Optimizing Identification of Allergic Sensitization to Seasonal Inhalant Allergens in the USA: Implications for Constructing Optimal Panels to Evaluate Patients with Allergy.

INTRODUCTION: While a specific number and type of antigens are recognized to detect perennial inhalant allergies, the optimal number and combination of allergens to reliably identify seasonal allergic sensitization is unclear due to limited national data. This study analyzed aeroallergen testing data from a large US clinical reference laboratory to provide guidance for optimizing seasonal allergen test selection. METHODS: The 2019 serum IgE tests for seasonal inhalant allergens were identified from the Quest Diagnostics database. Patients with results for at least 1 of 31 seasonal allergens across 4 allergen classes (11 trees, 7 weeds, 5 grasses, and 8 molds) were analyzed. A step-by-step conditional approach was employed to determine the minimum number and species of allergens needed to identify at least 98% of sensitized patients for each class. RESULTS: Of 88,042 patients tested for ≥1 seasonal allergen, 1.5%, 1.8%, 1.3%, and 1.6% were tested for all trees, weeds, grasses, and molds, respectively. Of those tested for all allergens within a class, 40.4%, 38.6%, 29.5%, and 21.2% were sensitized to at least one tree, weed, grass, or mold allergen, respectively. Identification of ≥98% of sensitized patients within a class required 8 allergens for trees (mountain cedar, maple box elder, walnut, white ash, elm, birch, cottonwood, and hickory/pecan), 5 for weeds (common ragweed short, rough pigweed, English plantain, lamb's quarters/goosefoot, and Russian thistle), 3 for grasses (June/Kentucky blue grass, Johnson grass, and Bermuda grass), and 7 for molds (Alternaria alternata, Aspergillus fumigatus, Mucor racemosus, Epicoccum purpurascens, Penicillium notatum, Helminthosporium halodes, and Fusarium moniliforme). CONCLUSION: A minimum of 23 antigens is required to optimally detect sensitization to four classes of seasonal allergens (i.e., ≥98% identification). The addition of these allergens to unique perennial allergens (cat, dog, mouse, cockroach, and 2 dust mite species) results in a comprehensive elucidation of inhalant allergen sensitization. This knowledge provides a pivotal guide for clinical laboratories as they construct allergen panels to optimize diagnostic yield.

A comparison of healthcare utilization and outcomes following skin vs. serum-specific IgE allergy testing.

OBJECTIVE: To compare the cost, healthcare utilization, and outcomes between skin and serum-specific IgE (sIgE) allergy testing. METHODS: This retrospective cohort study used IBM® MarketScan claims data, from which commercially insured individuals who initiated allergy testing between January 1 and December 31, 2018 with at least 12 months of enrollment data before and after index testing date were included. Cost of allergy testing per patient was estimated by testing pattern: skin only, sIgE only, or both. Multivariable linear regression was used to compare healthcare utilization and outcomes, including office visits, allergy and asthma-related prescriptions, and emergency department (ED) and urgent care (UC) visits between skin and sIgE testing at 1-year post testing (α = 0.05). RESULTS: The cohort included 168,862 patients, with a mean (SD) age of 30.8 (19.5) years; 100,666 (59.7%) were female. Over half of patients (56.4%, n = 95,179) had skin only testing, followed by 57,291 patients with sIgE only testing and 16,212 patients with both testing. The average cost of allergy testing per person in the first year was $430 (95% CI $426-433) in patients with skin only testing, $187 (95% CI $183-190) in patients with sIgE only testing, and $532 (95% CI $522-542) in patients with both testing. At 1-year follow-up post testing, there were slight increases in allergy and asthma-related prescriptions, and notable decreases in ED visits by 17.0-17.4% and in UC visits by 10.9-12.6% for all groups (all p < 0.01). Patients with sIgE-only testing had 3.2 fewer allergist/immunologist visits than patients with skin-only testing at 1-year follow-up (p < 0.001). Their healthcare utilization and outcomes were otherwise comparable. CONCLUSIONS: Allergy testing, regardless of the testing method used, is associated with decreases in ED and UC visits at 1-year follow-up. sIgE allergy testing is associated with lower testing cost and fewer allergist/immunologist visits, compared to skin testing.

