Rauno Joks

Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner‐city adults

Obesity is associated with increased asthma and atopy.

Prevalence of allergic disease in foreign-born American children.

IMPORTANCE Improved understanding of allergic disease epidemiology lead to novel therapeutic and prevention strategies. OBJECTIVES To study the association between US birthplace and prevalence of childhood allergic disease and to determine the effects of prolonged US residence on allergic disease. DESIGN, SETTING, PARTICIPANTS Cross-sectional questionnaire distributed to 91, 642 children aged 0 to 17 years enrolled in the 2007-2008 National Survey of Childrens Health. EXPOSURE Place of birth. MAIN OUTCOME AND MEASURE Prevalence of allergic disease, including asthma, eczema, hay fever, and food allergies. RESULTS Children born outside the United States had significantly lower odds of any atopic disorders than those born in the United States (logistic regression OR, 0.48; 95% CI, 0.38-0.61), including ever-asthma (0.53; 0.39-0.72), current-asthma (0.34; 0.23-0.51), eczema (0.43; 0.30-0.61), hay fever (0.39; 0.27-0.55), and food allergies (0.60; 0.37-0.99). The associations between childs birthplace and atopic disorders remained significant in multivariate models including age, sex, race/ethnicity, annual household income, residence in metropolitan areas, and history of child moving to a new address. Children born outside the United States whose parents were also born outside the United States had significantly lower odds of any atopic disorders than those whose parents were born in the United States (P = .005). Children born outside the United States who lived in the United States for longer than 10 years when compared with those who resided for only 0 to 2 years had significantly higher odds of developing any allergic disorders (adjusted OR, 3.04; 95% CI, 1.08-8.60), including eczema (4.93; 1.18-20.62; P = .03) and hay fever (6.25; 1.70-22.96) but not asthma or food allergies (P ≥ .06). CONCLUSIONS AND RELEVANCE Children born outside the United States have a lower prevalence allergic disease that increases after residing in the United States for 1 decade.

Allergen Sensitivity and Asthma Severity at an Inner City Asthma Center

The objective of this study was to examine the relationship of allergen sensitivity to asthma symptoms among inner-city asthmatics seen at our Brooklyn, NY, asthma center. We hypothesized that asthma severity would increase for adults and children with increased cockroach and dust mite allergen sensitivity. Data were gathered from retrospective chart review for all patients who were treated at the center with a diagnosis of asthma and had undergone skin-prick testing (SPT) for allergen sensitivity during 1998 (pediatric, n = 79; adult, n = 29). Asthma severity (determined by National Heart, Lung and Blood Institute [NHLBI] asthma severity class) was examined in relation to allergen sensitivity. Allergen sensitivity was measured by percent positive to skin-prick testing as well as by relative mean diameter of skin prick test wheals. For adults, mite sensitivity prevalence was 61% and cockroach sensitivity prevalence was 41%. For children, mite sensitivity prevalence was 49%; cockroach sensitivity prevalence was 42%. For adults, asthma severity correlated significantly with sensitivity to Cladosporium, tree, and grass as measured by percent positive skin tests and by increasing mean diameter of skin test wheals. There was a significant correlation with severity for adult dust mite sensitivity only as measured by increasing mean wheal diameter. Ragweed sensitivity showed a significant correlation with severity only as measured by percent positive skin tests. There was a significant positive association for adults between increasing asthma severity and total number of allergen sensitivities per subject. There was no significant correlation for children between asthma severity and total number of allergen sensitivities per subject. Among children, no specific allergen sensitization showed a significant positive association with asthma severity. By both measures of allergen sensitization, there was a significant negative association for children between Cladosporium and asthma severity. Among our inner-city asthmatic population significant correlation between mite sensitivity and asthma severity was found only in adults. No significant association was seen with cockroach. However, outdoor allergen sensitivity (Cladosporidium, tree, ragweed, and grass) significantly correlated with asthma for adults in this inner city population.

Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: A case-control study

BACKGROUND Wild-type varicella zoster virus infection (WTVZV) early in childhood has been shown to protect against the development of asthma and atopy. OBJECTIVE To determine whether WTVZV in childhood protects against atopic dermatitis (AD). METHODS This retrospective, practice-based, case-control study randomly sampled 256 children and adolescents (age 1-18 years) with AD and 422 age-matched healthy controls from 2005 to 2007. Observations were made before the a priori hypothesis. RESULTS (1) A single episode of WTVZV in childhood is associated with decreased odds ratio (OR) of developing AD (conditional logistic regression; OR, 0.55; 95% CI, 0.34-0.89; P = .01). (2) When using intervals for age corresponding to bimodal distribution of age of WTVZV infection, the effects of WTVZV infection are significant when occurring at age 0 to 8 years (OR, 0.56; 95% CI, 0.35-0.90; P = .02), but not at 8 to 18 years (OR, 0.50; 95% CI, 0.19-1.31; P = .16). Considering 5-year intervals has similar findings. (3) WTVZV is associated with decreased odds of moderate AD (multinomial logistic regression; OR, 0.08, 95% CI, 0.04-0.15; P < .0001) or severe AD (OR, 0.04; 95% CI, 0.01-0.13; P < .0001). (4) WTVZV in children is associated with prolonged AD-free survival (Kaplan-Meier; median, 15.3 years; 95% CI, 10.9-18.0) compared with controls (median, 7.5 years; 95% CI, 4.8-11.9; log-rank test, P < .0001). (5) Children with WTVZV, compared with vaccine, who eventually develop AD require fewer pediatrician sick visits for management of AD (logistic regression; OR, 0.17; 95% CI, 0.06-0.51; P = .001). CONCLUSION WTVZV in childhood protects up to 10 years of age against AD, delays onset of AD symptoms, and decreases AD severity and office visits.

Allergic disease is associated with epilepsy in childhood: a US population-based study

Previous studies using animal models suggest an association between allergic disease and epilepsy. We sought to determine whether allergic disease is associated with epilepsy in children.

Minocycline treatment results in reduced oral steroid requirements in adult asthma

The tetracycline antibiotics have pleiotropic anti-inflammatory properties that may explain their therapeutic benefit in rheumatoid arthritis and acne. As these agents suppress both cellular and humoral immune responses, they may be of benefit in treating asthma and other allergic disorders. The purpose of this study was to determine whether minocycline therapy of asthma has steroid sparing effects beyond its inherent antibiotic properties. Adult asthmatic patients (n = 17) were treated with minocycline 150 mg p.o. twice daily or placebo for 8 weeks in a randomized, double-blind, placebo-controlled crossover study. Patients were evaluated for clinical improvement in oral steroid requirements, spirometry, and symptom scores (Asthma Quality of Life Questionnaire). They underwent assessment for preexisting infection (CT facial sinuses, Chlamydia pneumoniae nasopharyngeal culture, and C. pneumoniae and Mycoplasma pneumoniae serology). Minocycline use was associated with a 30% reduction in mean daily prednisone use compared with placebo (8.8 mg versus 14.4 mg, respectively; p = 0.02). Pulmonary function testing showed improvement in forced vital capacity (FVC; percent predicted; p = 0.03) and improvement in actual FVC and forced expiratory volume in 1 second (percent predicted) approached statistical significance (p = 0.05 and 0.08, respectively). Minocycline treatment was associated with significant improvement in asthma symptoms brought on by environmental triggers (p = 0.01). This preliminary study of minocycline therapy showed oral steroid-sparing properties for those with moderate persistent and severe persistent asthma.

