Consequences of expiratory flow limitation at rest in subjects with cystic fibrosis

Rationale: Expiratory flow limitation at resting tidal volume (EFLTV) presents a severemechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis. Objectives: To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis. Methods: Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12±3.0 yr/person from108 subjects with cystic fibrosis. The year inwhich forced expiratory flow, midexpiratory phase (FEF_25-75%, L/s) was equal to tidal peak expiratory flow (L/s) was defined as EFLTV-onset year. Measurements and Main Results: EFLTV occurred in 55 (51%) subjects, at age 23±6 years. At EFLTV onset, tidal peak expiratory flow and FEF_25-75% values were 1.44±0.23 L/s and FEV₁ was 62±10% predicted. Within the following 2 years, FEV₁ dropped to 48±11% predicted, and 35 (63%) of the subjects reported shortness of breath at rest. Hospital days increased from 5.3±24.6 to 24.12± 9.0 d/yr (P = 0.0001). Of the 55 subjects, 29 (53%) received transplant or died, with survival time being 6.9±3.9 years. Conclusions: EFLTV onset may be an important pathophysiological event that could influence the natural history of lung function decline in subjects with cystic fibrosis. This may lead to a significant deterioration in lung function in the following 2 years alongside an increase in the number of hospitalization days. The monitoring of FEV₁ alone does not offer as good a threshold signal, because values are only moderately reduced. Therefore, identifying EFLTV appearance is potentially a signal for therapeutic intervention. Further studies are warranted to confirm our findings.