Assessing the contributions of phylogenetic and environmental determinants of allergic cosensitization to fungi in humans.

BACKGROUND: Understanding how allergies to 1 environmental fungus can lead to cosensitization to related fungi is important for the clinical management of allergies. Cosensitization can be caused by monosensitization combined with antibody cross-reactivity, or by coexposures driving independent sensitizations. A pioneering study showed that patterns of IgE cosensitization among 17 fungal species mirror fungal phylogeny. This could reflect either epitope or habitat similarity. Thanks to an improved understanding of fungal phylogeny, larger serologic testing datasets, and environmental data on household fungi, we can now characterize the relationship between cosensitization, species similarity, and likely coexposure with greater precision. OBJECTIVE: To assess the degree to which IgE cosensitization in a group of 17 fungi can be attributed to species similarity or environmental coexposure. METHODS: Cosensitization patterns among 17 fungal species were estimated from a dataset of approximately 8 million serologic tests on 1.6 million patients. Linear regression of cosensitization on phylogenetic distance and imputed coexposure was performed. In addition, branch lengths for the phylogenetic tree were re-estimated on the basis of cosensitization and compared with corresponding phylogenetic branch lengths. RESULTS: Phylogenetic distance explains much of the observed cosensitization (adjusted r2 = .68, p < .001). Imputed environmental coexposures and test co-ordering patterns do not significantly predict cosensitization. Branch length comparisons between the cosensitization and phylogenetic trees identified several species as less cosensitizing than phylogenetic distance predicts. CONCLUSION: Combined evidence from clinical IgE testing data on fungi, along with phylogenetic and environmental exposure data, supports the hypothesis that cosensitization is caused primarily by monosensitization plus cross-reactivity, rather than multisensitization. A serologic test result should be interpreted as pointing to a group of related species that include the sensitizing agent rather than as uniquely identifying the agent. The identified patterns of cross-reactivity may help optimize test panel design.

Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States.

BACKGROUND: Many fungal species are associated with the pathogenesis of allergic disease, yet most epidemiologic studies on IgE-mediated fungal sensitization have only included a few species. OBJECTIVE: We investigated fungal allergen sensitization prevalence, risk factors, and geographic variation in the United States. METHODS: From 2014 to 2019, a total of 7,912,504 serum-specific IgE (sIgE) test results for 17 fungal species were measured in 1,651,203 patients aged 0-85 years by a US-wide clinical laboratory. Fungal sensitization prevalence, patterns, and relationship with demographic characteristics, clinical diagnoses, and geographic regions were analyzed. RESULTS: Twenty-two percent of patients were positive (sIgE > 0.10 kUA/L) to at least 1 fungal allergen; 13.7% were positive to >2 fungal allergens. Fungal species-specific positivity rates ranged 7.4-18.6% and were highest for Candida albicans (18.6%), Alternaria alternata (16.6%), Stemphylium herbarum (14.9%), and Aspergillus fumigatus (14.2%). Other fungi that were frequently tested had relatively low positivity rates (eg, Cladosporium herbarum 11.1%, Penicillium chrysogenum 10.7%). Independent risk factors for test positivity for all fungal species included male sex, teen age (highest in those aged 10-19 years), atopic dermatitis, and asthma. Fungal sensitization was generally higher in urban areas and ecoregions composed predominantly of grasslands and prairies compared to woodlands and forest, although there was greater variation in sensitization risk to different fungi in different ecoregions. CONCLUSION: Independent risk factors for fungal sensitization include male sex, teen ages, atopic dermatitis, asthma, and ecoregion.

Cost of Serum Versus Skin Allergy Testing Among Medicare Fee-for-Service Beneficiaries in the United States.

