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Soluble CD14 in Cord Blood Predicts Wheeze, Cough at 1 Year



ORLANDO – Elevated levels of soluble CD14 in umbilical cord blood appear to be highly predictive of wheeze and cough in the first year of an infant’s life, Taiwanese investigators reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Children with elevated cord-blood soluble CD14 (sCD14) had nearly an eightfold risk for wheezing and a sixfold risk for cough in the first year, compared with children with low levels, said Dr. Yu-Lin Huang from the department of pediatrics at the Chang Gung Memorial Hospital and Chang Gung University in Keelung, Taiwan.

Dr. Yu Lin Huang

The finding lends credence to the hypothesis that prenatal factors play a role in the pathogenesis of asthma.

Soluble CD14 is a pathogen pattern receptor molecule that works with other receptors to recognize bacterial lipopolysaccharides (LPS) and mediate LPS-induced inflammation. Evidence for its utility as a biomarker for allergy and asthma has been decidedly mixed, however, said Dr. Huang.

One study, for example, showed that lower sCD14 levels at birth were associated with increased risk of wheeze at age 1 (Am. J. Respir. Crit. Care Med. 2004;169:70-6), whereas a different study showed that sCD14 levels are higher during acute asthma episodes (Am. J. Respir. Care Crit. Med. 2006;173:617-22).

Because allergic diseases have been steadily rising in Taiwan since the 1970s, the investigators hoped to clarify whether sCD14 level at birth and/or the urine leukotriene E4 to creatinine (LC) ratio at 1 month could be useful predictors of an individual child’s risk for future atopic diseases and asthma.

They recruited newborns delivered at the Chang Chung Memorial Hospital from October 2007 through September 2009, recording sCD14 levels at birth and collecting questionnaires from the mothers asking about parental medical and allergic histories. The questionnaires were repeated at 1, 6, 12, and 18 months.

At 1 month they collected and examined urine for the LC ratio, and followed with child blood and urine samples at 6 and 12 months, and mother’s blood sample at 6 months.

They defined outcomes at age 1 as parental report of wheezing, cough persisting for more than 3 weeks, rhinitis (runny or blocked nose in the absence of a cold or flu), rhinoconjunctivitis, rash (intermittent for at least 3 months), and atopy (positive specific immunoglobulin E to Dermatophagoides pteronyssinus, D.farinae, egg white, milk, Cladosporium herbarum, and wheat).

Of the 206 children available for follow-up at 1 year, wheeze was prevalent in 14%), and sCD14 levels in these children were significantly higher than in the 177 children with no reported wheeze (583 plus or minus 127 vs. 491 plus or minus 162 ng/mL, P = .001).

Similarly, prolonged cough was reported in 7% at 1 year, and these children also had significantly higher sCD14 levels in cord blood (615 plus or minus 170 vs. 496 plus or minus 157, P = .008).

There were no other significant associations with sCD14 and other outcomes. LC ratio at 1 month was not significantly associated with any of the outcomes.

In multiple logistic regression analysis, they found that factors significantly predictive for wheeze at 1 year included sCD14 (P = .002), duration of day care attendance (P = .005), and parental smoking, with each pack per day of cigarettes associated with a doubling of risk (P = .016).

Significant risk factors for prolonged cough include sCD14 (P = .008) and number of older siblings (P = .015).

In a comparison of high vs. low sCD14, the adjusted odds ratio for wheeze with high levels was 7.74 (P less than .001). The adjusted OR for prolonged cough was 5.99 (P = .021).

The study was supported by a Chang Gung Research project grant. Dr. Huang reported that he had no relevant disclosures.

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