Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide.

BACKGROUND: It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma. OBJECTIVES: The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children. METHODS: Forty-eight steroid-naïve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily. RESULTS: All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels. CONCLUSION: This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.

Leukotriene modifiers in the treatment of asthma in children.

Asthma is one of the most common respiratory disorders in clinical practice, affecting up to 13% of people worldwide. Inflammation is the most important component of asthma and inhaled corticosteroids (ICS) are recommended as the first line controller treatment for patients of all ages. Treatment with corticosteroids is often unable to fully control asthma symptoms and progression. Recently, leukotrienes have come to the forefront of research as they have been found play a pivotal role in the airway inflammatory process, and specific drugs have been developed to target them. Cysteiny leukotriene antagonists (LTRAs) have recently emerged as important therapeutic options that show a large potential clinical utility. Three specific LTRAs are licensed for clinical use: montelukast, zafirlukast and pranlukast, although montelukast is the only drug approved in the paediatric age range. It is well tolerated (although adverse effects such as headaches, abdominal pain, rashes, angioedema, pulmonary eosinophilia and arthralgia have been reported) and shows many positive effects in asthmatic patients. Current Global Initiative for Asthma guidelines recommend LTRAs as: (1) a second choice treatment to ICS for patients with mild persistent asthma, (2) an add-on therapy to reduce the dose of ICS in patients with moderate or severe asthma, due to the different and complementary mechanisms of action of these agents. LTRAs may be particularly appropriate choices in a number of clinical situations, including the following: patients with concomitant rhinitis; patients with viral-induced wheeze; patients with exercise-induced bronchoconstriction (EIB) and, in children aged 2-5 years, to reduce the frequency of asthma exacerbations.

Immune dysregulation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic, inflammatory skin disease characterized by cutaneous hyperreactivity to environmentals triggers. Recent data suggest the presence of two different forms of AD: an extrinsic AD with elevated IgE involving 70-80% of the patients and an intrinsic AD with serum IgE not elevated and no specific IgE. Patients with extrinsic AD have elevated Th2- and decreased Thl-expressing cells in the peripheral blood, with elevated IL-4 and IL-13 expression, as well as IL-5. On the contrary, the intrinsic AD is linked with much lower levels of IL-4 and IL-13. Genetic factors are involved in the control of the disease and in the intrinsic AD the same chromosomal regions seem to be associated with psoriasis susceptibility. The AD is characterized by a complex of immunological alterations involving interactions between IgE-bearing antigen-presenting cells, T-cell activation, mast-cell degranulation, keratinocytes, eosinophils, and a combination of immediate and cellular immune responses. Inflammatory dendritic epidermal cells constitute a distinct dendritic cells population that is mainly found in AD and could induce the Th2/Thl isotopic switch contributing to AD chronic phase. Therapy is based on interventation in the pathophysiology of atopic eczema and elimination of exogenous provocation factors.