Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study.

BACKGROUND: Whether children and people with asthma and allergic diseases are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: Our aims were to determine the incidence of SARS-CoV-2 infection in households with children and to also determine whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. METHODS: For 6 months, biweekly nasal swabs and weekly surveys were conducted within 1394 households (N = 4142 participants) to identify incident SARS-CoV-2 infections from May 2020 to February 2021, which was the pandemic period largely before a vaccine and before the emergence of SARS-CoV-2 variants. Participant and household infection and household transmission probabilities were calculated by using time-to-event analyses, and factors associated with infection and transmission risk were determined by using regression analyses. RESULTS: In all, 147 households (261 participants) tested positive for SARS-CoV-2. The household SARS-CoV-2 infection probability was 25.8%; the participant infection probability was similar for children (14.0% [95% CI = 8.0%-19.6%]), teenagers (12.1% [95% CI = 8.2%-15.9%]), and adults (14.0% [95% CI = 9.5%-18.4%]). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (adjusted hazard ratio [aHR] = 1.04 [95% CI = 0.73-1.46]), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR = 0.50 [95% CI = 0.32-0.81]); higher body mass index was associated with increased infection risk (aHR per 10-point increase = 1.09 [95% CI = 1.03-1.15]). The household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (adjusted odds ratio = 0.43 [95% CI = 0.19-0.96]; P = .04). CONCLUSION: Asthma does not increase the risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, whereas body mass index is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for preventing infection.

Clinical, psychological, and sensory characteristics associated with headache attributed to temporomandibular disorder in people with chronic myogenous temporomandibular disorder and primary headaches.

BACKGROUND: Headache attributed to Temporomandibular Disorder (HATMD) is a secondary headache that may have features resulting in diagnostic overlap with primary headaches, namely, tension-type (TTH) or migraine. This cross-sectional study of people with both chronic myogenous TMD and primary headaches evaluated characteristics associated with HATMD. METHODS: From a clinical trial of adults, baseline data were used from a subset with diagnoses of both TMD myalgia according to the Diagnostic Criteria for TMD (DC/TMD) and TTH or migraine according to the International Classification of Headache Disorders, 3rd edition. HATMD was classified based on the DC/TMD. Questionnaires and examinations evaluated 42 characteristics of facial pain, headache, general health, psychological distress, and experimental pain sensitivity. Univariate regression models quantified the associations of each characteristic with HATMD (present versus absent), headache type (TTH versus migraine), and their interaction in a factorial design. Multivariable lasso regression identified the most important predictors of HATMD. RESULTS: Of 185 participants, 114 (61.6%) had HATMD, while the numbers with TTH (n = 98, 53.0%) and migraine (n = 87, 47.0%) were similar. HATMD was more likely among migraineurs (61/87 = 70.1%) than participants with TTH (53/98 = 54.1%; odds ratio = 2.0; 95%CL = 1.1, 3.7). In univariate analyses, characteristics associated with HATMD included pain-free jaw opening and examination-evoked pain in masticatory muscles and temporomandibular joints (TMJ) as well as frequency and impact of headache, but not frequency or impact of facial pain. Lowered blood pressure but not psychological or sensory characteristics was associated with HATMD. Multiple characteristics of facial pain, headache, general health, and psychological distress differed between TTH or migraine groups. Few interactions were observed, demonstrating that most characteristics' associations with HATMD were consistent in TTH and migraine groups. The lasso model identified headache frequency and examination-evoked muscle pain as the most important predictors of HATMD. CONCLUSIONS: HATMD is highly prevalent among patients with chronic myogenous TMD and headaches and often presents as migraine. In contrast to primary headaches, HATMD is associated with higher headache frequency and examination-evoked masticatory muscle pain, but with surprisingly few measures of facial pain, general health, and psychological distress. A better understanding of HATMD is necessary for developing targeted strategies for its management. TRIAL IDENTIFICATION AND REGISTRATION: SOPPRANO; NCT02437383 . Registered May 7, 2015.

Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial.

INTRODUCTION: The migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine. METHODS: In this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy. RESULTS: Propranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant (p = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively; p = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate. CONCLUSIONS: Propranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact. STUDY IDENTIFICATION AND REGISTRATION: SOPPRANO; NCT02437383; https://clinicaltrials.gov/ct2/show/NCT02437383.

