Young J. Juhn

Increased risk of serious pneumococcal disease in patients with atopic conditions other than asthma

BACKGROUND We reported an increased risk of serious pneumococcal disease (SPD) among patients with asthma. It is not known whether this is true for patients with other atopic conditions. OBJECTIVE To determine the relationship between atopic conditions other than asthma and SPD. METHODS The study subjects were residents of Rochester, Minn, who developed SPD between 1964 and 1983 and their 2 sex-matched and age-matched controls. We used a population-based computer-linked medical diagnosis system to identify all individuals with potential SPD. All records were reviewed by using explicit predetermined criteria for SPD. All individuals with atopic conditions were identified by the physician diagnoses including atopic dermatitis or eczema, allergic rhinitis, and hay fever documented in medical records. The associations between these atopic conditions and SPD were assessed by using conditional logistic regression. RESULTS A total of 3941 records were reviewed, and we identified 174 SPD cases. Of these 174 cases, 50.6% were male, and 94.3% were Caucasian. Twenty-six (14.9%) of the SPD cases and 29 (8.3%) of the controls had atopy. Atopic conditions other than asthma were associated with an increased risk of SPD (odds ratio, 2.13; 95% CI, 1.04-4.35; P = .04) after adjusting for smoking status, previous high-risk conditions for SPD, educational status, and ethnicity. CONCLUSION Like asthma, other atopic conditions, particularly atopic dermatitis, are associated with an increased risk of SPD. There may be a common immunogenetic mechanism underlying increased risk of SPD among individuals with either asthma or other atopic conditions. Our study findings need to be studied further.

Increased risk of pertussis in patients with asthma

BACKGROUND The recent pertussis outbreak in California highlights the effect of pertussis on public health. In 2004, a pertussis outbreak occurred in Olmsted County, Minnesota, despite a high vaccine uptake. This outbreak provided a natural experiment to assess the relationship between asthma and pertussis. OBJECTIVE We sought to determine whether asthmatic subjects have a higher risk of pertussis than nonasthmatic subjects. METHODS We conducted a population-based case-control study. There were 223 pertussis cases identified by means of PCR in 2004 and 2005. We identified age- and sex-matched control subjects from 5537 patients with negative test results for pertussis. We conducted a comprehensive medical record review and applied predetermined criteria to ascertain asthma status. Conditional logistic regression was fit to assess the effect of asthma status on the risk of pertussis. RESULTS Of the 223 subjects, 164 were eligible for the study, and 328 matched control subjects (1:2 matching) were enrolled. Of these 164 subjects, 50% were male, and 82% were white. The median age at the index date of pertussis was 14 years. Sixty-two (38%) of the 164 cases had asthma before the index date of pertussis compared with 85 (26%) of the 328 control subjects (odds ratio, 1.73; 95% CI, 1.12-2.67; P = 013). The population attributable risk percentage of asthma for risk of pertussis was 17%. CONCLUSIONS Given the high prevalence of asthma and the ongoing risk of pertussis throughout the United States, consideration of defining asthmatic subjects as a target group for pertussis vaccination (eg, replacing decennial tetanus-diphtheria booster with tetanus, diphtheria, and acellular pertussis vaccine for adolescents and adults) should be given.

Asthma and Proinflammatory Conditions: A Population-Based Retrospective Matched Cohort Study

OBJECTIVE To determine the association between asthma and proinflammatory conditions. PARTICIPANTS AND METHODS This population-based retrospective matched cohort study enrolled all asthmatic patients among Rochester, Minnesota, residents between January 1, 1964, and December 31, 1983. For each asthmatic patient, 2 age-and sex-matched nonasthmatic individuals were drawn from the same population. The asthmatic and nonasthmatic cohorts were followed forward in the Rochester Epidemiology Project diagnostic index for inflammatory bowel disease (IBD), rheumatoid arthritis (RA), diabetes mellitus (DM), and coronary heart disease (CHD) as outcome events. Data were fitted to Cox proportional hazards models. RESULTS We identified 2392 asthmatic patients and 4784 nonasthmatic controls. Of the asthmatic patients, 1356 (57%) were male, and mean age at asthma onset was 15.1 years. Incidence rates of IBD, RA, DM, and CHD in nonasthmatic controls were 32.8, 175.9, 132.0, and 389.7 per 100,000 person-years, respectively; those for asthmatic patients were 41.4, 227.9, 282.6, and 563.7 per 100,000 person-years, respectively. Asthma was associated with increased risks of DM (hazard ratio, 2.11; 95% confidence interval, 1.43-3.13; P<.001) and CHD (hazard ratio, 1.47; 95% confidence interval, 1.05-2.06; P=.02) but not with increased risks of IBD or RA. CONCLUSION Although asthma is a helper T cell type 2-predominant condition, it may increase the risks of helper T cell type 1-polarized proinflammatory conditions, such as CHD and DM. Physicians who care for asthmatic patients need to address these unrecognized risks in asthmatic patients.

