Irene Guggenmoos-Holzmann

Indoor allergen exposure is a risk factor for sensitization during the first three years of life

BACKGROUND The purpose of the study was to investigate the influence of environmental allergen exposure on allergic sensitization in infancy and early childhood. METHODS A cohort of 1314 newborns was recruited and followed up prospectively at the ages 12, 24, and 36 months. The levels of major mite (Der p 1 and Der f 1) and cat (Fel d 1) allergens were determined from domestic carpet dust samples by sandwich ELISA. Specific serum IgE antibodies to mite and cat allergens were determined by CAP fluoroimmunoassay (Pharmacia). Logistic regression was used to assess the effects of allergen exposure, age, family history, and cord blood IgE simultaneously on the risk of sensitization. RESULTS Children, who had been found to be sensitized at least once during the first 3 years of life, were found to be exposed to significantly higher house dust mite (median, 868 ng/gm vs 210 ng/mg; p = 0.001) and cat (median, 150 ng/gm vs 64 ng/gm; p = 0.011) allergen concentrations in domestic carpet dust compared with the group without sensitization. In homes with low (< or = 25th percentile) dust concentrations, the risk of sensitization to mite (1.6%), and cat (2.0%) is low, compared with 6.5% for mite and 6.3% for cat if the domestic exposure is above the 75th percentile. The dose-response relationships between allergen levels and sensitization indicate that the increase in sensitization risk at low allergen levels is more pronounced in cat allergy (p = 0.002) than in mite allergy (p = 0.026). In the group with a positive family history, lower mite and cat allergen concentrations are needed to achieve specific sensitization compared with the group with a negative family history. CONCLUSION Our data indicate that avoidance measures in the domestic environment aimed at the primary prevention of allergen-driven sensitization should be introduced at the earliest possible stage, if possible during infancy.

Sensitization to hen's egg at the age of twelve months is predictive for allergic sensitization to common indoor and outdoor allergens at the age of three years

BACKGROUND Specific predictors for atopic sensitization in early infancy are prerequisites for preventive intervention studies. OBJECTIVE To identify predictors of allergic sensitization to common aeroallergens in infancy, 1314 children in five German cities were followed up from birth (1990) to the age of 3 years. METHODS Blood samples were taken from cord blood and at follow-up visits at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to common food and inhalant allergens were determined. RESULTS Among our study population, risk factors for sensitization to indoor and/or outdoor allergens at the age of 3 years were a positive family history, the presence of hens egg-specific IgE antibodies (> or = 0.35 kU/L), and increased log- [total IgE] levels at the age of 12 months. Elevated cord blood IgE was not associated with sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE greater than 2 kU/L in combination with a positive family history of atopy was a highly specific (specificity, 99%) and predictive (positive predictive value, 78%) marker for sensitization to inhalant allergens at 3 years of age. CONCLUSIONS Hens egg-specific IgE at the age of 12 months is a valuable marker for subsequent allergic sensitization to allergens that cause asthma, allergic rhinitis, and atopic dermatitis.

Primary cutaneous melanoma : identification of prognostic groups and estimation of individual prognosis for 5093 patients

Background. Numerous investigations have examined prognostic factors for patients with primary cutaneous melanoma. However, only a few studies have been published on the definition of prognostic groups. The first aim of the present study was to determine the relative importance of different prognostic factors in a large collective study. The second aim was to define prognostic groups of patients based on combinations of prognostic factors and to define a model that allows the estimation of individual survival probability.

Predictability of early atopy by cord blood‐IgE and parental history

Background Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood‐IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy.

Primary cutaneous melanoma. Prognostic classification of anatomic location

Background. Anatomic location has been identified by several investigators as a significant prognostic factor for patients with primary cutaneous melanoma (CM). However, the best determination of higher and lower risk sites is still controversial, and the biologic significance of tumor site in the course of primary CM is unknown. The aim of the present study was to identify higher and lower risk sites based on multivariate analysis.

Long‐lasting sensitization to food during the first two years precedes allergic airway disease

The purpose of the study was to investigate whether the duration of sensitization to food allergens during early childhood is related to later development of IgE mediated hypersensitivity to inhalant allergens and of allergic rhinitis and asthma in 5‐year‐old children and whether long‐lasting food‐sensitization may be used to predict subsequent allergic airway diseases. Five hundred and eight children of a prospective birth cohort study with available serum samples at one and two years of age were included and followed up until five years of age. Specific sensitization to food and inhalant allergens and the occurrence of subsequent allergic airway diseases were determined. Children with a long‐lasting sensitization to food allergens (persistently sensitized for more than one year) produced significantly higher total IgE and specific IgE levels than children who were only transiently food‐sensitized by two years of age. Children persistently sensitized to food had a 3.4 fold higher risk of developing allergic rhinitis and a 5.5 fold higher risk of developing asthma than infants who were only transiently food sensitized. Persistent food sensitization in combination with a positive atopic family history was a strong predictor for the development of allergic rhinitis and asthma at five years of age. The risks for these children are up to 50%, and 67% respectively. Persistently detectable sensitization to food over more than one year in early childhood is a strong prognostic factor for subsequent allergic airway disease. Persistently food‐sensitized children especially in atopic families have to be regarded as a high‐risk group and should be considered for preventive measures against respiratory atopy.