Implementation of the Addendum Guidelines for Peanut Allergy Prevention by US allergists, a survey conducted by the NIAID, in collaboration with the AAAAI.

BACKGROUND: In 2017, the Addendum Guidelines for the Prevention of Peanut Allergy were published with recommendations on early introduction of peanut-containing foods based on infants' clinical history. OBJECTIVE: We sought to conduct a nationwide US survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy. METHODS: Survey invitations were delivered to 3281 nonretired, US members of the American Academy of Asthma, Allergy & Immunology, board certified in allergy and immunology. The survey assessed awareness and implementation of the Guidelines and barriers to implementation. Descriptive statistics were generated. RESULTS: Twenty-nine percent (946 of 3281) of surveyed allergists/immunologists responded, and 87.1% (825 of 946) of responders met eligibility criteria. Among eligible responders, 97.1% were aware of the Guidelines. Of these, 64.5% reported full implementation of the Guidelines as published, 34.4% reported partial implementation, and 1.1% reported using none of the Guidelines. Barriers to Guidelines use included parental (47.6%) and self (21.8%) concerns about allergic reactions, lack of referrals (33.6%), parents uninterested in early feeding (28.2%), and lack of clinic time (20.9%). The 2 most common deviations from the Guidelines were considering additional factors not specified in the Guidelines such as family history (50.2%) and conducting skin prick testing in non-high-risk children (43.9%). Of respondents using the Guidelines, 45.7% indicated they needed more education or training. CONCLUSIONS: Essentially all allergists/immunologists who responded to the survey reported full or partial Guidelines implementation. Parental concerns and lack of referrals are major identifiable barriers. Improved Guidelines messaging to parents and referring physicians is warranted.

Efficacy and safety of propranolol for treatment of temporomandibular disorder pain: a randomized, placebo-controlled clinical trial.

Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100). Efficacy was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of participants with ≥30% or ≥50% reductions in FPI at week 9. Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization. Of 299 participants screened, 200 were randomized; 199 had at least one postrandomization FPI measurement and were included in intention-to-treat analysis. At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95% CL: -6.2, 2.6; P = 0.41). However, the proportion with a ≥30% reduction in FPI was significantly greater for propranolol (69.0%) than placebo (52.6%), and the associated number-needed-to-treat was 6.1 (P = 0.03). Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.

Assessment of Pediatrician Awareness and Implementation of the Addendum Guidelines for the Prevention of Peanut Allergy in the United States.

Importance: The 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States recommend that pediatricians assess infant peanut allergy risk and introduce peanut in the diet at age 4 to 6 months. Early introduction has the potential to prevent peanut allergy development. Objectives: To measure the rates of guideline awareness and implementation and to identify barriers to and factors associated with implementation among US pediatricians. Design, Setting, and Participants: This population-based study survey used a 29-item electronic survey instrument that was administered to pediatricians practicing across the United States from June 1, 2018, to December 1, 2018. Invitations to complete a survey were emailed to all pediatricians in the American Academy of Pediatrics vendor database. Eligible participants were nonretired US-based pediatricians providing general care to infants aged 12 months or younger. Main Outcomes and Measures: The primary outcome was the prevalence of guideline implementation, which was measured by 1 survey item about awareness followed by a second item about implementation. Secondary outcomes included identification of guidelines-focused services provided by pediatricians, knowledge of the guidelines (measured with 3 clinical scenarios), barriers to guideline implementation, need for training, and facilitators of guideline implementation. Results: A total of 1781 pediatricians were eligible to participate and completed the entire survey. Most respondents self-identified as white (1287 [72.5%]) and female (1210 [67.4%]) individuals. Overall, 1725 (93.4%; 95% CI, 92.2%-94.5%) pediatricians reported being aware of the guidelines. Of those pediatricians who had knowledge of the guidelines, 497 (28.9%; 95% CI, 26.8%-31.1%) reported full implementation and 1105 (64.3%; 95% CI, 62.0%-66.6%) reported partial implementation. Common barriers to implementation included parental concerns about allergic reactions (reported by 575 respondents [36.6%; 95% CI, 34.3%-39.1%]), uncertainty in understanding and correctly applying the guidelines (reported by 521 respondents [33.2%; 95% CI, 30.9%-35.6%]), and conducting in-office supervised feedings (reported by 509 respondents [32.4%; 95% CI, 30.1%-34.8%]). Many pediatricians (1175 [68.4%; 95% CI, 66.1%-70.5%]) reported a need for further training on the guidelines. Conclusions and Relevance: This survey found that most pediatrician respondents appeared to know of the 2017 guidelines, but less than one-third of respondents reported full implementation. Results of this study may inform future efforts to eliminate barriers to guideline implementation and adherence, thereby reducing the incidence of peanut allergy in infants.

