Prenatal exposure to pesticide ingredient piperonyl butoxide and childhood cough in an urban cohort

Abstract

Rationale

Previously we reported that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. We hypothesized that prenatal and age 5–6 year measures of PBO and permethrins would be associated with cough at age 5–6 years in this cohort. Further, we explored the associations between these pesticide measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO).

Methods

PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5–6 years (n = 224). Health outcome questionnaires were administered to the mothers of 5–6 year old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5–6 years. The hypotheses were tested using regression models adjusting for common confounders.

Results

Noninfectious cough was reported among 14% of children at age 5–6 years. Measures of prenatal PBO, but not age 5–6 year PBO or permethrins, increased the odds of cough [OR (95% CI): 1.27 (1.09–1.48), p < 0.01; n = 217]. No significant associations were found for other measured health outcomes.

Conclusions

Prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.

Introduction

Cough continues to be one of the most common complaints for which patients seek medical attention and spend health care money (Irwin et al., 1998, US CDC, 2012). For children under 5 years, conditions related to cold, cough, and runny nose accounted for 10% of the ambulatory care visits during 1993–1995 in data collected from the National Health Survey (Freid et al., 1998). Prenatal and early childhood exposures to both ambient and indoor air pollutants have been linked to pediatric respiratory disease including cough (Miller et al., 2004, Patel et al., 2009), wheeze (Patel et al., 2009), and asthma (Fedulov et al., 2008, Gergen et al., 1998, Rosa et al., 2011). The contributions of other common environmental exposure such as residential pesticides to the development of these disorders are not as well described.

With the phase-out of organophosphates in US homes (Horton et al., 2011a, US EPA, 2000, US EPA, 2001), pyrethroids have been used increasingly more commonly in residential settings, particularly for pest control. In the Columbia Center for Children's Environmental Health (CCCEH) birth cohort, following the phase-out, pyrethroids were the most common active insecticide ingredients used in both professional and non-professional pest controls, and permethrin was the most common pyrethroid type used (Horton et al., 2011a). Permethrin is also the most frequently detected pesticide in residential floor wipe samples measured nationwide (Stout et al., 2009). Given the pervasiveness of this exposure, it is important to understand the potential health impact on children resulting from long-term low-level residential pyrethroid use.

Despite these concerns, the effects of pyrethroid exposure on pediatric respiratory health have not been well-studied. In one of the few studies, exposure to permethrin in occupational/agricultural settings was associated with asthma (Hoppin et al., 2008) and wheeze in farmers (Hoppin et al., 2002). In addition, few cohort studies have measured airborne pyrethroid levels as indicators of respiratory exposure, and instead relied on surrogate measures detected from questionnaires (Salam et al., 2004) or considered urine metabolites that may detect exposures from other routes (Heudorf and Angerer, 2001, Lu et al., 2006).

Our previous research demonstrated that prenatal exposure to cis-permethrin, but not trans-permethrin, measured in prenatal personal air samples was associated positively with cough for children by age 5 (i.e. at 2, 3, and 5 years) (Reardon et al., 2009). Because no postnatal exposure measurement was available, and piperonyl butoxide (PBO), a common synergist used in pyrethroid formulations for residential use (Horton et al., 2011a, Horton et al., 2011b), was not considered, it was unclear whether subsequent exposure to permethrins or PBO exposure specifically during early childhood also may be associated with respiratory complaints in urban children.

In the current study, we address these gaps by examining prenatal and concurrent pyrethroid exposures and respiratory complaints in children at age 5–6 years. We hypothesized that prenatal and age 5–6 year exposures to PBO and permethrin would be associated with cough in 5–6 year old children. In addition, we explored the associations between pesticide exposure and other respiratory outcomes, including asthma, wheeze, immunoglobulin (Ig) E production, and fractional exhaled nitric oxide (FeNO). Our approach was to assess both prenatal and 5–6 year airborne PBO and permethrin concentrations, and determine their associations with age 5–6 year cough and other respiratory symptoms.