| Summary: | Background: Lung function deterioration in cystic fibrosis (CF) is typically measured by a decline in the forced expiratory volume in one second (FEV<sub>1</sub>%), which is thought to be a late marker of lung disease. Dynamic hyperinflation (DH) is seen in obstructive lung diseases while exercising. Our aim was to assess whether DH could predict pulmonary deterioration in CF; a secondary measure was the peak VO<sub>2</sub>. Methods: A retrospective study was conducted of people with CF who performed cardiopulmonary exercise tests (CPETs) during 2012–2018. The tests were classified as those demonstrating DH non-DH. Demographic, genetic, and clinical data until 12.2022 were extracted from patient charts. Results: A total of 33 patients aged 10–61 years performed 41 valid CPETs with valid DH measurements; sixteen (39%) demonstrated DH. At the time of the CPETs, there was no difference in the FEV<sub>1</sub>% measurements between the DH and non-DH groups (median 83.5% vs. 87.6%, respectively; <i>p</i> = 0.174). The FEV<sub>1</sub>% trend over 4 years showed a decline in the DH group compared to the non-DH group (<i>p</i> = 0.009). A correlation was found between DH and the lung clearance index (LCI), as well as the FEV<sub>1</sub>% (r = 0.36 and <i>p</i> = 0.019 and r = −0.55 and <i>p</i> = 0.004, respectively). Intravenous (IV) antibiotic courses during the 4 years after the CPETs were significantly more frequent in the DH group (<i>p</i> = 0.046). The peak VO<sub>2</sub> also correlated with the FEV<sub>1</sub>% and LCI (r = 0.36 and <i>p</i> = 0.02 and r = −0.46 and <i>p</i> = 0.014, respectively) as well as with the IV antibiotic courses (r = −0.46 and <i>p</i> = 0.014). Conclusions: In our cohort, the DH and peak VO<sub>2</sub> were both associated with lung function deterioration and more frequent pulmonary exacerbations. DH may serve as a marker to predict pulmonary deterioration in people with CF.
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