Childhood asthma after bacterial colonization of the airway in neonates.
BACKGROUND
Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.


METHODS
The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.


RESULTS
Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).


CONCLUSIONS
Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.
Bisgaard
Hans
H
Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen. bisgaard@copsac.dk
Hermansen
Mette Northman
MN
Buchvald
Frederik
F
Loland
Lotte
L
Halkjaer
Liselotte Brydensholt
LB
Bønnelykke
Klaus
K
Brasholt
Martin
M
Heltberg
Andreas
A
Vissing
Nadja Hawwa
NH
Thorsen
Sannie Vester
SV
Stage
Malene
M
Pipper
Christian Bressen
CB
D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology*; D001424:Bacterial Infections / Q000150:complications* / Q000276:immunology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D019819:Budesonide / Q000627:therapeutic use; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D006967:Hypersensitivity / Q000382:microbiology; D007013:Hypopharynx / Q000382:microbiology*; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D001936:Moraxella catarrhalis / Q000302:isolation & purification; D009504:Neutrophils / Q000502:physiology; D012135:Respiratory Sounds / Q000209:etiology*; D012141:Respiratory Tract Infections / Q000150:complications*; D012307:Risk Factors; D013211:Staphylococcus aureus / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
D001993:Bronchodilator Agents; D007073:Immunoglobulin E; D019819:Budesonide