The airway epithelium is the first line of defense for the lungs, detecting inhaled environmental threats through pattern recognition receptors expressed transmembrane or intracellularly. Activation of pattern recognition receptors triggers the release of alarmin cytokines IL-25, IL-33, and TSLP. These alarmins are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Many of the key effector cells in the allergic cascade also produce alarmins, thereby contributing to the airways disease by driving downstream type 2 inflammatory processes. Randomized controlled clinical trials have demonstrated benefit when blockade of TSLP and IL-33 were added to standard of care medications, suggesting these are important new targets for treatment of asthma. With genome-wide association studies demonstrating associations between single-nucleotide polymorphisms of the TSLP and IL-33 gene and risk of asthma, it will be important to understand which subsets of asthma patients will benefit most from anti-alarmin therapy.

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

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Asthma is a chronic disease of the airways characterized by inflammation, tightened muscles, and thickened airway walls leading to symptoms such as shortness of breath, chest tightness, and cough in patients. The increased risk of asthma in children of asthmatics parents supports the existence of genetic factors involved in the pathogenesis of this disease. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with asthma. These polymorphisms occur within several genes and can contribute to different asthma phenotypes, affect disease severity, and clinical response to different therapies. The complexity in the etiology of asthma also results from interactions between environmental and genetic factors. Environmental exposures have been shown to increase the prevalence of asthma in individuals who are genetically susceptible. This review summarizes what is currently known about the genetics of asthma in relation to risk, response to common treatments, and gene-environmental interactions.

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Hyperproliferation of keratinocytes leading to epidermal thickness contributes to the clinical features of atopic dermatitis. Corticosteroids are a first line treatment rapidly reducing symptoms. We examined the effect of prednisolone on histological outcomes in skin of patients with atopic dermatitis. METHODS: Sixteen patients with moderate-to-severe atopic dermatitis completed a double-blind, placebo-controlled study to evaluate the effect of oral prednisolone on histopathological changes in skin. After a 16-day run-in period (8 days of 0.25 mg/kg prednisone, 8 days withholding all medications) patients were randomized to placebo or prednisolone at 0.75mg/kg for 5 days, 0.5mg/kg for 5 days, tapering to 0.25 mg/kg for 5 days. Pre-and Day 14 post-treatment patients underwent intradermal challenges and 24h later four punch biopsies were collected (saline intradermal challenge, allergen intradermal challenge, lesional skin and unaffected skin). Changes in histopathology scores were compared between placebo and prednisolone using Mann-Whitney t-tests. RESULTS: The epidermis was two times thicker in lesional vs unaffected skin (p50.0275). There was no effect of allergen or saline challenge on epidermal thickness. Compared to placebo, 14 days of prednisolone treatment significantly reduced epidermal thickness in allergen-challenged skin (p50.0499) with trends for effects in unaffected skin (p50.0593) but not saline-challenged (p50.1605) or lesional skin (p50.1304). There was no effect of prednisolone treatment on measurements of spongiosis, lymphocytic infiltration or neutrophilic infiltration. CONCLUSIONS: Epidermal thickening in this small study of patients with atopic dermatitis is somewhat reduced after 14 days of prednisolone treatment, and this improvement not does not appear to be regulated by lymphocyte or neutrophil levels.

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