Wheeze during the First 18 Months of Life: A Prospective Cohort Study to Explore the Associations with Indoor Nitrogen Dioxide, Formaldehyde and Family History of Asthma

Objectives: To investigate whether exposures to NO2 and formaldehyde at home would increase the risk of wheezing in the first 18 months of life, and to examine if such relationship could be modified by family history of asthma.;Methods: A total of 2,423 infants born in Hong Kong from 1st April 2008 to 31st March 2009 were enrolled from 29 Maternal and Child Health Centers between 8th August 2008 and 31st March 2009 for the prospective cohort study. Infants were first stratified into 3 groups: having a family history of asthma, having a family history of allergy and having no family histories of asthma or allergy. Roughly equal numbers of infants from each group were selected by systematic sampling, resulting in a total of 702 infants being recruited into the study. Their parents provided baseline information through the validated ISAAC questionnaire before the infants turning 4 months old, completed the indoor sampling of NO2 and fonnaldehyde in the bedrooms when the infants were 6 months old, and answered monthly health telephone survey based on infonnation recorded in health diaries. New onset of wheeze between 6 and 18 months old was used as outcome. Cox model was used to document the effects of the family history of asthma or allergy, NO2 and formaldehyde on the risk of new onset of wheezing after adjusting for the possible confounders, including neo-natal respiratory illness (excluded wheezing and persistent cough), having siblings, family health history, living area, keeping pets and cooking fuel used in household.;Results: Out of 702 cohort subjects, 528 subjects completed all observations and air sampling, giving a completion rate of 75.2%. Most infants (n=470, 89.0%) never wheezed and 58 infants (11.0%) wheezed within the observation period between 6 to 18 months old. Indoor exposure to formaldehyde was significantly associated with the risk of new onset wheezing, with 4% increase (95% CI: 1 %, 7%; P value = 0.02) for each 10 units (mugm -3) increase in formaldehyde. Indoor exposure to NO2 did not seem to have any significant effect on the risk. Stratified analysis showed that the infants with a family history of allergy were particularly sensitive to formaldehyde, and appeared a J-shape exposure-response relationship. Compared to those exposed to formaldehyde <20 mugm-3, those with exposure ≥60 mugm-3 had a hazard ratio of 2.45 (95% CI: 1.09, 5.52; P value = 0.03) whereas those with exposure levels of 20--39 mugm-3 had a hazard ratio of 0.07 (95% CI: 0.01, 0.89; P value = 0.04). No significant exposure-response relationships were observed among those with a family history of asthma or those without any family histories of asthma or allergy.;Conclusion: The results suggested that an indoor exposure to high level of formaldehyde increased the risk of new onset of wheezing, especially among infants with a family history of allergy.