Changes in exercise capacity in people with Cystic Fibrosis after one year of Elexacaftor/Tezacaftor/Ivacaftor treatment - A Danish prospective cohort.

BACKGROUND: Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. OBJECTIVE: The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. METHODS: A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO2 peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. RESULTS: We included 229 pwCF in the analyses. An increase in oxygen uptake, VO2 peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV1% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. CONCLUSION: Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.

Risk stratification for post-operative pulmonary complications following major cardiothoracic or abdominal surgery: Validation of the PPC Risk Prediction Score for physiotherapist's clinical decision-making.

INTRODUCTION: Patients undergoing major cardiothoracic or abdominal surgery are at increased risk of developing post-operative pulmonary complications (PPC), but respiratory physiotherapy can prevent PPC. We have previously developed the PPC Risk Prediction Score to allocate physiotherapists' resources and stratify patients into three risk groups. In this study, we performed a temporal external validation of the PPC Risk Prediction Score. Such validation is rare and adds to the originality of this study. METHODS: A cohort of 360 patients, admitted to undergo elective cardiothoracic or abdominal surgery, were included. Performance and clinical usefulness of the PPC Risk Prediction Score were estimated through discrimination, calibration and clinical usefulness, and the score was updated. RESULTS: The score showed c-statistics of 0.62. Related to clinical usefulness, a cut point at 8 gave a sensitivity of 0.49 and a specificity of 0.70, whereas a cut point at 12 gave a sensitivity of 0.13 and a specificity of 0.95. Two predictors included in the development sample score, thoraco-abdominal incision odds ratio (OR) 2.74 (1.12;6.71) and sternotomy OR 2.09 (1.18;3.72), were statistically significantly associated to PPC in the validation sample. CONCLUSIONS: The score was not able to discriminate between patients with and without PPC; neither was the updated score, but the study identified clinically relevant risk factors for developing PPC.

Risk Stratification for Postoperative Pulmonary Complications following Major Cardiothoracic and Abdominal Surgery - development of the PPC Risk Prediction Score for Physiotherapists Clinical Decision-making.

INTRODUCTION: Major cardiothoracic or abdominal surgery can lead to the development of postoperative pulmonary complications (PPC), associated with increased morbidity and prolonged length of hospital stay. Preventive chest physiotherapy is routinely provided, but optimization of treatment strategies is needed to improve patient outcome and resource utilization. OBJECTIVE: To develop a preoperative risk prediction scorelr to assist clinical decision-making regarding physiotherapy interventions. METHODS: A prospective observational single-center study included 339 of 577 eligible patients admitted for major elective cardiothoracic or abdominal surgery. Primary outcome measure was PPC amendable to chest physiotherapy. RESULTS: A total of 113 patients (33.3%) developed a PPC. Logistic regression modeling identified four independent predictors of PPC presented with odds ratio (OR) and 95% confidence interval. Reduced lung function (FEV1 > 50% to <75% OR 2.4 (1.4; 4.3) and FEV1 ≤ 50% OR 4.7 (1.4;16.0)), Recent unintended weight loss OR 4.5 (1.1; 18.7), Sternotomy OR 3.5 (2.0; 6.0) and Thoraco-abdominal incision OR 4.5 (2.1; 10.1). Based on assigned point values, a score dividing patients into three risk groups was developed. The score had moderate discrimination (c-statistic 0.70). CONCLUSION: By following recommended guidelines (TRIPOD) a preoperative risk prediction score including four predictors of PPC was developed. External validation of the score is currently being investigated.

Change in exercise capacity measured by Cardio-pulmonary Exercise Testing (CPET) in Danish people with cystic fibrosis after initiation of treatment with Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor.

BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.