Primary Cutaneous Melanoma. Optimized Cutoff Points of Tumor Thickness and Importance of Clark's Level for Prognostic Classification.

Background. Maximum tumor thickness and level of invasion are known to be the most important prognostic factors for patients with primary cutaneous melanoma. However, the classification of tumor thickness and the question of whether the combination of tumor thickness and level of invasion provides a better prognostic classification than tumor thickness alone are still matters of debate. The present study examined the relationship between tumor thickness and survival probability to define cutoff points of tumor thickness. Secondly, it investigated the prognostic value of the combination of tumor thickness and level of invasion as proposed in the current TNM classification system.

Markers and Relative Risk in a German Population for Developing Malignant Melanoma

ABSTRACT: The relationship between cutaneous malignant melanoma (MM) and possible risk factors was assessed in a case‐controlled study. Two hundred patients and 200 non‐melanoma controls of German origin matched for age and sex were interviewed and examined for pigmented moles and pigmentation characteristics. In patients with MM significantly more melanocytic nevi ≥ 2 mm (MCN) were found (mean, 53 MCN) compared to control cases (mean, 18 MCN). For persons with >60 MCN the relative risk (RR) for developing MM increased 15 times compared to ≤ MCN. Additional independent markers for an increased risk were presence of atypical MCN (RR = 7 vs. none) found in 45% of patients and in 5% of the control group, moderate to large numbers of actinic lentigines (RR = 6.2 vs. none), and lack of tanning as well as a tendency to sunburn (skin type I; RR = 2.2 vs. skin type IV) No significant correlation was found between the relative risk for MM and hair color, eye color, duration of free time sun exposure and number of sunburns. Individuals with permanent outdoor profession and sun exposure, however, showed a clearly increased relative risk for developing MM.

Case-control study of oral contraceptives and risk of thromboembolic stroke: results from international study on oral contraceptives and health of young women

Abstract Objective: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16–44 years. Design: Matched case-control study. Setting: 16 centres in the United Kingdom, Germany, France, Switzerland, and Austria. Subjects: Cases were 220 women aged 16–44 who had an incident ischaemic stroke. Controls were 775 women (at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview. Main outcome measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding. Results: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 (2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription. Conclusion: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure. Key messages This study shows a slightly increased relative risk of thromboembolic stroke in women currently using oral contraceptives compared with women not using them. The high dose oestrogen pills carry a higher risk than the low dose formulations, irrespective of the type of progestin The absolute risk of occlusive stroke for women who currently use modern oral contraceptives is very small—that is, the incidence in this age range is very low and not different between second and third generation oral contraceptives This small increase in risk can be controlled by avoiding prescription of oral contraceptives to women who have evidence of cardiovascular disease, in particular high blood pressure

Epidemiologic evidence for the role of melanocytic nevi as risk markers and direct precursors of cutaneous malignant melanoma: Results of a case control study in melanoma patients and nonmelanoma control subjects

BACKGROUND Melanocytic nevi (MN) are markers of melanoma risk, but their potential role as precursors of cutaneous malignant melanoma (CMM) is still controversial. OBJECTIVE The overall and site-specific relative risk (RR) of developing CMM was evaluated according to site-specific MN counts. METHODS MN prevalence by anatomic site and by age was compared in 200 CMM patients and in 200 nonmelanoma control subjects; RRs were calculated. RESULTS In CMM patients both MN and CMM were mainly found on the legs in women and on the posterior trunk in men, whereas in the control subjects most MN were found on the arms. MN counts on the trunk in men and on the legs in women were best predictors of the overall CMM risk (RR: 33-fold and 15-fold, respectively, for greater than 20 vs up to 4 MN). For both genders combined, the RR for CMM developing on the trunk and legs (predominant CMM locations) was best predicted by MN counts in the respective body region (RR: 24-fold and 27-fold, respectively). MN prevalence peaked in the fourth to fifth decade of life and most CMM were diagnosed during the fifth and sixth decades. CONCLUSION The site-specificity of melanoma risk found for high MN counts on the trunk and the legs and the close similarities in age distribution suggest that the role of MN as direct precursors of CMM has been underestimated and exceeds the number of histologically evident MN associated with CMM.