Background: Testing for allergic sensitization can be achieved similarly via skin or serum specific immunoglobulin E (sIgE) testing, although the costs of each method differ. Objective: This study compared cost and utilization of allergy testing utilizing skin vs sIgE testing and whether equal access (parity) to both testing methods affects overall allergy testing costs among Medicare fee-for-service beneficiaries in the United States. Methods: Allergy test utilization and payment data were analyzed using 100% 2019 Medicare fee-for-service claims data. Beneficiaries with any sIgE test, skin prick test, or intradermal skin test associated with ICD-10 codes of allergic rhinitis, asthma, and food allergy were included. Aggregate and per-beneficiary testing cost, number of allergens tested, and number of allergy-related specialist visits incurred were estimated by the testing patterns of sIgE only, skin prick only, intradermal only, skin prick and intradermal, and sIgE plus prick and/or intradermal. Medicare Administrative Contractors (MACs) with parity for all allergy tests and those which restricted sIgE testing were compared. Multivariate linear regression was performed on the association between testing patterns and each cost and utilization measure, controlling for parity, age, sex, race/ethnicity, and dual-eligible status. Results: We analyzed 270 831 patients and 327 263 allergy-related claims. Total payment for all allergy tests was $71 380 866, including $15 903 954 for sIgE tests, $42 223 930 for skin prick tests, and $13 252 982 for intradermal tests. Beneficiaries receiving sIgE tests had only 1.8 fewer allergist visits than those with skin prick tests only (0.8 vs 2.6). Cost of testing per beneficiary was also lower in sIgE testing only compared with skin prick tests only ($161 vs $247). Multivariable regression results showed per-beneficiary payments for allergy testing were on average $22 lower in MACs with parity compared with MACs without parity. Discussion: Serum specific IgE testing is associated with lower costs and fewer allergy specialist visits compared with skin testing. Insurance coverage with parity toward sIgE and skin testing is associated with lower overall costs of allergy testing. Conclusion: Among Medicare fee-for-service beneficiaries in the United States, sIgE testing may be more cost effective compared with skin testing in the management of allergic disease.

Patterns of allergenic food introduction in Los Angeles inner-city children.

Background: Early introduction of allergenic foods is recommended to reduce the risk of developing food allergies, but it is unclear whether recommendations are being followed. Objective: We examine patterns of allergenic food introduction in inner-city children enrolled in an academic pediatric practice in the greater Los Angeles area. Methods: This was a prospective study with patients ages 12 to 24 months recruited from the pediatrics continuity clinic at an inner-city tertiary medical center in the greater Los Angeles area. Caregivers were asked via anonymous surveys about their child's history of atopic diseases and at what age they first introduced egg, soy, wheat, peanut, tree nuts, fish, shrimp, and shellfish into their child's diet. Results: Two hundred caregivers responded to the survey. The average age of introduction of egg was 9.2 months, soy 10 months, wheat 9.3 months, peanut 10.5 months, tree nuts 10.9 months, fish 10.9 months, shrimp 11.3 months, and shellfish 11.5 months. Between ages 4-11 months, 65.3% of children were introduced egg, 19.1% soy, 55.8% wheat, 28.6% peanut, 17.1% tree nuts, 28.1% fish, 13.6% shrimp, and 7.0% shellfish. By age 24 months, 92% of children were introduced egg, 37.7% soy, 85.4% wheat, 67.3% peanut, 47.7% tree nuts, 67.8% fish, 48.2% shrimp, and 30.2% shellfish. Of the 14 children with eczema or egg allergy, 26.1% were introduced peanut by age 4-6 months and 50% by age 4-11 months. Conclusion: Despite recommendations, inner-city caregivers may not be introducing allergenic foods in a timely manner to their children.

Persistent airflow obstruction in inner-city children with asthma.

Background: Airway remodeling has been shown to be persistent in patients with asthma despite treatment with controller medications. Patients with early airflow obstruction may continue to experience poor lung function despite treatment. Objectives: To determine whether early airflow obstruction in inner-city children with asthma persists despite guideline-based asthma care. Methods: In a retrospective study that used a cohort of inner-city children with asthma treated by using an asthma-specific disease management system, the patients were stratified into "low" or "high" lung function groups at the time of the initial visit (high, forced expiratory volume in the first second of expiration [FEV1] % predicted and FEV1/forced vital capacity [FVC] ≥ 80%; and low, FEV1% predicted and FEV1/FVC < 80%). These patients then received National Heart, Lung, and Blood Institute guideline-based asthma treatment at regular follow-up intervals with spirometry performed at these visits as part of regular care. FEV1% predicted and FEV1/FVC were followed up for up to 10 years for both the high and low cohorts. Results: Over 10 years, the patients initially in the "high" group maintained FEV1% predicted and FEV1/FVC at values similar to the initial visit (94 to 96% and 87 to 89%, respectively), whereas those in the low group had only slight increases of FEV1% predicted and FEV1/FVC over the same time (77 to 82% and 78 to 82%, respectively). Low FEV1% predicted and FEV1/FVC at the time of the first visit was significantly associated with an increased risk of low values of these lung functions over the next 3-5 years despite treatment. African American ethnicity and male gender were also associated with lower lung function over time. Conclusion: Early airflow obstruction in inner city children asthma is associated with poor lung function in later life despite guideline-based asthma care. Current asthma therapy may not affect pathways and leads to airway remodeling in children with asthma.