Effect of minocycline and doxycycline on IgE responses

BACKGROUND We have recently found that the tetracycline minocycline suppresses inflammatory responses in serum immunoglobulin (Ig)E-positive asthmatic patients, and that IgE levels can decrease in these patients. The mechanism by which minocycline suppresses these responses is unknown. OBJECTIVE We have now investigated the ability of the tetracyclines, minocycline and doxycycline, to regulate IgE responses of peripheral blood mononuclear cells (PBMC) obtained from serum IgE-positive asthmatic patients. METHODS The distributions of CD3+, CD4+, CD8+, and CD19+ lymphocytes in peripheral blood of serum IgE-positive asthmatic patients and IgE-negative nonasthmatic controls, and cytokine-specific mRNA expression by their PBMC were determined by flow cytometry (reverse transcriptase-polymerase chain reaction). Serum Ig levels also were determined (nephelometry, fluoroenzymeimmunoassay, enzyme-linked immunoadsorbent assay; n = 7/group). PBMC (1.5 x 10(6)/mL) were cultured with anti-CD40 monoclonal antibody and recombinant human interleukin-4 in the presence/absence of minocycline or doxycycline (0.1 to 10 microg/mL), and IgE levels in supernatants determined on days 0, 3, and 10 (enzyme-linked immunoadsorbent assay). RESULTS Asthmatic and nonasthmatic subjects had similar numbers of blood CD4+ T cells (779/mm3 +/- 73 and 766 +/- 115, respectively) and CD19+ B-cells (239/mm3 +/- 35 and 379 +/- 95, respectively); however, CD8+ T cell numbers were decreased in asthmatic compared with nonasthmatic subjects (378/mm3 +/- 66 and 568 +/- 53, respectively; P = 0.045). High IgE levels were detected in supernatants of asthmatic PBMC on day 10 (28 ng/mL +/- 12), whereas control IgE levels did not change (<2.5 ng/mL). When either minocycline or doxycycline was included in culture, IgE production by asthmatic PBMC was strongly suppressed in dose-dependent fashion on day 10 (>80% with 10 microg/mL); control IgE did not change (<2.5 ng/mL). CONCLUSIONS The results are consistent with the idea that the therapeutic benefits obtained by asthmatic patients from minocycline may, in part, result from IgE suppression.

Chickenpox in childhood is associated with decreased atopic disorders, IgE, allergic sensitization, and leukocyte subsets

To cite this article: Silverberg JI, Kleiman E, Silverberg NB, Durkin HG, Joks R, Smith‐Norowitz TA. Chickenpox in childhood is associated with decreased atopic disorders, IgE, allergic sensitization, and leukocyte subsets. Pediatric Allergy Immunology 2012: 23: 50–58.

Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs.

All available therapies for human allergic disease target IgE mediated pathologic responses after IgE has been produced. We are developing tetracyclines as anti-allergy drugs to prevent IgE production, based on our findings that minocycline or doxycycline treatment of allergic asthmatic humans significantly improves their asthma symptoms, reduces their oral steroid requirements, and strongly suppresses their ongoing IgE responses (ELISA, mast cell mediated cutaneous late phase responses); the tetracyclines also strongly suppress peak IgE responses of BPO-KLH sensitized mice (ELISPOT assay, ELISA, skin tests). The antibiotic activity of the tetracyclines is not required for suppression of IgE responses; inclusion of minocycline or doxycycline in sterile culture prevents anti-CD40/IL-4 mediated induction of memory IgE responses by PBMC of allergic asthmatic patients (ELISA), and induction of specific memory IgE responses by spleen cells of BPO-KLH sensitized mice (ELISPOT assay, ELISA). The tetracyclines affect an epsilon specific pathway because IgM, IgG and IgA responses did not decrease. Further, in humans, DTH responses to recall antigens did not decrease. In related studies, we found that two distinct T cell subsets: CD4+CD60 negative and CD8+CD60+ (CD60 is a ganglioside) (humans) and CD4+ Asialo GM1 ganglioside negative and CD8+Asialo GM1 ganglioside+ (mice), both are required for induction of memory IgE responses. Phosphorylated (phos) p38 MAP kinase, but not phos ERK or phos JNK expression by CD4+ and CD8+, including CD8+CD60+, T cells is increased in allergic asthmatic humans, as is IL-4 and IL-10 production. The tetracyclines appear to target T cell pathways to induce suppression of IgE responses because they suppress phos p38 MAP kinase expression by both CD4+ and CD8+, including CD8+CD60+, T cell subsets, and IL-4 and IL-10, while upregulating IL-2 and IFN gamma, and suppressing IgE responses. Our finding that tetracyclines do not require antibiotic activity to suppress IgE responses opens the door to development of new tetracycline-based and other therapeutics for human allergic disease.

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV‐infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV‐disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV‐infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non‐atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV‐infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.