Mode of delivery at birth and development of asthma: a population-based cohort study.

BACKGROUND: To test the hygiene hypothesis, previous studies have assessed the relationship between mode of delivery at birth and asthma incidence, but the results have been inconsistent because of potential selection and ascertainment biases. OBJECTIVE: To assess the relationship between mode of delivery at birth and asthma by following all children born in Rochester, Minn, between 1976 and 1982. METHODS: From the birth certificate, we determined mode of delivery (cesarean section vs vaginal delivery). Asthma status during the first 7 years of life was ascertained from comprehensive medical record reviews. The association between mode of delivery and asthma status was evaluated in a proportional hazards model adjusted for sex, birth weight, maternal education, and maternal age. RESULTS: The cumulative incidence rates of asthma among children who were born by cesarean section and vaginal delivery were 3.2% versus 2.6%, 4.6% versus 4.6%, 4.6% versus 5.8%, and 5.7% versus 6.7% at the 1st, 3rd, 5th, and 7th years of life, respectively. The adjusted hazard ratios for cesarean section in predicting asthma and wheezing episode were 0.93 (95% CI, 0.6-1.4; P=.71) and 0.93 (95% CI, 0.7-1.3; P=.67), respectively. CONCLUSION: Mode of delivery is not associated with subsequent risk of developing childhood asthma or wheezing episodes. Because the effect of mode of delivery on a risk of developing asthma or wheezing episodes varies over time (ie, age), selection of the study subjects according to their ages may have influenced the findings of previous studies with a shorter follow-up period.

The influence of neighborhood environment on the incidence of childhood asthma: a multilevel approach.

Some ecological analyses suggest an influence of neighborhood environment on asthma outcomes. However, no previous study has applied a multilevel approach to assess an ecological effect of neighborhood environment on the incidence of childhood asthma accounting for individual risk factors. This study assessed the influence of neighborhood and individual-level factors on the incidence of childhood asthma among all children born in Rochester, Minnesota, between 1976 and 1979. We identified asthmatics among all children born in Rochester, between 1976 and 1983. We applied a multilevel survival model with the frailty term to assess the effects of neighborhood characteristics, such as mean family income per census tract (n = 16) from the 1980 census report and the status of whether a census tract faces intersections with major highways or railroads, on asthma incidence. The relative risks (RR) of neighborhood socioeconomic status (SES), the status of whether census tracts face intersections with highways or railroads and the variance of random effect of census tracts were calculated adjusting individual-level covariates for asthma, including gender, birth weight, mother's age at birth and parental educational level at birth. We found that the RR of developing asthma among children living in census tracts facing intersections with highways or railroads was 1.6 (95% CI: 1.1-2.2) compared to those who lived in census tracts not facing intersections, adjusting individual- and neighborhood-level covariates. The variance of the frailty term attributable to census tracts was small (0.0085) and was modified (from 0.004 to 0.0085, 112% change) by adding neighborhood covariates. The overall effects of individual-level factors on asthma incidence were independent of neighborhood environment. The influence of neighborhood environment on childhood asthma in a non-inner-city setting, like Rochester, Minnesota, was small to modest. Incorporating pertinent neighborhood-level covariates into multilevel models needs to be considered in assessing the random effect of clusters.

Long-term fracture risk among children with asthma: a population-based study.

UNLABELLED: Fracture risk among patients diagnosed with asthma in childhood is greater in males and oral corticosteroid users, but most fractures are of the appendicular skeleton and may relate to impaired skeletal development. INTRODUCTION: There are no population-based data on fracture outcomes among the growing number of patients with asthma diagnosed in childhood. MATERIALS AND METHODS: We conducted a population-based retrospective (historical) cohort study among 279 Rochester, Minnesota, residents who were <35 years of age (mean, 6.2 years) when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and cases were compared directly with age- and sex-matched controls in a stratified proportional hazards model. Risk factors for fractures among the asthma cases were assessed using Andersen-Gill time-to-fracture regression models. RESULTS: During 6649 person-years of follow-up (median, 24.3 years/subject), 107 asthma patients experienced 189 fractures, for a crude fracture incidence rate of 2.8 per 100 person-years. The actuarially estimated cumulative fracture incidence after 20 years was 40% compared with 34% among controls (p = 0.122). There was no significant increase in overall fracture risk among cases compared to their age- and sex-matched controls (hazard ratio [HR], 1.3; 95% CI, 0.9-1.9), but males with asthma had a 2.6-fold greater risk of hand and finger fractures than control males. The independent predictors of overall fracture risk among the asthma patients included male gender (HR, 2.2; 95% CI, 1.5-3.2) and use of oral corticosteroids (HR, 2.0; 95% CI, 1.2-3.1) or anti-cholinergic agents (HR, 3.9; 95% CI, 1.5-10). CONCLUSIONS: Rather than osteoporotic fractures of the axial skeleton, oral corticosteroid therapy was associated here with limb fractures, suggesting a relationship with impaired development of a biomechanically competent skeleton. Additional studies are needed to assess this possibility.