Multidrug Therapy for Refractory Immune Thrombocytopenia in Pregnancy.

BACKGROUND: Severe immune thrombocytopenia complicating pregnancy may require treatment beyond first-line medications (intravenous immunoglobulins or corticosteroids), but there is a paucity of literature on the use of such second-line agents in pregnancy. CASE: The patient is a 29-year-old woman with early-onset severe immune thrombocytopenia at 13 weeks of gestation. Maternal platelet counts reached a nadir of less than 5×10/L. The thrombocytopenia persisted despite first-line medications. Romiplostim, rituximab, and azathioprine were added to the therapeutic regimen. Platelet counts eventually stabilized at greater than 150×10/L before delivery. After delivery at term, the neonate had transient B-cell suppression, which was presumed to be secondary to rituximab, but was otherwise doing well and meeting all milestones at 7 months of age. CONCLUSION: The addition of second-line agents was associated with sustained elevation in maternal platelet counts and may have obviated the need for splenectomy.

Asthma Hospitalizations Among Homeless Children in New York State.

BACKGROUND AND OBJECTIVES: Asthma is widely prevalent among US children, particularly in homeless children, who often lack proper medication storage or the ability to avoid environmental triggers. In this study, we assess asthma-attributed health care use among homeless youth. We hypothesize that asthma hospitalization rates, symptom severity, and admission through the emergency department (ED) will be higher among homeless youth compared with nonhomeless youth. METHODS: This secondary data analysis identified homeless and nonhomeless pediatric patients (<18 years old) with a primary diagnosis of asthma from New York statewide inpatient databases between 2009 and 2014. Hospitalization rate, readmission rate, admission through the ED, ventilation use, ICU admittance, hospitalization cost, and length of stay were measured. RESULTS: We identified 71 837 asthma hospitalizations, yielding 73.8 and 2.3 hospitalizations per 1000 homeless and nonhomeless children, respectively. Hospitalization rates varied by nonhomeless income quartile, with low-income children experiencing higher rates (5.4) of hospitalization. Readmissions accounted for 16.0% of homeless and 12.5% of nonhomeless hospitalizations. Compared with nonhomeless patients, homeless patients were more likely to be admitted from the ED (odds ratio 1.96; 95% confidence interval: 1.82-2.12; P < .01), and among patients >5 years old, homeless patients were more likely to receive ventilation (odds ratio 1.45; 95% confidence interval: 1.01-2.09; P = .04). No significant differences were observed in ICU admittance, cost, or length of stay. CONCLUSIONS: Homeless youth experience an asthma hospitalization rate 31 times higher than nonhomeless youth, with higher rates of readmission. Homeless youth live under uniquely challenging circumstances. Tailored asthma control strategies and educational intervention could greatly reduce hospitalizations.

Adaptation of an asthma management program to a small clinic.

