Background: The most common immediate hypersensitivity to macrogols is associated with PEG 3350, however the epidemiology, mechanisms and cross-reactivity are poorly understood. Thousands of medications contain either PEGs or structurally similar polysorbates. Objective: Our objective was to better understand the mechanism, cross-reactivity and scope of PEG hypersensitivity. Methods: Two cases with a past history of immediate hypersensitivity to PEG-containing medications were used to study potential mechanisms and cross-reactivity of immediate reactions to PEG 3350. Skin testing and oral challenges with PEG and polysorbate-containing agents were employed to determine clinical reactivity and cross-reactivity between the two allergens. Enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescent immunoassay were used to detect anti-PEG specific IgG and IgE respectively, using PEGylated protein or PEG alone as antigens in two cases and six PEG 3350 tolerant controls. We searched FDA adverse event reports for immediate reactions to PEG 3350 to determine the potential scope of this problem in the United States. Results: Skin and provocation testing demonstrated symptomatic reactivity in both cases to PEG 3350 and polysorbate 80. Plasma samples were positive for anti-PEG specific IgE and IgG antibodies only in cases and binding increased directly proportional to the molecular weight of PEG tested. FDA adverse event reports revealed 53 additional cases of possible PEG 3350 anaphylaxis. Conclusions: Immediate hypersensitivity to PEG 3350 with cross-reactive polysorbate 80 hypersensitivity may be under recognized in clinical practice and can be detected with clinical skin testing. Our studies raise the possibility of an IgE mediated Type I hypersensitivity mechanism in some cases.
Background Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma. Methods Singleton, term-birth, non–low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models. Results Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19–1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05–1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma. Conclusions We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.
Background The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. Methods We conducted a population-based cohort study of 84 214 mother–child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. Results Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0–2], 1.26 [95% confidence interval {CI}, 1.20–1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum–only antibiotic use, broad spectrum–only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05–1.24]). There were effect modifications (P < .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. Conclusions Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.
Childhood asthma is responsible for significant morbidity and health care expenditures in the United States. The incidence of asthma is greatest in early childhood, and the prevalence is projected to continue rising in the absence of prevention and intervention measures. The prevention of asthma will likely require a multifaceted intervention strategy; however, few randomized controlled trials have assessed such approaches. The purpose of this review was to use previous meta-analyses to identify the most impactful risk factors for asthma development and evaluate the effect of risk factor reduction on future childhood asthma prevalence. Common and modifiable risk factors with large effects included acute viral respiratory infections, antibiotic use, birth by cesarean section, nutritional disorders (overweight, obesity), second hand smoke exposure, allergen sensitization, breastfeeding, and sufficient prenatal vitamin D level. Evaluation and estimates of risk factor modification on populations at risk should guide scientists and policymakers toward high impact areas that are apt for additional study and intervention. Electronic supplementary material The online version of this article (10.1186/s40169-018-0195-4) contains supplementary material, which is available to authorized users.
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