Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age.
BACKGROUND
Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years.


METHODS
Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry.


RESULTS
168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05).


CONCLUSIONS
Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.
Department of Paediatrics, University of Auckland, , Auckland, New Zealand. c.byrnes@auckland.ac.nz
Catherine Ann
CA
Byrnes
Suzanna
S
Vidmar
Joyce L
JL
Cheney
John B
JB
Carlin
David S
DS
Armstrong
Peter J
PJ
Cooper
Keith
K
Grimwood
Marj
M
Moodie
Colin F
CF
Robertson
Margaret
M
Rosenfeld
Harm A
HA
Tiddens
Claire E
CE
Wainwright
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D018893:Bronchoalveolar Lavage / Q000379:methods*; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006760:Hospitalization / Q000639:trends*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008171:Lung Diseases / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D009520:New Zealand / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D013902:Radiography, Thoracic; D013147:Spirometry; D014057:Tomography, X-Ray Computed
D000900:Anti-Bacterial Agents
Bronchiectasis; Cystic Fibrosis; Respiratory Infection