OBJECTIVES: Asthma management programs, such as the Breathmobile program, have been extremely effective in reducing asthma morbidity and increasing disease control; however, their high start-up costs may preclude their implementation in smaller health systems. In this study, we extended validated asthma disease management principles from the Breathmobile program to a smaller clinic system utilizing existing resources and compared clinical outcomes. STUDY DESIGN: Cox-regression analyses were conducted to determine the cumulative probability that a new patient entering the program would achieve improved clinical control of asthma with each subsequent visit to the program. METHODS: A weekly asthma disease management clinic was initiated in an existing multi-specialty pediatric clinic in collaboration with the Breathmobile program. Existing nursing staff was utilized in conjunction with an asthma specialist provider. Patients were referred from a regional healthcare maintenance organization and patients were evaluated and treated every 2 months. Reduction in emergency department (ED) visits and hospitalizations, and improvements in asthma control were assessed at the end of 1 year. RESULTS: A total of 116 patients were enrolled over a period of 1 year. Mean patient age was 6.4 years at the time of their first visit. Patient ethnicity was self-described predominantly as Hispanic or African American. Initial asthma severity for most patients, classified in accordance with national guidelines, was "moderate persistent." After 1 year of enrollment, there was a 69% and 92% reduction in ED/urgent care visits and hospitalizations, respectively, compared with the year before enrollment. Up to 70% of patients achieved asthma control by the third visit. Thirty-six different patients were seen during 1 year for a total of $15,938.70 in contracted reimbursements. CONCLUSIONS: A large-scale successful asthma management program can be adapted to a stationary clinic system and achieve comparable results.

Asthma control and need for future asthma controller therapy among inner-city Hispanic asthmatic children engaged in a pediatric asthma disease management program (the Breathmobile program, Mobile Asthma Care for Kids Network).

OBJECTIVE: To determine whether significant numbers of asthmatic children with initially rated intermittent asthma later suffer poor asthma control and require the addition of controller medications. METHODS: Inner-city Hispanic children were followed prospectively in an asthma-specific disease management system (Breathmobile) for a period of 2 years. Clinical asthma symptoms, morbidity treatment, and demographic data were collected at each visit. Treatment was based upon National Heart, Lung, and Blood Institute (NHLBI) Expert Panel Report 3 asthma guidelines. Primary outcome was percentage of patients with intermittent asthma who had not well or poorly controlled asthma during subsequent visits and required controller agents. Secondary outcomes were factors associated with the maintenance of asthma control. RESULTS: About 30.9% of the patients with initial rating of intermittent asthma had not well controlled and poorly controlled asthma during subsequent visits and required the addition of controller agents. Factors associated with good asthma control were compliance, no previous emergency room visits and previous visit during spring season. CONCLUSION: Asthmatic children with intermittent asthma often lose asthma control and require controller therapy. This justifies asthma guideline recommendations to assess asthma control at follow-up visits and adjust therapy accordingly.

Factors affecting ability to achieve asthma control in adult patients with moderate to severe persistent asthma.

OBJECTIVE: Despite the use of optimal therapy and guidelines, the rate of asthma control is suboptimal in adult populations. Purpose of this study is to describe factors associated with ability to achieve well-controlled asthma over time for adult patients treated in a tertiary medical center-based asthma outpatient specialty clinic. METHODS: Existing clinical data collected for 320 adult patients enrolled in a hospital-based outpatient asthma specialty clinic from July 1, 2003 through June 30, 2011 evaluated time to achieve well-controlled asthma and factors associated with well-controlled asthma such as adherence and lack of previous exacerbations. RESULTS: Adherence to prescribed therapy (p = 0.004) and no previous asthma related ED visits (p = 0.004) were associated with well-controlled asthma for moderate persistent baseline. BMI on a continuous spectrum (p = 0.120) and the diagnosis of allergic rhinitis (p = 0.769) were not independently significant. Body-mass-index (BMI) in combination with adherence did influence ability to achieve well-controlled asthma (p < 0.05). Adherence (p = 0.615), allergic rhinitis (p = 0.172), BMI continuous scale (p = 0.074) and visit interval <90 days (p = 0.653) were not independently associated with likelihood of achieving well-controlled asthma in severe persistent asthmatics. Significance of particular factors in combination (adherence, allergic rhinitis, sex, BMI) showed dependency on other variables in achieving well-controlled asthma. CONCLUSIONS: Different factors are associated with asthma control for different patient subpopulations. Adherence to standard therapy did not improve obese (BMI > 30) patients' ability to achieve asthma control. Female patients were less likely to obtain well-controlled asthma per unit increase of BMI. Multiple factors must be addressed to optimize attaining asthma control.

The relationship of aeroallergen sensitization phenotypes to asthma control in primarily Hispanic asthmatic children.

