Asthma is an inflammatory disorder of the airways, characterized by infiltration of mast cells, eosinophils, and Th2-type CD4+ T cells in the airway wall. Airway epithelium constitutes the first line of interaction with our atmospheric environment. The protective barrier function of the airway epithelium is likely impaired in asthma. Furthermore, recent studies suggest critical immunogenic and immunomodulatory functions of airway epithelium. In particular, a triad of cytokines, including IL-25, IL-33 and TSLP, is produced and released by airway epithelial cells in response to various environmental and microbial stimuli or by cellular damage.

These cytokines induce and promote Th2-type airway inflammation and cause remodeling and pathological changes in the airway walls, suggesting their pivotal roles in the pathophysiology of asthma. Thus, the airway epithelium can no longer be regarded as a mere structural barrier, but must be considered an active player in the pathogenesis of asthma and other allergic disorders.

Seeing children (and not so young people) crying is not an expected sight in Orlando, but during the pollen season this may not be so uncommon. Unfortunately, allergies are very frequent in the population, and although effective therapies are available, many have disadvantages, and research continues to develop novel medicines and immunotherapies that will more rapidly, effectively and safely help people with allergies to enjoy their lives without teary eyes, runny nose and, most particularly, dramatic fights for inhaling air.

Orlando was the site of this year's American Academy of Allergy, Asthma and Immunology meeting, many of the findings reported during which in relation with treatments for allergic and immunological diseases are presented in the following report.

The first discovery that interleukin-4 (IL-4) is crucial in the development of allergic airway inflammation originates from the early nineties. Whereas initial studies in experimental animal models were providing the community the optimistic view that targeting IL-4 would be the ultimate solution for treating asthma, the translation of these findings to the clinic has not been evident and has not yet fulfilled the expectations.

Many technical challenges have been encountered in the attempts to modulate IL-4 expression or activity and in transferring knowledge of preclinical studies to clinical trials. Moreover, biological redundancies between IL-4 and IL-13 have compelled a simultaneous blockade of both cytokines. A number of phase I/II studies are now providing us with clinical evidence that targeting IL-4/IL-13 may provide some clinical benefit. However, the initial view that asthma is a purely Th2-mediated disease had to be revised. Currently, different asthma phenotypes have been described, implicating that blocking specifically Th2 cytokines, such as IL-4, IL-5 and IL-13, should be targeted to only a specific subset of patients.

Taking this into consideration, IL-4 (together with IL-13) deserves attention as subject of further investigations to treat asthma. In this review, we will address the role of IL-4 in asthma, describe IL-4 signaling and give an overview of preclinical and clinical studies targeting the IL-4-(Receptor)-pathway.

Conclusion:  All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 h making it unsuitable for once‐daily dosing.Please cite this paper as: Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C and Crater G. Efficacy and safety of the long‐acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD.
Clin Respir J 2012; DOI:10.1111/j.1752‐699X.2011.00278.x.