Association of Oxygen Therapy with the Natural Disease Progression of Cystic Fibrosis: A Multi-State Model of the European Cystic Fibrosis Society Patient Registry

Abstract

Simone Gambazza,1,2,* Annalisa Orenti,2,* Giovanna Pizzamiglio,3 Anna Zolin,2 Carla Colombo,4,5 Dario Laquintana,1 Federico Ambrogi2,6 On behalf of ECFSPR1Healthcare Professions Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Biometry and Epidemiology “G. A. Maccacaro”, Università degli Studi di Milano, Milan, Italy; 3Cystic Fibrosis Center – Adult Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 4Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 5Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy; 6Scientific Directorate, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy*These authors contributed equally to this workCorrespondence: Simone Gambazza, Healthcare Professions Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan, 20122, Italy, Email [email protected]: Association between dependence on oxygen therapy (OT) and natural disease progression in people with cystic fibrosis (pwCF) has not been estimated yet. The aim of this study is to understand the prognosis for pwCF on OT, evaluating how the transition probabilities from being alive without lung transplantation (LTx) to LTx and to death, and from being alive after LTx to death change in pwCF with and without OT.Methods: We used 2008– 2017 data from the 35-country European CF Society Patient Registry. A multi-state model was fitted to assess the effects of individual risk factors on transition probabilities.Results: We considered 48,343 pwCF aged from 6 to 50 years. OT (HR 5.78, 95% CI: 5.32– 6.29) and abnormal FEV1 (HR 6.41, 95% CI: 5.28– 7.79) were strongly associated with the probability of having LTx; chronic infection with Burkholderia cepacia complex (HR 3.19, 95% CI: 2.78– 3.67), abnormal FEV1 (HR 5.00, 95% CI: 4.11– 6.08) and the need for OT (HR 4.32, 95% CI: 3.93– 4.76) showed the greatest association with the probability of dying without LTx. Once pwCF received LTx, OT (HR 1.75, 95% CI: 1.41– 2.16) and abnormal FEV1 (HR 1.63, 95% CI: 1.18– 2.25) were the main factors associated with the probability of dying. An association of gross national income with the probability of receiving LTx and with the probability of dying without LTx was also found.Conclusion: Oxygen therapy is associated with poor survival in pwCF with and without LTx; harmonization of CF care throughout European countries and minimization of the onset of pulmonary gas exchange abnormalities using all available means remains of paramount importance.Keywords: cystic fibrosis, oxygen therapy, epidemiology, mortality, lung transplantation

Keywords

• cystic fibrosis
• oxygen therapy
• epidemiology
• mortality
• lung transplantation