Phthalates and asthma in children and adults: US NHANES 2007-2012

Abstract

Environmental exposure to phthalates may contribute to an increased risk of asthma in children and adults. We aimed to assess the direction and strength of the association between urinary phthalates metabolites and current asthma in children and adults that participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Data on ten urinary phthalate metabolites, self-reported questionnaires, spirometry measures, and covariates were obtained from 7765 participants (28.1% were children aged 6-17 years) taking part in the NHANES 2007-2012. Asthma was assessed using self-reported questionnaires for children and adults, and via spirometry measures for adults alone. We used crude and adjusted logistic regression models to estimate the odds ratios (ORs) and 95% confidence interval (CI) per one log₁₀ unit change in the concentration of phthalate metabolites. We further modeled the effect modification by sex. Out of 10 metabolites, only mono-benzyl phthalate (MBzP) was positively associated with the prevalence of self-reported asthma in children, after adjusting for a range of potential confounders (odds ratio 1.54; 95% confidence interval 1.05-2.27). No significant relationship was observed for adults. The association of mono-ethyl phthalate (MEP) was modified by sex, with significantly increased odds of asthma among males [boys (2.00; 1.14-3.51); adult males (1.32; 1.04-1.69)]. While no other phthalates showed a positive relationship with current asthma in males, mono-(carboxynonyl) phthalate (MCNP) and mono-(3-carboxylpropyl) phthalate (MCPP) were inversely associated with spirometrically defined asthma in adult females. A sex-specific relationship in adults was evident when spirometry, but not self-reported measures were used to define asthma. We found no clear association between exposure to phthalates and current asthma, except for a significant relationship between MBzP metabolites and self-reported asthma in children. As a result, exposure to phthalates and asthma development and/or exacerbations remains controversial, suggesting a need for a well-designed longitudinal study.

Keywords: Adult asthma; Childhood asthma; Mono-benzyl phthalate; NHANES; Phthalate metabolites.

Fig. 1

a Model 1 (crude) - associations of urinary phthalate metabolites with self-reported asthma in children, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with an odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. b Model 2 (adjusted)—associations of urinary phthalate metabolites with self-reported asthma in children, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with an OR presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, sex, ethnicity/race, waist circumference, cotinine, poverty and urinary creatinine

Fig. 2

Associations between urinary phthalate metabolites and asthma (self-reported) in children stratified by sex. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, race/ethnicity, waist circumference, poverty, urinary creatinine and cotinine

Fig. 3

a Model 1 (crude)—associations of urinary phthalate metabolites with self-reported asthma in adults, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. b Model 2 (adjusted) - associations of urinary phthalate metabolites with self-reported asthma in children, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, sex, ethnicity/race, waist circumference, cotinine, poverty and urinary creatinine

Fig. 4

Associations between urinary phthalate metabolites and asthma (self-reported) in adults stratified by sex. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, race/ethnicity, waist circumference, urinary creatinine and cotinine

Fig. 5

a Model 1 (crude)—associations of urinary phthalate metabolites with current asthma (spirometry measure) in adults, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. b Model 2 (adjusted)—associations of urinary phthalate metabolites with current asthma (spirometry measure) in adults, NHANES 2007–2012. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, sex, ethnicity/race, waist circumference, cotinine, poverty, and urinary creatinine

Fig. 6

Associations between urinary phthalate metabolites and current asthma (spirometry measure in adults stratified by sex. Logistic regression modeling was used to access the effect of individual phthalate metabolites on asthma prevalence, with odds ratio (OR) presented for 1 log₁₀ unit change in urinary phthalate concentration. MEP mono-ethyl phthalate, MiBP mono-isobutyl phthalate, MnBP mono-n-butyl phthalate, MBzP mono-benzyl phthalate, MCNP mono-(carboxynonyl) phthalate, MCPP mono-(3-carboxylpropyl) phthalate, ΣDEHP molar sum of DEHP metabolites (MEHP, MEHHP, MECPP and MEOHP). All models were adjusted for age, race/ethnicity, waist circumference, urinary creatinine and cotinine