated. We observed increased FVC and FEV1 immediately after AS with a mean difference of respectively 0.090 L (95% CI 0.045; 0.135, p < .001) and 0.073 L (95% CI 0.017; 0.128, p = .012). Increased FVC immediately after MI-E (mean difference 0.059 L (95% CI 0.010; 0.109, p = .021) persisted 1 hour (mean difference 0.079 L (95% CI 0.034; 0.125, p = .003). The effect of treatment was more pronounced in patients diagnosed with Spinal Muscular Atrophy, compared to patients with Duchenne muscular dystrophy. AS and MI-E improved FVC immediately after treatment, which persisted 1 h after MI-E. There is insufficient evidence that short-lasting increases in FVC would explain the possible beneficial effect of AS and MI-E

Therapeutic Validity and Effectiveness of Preoperative Exercise on Functional Recovery after Joint Replacement: A Systematic Review and Meta-Analysis

Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the association between therapeutic validity of preoperative therapeutic exercise and its effectiveness in terms of postoperative functional recovery. Methods: (Quasi) randomised clinical trials on preoperative therapeutic exercise in adults awaiting TJR on postoperative recovery of functioning within three months after surgery were identified through database and reference screening. Two reviewers extracted data and assessed the risk of bias and therapeutic validity. Therapeutic validity of the interventions was assessed with a nine-itemed, expert-based rating scale (scores range from 0 to 9; score ≥6 reflecting therapeutic validity), developed in a four-round Delphi study. Effects were pooled using a random-effects model and meta-regression was used to study the influence of therapeutic validity. Results: Of the 7,492 articles retrieved, 12 studies (737 patients) were included. None of the included studies demonstrated therapeutic validity and two demonstrated low risk of bias. Therapeutic exercise was not associated with 1) observed functional recovery during the hospital stay (Standardised Mean Difference [SMD]: −1.19; 95%-confidence interval [CI], −2.46 to 0.08); 2) observed recovery within three months of surgery (SMD: −0.15; 95%-CI, −0.42 to 0.12); and 3) self-reported recovery within three months of surgery (SMD −0.07; 95%-CI, −0.35 to 0.21) compared with control participants. Meta-regression showed no statistically significant relationship between therapeutic validity and pooled-effects. Conclusion: Preoperative therapeutic exercise for TJR did not demonstrate beneficial effects on postoperative functional recovery. However, poor therapeutic validity of the therapeutic exercise programmes may have hampered potentially beneficial effects, since none of the studies met the predetermined quality criteria. Future review studies on therapeutic exercise should address therapeutic validity. (aut.ref.

The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus

This is the final version. Available on open access from SAGE Publications via the DOI in this recordData availability statement: All results are presented within the manuscript and supplementary files.BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.Cystic Fibrosis Trus

Cardiopulmonary Exercise Testing in Pediatrics

Aerobic fitness is an important determinant of overall health. Higher aerobic fitness has been associated with many health benefits. Because myocardial ischemia is rare in children, indications for exercise testing differ in children compared to adults. Pediatric exercise testing is imperative to unravel the physiological mechanisms of a reduced aerobic fitness and to evaluate intervention effects in children and adolescents with a chronic disease or disability. Cardiopulmonary exercise testing includes the measurement of respiratory gas exchange and is the gold standard for determining aerobic fitness, as well as for examining the integrated physiological responses to exercise in pediatric medicine. As the physiological responses to exercise change during growth and development, appropriate pediatric reference values are essential for an adequate interpretation of the cardiopulmonary exercise test

Cyclosporin A and enterohepatic circulation of bile salts in rats: Decreased cholate synthesis but increased intestinal reabsorption