The influence of neighborhood environment on the incidence of childhood asthma: A propensity score approach

BACKGROUND The propensity score method has been underused in research concerning asthma epidemiology, which is useful for addressing covariate imbalance in observational studies. OBJECTIVE To examine the impact of neighborhood environment on asthma incidence by applying the propensity score method. METHODS The study was designed as a retrospective cohort study. Study subjects were all children born in Rochester, Minn, between 1976 and 1979. Asthma status was previously determined by applying predetermined criteria. We applied the propensity score method to match children who lived in census tracts facing or not facing intersections with major highways or railroads. The propensity score of children living in a census tract facing intersections was formulated from a logistic regression model with 16 variables that may not be balanced between comparison groups. The Cox proportional hazard models were used in the matched samples to estimate hazard ratios of neighborhood environment and some other variables of interest and their corresponding 95% CIs. RESULTS After matching with propensity scores, we found that children who lived in census tracts facing intersections with major highways or railroads had a higher risk of asthma (hazard ratios, 1.385-1.669 depending on the matching methods) compared with the matched counterparts who lived in census tracts not facing intersections with major highways or railroads. CONCLUSION Neighborhood environment may be an important risk factor in understanding the development of pediatric asthma. The propensity score method is a useful tool in addressing covariate imbalance and exploring for causal effect in studying asthma epidemiology.

Influence of asthma status on serotype-specific pneumococcal antibody levels

Abstract Background: Asthma has been reported to be associated with an increased risk of invasive pneumococcal disease (IPD). Objective: We compared serotype-specific antibody responses with pneumococcal polysaccharide antigens of individuals with and without asthma. Methods: A cross-sectional study was conducted for 16 subjects with asthma and 14 subjects without asthma from the community of Rochester, MN. Asthma was determined by predetermined criteria based on comprehensive medical record reviews. Serotype-specific antibody to 23 pneumococcal polysaccharide antigens was measured by enzyme-linked immunosorbent assay, and seropositivity was considered ≥ 1.3 μg/mL. Interferon-γ (IFN-γ) and interleukin-5 (IL-5) were measured from peripheral blood mononuclear cells cultured with house dust mites and staphylococcal enterotoxin B. Results: Of the 30 subjects, 16 (53%) were male, 21 (70%) were white, and the median age was 26 years. The median numbers of positive serotype-specific antibodies for asthmatics and nonasthmatics were 8.5 and 15.5, respectively (P = 0.034). There was an inverse relationship between the ratio of log-transformed IL-5/IFN-γ and the number of positive serotype-specific antibodies (r = –0.36; P = 0.052). As potential covariates and confounders, a history of pneumococcal vaccination (P = 0.84), having a high-risk condition for IPD (P = 0.68), and taking asthma medications, including inhaled/systemic corticosteroids (P = 0.79), were not associated with the number of positive serotype-specific antibodies. Conclusion: Asthmatics had significantly lower serotype-specific pneumococcal antibody levels than nonasthmatics. House dust mite-induced T-helper 2 (Th2) cytokine immune profile may be related to the association. This may account for an increased risk of IPD in asthmatics and deserves further investigation.

Assessment of the association between pediatric asthma and Streptococcus pyogenes upper respiratory infection.

This study was designed to determine the relationship between asthma and the risk of developing Streptococcus pyogenes infections of the upper respiratory tract among children and adolescents. We conducted a retrospective cohort study that followed a convenience sample of 340 healthy children who participated in the Rochester Family Measles Study. Comprehensive medical record reviews determined asthma status by applying predetermined criteria. All laboratory test results of cultures, rapid antigen, and polymerase chain reaction tests for S. pyogenes infections during the first 18 years of life were collected to compare the incidence of S. pyogenes infections between asthmatic and nonasthmatic subjects. A Poisson regression was fit to determine the association between asthma and S. pyogenes infections controlling for other risk factors. Of the 340 subjects, we enrolled 327 who were eligible for this study. Of the 327 subjects, 114 (35%) had asthma. The incidences of S. pyogenes infections for asthmatic and nonasthmatic subjects were 0.25 per person-year and 0.18 per person-year, respectively. The adjusted risk ratio for asthma was 1.40 (95% CI, 1.12-1.74; p = 0.0029). Asthma in children is associated with an increased risk of S. pyogenes upper respiratory infections. The impact of asthma status on susceptibility to microbial infections needs to be considered in the context of a possible causal relationship between asthma and microbial infections. The mechanisms underlying this risk need to be elucidated.

Assessment of humoral and cell-mediated immune response to measles-mumps-rubella vaccine viruses among patients with asthma.

Little is known about the influence of asthma status on humoral and cell-mediated immune responses to measles-mumps-rubella (MMR) vaccine viruses. We compared the virus-specific IgG levels and lymphoproliferative response of peripheral blood mononuclear cells to MMR vaccine viruses between asthmatic and nonasthmatic patients. The study subjects included 342 healthy children aged 12-18 years who had received two doses of the MMR vaccine. We ascertained asthma status by applying predetermined criteria. Of the 342 subjects, 230 were available for this study of whom 25 were definite asthmatic patients (10.9%) and the rest of subjects were nonasthmatic patients. The mean of the log-transformed lymphoproliferative responses between definite asthma and nonasthma who had a family history of asthma were for measles, 0.92 ± 0.31 versus 1.54 ± 0.17 (p = 0.125); for mumps, 0.98 ± 0.64 versus 2.20 ± 0.21 (p = 0.035); and for rubella, 0.12 ± 0.37 versus 0.97 ± 0.16 (p = 0.008), respectively, adjusting for the duration between the first MMR vaccination and determination of the immune responses. There were no such differences among children without a family history of asthma. MMR virus-specific IgG levels were not different between study subjects with or without asthma. The study findings suggest asthmatic patients may have a suboptimal cell-mediated immune response to MMR vaccine viruses and a family history of asthma modifies this effect.