Did Arkansas' Medicaid Patient-Centered Medical Home Program Have Spillover Effects on Commercially Insured Enrollees?

Patient-centered medical homes are increasingly being implemented by state Medicaid programs to incentivize high-quality, coordinated care and ultimately lower health care spending. This study examined whether the Arkansas Medicaid Patient-Centered Medical Home Program's practice-wide transformation activities had spillover effects on commercial beneficiaries. We used difference-in-differences to compare utilization and expenditures of commercially insured enrollees as their practices received Medicaid patient-centered medical home certification on a rolling basis between 2014 and 2016. We found a 5.7% increase in outpatient visits and 13% higher expenditures among early adopting practices. Even without associated reductions in costly emergency department visits or inpatient hospital admissions, decisionmakers should not lose sight of the potential value of increased engagement in and coordination of professional services for a population with high unmet health needs. Our results also emphasize that states can leverage Medicaid to spur system-wide transformation, and the investments generate spillover effects beyond those covered directly by Medicaid.

Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia.

Stimuli such as inflammation or hypoxia induce cytochrome P450 epoxygenase-mediated production of arachidonic acid-derived epoxyeicosatrienoic acids (EETs). EETs have cardioprotective, vasodilatory, angiogenic, anti-inflammatory, and analgesic effects, which are diminished by EET hydrolysis yielding biologically less active dihydroxyeicosatrienoic acids (DHETs). Previous in vitro assays have suggested that epoxide hydrolase 2 (EPHX2) is responsible for nearly all EET hydrolysis. EPHX1, which exhibits slow EET hydrolysis in vitro, is thought to contribute only marginally to EET hydrolysis. Using Ephx1-/-, Ephx2-/-, and Ephx1-/-Ephx2-/- mice, we show here that EPHX1 significantly contributes to EET hydrolysis in vivo Disruption of Ephx1 and/or Ephx2 genes did not induce compensatory changes in expression of other Ephx genes or CYP2 family epoxygenases. Plasma levels of 8,9-, 11,12-, and 14,15-DHET were reduced by 38, 44, and 67% in Ephx2-/- mice compared with wildtype (WT) mice, respectively; however, plasma from Ephx1-/-Ephx2-/- mice exhibited significantly greater reduction (100, 99, and 96%) of those respective DHETs. Kinetic assays and FRET experiments indicated that EPHX1 is a slow EET scavenger, but hydrolyzes EETs in a coupled reaction with cytochrome P450 to limit basal EET levels. Moreover, we also found that EPHX1 activities are biologically relevant, as Ephx1-/-Ephx2-/- hearts had significantly better postischemic functional recovery (71%) than both WT (31%) and Ephx2-/- (51%) hearts. These findings indicate that Ephx1-/-Ephx2-/- mice are a valuable model for assessing EET-mediated effects, uncover a new paradigm for EET metabolism, and suggest that dual EPHX1 and EPHX2 inhibition may represent a therapeutic approach to manage human pathologies such as myocardial infarction.

Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.

BACKGROUND: Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. OBJECTIVE: We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. METHODS: A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. RESULTS: Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms. CONCLUSIONS: Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.

Prevalence of allergic sensitization in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2005-2006.