Cyclosporin A (CsA) has been shown to inhibit synthesis and hepatobiliary transport of bile salts. However, effects of CsA on the enterohepatic circulation of bile salts in vivo are largely unknown. We characterized the effects of CsA on the enterohepatic circulation of cholate, with respect to synthesis rate, pool size, cycling time, intestinal absorption, and the expression of relevant transporters in liver and intestine in rats. CsA (1 mg.100 g(-1).day(-1) s.c.) or its solvent was administered daily to male rats for 10 days. Cholate synthesis rate and pool size were determined by a H-2(4)-cholate dilution technique. Bile and feces were collected for determination of cholate and total bile salts, respectively. Cycling time and intestinal absorption of cholate were calculated. The mRNA levels and corresponding transporter protein levels in liver and intestine were assessed by real-time polymerase chain reaction and Western analysis, respectively. CsA treatment decreased cholate synthesis rate by 71%, but did not affect pool size or cycling time. CsA reduced the amount of cholate lost per enterohepatic cycle by similar to70%. Protein levels of the apical sodium-dependent bile salt transporter (Asbt) were 2-fold increased in distal ileum of CsA-treated rats, due to post-transcriptional events. In conclusion, chronic CsA treatment markedly reduces cholate synthesis rate in rats, but does not affect cholate pool size or cycling time. Our results strongly suggest that CsA enhances efficacy of intestinal cholate reabsorption through increased Asbt protein expression in the distal ileum, which contributes to maintenance of cholate pool size in CsA-treated rats

Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice

Baekground/Aims: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes suggesting a role in control of BSDF and/or in control of bile salt synthesis, through cholehepatic shunting. Methods: We studied effects of bile duct proliferation under non-cholestatic conditions in multidrug resistance-2 P-glycoprotein (Abcb4)-deficient multidrug resistance gene-2 (Mdl-2((-/-))) mice. BSDF and BSIF were determined in wild-type and Mdr2((-/-)) mice during infusion of step-wise increasing dosages of tauroursodeoxycholate (TUDC). Cholate synthesis rate was determined by H-2(4)-cholate dilution. Results were related to expression of transport proteins in liver and intestine. Results: During TUDC infusion, BSDF was increased by similar to 50% and BSIF by similar to 100% in Mdr2((-/-)) mice compared with controls. Cholate synthesis rate was unaffected in Mdr2((-/-)) mice. Hepatic expression of the apical sodium-dependent bile salt transporter (Asbt), its truncated form (tAsbt) and the multidrug resistance-related protein 3 were upregulated in Mdr2((-/-)) mice. Conclusions: Bile duct proliferation in Mdr2((-/-)) mice enhances cholehepatic shunting of bile salts, which is associated with a disproportionally high bile flow but does not affect bile salt synthesis

Cyclosporine A - Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation

Hyperlipidemia is a common side effect of cyclosporine A (CsA) after solid organ transplantation. CsA also markedly reduces the synthesis rate of bile salts in rats and can inhibit biliary bile salt secretion. It is not known, however, whether CsA inhibits the synthesis of bile salts in humans, and whether the hyperlipidemic effects of CsA are related to bile salt metabolism. Our objective was to assess the effects of CsA on the synthesis rate of bile salts and on plasma triglycerides and cholesterol levels in pediatric liver transplant patients. Before and after discontinuation of CsA treatment after liver transplantation, synthesis rate and pool size of the primary bile salts cholate and chenodeoxycholate were determined using a stable isotope dilution technique and related to plasma lipids. In 6 children (age: 3-16 years) CsA treatment was discontinued at 2 years (median 2.3 years) after liver transplantation. Discontinuation of CsA increased synthesis rate of chenodeoxycholate (+38%, P <.001) and cholate (+21%, P <.05) and the pool size of chenodeoxycholate (+54%, P <.001). Discontinuation of CsA. decreased plasma levels of cholesterol (-18%, P <.05) and triglycerides (-23%, P <.05). Bile salt synthesis rate appeared to be inversely correlated with plasma cholesterol (Spearman rank correlation coefficient [r(s)] = -0.82, P <.01) and plasma triglyceride levels (r(s) = -0.62, P <.05). In conclusion, CsA inhibits bile salt synthesis and increases plasma concentration of cholesterol and triglycerides in pediatric liver transplant patients. Suppression of bile salt synthesis by long-term CsA treatment may contribute to hypertipidernia and thus to increased risk for cardiovascular disease