Childhood asthma and measles vaccine response

BACKGROUND Asthmatic patients have a TH2-predominant milieu that is associated with humoral immunity. However, little is known about whether humoral immune responses to viral antigens differ between asthmatic and nonasthmatic children. OBJECTIVE To determine whether humoral immune response differs in asthmatic patients vs nonasthmatic patients. METHODS Measles virus specific IgG antibody levels were determined for the Rochester Family Measles Study cohort (n = 876), a convenience sample of healthy children 5 to 12 years of age in Rochester, MN. We conducted comprehensive medical record reviews of 838 children who were eligible for this study. We determined the childs asthma status at the time of determination of antibody levels by applying predetermined criteria for asthma. Comparisons were made using the 2-sample t test or chi2 test. RESULTS Of the 838 children, 156 (18.6%) had asthma at the time of the determination of antibody levels and were not taking systemic steroids within 14 days of specimen collection. Among those with a nonequivocal antibody reading, the seropositive response rates were similar in asthmatic patients and nonasthmatic patients (89.7% vs 90.3%, respectively; P = .83). However, the equivocal response rates were slightly higher among asthmatic patients than nonasthmatic patients (6.4% vs 4.7%, respectively). CONCLUSION Asthmatic children seem to have similar humoral immune responses to measles vaccine as those without asthma. Although the findings reassure health care practitioners, whether this finding is generalizable to other vaccines and whether asthmatic patients with low antibody levels have normal cell-mediated immunity need to be elucidated in future studies.

Comparison of individual-level versus area-level socioeconomic measures in assessing health outcomes of children in Olmsted County, Minnesota

Background Socioeconomic status (SES) is an important determinant of health, but SES measures are frequently unavailable in commonly used datasets. Area-level SES measures are used as proxy measures of individual SES when the individual measures are lacking. Little is known about the agreement between individual-level versus area-level SES measures in mixed urban–rural settings. Methods We identified SES agreement by comparing information from telephone self-reported SES levels and SES calculated from area-level SES measures. We assessed the impact of this agreement on reported associations between SES and rates of childhood obesity, low birth weight <2500 g and smoking within the household in a mixed urban–rural setting. Results 750 households were surveyed with a response rate of 62%: 51% male, 89% Caucasian; mean child age 9.5 years. Individual-level self-reported income was more strongly associated with all three childhood health outcomes compared to area-level SES. We found significant disagreement rates of 22–31%. The weighted Cohens κ indices ranged from 0.15 to 0.22, suggesting poor agreement between individual-level and area-level measures. Conclusion In a mixed urban–rural setting comprised of both rural and urbanised areas, area-level SES proxy measures significantly disagree with individual SES measures, and have different patterns of association with health outcomes from individual-level SES measures. Area-level SES may be an unsuitable proxy for SES when individual rather than community characteristics are of primary concern.

Asthma and Risk of Selective IgA Deficiency or Common Variable Immunodeficiency: A Population-Based Case-Control Study

OBJECTIVE To determine the association between a history of asthma and a diagnosis of selective IgA deficiency (sIgAD)/common variable immunodeficiency (CVID). PATIENTS AND METHODS This population-based case-control study included residents of Olmsted County, Minnesota, who met the Pan-American Group for Immunodeficiency/European Society for Immunodeficiencies diagnostic criteria for sIgAD/CVID between January 1, 1964, through December 31, 2008. Each case had 4 age- and sex-matched controls (2 from the community and 2 from a list of individuals who had undergone an immune work-up). We ascertained asthma status by applying predetermined criteria for asthma. RESULTS We identified 39 cases: 26 (66.7%) had sIgAD and 13 (33.3%) had CVID. Of the 39 cases, 51.3% were men (n=20) and 97.1% were white (33 of 34 patients). The mean age at the index date (the time when criteria were met) of sIgAD/CVID was 34.2 years. Of the 39 cases, 9 (23.1%) had a history of asthma before the index date of sIgAD/CVID; of the 156 controls, 16 (10.3%) had a history of asthma before the index date (odds ratio, 2.77; 95% CI, 1.09-7.06; P=.03). A history of asthma (before or after the index date of sIgAD/CVID) was more prevalent in sIgAD/CVID cases (30.8%; n=12) than in matched controls (11.5%; n=18) (odds ratio, 3.57; 95% CI, 1.50-8.51; P=.01). CONCLUSION Asthmatic patients are more likely to have a diagnosis of sIgAD/CVID than nonasthmatic individuals. This association may potentially account for the increased risks of bacterial infections in some individuals with asthma.