P91 Cardiopulmonary exercise testing in CF adolescents after starting Tezacaftor/Ivacaftor

Ahmed, Molla Imaduddin; Dayman, N.; Madge, Joe; Gaillard, Erol

doi:10.1136/thorax-2020-btsabstracts.236

Cited by 3 publications

(9 citation statements)

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“…CFTR is expressed within skeletal muscle tissue 25 and CFTR activity might be involve in regulating mitochondrial function. 28 As reported in other studies, 12,14,16,29 BMI increased in all three of our adolescents. Understanding the pattern of weight gain after modulator treatment is an important area of research.…”

Section: Discussionsupporting

confidence: 86%

“… 9 The majority of clinical trials examining the effects of CFTR modulator treatment have studied changes in FEV 1 , with relatively few evaluating changes in exercise capacity. 11 , 12 , 13 , 14 , 15 , 16 , 22 The present findings of clinically meaningful improvements in

O 2 peak are promising given the findings of previous studies. A small case series of Ivacaftor, reported an increase in

O 2 peak in an adolescent with severe lung disease, but no improvement in milder disease following 12 weeks treatment.…”

Section: Discussionsupporting

confidence: 80%

“…Ventilatory, cardiovascular and intramuscular abnormalities have been reported 9 . The majority of clinical trials examining the effects of CFTR modulator treatment have studied changes in FEV 1 , with relatively few evaluating changes in exercise capacity 11–16,22 . The present findings of clinically meaningful improvements in

\dot{{\rm{V}}}

O 2 peak are promising given the findings of previous studies.…”

Section: Discussionmentioning

confidence: 51%

“…Of the evidence available for Lumacaftor/Ivacaftor, despite initial case series reports that 2 years of treatment could improve physical activity and exercise tolerance in adults with CF, 14 a more recent pilot study reported no improvements in exercise tolerance following treatment with Lumacaftor/Ivacaftor 15 . Most recently, a small study of four adolescents commencing Tezacaftor/Ivacaftor demonstrated increased

\dot{{\rm{V}}}

O 2 peak in only one patient at 7–8 months follow‐up, with the remaining three experiencing reductions, although submaximal aerobic fitness (the AT) was improved in all cases 16 . The present case series adds to this evidence base and provides the first exercise‐related data in response to eElexacaftor/Tezacaftor/Ivacaftor in modulator naïve patients.…”

Section: Discussionmentioning

confidence: 99%

“…Small case studies have reported some promising effects on V̇O 2 peak following treatment with Ivacaftor 11,12 with a larger randomized, double‐blind, crossover trial reporting improved exercise duration but not V̇O 2 peak 13 . Despite initial case series reports that 2 years of treatment with lumacaftor/Ivacaftor could improve physical activity and exercise tolerance in adults with CF, 14 a more recent pilot study reported no improvements in exercise tolerance 15 and a small study of four adolescents commencing Tezacaftor/Ivacaftor combination therapy demonstrated increased

\dot{{\rm{V}}}

O 2 peak in only one of four patients at 7–8 months follow‐up, 16 with submaximal aerobic fitness (anaerobic threshold [AT]) improved in all cases. To date, there is no data regarding the response to Elexacaftor/Tezacaftor/Ivacaftor.…”

Section: Introductionmentioning

confidence: 99%

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Elexacaftor–Tezacaftor–Ivacaftor improves exercise capacity in adolescents with cystic fibrosis

