Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index.
BACKGROUND
Unrecognized airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease; therefore early detection and treatment is highly desirable.


OBJECTIVE
To determine whether the lung clearance index (LCI) is a sensitive and repeatable noninvasive measure of airway infection and inflammation in newborn-screened children with CF.


METHODS
Forty-seven well children with CF (mean age, 1.55 yr) and 25 healthy children (mean age, 1.26 yr) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage performed.


RESULTS
The mean (SD) LCI in healthy children was 6.45 (0.49). The LCI was higher in children with CF (7.21 [0.81]; P < 0.001). The upper limit of normal for the LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF, including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. The LCI was higher in children with Pseudomonas (7.92 [1.16]) than in children without Pseudomonas (7.02 [0.56]) (P = 0.038). The LCI correlated with bronchoalveolar lavage IL-8 (R(2) = 0.20, P = 0.004) and neutrophil count (R(2) = 0.21, P = 0.001). An LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas.


CONCLUSIONS
The LCI is elevated early in CF, especially in the presence of Pseudomonas and airway inflammation. The LCI is a feasible, repeatable, and sensitive noninvasive marker of lung disease in young children with CF.
Department of Respiratory Medicine, Sydney Children's Hospital, NSW, Australia. y.belessis@unsw.edu.au
Yvonne
Y
Belessis
Barbara
B
Dixon
Glenn
G
Hawkins
John
J
Pereira
Jenny
J
Peat
Rebecca
R
MacDonald
Penny
P
Field
Andrew
A
Numa
John
J
Morton
Kei
K
Lui
Adam
A
Jaffe
D001315:Australia; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D016022:Case-Control Studies; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis*; D042241:Early Diagnosis; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000175:diagnosis* / Q000209:etiology / Q000382:microbiology; D008297:Male; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000209:etiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D012372:ROC Curve; D012016:Reference Values; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric