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Ventilation Inhomogeneities in Relation to Standard Lung Function in Patients with Cystic Fibrosis

Department of Pediatrics and Division of Human Genetics, University of Berne, Berne, Switzerland

Correspondence and requests for reprints should be addressed to Richard Kraemer, M.D., Professor and Chairman, Department of Pediatrics, University of Berne, Inselspital, Berne CH-3010, Switzerland. E-mail: richard.kraemer{at}insel.ch

Based on serial lung function measurements performed in 142 children (68 males; 74 females) with cystic fibrosis (CF), prospectively evaluated over an age range of 6 to 20 years, we attempted to determine whether the lung clearance index (LCI) as a measure of ventilation inhomogeneities could be a discriminating factor of disease progression. Annual follow-up lung function measurements featuring FRC determined by whole-body plethysmography and multibreath nitrogen washouts, effective specific airway resistance, flow–volume curves, LCI, and gas exchange characteristics were analyzed by linear mixed-model analysis and Kaplan-Meier statistics. The earliest occurring and strongest factor of progression was the LCI, followed by maximal expiratory flow (MEF₅₀) and FRC determined by plethysmography (p < 0.0001). Associations between onset of chronic Pseudomonas aeruginosa infection and CF transmembrane conductance regulator (CFTR) genotype with FEV₁ (p = 0.027) and FVC (p = 0.007) were identified. The study shows that the LCI predicts earlier in life and represented much better functional progression than FEV₁. Moreover, there is no single functional predictor of progression in CF, but aside from risk factors, such as onset of chronic P. aeruginosa infection and genotype, pulmonary hyperinflation, airway obstruction, and ventilation inhomogeneities are important pathophysiologic processes that should be evaluated concomitantly as determinants of lung progression in CF.

Key Words: cystic fibrosis • genotype • onset of progression • Pseudomonas aeruginosa • ventilation inhomogeneities

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