Safety Of Long-acting Β2-agonists Research Articles

Tiotropium: efficacy and safety in pediatric bronchial asthma

Bronchial asthma is one of the most common chronic lung diseases observed in children. According to the international and Russian guidelines, the long-term objectives of asthma treatment in children and adolescents are to achieve good symptom control, minimize the risk of asthma exacerbations, reduce hospital admissions, decrease the use of short-acting bronchodilators, reduce restrictions in the airflow and side effects, and ensure that normal activity levels are maintained. The asthma treatment is based on the use of inhaled corticosteroids as a backbone therapy and addition of adjunctive therapy if the disease control is poor or worsening. Tiotropium bromide is the first anticholinergic drug that has been approved for children and adults with poorly controlled asthma and is currently used as a treatment option for moderate to severe bronchial asthma. Randomized clinical trials in children and adolescents with persistent bronchial asthma showed high efficacy and safety of tiotropium. The addition of tiotropium in the form of 2 inhalations of 2.5 μg once a day to the bronchial asthma therapy in children over 6 years old, including medium doses of inhaled corticosteroids, is a preferred and safe option to increase the therapy coverage compared to an increase of a dose of inhaled corticosteroids to high levels, regardless of the disease phenotype (In atopic, non-atopic bronchial asthma, bronchial asthma with obesity, etc.). Tiotropium adjunctive therapy may also be a therapeutic option for children using inhaled corticosteroids, who have asthma that does not respond well to long-acting β2-agonist therapy, or for those, who are worried about the safety of long-acting β2-agonists.

Controversies regarding long-acting β2-agonists

This review examines the literature regarding the efficacy and safety of long-acting β2-agonists as add-on therapy to inhaled corticosteroids. The Global Initiative for Asthma (GINA) 2009 guidelines and the National Heart, Lung, and Blood Institute (NHLBI) 2007 asthma guidelines recommend adding long-acting β2-agonists to patients inadequately controlled on inhaled corticosteroids. These recommendations must be balanced against published data which demonstrate a signal of increased morbidity and mortality with use of long-acting β2-agonists. These conflicting data raise the question of whether or not there may be genotypic or phenotypic discriminators leading to disparate responses to long-acting β2-agonists. The combination of long-acting β2-agonists and inhaled corticosteroids demonstrates improvement in asthma control and exacerbation rates; however, long-acting β2-agonists are not recommended for use as monotherapy or without optimization of inhaled corticosteroid dose. Although the majority of asthmatic patients appear to benefit from the addition of long-acting β2-agonists, there are concerns that a small proportion of patients, including steroid-naïve patients and African Americans, may not obtain such benefits. Thus far, studies have not clearly demonstrated genotypic or phenotypic differences explaining the variability in response.

Safety of formoterol in adults and children with asthma: a meta-analysis

The safety of long-acting β2 agonists (LABA) for the treatment of persistent asthma remains a topic of ongoing debate. To evaluate the risk of serious asthma-related events among patients treated with formoterol, a meta-analysis of all Novartis-sponsored controlled clinical trials was conducted. Forty-five randomized, placebo- and active-controlled, parallel-group or crossover studies with formoterol were included. Background inhaled corticosteroid (ICS) use was permitted in all studies; however, in only 2 studies was ICS randomized as study medication. Sub-analyses of the pooled data were performed according to age (5-12; 13-18; >18 years), baseline ICS use, and lung function. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated between formoterol (twice-daily), albuterol (salbutamol) 4 times per day (active control), and placebo. Patients were randomized to formoterol (n = 5,367), placebo (n = 2,026), and albuterol (n = 976). Two deaths were reported, 1 each in the formoterol (asthma exacerbation) and the placebo (hemorrhagic pancreatitis) groups. No statistically significant differences in serious asthma exacerbations were observed compared with placebo in adolescents and adults. In children, a higher frequency of hospitalizations was observed among patients treated with formoterol compared with placebo (OR 8.4; 95% CI: 1.1-65.3). A trend toward fewer exacerbations was observed among subjects reporting concomitant ICS use at baseline. This analysis supports current guideline recommendations for the use of LABAs only as add-on therapy to ICS.

A retrospective observational study comparing rescue medication use in children on combined versus separate long-acting β-agonists and corticosteroids

BackgroundData on the efficacy and safety of long-acting β2-agonists (LABA) in children are limited, and current guidelines recommend that LABA always be used with inhaled corticosteroids (ICS).ObjectiveTo compare asthma control,...

Safety of Long-Acting β-Agonists: Are New Data Really Required?

Safety of Long-Acting β-Agonists: Are New Data Really Required?

Use of long-acting β2 agonists in arginine-16 homozygous patients with asthma

We read with interest the study by Palmer and colleagues.1 Their findings suggest that patients who are Arg/Arg homozygous at position 16 of the β2 adrenoceptor may be at increased...