Long-term fracture risk following adult-onset asthma: a population-based study.

There are few data on skeletal outcomes in the growing population of patients with adult-onset asthma. We conducted a population-based retrospective (historical) cohort study among 226 residents of Rochester, Minnesota, USA, who were 35 years of age or older when first diagnosed with asthma. Fractures were ascertained by review of comprehensive community medical records, and observed fractures were compared with expected numbers based on incidence rates in the local population (standardized incidence ratios, SIR). During 4,022 person-years of follow-up, 100 patients experienced 211 fractures, for an actuarially estimated cumulative incidence of 63% after 30 years compared with 59% expected ( p=0.004). Statistically significant increases were seen for moderate trauma fractures of the vertebrae (SIR, 2.9; 95% CI, 2.1 to 3.8) and ribs (SIR, 2.0; 95% CI, 1.2 to 3.2), as well as the proximal femur (SIR, 1.8; 95% CI, 1.02 to 2.8). As assessed by proportional hazards models, the only independent predictors of any subsequent moderate trauma fracture were age (hazard ratio [HR] per 10-year increase, 1.7; 95% CI, 1.5 to 2.1) and cumulative corticosteroid dose greater than the median of 1,775 mg (HR, 1.8; 95% CI, 1.1 to 3.0). In another multivariate analysis, the predictors of a moderate trauma vertebral fracture were older age (HR, 1.6; 95% CI, 1.3 to 2.1), concomitant chronic obstructive pulmonary disease (HR, 2.4; 95% CI, 1.2 to 4.9), cigarette smoking (HR, 2.3; 95% CI, 1.2 to 4.8), and cumulative corticosteroid dose greater than the median (HR, 2.6; 95% CI, 1.4 to 5.0). Other asthma therapies did not contribute significantly to these models. Thus, a 70% increase in overall fracture risk among unselected community patients with adult onset asthma was mainly confined to the subset who also had chronic obstructive pulmonary disease and was influenced by substantial corticosteroid use.

Occupational allergies caused by latex.

Allergy to natural rubber latex is an important cause of occupational allergy in healthcare workers. Disposable medical gloves are the major reservoir of latex allergens, particularly powdered gloves, in healthcare delivery settings. Diagnosis of latex allergy requires a history of exacerbation of cutaneous, respiratory, ocular, or systemic signs and symptoms after exposure to natural rubber latex products; and evidence of sensitization by patch testing, skin testing, measurement of latex-specific IgE antibodies, or challenge testing. Optimal management of latex allergy involves education concerning cross-reacting allergens, reduction of cutaneous or mucosal contact with dipped rubber products, and minimization of exposure to latex aeroallergens in work environments.

Effect of anti-IgE therapy in patients with peanut allergy.

BACKGROUND: Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fc(epsilon) receptor on mast cells and basophils. METHODS: We conducted a double-blind, randomized, dose-ranging trial in 84 patients with a history of immediate hypersensitivity to peanut. Hypersensitivity was confirmed and the threshold dose of encapsulated peanut flour established by a double-blind, placebo-controlled oral food challenge at screening. Patients were randomly assigned in a 3:1 ratio to receive either TNX-901 (150, 300, or 450 mg) or placebo subcutaneously every four weeks for four doses. The patients underwent a final oral food challenge within two to four weeks after the fourth dose. RESULTS: From a mean base-line threshold of sensitivity of 178 to 436 mg of peanut flour in the various groups, the mean increases in the oral-food-challenge threshold were 710 mg in the placebo group, 913 mg in the group given 150 mg of TNX-901, 1650 mg in the group given 300 mg of TNX-901, and 2627 mg in the group given 450 mg of TNX-901 (P<0.001 for the comparison of the 450-mg dose with placebo, and P for trend with increasing dose <0.001). TNX-901 was well tolerated. CONCLUSIONS: A 450-mg dose of TNX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.

Psyllium-associated anaphylaxis and death: a case report and review of the literature.

BACKGROUND: Psyllium use has increased significantly in the United States in part due to its lipid-lowering property. The increased prevalence of consumption has led to its recognition as an emerging food allergen. OBJECTIVES: To report the case of a 42-year-old woman who experienced fatal anaphylaxis after ingesting a psyllium-based product and to review the literature. METHODS: The MEDLINE database was searched for articles from 1966 to 2002 using the keywords psyllium or ispaghula and each of the following: allergy, hypersensitivity, anaphylaxis, and asthma. Both English and non-English articles were included. RESULTS: Psyllium hypersensitivity has been well described in health care workers and pharmaceutical plant employees. Clinical manifestations of allergy range from upper respiratory tract symptoms on inhalation to anaphylaxis on ingestion. The prevalence of sensitization varies between these 2 groups. The allergenic epitope is not known. CONCLUSIONS: We present a case of psyllium hypersensitivity that resulted in death. There is a clear association between atopy and psyllium allergy. The case underscores the fact that even nonprescription "natural" products can be harmful to people with allergies.

