Provider Practices in Pulmonary Exacerbations of Cystic Fibrosis in the Era of Highly Effective Modulator Therapy

<b>Rationale:</b> Since the approval of elexacaftor/tezacaftor/ivacaftor (ETI), data suggest that there have been changes in the management of pulmonary exacerbations (PEx) of cystic fibrosis. <b>Objectives:</b> Given the subjective nature of PEx diagnosis and management, we sought to characterize provider PEx management practices in people with cystic fibrosis (pwCF) prescribed highly effective modulator therapy (HEMT) and to identify practice changes that may impact clinical outcomes. <b>Methods:</b> We conducted semistructured qualitative interviews among clinicians in the United States from late 2021 to 2022 to investigate changes in the management of PEx in pwCF prescribed ETI. Inductive coding of transcripts was used in a thematic analysis. <b>Results:</b> We conducted 19 qualitative interviews with providers at 15 cystic fibrosis centers. Thematic analysis identified five themes regarding the presentation, diagnosis, and management of PEx in pwCF prescribed ETI. <i>1</i>) PEx have changed in the era of HEMT to become a more subtle pathology that may result in providers questioning PEx diagnosis. <i>2</i>) Providers feel less anxious about clinical outcomes after PEx. <i>3</i>) Providers are expanding their assessment of PEx in the era of HEMT to identify more subtle PEx phenotypes. <i>4</i>) pwCF are driving their care during PEx more than in the pre-HEMT era, with interviewees reporting that some <i>"patients don't really contact us</i> [with mild PEx symptoms].<i>… We hear about it in retrospect."</i> Interviewees expressed concern that this may result in more severe PEx. 5) Provider management is less aggressive in the post-HEMT era, reflecting reduced PEx severity. Participants emphasized that their approach to PEx in general is unchanged and that <i>"</i>[providers] <i>treat depending on severity … and the background of the patient</i>." Interviewees reported they increasingly recommend maintenance therapies for PEx treatment before prescribing antibiotics. <b>Conclusions:</b> Participants report that PEx in pwCF prescribed ETI appear milder, resulting in less anxiety about outcomes and a more conservative approach to management. Providers express uncertainty regarding the diagnosis of PEx, given its evolving presentation and reduced in-person evaluation. Further research is necessary to identify sensitive markers of PEx and to assess the impact of conservative management on clinical outcomes.