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).

Conclusion: 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.

Figure 1

Progression of lung function with age. A) Changes assessed by repeated measurements of plethysmographic functional residual capacity (FRC_pleth), functional residual capacity obtained by the multibreath nitrogen washout (FRC_MBNW), and volume of trapped gas (V_TG). V_TG was calculated as the difference between FRC_pleth and FRC_MBNW. B) Changes of lung clearance index (LCI) as a measure of ventilation inhomogeneities and effective specific airway resistance (sR_eff), as measure of airway narrowing. C) Changes of forced vital capacity (FVC), forced expired volume in one second (FEV1) and maximal expired flow at 50% FVC (FEF₅₀) in relation to age. All parameters expressed as z-scores.

Figure 2

Progression of FRC_pleth over time in 152 patients with lung function stratified at age 6 to 8 years into 4 functional severity groups. Group PH&TG (pulmonary hyperinflation and trapped gas): FRC_pleth and V_TG > 2SDS; group PH (pulmonary hyperinflation without trapped gas): FRC_pleth > 2SDS; group VIH (ventilation inhomogeneities): LCI > 2SDS; group FN: functionally normal.

Figure 3

Progression with age within 5 different types of colonization or infection respectively, depicted for each lung function parameter. Slopes were calculated from the fixed values predicted according to group using linear mixed-effect model analysis. (PA: chronically infected by P. aeruginosa; PA_comb: chronically infected by P. aeruginosa and other bacteria; SA: chronically infected only by S. aureus; intermit.: intermittently colonized by several bacteria; free: free from any bacterial colonisations).