Immunization of egg-allergic individuals with egg- or chicken-derived vaccines.

Viruses used in several vaccines are propagated in embryonated eggs. These vaccines contain variable quantities of residual egg or chicken proteins and pose risks when administered to egg- or chicken-sensitive persons. This article highlights differences in how vaccines are prepared, with emphasis on the quantitation of residual egg-derived protein in each vaccine. Published reports on the frequency and severity of these vaccine-induced allergic reactions are reviewed, and an algorithm is provided for the preimmunization evaluation of egg-sensitive persons.

Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.

OBJECTIVE: Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. METHODS: We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. RESULTS: Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy. CONCLUSION: Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization.

Management of occupational allergy to natural rubber latex in a medical center: the importance of quantitative latex allergen measurement and objective follow-up.

When our employees began coming to the Occupational Health Service, Dermatology, and Allergy Clinics with symptoms of allergy to rubber gloves 12 years ago, the Mayo Clinic initiated 3 responses. (1) The Allergic Disease Research Laboratory adapted well-established technology to measure both the IgE antibody specific to natural rubber allergens, and by use of this IgE antibody, the allergens in rubber products and in the air of the workplace. (2) The Division of Allergic Diseases and Internal Medicine reviewed the prevalence and severity of the problem. (3) The Clinical Practice Committee appointed a multidisciplinary task force to implement measures to reduce exposure. The 3 sections of this article describe the Mayo Clinic's experience of successful control of this occupational health problem. Use of only gloves with low or undetectable allergen content greatly reduced the concentration of allergen in the work site, reduced the number of new cases of occupational allergy to rubber, and allowed individuals with latex allergy to work at their usual jobs.

Natural rubber latex allergy after 12 years: recommendations and perspectives.

Natural rubber latex (NRL) allergy is a "new" illness whose prevalence reached epidemic proportions in highly exposed populations during the last decade. In children with spina bifida and in patients exposed to NRL during radiologic procedures, institution of prophylactic safety measures has had demonstrable effects in preventing allergic reactions. The risk of NRL allergy appears to be largely linked to occupational exposure, and NRL-associated occupational asthma is due almost solely to powdered latex glove use. Prevalence of NRL-allergic sensitization in the general population is quite low; several studies of young adults demonstrate rates of positive skin test results that are less than 1%. After occupational exposure, rates of sensitization and NRL-induced asthma rise dramatically in individuals using powdered NRL gloves but not in individuals using powder-free gloves. Airborne NRL is dependent on the use of powdered NRL gloves; conversion to non-NRL or nonpowdered NRL substitutes results in predictable rapid disappearance of detectable levels of aeroallergen. For these reasons, adoption of the following institutional policies designed to prevent new cases of NRL allergy and maximize safety is recommended: (1) NRL gloves should be used only as mandated by accepted Standard Precautions; (2) only nonpowdered, nonsterile NRL gloves should be used; and (3) nonpowdered, sterile NRL gloves are preferred for use. Low-protein powdered, sterile gloves may be used, but only in conjunction with an ongoing assessment for development of allergic reactions.

A Sandwich Enzyme-Linked Immunosorbent Assay (ELISA) for the Quantitation of Selected Peanut Proteins in Foods.

A sandwich-type, enzyme-linked immunosorbent assay (ELISA) was developed for the detection of selected peanut proteins in foods. Monoclonal antibodies against a series of allergenic peanut proteins were used as the capture antibody. Food sample extracts were then added, and polyclonal rabbit antibodies directed against roasted peanut proteins were employed as secondary antibodies. The amount of allergen bound to the solid-phase was determined by a biotin and streptavidin-peroxidase system. Radioallergosorbent assay (RAST) inhibition studies of the food extracts were done as a comparison. The coefficient of determination for the ELISA and RAST assays was 0.85. Selected food samples were tested by RAST inhibition at another laboratory for comparison. Skin tests were done with selected samples in peanut-allergic adults, and the results correlated to the ELISA and RAST inhibition results. In other studies, defatted peanut protein (0.01 to 5.0%) were added to vanilla ice cream, then extracted and analyzed using ELISA and skin tests. The sensitivity of the ELISA in ice cream was approximately 40 µg/ml. In six of seven peanut-sensitive adults tested, the lowest level of added peanut protein (0.01%, 21 µg/ml) still caused a positive skin test reaction.