Two long-acting ß 2 -adrenergic agonists (LABAs), salmeterol and formoterol, have been demonstrated to be safe and effective agents in children, both in terms of bronchodilation and prevention of exercise-induced bronchospasm. Their onsets of action differ, with formoterol having an onset similar to albuterol (3 minutes), while salmeterol has a slower onset of action (10–20 minutes). Following a single-dose administration, both agents demonstrate durations of action up to 12 hours. Following regular twice-daily administration, bronchodilation remains effective; however, a level of tolerance (or tachyphylaxis) (more…)

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…)

Vocal cord dysfunction (VCD) is a functional respiratory tract disorder resulting from paradoxical adduction of the vocal cords, complicates the diagnosis and management of common respiratory tract problems, including asthma. The recognition of VCD in a patient with atypical or difficult-to-control asthma is critical in minimizing symptoms and potential side-effects associated with treatment of severe asthma. The symptoms of VCD are not unique to the disorder and include cough, wheeze, stridor, dyspnea, hoarseness, and choking. (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…)

A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)

Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid dose (400–800 µg/day of beclomethasone or equivalent) alone should preferentially be commenced on a long-acting agonist ß2 prior to an leukotriene receptor antagonists LTRA (British guideline on the management of asthma 2003; GINA Workshop Report 2004). However, two recent large trials have performed head to-head comparisons of add-on long-acting ß2 agonist versus LTRA as therapeutic adjuncts to inhaled corticosteroids, using exacerbation frequency (rather than lung function and symptoms) as the primary end point. (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…)

The genetic basis of asthma heritability has been extensively studied and the studies are yielding some understanding. There is, as yet, no set genetic pattern that predicts presence of asthma or defines it severity. There are usually reasons or risk of asthma factors that makes someone susceptible to asthma and respiratory allergy problems. Asthma doesn’t just happen randomly to anyone without asthma gene factors risk factors.

Let’s consider some asthma risk factors and see how they increase the chance that a individual will have the asthma signs or symptoms of cough, wheezing, as well as shortness of breathing associated with the disease. After determining your personal risk factors for asthma, decide on the ones you can control as well as try to make some lifestyle changes. Avoidance of the risk factors you can control is important in preventing asthma symptoms. While you cannot change your own gender to family history, you can avoid smoking with asthma, breathing polluted air, and obesity. Take control of your asthma by controlling the asthma risk factors. By understanding all of the risk factors, you are able to prevent to control your asthma.

Genetic factors cannot explain the rise in asthma prevalence, morbidity, or mortality. However, a small change in the prevalence of relevant environmental exposures could explain a significant rise in disease prevalence among genetically susceptible individuals. Gene-environment interaction, defined as the co-participation of genetic and environmental factors, is particularly relevant to the etiology of asthma morbidity, especially in individuals who experience a disproportionate burden of environmental exposures. Relevant exposures include smoking, stress, nutritional factors, infections, allergens, and occupational asthma exposures. In addition, racial/ethnic variability in the distribution of genetic polymorphisms can potentially modify the response to pharmacotherapeutic agents, such as the ß 2 -adrenergic receptor. A genetic polymorphism in the ß 2 -adrenergic receptor gene has been associated with asthma severity, as well as with the susceptibility to develop asthma among individuals who smoked.

Childhood asthma happens more frequently in boys than in girls. It is still not known precisely why this occurs even though some experts find a young male’s airway size is small compared to the female’s airway, that may contribute to increased risk of wheezing after a cold or perhaps other viral infection. Around age 20, the ratio of asthma between people is the same. At age 40, more females than men have adult asthma.

The inherited genetic makeup predisposes you to having asthma. In fact, it’s thought that three-fifths of all asthma cases are hereditary. Based on CDC report, if a person has a parent with asthma, there is 3 to 6 times more probably to develop asthma than someone who does definitely not have a parent with asthma.

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…)

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.