Cromolyn sodium and nedocromil sodium are inhaled agents that are alternatives to inhaled corticosteroids (ICS) in the management of mild persistent asthma in children. Both drugs have been shown to possess anti inflammatory properties through nonsteroidal mechanisms, although the exact mechanisms for their actions remain unclear. (more…)

The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The characteristic features include profound bronchoconstriction asthma following aspirin ingestion, rhinosinusitis, nasal polyps, and abdominal cramps. Aspirin and nonsteroidal antiinflammatory drugs selectively inhibit COX-1, which in turn shunts arachidonic acid down the 5-lipoxygenase activating protein pathway, causing overproduction of cysteinyl leukotrienes. As a consequence, elevated levels of cysteinyl leukotrienes can be found in bronchial asthma and nasal aspirates, and in urine following aspirin challenge. (more…)

Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bronchoconstrictor stimuli in the laboratory. This in turn indicates that they may have a role in the pathogenesis of acute episodes of bronchoconstriction. Although antileukotrienes are not currently advocated in the management of acute asthma, there are data to suggest that they might be of some potential benefit. Prior treatment with montelukast asthma has been shown in several studies to significantly shorten the time taken to recover (in terms of FEV 1 ) following exposure to a bronchoconstrictor stimulus. (more…)

In the UK, Europe and the USA, montelukast is licensed for once-daily oral administration in adults and is also available as a cherry flavored pink tablet or as granules for use in children over the age of 6 months. Zafirlukast is licensed for use in individuals over 12 years of age (Fig above). In some countries such as Japan, another leukotriene receptor antagonists (LTRA), pranlukast, is available for use. In the USA, zileuton is licensed for use in those over 12 years of age (Table below). (more…)

Two main strategies have been developed to block the effects of cysteinyl leukotrienes in the airway. One method is to use drugs that prevent their synthesis (using a 5-lipoxygenase inhibitor) and the other involves interfering with the binding of cysteinyl leukotrienes to their cellular receptor using a leukotriene receptor antagonist (LTRA). (more…)

The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following a series of enzymatic steps. Arachidonic acid is firstly released from the phospholipid bilayer by phospholipase A 2 and may be metabolized by either the cyclooxygenase (COX) or 5-lipoxygenase pathway. Once the unstable precursor LTA 4 has been produced, it may be converted in neutrophils or monocytes to the noncysteinyl LTB 4 by LTA 4 hydrolase. In mast cells, eosinophils, macrophages, and basophils, LTA 4 may alternatively be converted into LTC 4 by LTC 4 synthase and subsequently into LTD 4 and LTE 4. (more…)

A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)

Normally present at very low levels in plasma, antibodies of the immunoglobulin E (IgE) isotype were first discovered in 1967, decades after the description of IgA, IgG, and IM. IgE antibodies are produced primarily by plasma cells in mucosal-associated lymphoid tissue and their levels are uniformly elevated in patients suffering from atopic conditions like allergic rhinitis, asthma and atopic dermatitis. Production of allergen-specific IgE in atopic individuals is driven both by a genetic predisposition to the synthesis of this isotype as well as by environmental factors, including chronic allergen exposure. (more…)

The new corticosteroid ciclesonide has been evaluated in various studies to assess its efficacy and adverse effect profile in asthma. However, there are no data comparing the effects of high-dose ciclesonide with those of fluticasone propionate on airway and systemic outcomes in patients with moderate persistent asthma.

The relative effects of 4 weeks of treatment with ciclesonide and fluticasone propionate on airway hyper-reactivity, exhaled nitric oxide levels, lung function, symptoms, and quality of life were compared in 14 patients with moderately persistent asthma. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyper-responsiveness and exhaled nitric oxide levels. Fluticasone propionate 2000 µg daily but not ciclesonide 1600 µg daily significantly suppressed hypothalamic pituitary adrenal (HPA) axis outcomes, overnight 10 h urinary cortisol levels being lower after fluticasone propionate administration than after ciclesonide administration.

The efficacy of a new medication depends upon comparison with an existing medication that is used in the community for the treatment of a particular condition. Inhaled corticosteroid, namely beclomethasone, budesonide and fluticasone, have been used in the treatment of asthma. The introduction of newer inhaled corticosteroid would depend on the efficacy of the medication in comparison with existing medication. Ciclesonide has been evaluated in various studies essentially looking at the adverse effect profile and its effectiveness in asthma. There are no reports of head-to-head comparisons with the standard inhaled corticosteroid asthma. This study compared the effects of ciclesonide with those of fluticasone propionate, albeit in a small population of moderately persistent asthmatics. The absence of significant differences between the group receiving fluticasone propionate and the group receiving ciclesonide in airway parameters, including spirometry, PEF, symptoms and Mini-AQLQ (Asthma Quality of Life Questionnaire) score, suggest that ciclesonide could prove to be a useful option in the management of asthma. With regard to safety, the treatment period of 4 weeks may not be adequate to cause significant suppression of the hypothalamic–pituitary–adrenal axis and long-term trials are required to evaluate the effects of ciclesonide on the HPA axis.

The findings of these studies, coupled with the results of earlier studies on the pharmacology, pharmacokinetics and efficacy of ciclesonide, indicate great promise for this new inhaled steroid in the treatment of asthma. The higher bioavailability and improved plasma binding of this steroid provide it with greater efficacy and minimal side effects. Furthermore, ciclesonide nasal spray with its minimal effect on the hypothalamic–pituitary–adrenal axis, could be useful in the treatment of children with asthma. However, data on the long-term effects on the HPA axis with ciclesonide are necessary if they are to be considered to be safe medications with no effect on the HPA axis.

Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limitation. The neutrophil chemoattractant leukotriene B 4 (LTB 4) may play a role in Chronic Obstructive Pulmonary Disease and in some forms of asthma. In this study, 55 smokers with no disease, Chronic Obstructive Pulmonary Disease (with or without bronchodilator reversibility of airflow limitation) or asthma underwent measurement of LTB 4 in sputum supernatants and exhaled breath condensate asthma (EBC). Both Chronic Obstructive Pulmonary Disease and asthma patients had higher levels of LTB 4 than control subjects; patients with asthma or reversible Chronic Obstructive Pulmonary Disease exhibited significantly higher levels of LTB 4 than those with irreversible Chronic Obstructive Pulmonary Disease. (more…)