OBJECTIVE: The purpose of this study was to determine whether aeroallergen sensitization phenotypes could predict maintenance of well-controlled asthma. METHODS: Asthmatic children age 2-18 years who enrolled in the CHOC Children's Breathmobile™ program from April 2002 to December 2011 were included in this retrospective analysis if they had been skin tested to a panel of indoor and outdoor aeroallergens and had returned for follow-up care within 6 months of their baseline visit. The study observation period encompassed all year one visits. Asthma severity and control were defined by NHLBI EPR-3 Guidelines criteria. RESULTS: In the 1627 primarily Hispanic children evaluated, those with persistent asthma were more likely than those with intermittent disease to be sensitized to each aeroallergen tested and to have more total sensitizations. Children with intermittent, but not persistent, asthma at baseline who were sensitized to pollen2 (trees or weeds) were less likely to maintain well-controlled asthma at follow-up visits. Whereas, sensitization to dander (cat, dog or feather) showed a protective effect to maintenance of well-controlled asthma in patients with persistent, but not intermittent, baseline disease severity. CONCLUSIONS: Our data suggest that both indoor and outdoor aeroallergens should be assessed regardless of baseline asthma severity, including those with intermittent asthma.

Sex-specific perinatal nicotine-induced asthma in rat offspring.

Recently, we have suggested that down-regulation of homeostatic mesenchymal peroxisome proliferator-activated receptor γ signaling after in utero nicotine exposure might contribute to asthma. Here, we have exploited an in vivo rat model of asthma to determine if the effects of perinatal nicotine exposure on offspring pulmonary function and mesenchymal markers of airway contractility in both tracheal and lung parenchymal tissue are sex specific, and whether the protection afforded by the peroxisome proliferator-activated receptor γ agonist, rosiglitazone (RGZ), against the perinatal nicotine-induced effect on offspring lung is also sex specific. Pregnant rat dams received placebo, nicotine, or nicotine plus RGZ daily from Embryonic Day 6 until Postnatal Day 21, at which time lung resistance, compliance, tracheal contractility, and the expression of structural and functional mesenchymal markers of pulmonary contractility were determined. Compared with control animals, perinatal nicotine exposure caused a significant increase in airway resistance and a decrease in airway compliance after a methacholine challenge in both male and female offspring, with more pronounced changes in the males. In contrast to this, the effects of perinatal nicotine exposure on acetylcholine-induced tracheal constriction, along with the expression of its mesenchymal markers, were observed exclusively in the male offspring. Concomitant treatment with RGZ normalized the nicotine-induced alterations in pulmonary function in both sexes, as well as the male-specific effects on acetylcholine-induced tracheal constriction, along with the affected mesenchymal markers. These data suggest that perinatal nicotine exposure causes sex-specific perinatal cigarette smoke exposure-induced asthma, providing a powerful phenotypic model for unequivocally determining the underlying nature of the cell molecular mechanism for this disease.

Depression care management for Chinese Americans in primary care: a feasibility pilot study.

This study describes a culturally relevant intervention using a collaborative depression care model to integrate mental health and primary care services for depressed low income Chinese-Americans at a community health center. A total of 6,065 patients were screened for depression. Of the 341 who screened positive, 57 participated and were randomly assigned to receive either enhanced physician care with care management (32) or enhanced physician care only (25). All enrolled participants were assessed at baseline and 4 monthly follow-up visits for depression, physical and mental health functioning, and perceived stigma toward receiving depression care, to determine the impact, if any, of their mental health treatment. Both groups reported significant reduction of depressive symptoms and improved mental health functioning from baseline to follow-up assessments although there was no significant difference between the two groups. Although the study found no advantage to adding the care management component in the treatment of depression, screening and assertive treatment of immigrant Chinese Americans who tend to underutilize mental health services is important and consistent with the increased adoption of team based care models in patient centered medical homes. High refusal rates for enrollment in the study have implications for future study designs for this group.

Perinatal nicotine exposure induces asthma in second generation offspring.

