Progressive flow-to-volume dysanapsis in cystic fibrosis: A predictor for lung transplantation?

Rationale: Airways obstruction and lung volume restriction, major features of lung disease in cystic fibrosis (CF), may regress independently, causing dysanapsis between these parameters. Objectives: To explore the significance of dysanapsis (FEF _25-75/FVC) ratio in CF. Methods: Yearly best spirometry data, collected during 8.6 ± 1 year per patient, was determined from 93 patients with CF. Three groups wereformed according to initial FEV ₁. Group-N (n=35; control, FEV ₁above 80%predicted); Group-B (n=38; FEV ₁ below 80%predicted); and Group-LT (n = 20; data collected before lung transplantation). The yearly decline in spirometry indices was defined in relation to the preceding year. Decline exceeding22z scores from Group-N in each index was considered "rapid decline."Measurements and Main Results: Group-N's yearly decline of FEV ₁, FEF _25-75, and FEF _25-75/FVC were similar and reached -1.88±2.93%, -1.41±3.37%, and -1.81±4.48%, respectively. Rapid decline was equal to -6.5%, -10.8%, and -8.1%, respectively. Group-B's indices declined faster than that of Group-N, but did not exceed 1 z score. Group-LT showed a rapid decline solely in FEF _25-75/FVC (mean z score= -6.4±2.5; P<0.0001), which sprouted abruptly fromthe regular course of regression 4 ± 1.3 years before transplantation. The rapid decline in FEF _25-75/FVC was found in 19 of 20 patients from Group-LT and five patients from other groups (now waiting for transplantation). Thephenomenondid not correlate with initial FEV ₁ (%predicted) or age. Having airway hyperreactivity increased the risk of rapid decline in FEF _25-75/FVC. Conclusions: Roughly 4 years before lung transplantation and independent of FEV ₁ (%predicted), FEV ₁ decline rate, or age, an abrupt rapid dysanapsis occurs. Findings imply insufficient ventilation/lung volume unit and insinuate a powerful marker for estimating lung translation time in CF.