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Summary: We studied, whether asthma diagnosed in childhood or early adulthood affects work ability 20 years later. We used Finnish Defence Force registers, 1986–1990, to select: (1) conscripts with asthma to represent a mild/moderate asthma group (n = 485), (2) asthmatics who were exempted from military service to represent a relatively severe asthma group (n = 393) and (3) a control group (n = 1500) without asthma. A questionnaire consisting of validated questions on asthma and work ability was sent out in 2009. A total of 54% of the men in the first study group, 44% of those in the second study group and 44% of the controls answered. The mean age of the participants was 41 (range 37–51). Self-assessed current work ability compared with lifetime best had decreased in 28.9% of the first asthma group, in 31.1% of the second asthma group, and in 19.7% of the controls (p = 0.0007). Current smoking (OR 2.5), only basic education (OR 2.6), being a manual worker (OR 2.7) and current severe asthma (OR 3.8) associated most strongly with decreased work ability among the asthmatics. Both mild and more severe asthma at the age of around 20 seems to be associated with reduced work ability in 40-year-old males. [Copyright &y& Elsevier]

Summary: Background: During military service young men (age 19–21 years) are exposed to many predisposing factors for asthma. We aimed to study the short-term prognosis of asthma after the military service. Methods: All 216 men with verified asthma in 2004–2005 from the register of the Central Military Hospital were included in the study. A questionnaire was mailed to them in autumn 2007 and the 146 responders (68%) formed the final study population. Asthma severity was evaluated during military service according to the medical records of the subjects and two years later based on the questionnaire using modified GINA guidelines. The results on lung function and allergy tests during military service and asthma history were used as predictors of asthma severity at two-year follow-up. Results: Two groups of asthmatics were identified: those who already had asthma when entering the military service (n =71, 48.6%) and those, who had a new onset of asthma during the service (n =75, 51.4%). Overall asthma was less severe at two-year follow-up than during military service (p =0.036). Both during military service and at two-year follow-up, asthma was milder among the men, who had a new onset of asthma during military service. Atopy (p =0.002), number of positive skin-prick tests (p =0.005) and higher total serum IgE (p =0.001) were significant predictors for persistent asthma at follow-up. Conclusions: Asthma, which had aggravated or started during military service, was significantly less severe two years later. The degree of atopy was a major determinant of the two-year prognosis of asthma after military service. [Copyright &y& Elsevier]

Background: As clinical and histological features of allergic and irritant contact dermatitis share common characteristics, the differentiation between them in the preclinical and clinical evaluations of chemicals remains difficult. Objective: To identify the differences in the underlying immunological mechanisms of chemical-induced allergic or irritant skin responses. Methods: We systematically studied the involvement of chemokines in both diseases by quantitative real-time polymerase chain reaction in mice and humans. The cellular origin of relevant chemokines and receptors was determined using immunohistochemistry; functional relevance was demonstrated in vitro by transwell chemotaxis and in vivo by adoptive transfer experiments using a model of hapten-induced murine contact hypersensitivity. Results: Independent of overall skin inflammation, chemical-induced allergic and irritant skin responses showed distinct molecular expression profiles. In particular, chemokine genes predominantly regulated by T-cell effector cytokines demonstrated differential upregulation in hapten-specific skin inflammation. Notably, the expression of CXCR3 ligands, such as CXCL9 (Mig) and CXCL10 (IP-10), was upregulated in chemical-induced allergic skin responses when compared with irritant skin responses. Furthermore, we showed that inflammatory chemokines such as CXCL10 prime leukocytes to respond to CXCL12 (SDF-1), increasing their recruitment both in vitro and in vivo. Conclusion: We provide important insights into the molecular basis of chemical-induced allergic and irritant contact dermatitis, identify novel markers suitable for their differentiation, and demonstrate the cooperation of inflammatory and homeostatic chemokines in the recruitment of pathogenic leukocyte subsets. Clinical implications: Molecular differences between both diseases represent the basis for new approaches to diagnostics and therapy. [Copyright &y& Elsevier]

Background: IL-31 is a novel T-cell–derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. Objective: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. Methods: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. Results: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or TH1 and TH2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Conclusion: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development. [Copyright &y& Elsevier]

Background: MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the posttranscriptional level. Atopic dermatitis is a common chronic inflammatory skin disease characterized by the presence of activated T cells within the skin. Objective: We sought to explore the role of miRNAs in the pathogenesis of atopic dermatitis. Methods: Global miRNA expression in healthy and lesional skin of patients with atopic dermatitis was compared by using TaqMan MicroRNA Low Density Arrays. miR-155 expression in tissues and cells was quantified by means of quantitative real-time PCR. The cellular localization of miR-155 was analyzed by means of in situ hybridization. The regulation of cytotoxic T lymphocyte–associated antigen (CTLA-4) by miR-155 was investigated by using luciferase reporter assays and flow cytometry. CTLA-4 expression and functional assays were performed on TH cells overexpressing miR-155. Results: miR-155 was one of the highest-ranked upregulated miRNAs in patients with atopic dermatitis. In the skin miR-155 was predominantly expressed in infiltrating immune cells. miR-155 was upregulated during T-cell differentiation/activation and was markedly induced by T-cell activators in PBMCs in vitro and by superantigens and allergens in the skin in vivo. CTLA-4, an important negative regulator of T-cell activation, was identified as a direct target of miR-155. Overexpression of miR-155 in TH cells resulted in decreased CTLA-4 levels accompanied by an increased proliferative response. Conclusion: miR-155 is significantly overexpressed in patients with atopic dermatitis and might contribute to chronic skin inflammation by increasing the proliferative response of TH cells through the downregulation of CTLA-4. [Copyright &y& Elsevier]

Several drugs and chemicals applied to the skin result in some local reaction by the skin to the applied compound or its formulation. These reactions may range from generalized reactions as characterized by an adaptive immune or allergic response to a specific reaction such as to light to a localized alteration in the barrier properties of the outermost physical skin barrier, the stratum corneum. This overview considers the mechanisms by which the skin reacts to various chemicals it becomes exposed to, giving some examples of how the interactions can occur, the compounds involved, and chemical structure activity relationships associated with the interaction between specific compounds and the skin. [Copyright &y& Elsevier]