BACKGROUND: Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005-2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. OBJECTIVE: We investigated clustering, sociodemographic, and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. METHODS: Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Participants aged 1 year or older (n = 9440) were tested for serum specific IgEs (sIgEs) to inhalant and food allergens; participants 6 years or older were tested for 19 sIgEs, and children aged 1 to 5 years were tested for 9 sIgEs. Serum samples were analyzed by using the ImmunoCAP System. Information on demographics and participants' characteristics was collected by means of questionnaire. RESULTS: Of the study population aged 6 years and older, 44.6% had detectable sIgEs, whereas 36.2% of children aged 1 to 5 years were sensitized to 1 or more allergens. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling young age, male sex, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. CONCLUSIONS: The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs based on sociodemographic and regional factors. Biological cross-reactivity might be an important but not the sole contributor to the clustering of allergen-specific IgEs.

A multi-center ring trial of allergen analysis using fluorescent multiplex array technology.

BACKGROUND: Consistent performance of allergen assays is essential to ensure reproducibility of exposure assessments for investigations of asthma and occupational allergic disease. This study evaluated intra- and inter-laboratory reproducibility of a fluorescent multiplex array, which simultaneously measures eight indoor allergens in a single reaction well. METHODS: A multi-center study was performed in nine laboratories in the US and Europe to determine the inter-laboratory variability of an 8-plex array for dust mite, cat, dog, rat, mouse and cockroach allergens. Aliquots of 151 dust extract samples were sent to participating centers and analyzed by each laboratory on three separate occasions. Agreement within and between laboratories was calculated by the concordance correlation coefficient (CCC). RESULTS: Results were obtained for over 32,000 individual allergen measurements. Levels covered a wide range for all allergens from below the lower limit of detection (LLOD = 0.1-9.8 ng/ml) to higher than 6800 ng/ml for all allergens except Mus m 1, which was up to 1700 ng/ml. Results were reproducible within as well as between laboratories. Within laboratories, 94% of CCC were ≥ 0.90, and 80% of intra-laboratory results fell within a 10% coefficient of variance (CV%). Results between laboratories also showed highly significant positive correlations for all allergens (~0.95, p<0.001). Overall means of results were comparable, and inter-laboratory CV% for all allergens except Rat n 1 ranged between 17.6% and 26.6%. CONCLUSION: The data indicate that performance criteria for fluorescent multiplex array technology are reproducible within and between laboratories. Multiplex technology provides standardized and consistent allergen measurements that will streamline environmental exposure assessments in allergic disease.

Can oral pathogens influence allergic disease?

The hygiene hypothesis contends that fewer opportunities for infections and microbial exposures have resulted in more widespread asthma and atopic disease. Consistent with that hypothesis, decreases in infectious oral diseases over the past half century have coincided with increases in the prevalence of asthma and other allergic diseases. This observation has led some researchers to speculate that exposures to oral bacteria, including pathogens associated with periodontal diseases, such as gingivitis and periodontitis, might play a protective role in the development of asthma and allergy. Colonization of the oral cavity with bacteria, including some species of periodontal pathogens, begins shortly after birth, and the detection of serum antibodies to oral pathogens in early childhood provides evidence of an early immune response to these bacteria. Current knowledge of the immune response to oral bacteria and the immunologic pathogenesis of periodontal diseases suggests biologically plausible mechanisms by which oral pathogens could influence the risk of allergic disease. However, studies investigating the association between oral pathogen exposures and allergic disease are few in number and limited by cross-sectional or case-control design, exclusion of young children, and use of surrogate measures of oral bacterial colonization. Additional studies, particularly well-designed case-control studies among very young children and prospective birth cohort studies, are needed.

Allergy-related outcomes in relation to serum IgE: results from the National Health and Nutrition Examination Survey 2005-2006.

BACKGROUND: The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. OBJECTIVE: We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. METHODS: Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. RESULTS: In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). CONCLUSION: In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE.

Modulation of allergic airway inflammation by the oral pathogen Porphyromonas gingivalis.