Causer

Shute

Cummings

et al. 2022

Pediatric Pulmonology

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Methods: Three adolescents (14.0 ± 1.4 years) with CF (FEV 1 % predicted: 62.5 ± 17.1; F508del/F508del genotype) completed an exhaustive maximal cardiopulmonary exercise test on a cycle ergometer to determine peak oxygen uptake ( VO 2peak ) and measure changes in gas exchange and ventilation during exercise at 6 weeks. We also analyzed wrist-worn device-based physical activity (PA) data in two of the three cases. Validated acceleration thresholds were used to quantify time spent in each PA intensity category.Results: Clinically meaningful improvements in VO 2peak were observed in all three cases (+17.6%, +52.4%, and +32.9%, respectively), with improvements greatest in those with more severe lung disease and lower fitness at baseline. Although lung function increased in all cases, inconsistent changes in markers of ventilatory and peripheral muscle efficiency likely suggest different mechanisms of improvement in this case group of adolescents with CF. Device-based analysis of PA was variable, with one case increasing and one case decreasing. Conclusion:In this case series, we have observed, for the first time, improvements in exercise capacity following 6 weeks of treatment with Elexacaftor/Tezacaftor/ Ivacaftor. Improvements were greatest in the presence of more severe CF lung disease and lower aerobic fitness at baseline. The mechanism(s) responsible for these changes warrant further investigation in larger trials.

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Section: Discussionsupporting

confidence: 86%

O 2 peak are promising given the findings of previous studies. A small case series of Ivacaftor, reported an increase in

O 2 peak in an adolescent with severe lung disease, but no improvement in milder disease following 12 weeks treatment.…”

Section: Discussionsupporting

confidence: 80%

\dot{{\rm{V}}}

O 2 peak are promising given the findings of previous studies.…”

Section: Discussionmentioning

confidence: 51%

\dot{{\rm{V}}}

Section: Discussionmentioning

confidence: 99%

\dot{{\rm{V}}}

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Elexacaftor–Tezacaftor–Ivacaftor improves exercise capacity in adolescents with cystic fibrosis

Causer

Shute

Cummings

et al. 2022

Pediatric Pulmonology

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Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study

Gur

Bar‐Yoseph

Hanna

et al. 2022

Pediatric Pulmonology

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Background While the positive effect of Trikafta on cystic fibrosis (CF) pulmonary disease is well established, there is limited data about its effect on bone mineral density (BMD), body composition and exercise capacity. Methods A pilot single center study. BMD and body composition were measured three months after the initiation of Trikafta (study group) and compared to values obtained 2 years earlier. CF patients not treated with Trikafta, for whom BMD was measured 2 years apart, served as controls. Spirometry, lung clearance index (LCI), sweat test, six‐min walk test (6MWT) and cardio‐pulmonary exercise test (CPET) were performed before and three months after the initiation of Trikafta. Results Nine study patients, aged 18.6 ± 4.7 years, and nine controls. For the study group, BMI and hip and spine BMD increased significantly (19.4 ± 2.6 to 20.3 ± 2.19 BMI, p = 0.05; 0.73 ± 0.098 to 0.81 ± 0.12 gr/cm2 hip, p = 0.017; 0.76 ± 0.14 to 0.82 ± 0.14 gr/cm2 spine, p = 0.025). For the control group, there was no difference in hip or spine BMD. Lean body mass, %fat z‐score and fat mass/height2 z‐score increased significantly (34770.23 ± 10521.21 to 37430.16 ± 10330.09gr, p = 0.017; –0.8 ± 0.75 to 0.46 ± 0.58, p = 0.012; and −0.98 ± 0.66 to −0.04 ± 0.51, p = 0.025, respectively). 6MWT improved from 541.1 ± 48.9 to 592.9 ± 54.5 m (p = 0.046). As expected, FEV1%pred increased (p = 0.008) and sweat chloride decreased significantly (p = 0.017). In CPET, VE/VCO2 improved, indicating better ventilatory efficiency. Conclusions To the best of our knowledge, this is the first study evaluating the metabolic effects of Trikafta. The results are encouraging and offer hope beyond the well‐established effect on pulmonary disease. Larger long‐term studies are warranted to unpin the underlying physiological mechanisms.

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The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study

Stastna,

Hrabovska,

Homolka

et al. 2024

BMC Pulm Med

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Background Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. Methods We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. Results We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. Conclusion Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

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P91 Cardiopulmonary exercise testing in CF adolescents after starting Tezacaftor/Ivacaftor

Cited by 3 publications

References 0 publications

Elexacaftor–Tezacaftor–Ivacaftor improves exercise capacity in adolescents with cystic fibrosis

Elexacaftor–Tezacaftor–Ivacaftor improves exercise capacity in adolescents with cystic fibrosis

Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study

The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study

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