title: Progression of pulmonary hyperinflation and trapped gas associated with genetic and environmental factors in children with cystic fibrosis.
abstract: BACKGROUND
  Functional deterioration in cystic fibrosis (CF) may be reflected by increasing bronchial obstruction and, as recently shown, by ventilation inhomogeneities. This study investigated which physiological factors (airway obstruction, ventilation inhomogeneities, pulmonary hyperinflation, development of trapped gas) best express the decline in lung function, and what role specific CFTR genotypes and different types of bronchial infection may have upon this process.
  
  
  METHODS
  Serial annual lung function tests, performed in 152 children (77 males; 75 females) with CF (age range: 6-18 y) provided data pertaining to functional residual capacity (FRCpleth, FRCMBNW), volume of trapped gas (VTG), effective specific airway resistance (sReff), lung clearance index (LCI), and forced expiratory indices (FVC, FEV1, FEF50).
  
  
  RESULTS
  All lung function parameters showed progression with age. Pulmonary hyperinflation (FRCpleth > 2SDS) was already present in 39% of patients at age 6-8 yrs, increasing to 67% at age 18 yrs. The proportion of patients with VTG > 2SDS increased from 15% to 54% during this period. Children with severe pulmonary hyperinflation and trapped gas at age 6-8 yrs showed the most pronounced disease progression over time. Age related tracking of lung function parameters commences early in life, and is significantly influenced by specific CFTR genotypes. The group with chronic P. aeruginosa infection demonstrated most rapid progression in all lung function parameters, whilst those with chronic S. aureus infection had the slowest rate of progression. LCI, measured as an index of ventilation inhomogeneities was the most sensitive discriminator between the 3 types of infection examined (p < 0.0001).
  
  
  CONCLUSIONS
  The relationships between lung function indices, CFTR genotypes and infective organisms observed in this study suggest that measurement of other lung function parameters, in addition to spirometry alone, may provide important information about disease progression in CF.
authors.affiliation: Department of Paediatrics, University of Berne, Inselspital CH-3010 Berne, Switzerland. richard.kraemer@insel.ch
authors.forename: Richard
authors.initials: R
authors.lastname: Kraemer
authors.forename: David N
authors.initials: DN
authors.lastname: Baldwin
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
authors.forename: Urs
authors.initials: U
authors.lastname: Frey
authors.forename: Sabina
authors.initials: S
authors.lastname: Gallati
mesh_terms: D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D011659:Pulmonary Gas Exchange; D012042:Registries; D013147:Spirometry
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator