{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:50:51Z","timestamp":1791294651467,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to relevant clinical advances in people with cystic fibrosis (pwCF). However, its effects on aerobic fitness are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the effects of CFTR modulator therapy on aerobic fitness in pwCF through a systematic review and meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This systematic review (CRD420251066602) was conducted by searching major databases without date or language restrictions. Analytical studies evaluating cardiopulmonary exercise testing outcomes before and after CFTR modulator therapy were included. The primary outcome was peak oxygen uptake (peak VO\n                      <jats:sub>2<\/jats:sub>\n                      ). Secondary outcomes included peak VO\n                      <jats:sub>2<\/jats:sub>\n                      (% predicted), VO\n                      <jats:sub>2<\/jats:sub>\n                      at the first ventilatory threshold (VT\n                      <jats:sub>1<\/jats:sub>\n                      ), breathing reserve, workload, forced expiratory volume in one second (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ), and body mass index. Meta\u2010analyses were performed using a random\u2010effects model with heterogeneity assessed by the\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      statistic, and sensitivity analyses conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009578 participants) were included, of which 11 were eligible for meta\u2010analysis. The meta\u2010analysis did not identify a significant improvement in peak VO\n                      <jats:sub>2<\/jats:sub>\n                      (mL\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) after CFTR modulator use (MD\u2009=\u2009\u22120.22; 95% CI: \u22122.10 to 1.65;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.82). For submaximal outcomes, after sensitivity analysis, VO\n                      <jats:sub>2<\/jats:sub>\n                      at VT\n                      <jats:sub>1<\/jats:sub>\n                      was significantly lower in the post\u2010intervention period (MD\u2009=\u2009\u22121.85; 95% CI: \u22122.61 to \u22121.10;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001). Breathing reserve increased significantly (MD\u2009=\u20097.94; 95% CI: 2.15 to 13.73;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), and workload also increased significantly (MD\u2009=\u200915.39; 95% CI: 2.20 to 28.58;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CFTR modulator therapy is not consistently associated with improvements in aerobic fitness, as assessed by peak VO\n                      <jats:sub>2<\/jats:sub>\n                      , although it appears to variably influence outcomes related to ventilatory response and exercise performance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71826","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:37:44Z","timestamp":1788431864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Aerobic Fitness Following Initiation of CFTR Modulator Therapy: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-5933","authenticated-orcid":false,"given":"Ingrid Silveira","family":"de Almeida","sequence":"first","affiliation":[{"name":"Laboratory of Physical Activity in Pediatrics, Centro Infant Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS) Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-3476","authenticated-orcid":false,"given":"Fernanda Maria","family":"Vendrusculo","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Activity in Pediatrics, Centro Infant Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS) Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-5223","authenticated-orcid":false,"given":"Mariana Severo","family":"da Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Activity in Pediatrics, Centro Infant Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS) Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8836-9109","authenticated-orcid":false,"given":"M\u00e1rcio Vin\u00edcius Fagundes","family":"Donadio","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Activity in Pediatrics, Centro Infant Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS) Porto Alegre Rio Grande do Sul Brazil"},{"name":"Department of Physiotherapy, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya (UIC) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"issue":"6","key":"e_1_2_9_2_1","first-page":"6536","article-title":"Cystic Fibrosis: Current Concepts","volume":"78","author":"L\u00f3pez\u2010Valdez J. 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