Accumulating evidence suggests that bacteria associated with periodontal disease may exert systemic immunomodulatory effects. Although the improvement in oral hygiene practices in recent decades correlates with the increased incidence of asthma in developed nations, it is not known whether diseases of the respiratory system might be influenced by the presence of oral pathogens. The present study sought to determine whether subcutaneous infection with the anaerobic oral pathogen Porphyromonas gingivalis exerts a regulatory effect on allergic airway inflammation. BALB/c mice sensitized and subsequently challenged with ovalbumin exhibited airway hyperresponsiveness to methacholine aerosol and increased airway inflammatory cell influx and Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13) content relative to those in nonallergic controls. Airway inflammatory cell and cytokine contents were significantly reduced by establishment of a subcutaneous infection with P. gingivalis prior to allergen sensitization, whereas serum levels of ovalbumin-specific IgE and airway responsiveness were not altered. Conversely, subcutaneous infection initiated after allergen sensitization did not alter inflammatory end points but did reduce airway responsiveness in spite of increased serum IgE levels. These data provide the first direct evidence of a regulatory effect of an oral pathogen on allergic airway inflammation and responsiveness. Furthermore, a temporal importance of the establishment of infection relative to allergen sensitization is demonstrated for allergic outcomes.

Novel relationship of serum cholesterol with asthma and wheeze in the United States.

BACKGROUND: Cholesterol exerts complex effects on inflammation. There has been little investigation of whether serum cholesterol is associated with asthma, an inflammatory airways disease with great public health impact. OBJECTIVE: To determine relationships between levels of 3 serum cholesterol measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and non-HDL-C) and asthma/wheeze in a sample representative of the US population. METHODS: Cross-sectional study of 7005 participants age >or=6 years from the 2005 to 2006 National Health and Nutrition Examination Survey. RESULTS: Serum TC and non-HDL-C were lower in patients with current asthma than in subjects without current asthma in the overall population (TC, 188.5 vs 192.2 mg/dL; non-HDL-C, 133.9 vs 137.7 mg/dL; P < .05 for both), whereas HDL-C was not different. Adjusted odds ratios (ORs) from multivariate logistic regression per 1-SD increase of TC and non-HDL-C for current asthma were 0.92 (95% CI, 0.86-0.98) and 0.91 (95% CI, 0.85-0.98), respectively. On racial/ethnic stratification, these relationships reflect marked reductions unique to Mexican Americans (MAs; TC, 171.4 vs 189.3 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.80; non-HDL-C, 119.8 vs 137.9 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.79). Among MAs, the adjusted OR for wheeze requiring medical attention was 0.57 (95% CI, 0.43-0.75) for TC and 0.53 (95% CI, 0.33-0.85) for non-HDL-C. Relationships between cholesterol and asthma/wheeze were independent of body mass index and serum C-reactive protein, and similar between atopic and nonatopic participants. CONCLUSION: Serum TC and non-HDL-C are inversely related to asthma in the US population, chiefly reflecting a relationship among MAs.

Total IgE levels and asthma prevalence in the US population: results from the National Health and Nutrition Examination Survey 2005-2006.

BACKGROUND: The inability to measure IgE-based sensitivity to all allergens has limited our understanding of what portion of asthma is related to IgE. Total IgE measurement can potentially overcome this limitation. OBJECTIVE: We sought to determine the association between total IgE levels and asthma. METHODS: The National Health and Nutrition Examination Survey 2005-2006 examined a representative sample of the US population 6 years of age and older. RESULTS: The median total IgE level was 40.8 kU/L (interquartile range, 15.5-114 kU/L). Total IgE levels varied with age, sex, race/ethnicity, serum cotinine level, body size, and socioeconomic status. The prevalence of current asthma was 8.8%. The prevalence of atopy was 42.5%, as defined by 15 specific IgEs. The adjusted odds ratio (OR) for asthma with a 10-fold increase in total IgE level was 2.18 (95% CI, 1.66-2.87). Total IgE level predicted asthma only among atopic subjects (OR, 2.41; 95% CI, 1.62-3.60) and not among nonatopic subjects (OR, 1.11; 95% CI, 0.72-1.71; interaction P = .005). Among atopic subjects, the association between total IgE level and asthma became stronger as the number of positive specific IgE test results increased. Asthma was present at even the lowest levels of total IgE, regardless of atopic status. Approximately 92% of atopic subjects were identified by 6 specific IgEs, but to increase the identification to more than 99% required 11 specific IgEs. CONCLUSION: Total IgE levels are associated with asthma only among persons who have positive results for at least 1 allergen-specific IgE. Asthma independent of IgE is not uncommon in the US population. The complete identification of atopic subjects in a population requires a large panel of allergen-specific IgEs.