BACKGROUND: By altering specific developmental signaling pathways that are necessary for fetal lung development, perinatal nicotine exposure affects lung growth and differentiation, resulting in the offsprings' predisposition to childhood asthma; peroxisome proliferator-activated receptor gamma (PPARγ) agonists can inhibit this effect. However, whether the perinatal nicotine-induced asthma risk is restricted to nicotine-exposed offspring only; whether it can be transmitted to the next generation; and whether PPARγ agonists would have any effect on this process are not known. METHODS: Time-mated Sprague Dawley rat dams received either placebo or nicotine (1 mg/kg, s.c.), once daily from day 6 of gestation to postnatal day (PND) 21. Following delivery, at PND21, generation 1 (F1) pups were either subjected to pulmonary function tests, or killed to obtain their lungs, tracheas, and gonads to determine the relevant protein markers (mesenchymal contractile proteins), global DNA methylation, histone 3 and 4 acetylation, and for tracheal tension studies. Some F1 animals were used as breeders to generate F2 pups, but without any exposure to nicotine in the F1 pregnancy. At PND21, F2 pups underwent studies similar to those performed on F1 pups. RESULTS: Consistent with the asthma phenotype, nicotine affected lung function in both male and female F1 and F2 offspring (maximal 250% increase in total respiratory system resistance, and 84% maximal decrease in dynamic compliance following methacholine challenge; P < 0.01, nicotine versus control; P < 0.05, males versus females; and P > 0.05, F1 versus F2), but only affected tracheal constriction in males (51% maximal increase in tracheal constriction following acetylcholine challenge, P < 0.01, nicotine versus control; P < 0.0001, males versus females; P > 0.05, F1 versus F2); nicotine also increased the contractile protein content of whole lung (180% increase in fibronectin protein levels, P < 0.01, nicotine versus control, and P < 0.05, males versus females) and isolated lung fibroblasts (for example, 45% increase in fibronectin protein levels, P < 0.05, nicotine versus control), along with decreased PPARγ expression (30% decrease, P < 0.05, nicotine versus control), but only affected contractile proteins in the male trachea (P < 0.05, nicotine versus control, and P < 0.0001, males versus females). All of the nicotine-induced changes in the lung and gonad DNA methylation and histone 3 and 4 acetylation were normalized by the PPARγ agonist rosiglitazone except for the histone 4 acetylation in the lung. CONCLUSIONS: Germline epigenetic marks imposed by exposure to nicotine during pregnancy can become permanently programmed and transferred through the germline to subsequent generations, a ground-breaking finding that shifts the current asthma paradigm, opening up many new avenues to explore.

Disability beliefs and help-seeking behavior of depressed Chinese-American patients in a primary care setting.

In this study the authors assessed the effects of disability beliefs, conceptualization and labeling of emotional disabilities, and perceived barriers on help-seeking behaviors among depressed Chinese Americans in a primary care setting. Forty-two Chinese Americans participated in semistructured interviews using established psychological measures and open-ended questions adapted from the Explanatory Model Interview Catalogue. The authors found that care utilization appears to be complicated by somatization of emotional problems, variations in causal attribution to depression, barriers to receiving mental health care, and the burden of comorbid physical conditions. Their findings highlight the importance of addressing these issues and educating patients about body-mind dialectic common to depression.

The benefits of specific immunoglobulin E testing in the primary care setting.

A common link among allergic diseases remains the many allergens that can provoke symptoms. The National Institutes of Health Guidelines for the Diagnosis and Management of Asthma and Guidelines for the Diagnosis and Management of Food Allergy support the use of in vivo (skin prick) or in vitro (blood) specific immunoglobulin E (IgE) testing, along with a detailed clinical history and physical examination, to document an allergy diagnosis. The initial responsibility of diagnosing allergic diseases falls principally on primary care providers, for whom skin prick testing is impractical. Access to in vitro testing provides a valuable diagnostic tool, in conjunction with patient history, for comprehensive allergy and asthma management, which can result in significant clinical and economic benefits and improved patient outcomes. Identification of specific allergens in patients enhances management through education, targeted allergen avoidance, pharmacotherapy, and immunotherapy. The utilization of specific IgE in vitro allergy testing may also drive efficient and effective utilization of healthcare resources. Testing can facilitate a close collaboration between the primary care provider and the allergy specialist, who is experienced in interpreting allergy tests and correlating them with clinical history, conducting food and drug challenges, educating about environmental controls, and managing chronic or recurrent conditions where allergy is not easily recognized. As healthcare reimbursement moves from fee-for-service to fee-for-outcomes, cooperative, comprehensive, and outcome-based patient management will gain in importance.