Longitudinal assessment of lung function from infancy to childhood in patients with cystic fibrosis

Rationale: Infant pulmonary function testing (IPFT) has become an important clinical tool for the evaluation of lung function in infants with Cystic Fibrosis (CF); however, it is still unclear whether lung function in infancy is predictive of lung function later in life. We hypothesized that measures of airflow obstruction by IPFT would correlate strongly with lung function by conventional spirometry later in childhood.

Study design and methodology: A retrospective analysis was performed of all CF infants studied with IPFT at the University of Minnesota Children's Hospital between September 1994 and March 2003. A total of 41 patients underwent IPFT and had valid spirometry results available at age 6 or later. IPFT values, such as I:E ratio, respiratory rate, tidal volume, and T(ptef)/T(e), were calculated from tidal breathing loops. Passive respiratory system mechanics, which included C(rs), R(rs), and tau(rs), were measured by the single breath end-inspiratory occlusion technique. Forced expiratory flows, including V(max)FRC, FVC, FEF(50), and FEF(75), were obtained by rapid thoracic compression and included a full vital capacity maneuver by the multiple inflation method. FRC measurements were calculated from data obtained via nitrogen washout in a subset of patients. In addition, information on age at diagnosis and results of oropharyngeal (OP) cultures at diagnosis and on subsequent visits was recorded. Standard spirometry was performed in all patients starting at age 5. The first valid flow-volume loop after age six was selected for analysis.

Results: Significant correlations were observed for the R(rs) and the FEF(50) by IPFT and the FEV(1) and the FEF(25-75) by standard spirometry (r > 0.4 and P < 0.03 for all correlations). These correlations were the strongest for those IPFT measurements obtained within 1 month of diagnosis and when R(rs) was expressed as sG(rs). The correlations observed were independent of the effects of age at diagnosis, gender and presence of Pseudomonas in oropharyngeal cultures at the time of diagnosis. Mean R(rs) declined from 0.050 to 0.027 cm H(2)O/ml/sec with treatment (P < 0.0001). There were no other significant associations found between other IPFT values measured and FEV(1) by spirometry.

Conclusions: Measures of airflow obstruction on IPFT, specifically R(rs), sG(rs), and FEF(50), were strongly correlated with future lung function. IPFT measurement of R(rs) in addition to forced expiratory flows may help select patients at the greatest risk of early lung function decline. This study supports the use of R(rs) as a surrogate variable to help assess the impact of early therapies in CF.