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Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: results from two observational studies.

ABSTRACT: BACKGROUND:Epidemiologic studies have demonstrated associations between acetaminophen use and asthma. This investigation sought to determine whether sex modifies the acetaminophen-asthma association and whether leptin (LEP) and leptin receptor (LEPR) gene polymorphisms modulate the sex-specific associations. METHODS:Data from the Isle of Wight birth cohort (IOW; n?=?1456, aged 18 years) and Kuwait University Allergy (KUA; n?=?1154, aged 18-26 years) studies were analyzed. Acetaminophen use and current asthma were self-reported. Genotype information for eighteen polymorphisms in LEP and LEPR genes were available in the IOW study. Associations between acetaminophen use and asthma were stratified by sex and genotype. Poisson regression models with robust variance estimation were evaluated to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). RESULTS:Acetaminophen use was dose-dependently associated with an increased prevalence of current asthma in the IOW and KUA studies. In both studies, sex-stratified analysis showed that acetaminophen use was associated with asthma among males, but not in females (Pinteraction?

SUBMITTER: Ziyab AH

PROVIDER: S-EPMC6146615 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: results from two observational studies.

Ziyab Ali H AH Mukherjee Nandini N Kurukulaaratchy Ramesh J RJ Zhang Hongmei H Ewart Susan S Arshad Hasan H Karmaus Wilfried W

Respiratory research 20180919 1

<h4>Background</h4>Epidemiologic studies have demonstrated associations between acetaminophen use and asthma. This investigation sought to determine whether sex modifies the acetaminophen-asthma association and whether leptin (LEP) and leptin receptor (LEPR) gene polymorphisms modulate the sex-specific associations.<h4>Methods</h4>Data from the Isle of Wight birth cohort (IOW; n = 1456, aged 18 years) and Kuwait University Allergy (KUA; n = 1154, aged 18-26 years) studies were analyzed. Acetamin ...[more]

PMID: 30231898

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Project description:BACKGROUND:Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. METHODS:In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. RESULTS:Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. CONCLUSIONS:Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

Project description:BACKGROUND:Prenatal and infant acetaminophen exposure has been associated with an increased risk of childhood asthma phenotypes. Demonstration of biologically plausible interactions between these exposures and maternal and child antioxidant gene polymorphisms would strengthen causal inference. OBJECTIVE:To explore potential interactions between prenatal and infant acetaminophen exposure and antioxidant genotypes on childhood asthma. METHODS:In the Avon Longitudinal Study of Parents and Children, we typed a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms. Effects of prenatal and infant acetaminophen exposure on asthma phenotypes at 7 years were stratified by genotype in >4000 mothers and >5000 children. RESULTS:Risk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child. CONCLUSION:Maternal antioxidant gene polymorphisms may modify the relation between prenatal acetaminophen exposure and childhood asthma, strengthening evidence for a causal association. In contrast, relations between infant acetaminophen use and asthma and atopy were not modified by child genotype and may be confounded by pre-existing wheeze or allergy.

Project description:INTRODUCTION:Fibromyalgia syndrome (FM) is characterized by persistent pain which is often refractory to common analgesic therapies and is particularly disabling. The objective of this study was to evaluate the therapeutic efficacy of duloxetine (DLX) + pregabalin (PGB) in patients suffering from FM and the possible added benefit of the lipid signaling molecule, palmitoylethanolamide (PEA). PEA is well-documented to exert anti-inflammatory, analgesic, and pain-relieving effects at both the preclinical and clinical level. METHODS:A total of 80 patients were recruited in two steps. The first was a retrospective observational study comprising 45 patients. This patient group received DLX + PGB for 6 months. The second step was a prospective observational study with 35 patients. Patients in this cohort began treatment with DLX + PGB at the same dosage as for the retrospective study plus micronized PEA (PEA-m(®); Epitech Group, Italy) and ultramicronized PEA (PEA-um(®); Epitech Group, Italy) for 3 months. Positive tender points (TPs), pain evoked, and pain intensity were evaluated at baseline and after 3 and 6 months in both studies. Statistical analyses were employed for comparison of data within the two studies and between them. RESULTS:The retrospective observational study (DLX + PGB), after 3 months of treatment showed a decrease of positive TPs, pain evoked, and pain intensity. After 6 months of treatment, these parameters had further improvement. In the prospective observational study (DLX + PGB + PEA), PEA introduction after 3 months of therapeutic regimen with DLX + PGB provided a significant improvement in pain symptoms, with a further reduction in the number of TPs and significant reduction in pain, compared to combined DLX + PGB only (p < 0.0001 for TPs and Visual Analog Scale comparisons). None of the patients experienced adverse side effects. CONCLUSION:Our study confirms the efficacy of DLX + PGB and demonstrates as well the added benefit and safety of PEA in the treatment of pain in patients affected by FM.

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Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: results from two observational studies.

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Leptin receptor gene polymorphisms and sex modify the association between acetaminophen use and asthma among young adults: results from two observational studies.

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