A Link to Asthma Exacerbation in Children Receiving Salmeterol
Palmer CN, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S Thorax. 2006 Jun 13; [Epub ahead of print]
Palmer and colleagues used a cross-sectional survey of electronic medical records, parental recall (over the previous 6 months), and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples for 546 children and young asthmatics attending an asthma clinic in Tayside, Scotland, in 2004 and 2005.
Asthma exacerbation rates, as characterized by school absences, hospitalizations, or requirement for oral corticosteroids, were assessed. They collected clinical information in children with physician-diagnosed asthma in 12 primary care practices and a secondary asthma clinic in Scotland over the 2-year period.
One hundred sixty-four patients who were taking regular inhaled salmeterol and 382 patients who were not taking salmeterol were identified. Patients were investigated and defined on the basis of their "step of treatment" as defined by the British Thoracic Society guidelines (step 1, inhaled beta2 agonists alone; step 2, step 1 plus inhaled corticosteroids [ICS]; step 3, step 2 plus long-acting beta agonists [LABAs]; and step 4, step 3 plus leukotriene antagonists ). Age, sex, and exposure to tobacco smoke were included in the study as covariates.
Fifteen percent of the patients who were studied had the Arg/Arg genotype and 38% had the Gly/Gly genotype. Those with the Arg/Arg genotype demonstrated a significant overall increased hazard for asthma exacerbations. They pointed out recent data showing worsened lung function in those homozygous for the Arg/Arg genotype at the 16 codon location, termed the ADRB2 gene. Of interest, an increased risk for the Arg/Arg genotype was only seen in those patients in the step 3 severity level with the British Thoracic Society guideline criteria (ie, those being treated with ICS, LABAs, and as-needed short-acting beta agonists [SABAs]). Increased risk for asthma exacerbations was not seen in patients with more severe asthma, who were treated with the same medications with the addition of leukotriene modifiers. This finding is interesting, and at present with no plausible explanation. A possible protective effect of leukotriene modifiers may offer an explanation. It is also noteworthy that those patients with the Arg/Arg genotype not taking salmeterol also had an increased risk for exacerbations; however, this did not reach statistical significance (P = .092). The study authors acknowledged that the lack of statistical significance may be due to the fact that the study design was not statistically powered to detect this difference. They concluded that the Arg/Arg genotype at the 16 codon location predisposes patients with asthma to an increased risk for asthma exacerbations, particularly those who are exposed to regular salmeterol. They suggested the need for further study in this area.
Palmer CN, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S Thorax. 2006 Jun 13; [Epub ahead of print]
Palmer and colleagues used a cross-sectional survey of electronic medical records, parental recall (over the previous 6 months), and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples for 546 children and young asthmatics attending an asthma clinic in Tayside, Scotland, in 2004 and 2005.
Asthma exacerbation rates, as characterized by school absences, hospitalizations, or requirement for oral corticosteroids, were assessed. They collected clinical information in children with physician-diagnosed asthma in 12 primary care practices and a secondary asthma clinic in Scotland over the 2-year period.
One hundred sixty-four patients who were taking regular inhaled salmeterol and 382 patients who were not taking salmeterol were identified. Patients were investigated and defined on the basis of their "step of treatment" as defined by the British Thoracic Society guidelines (step 1, inhaled beta2 agonists alone; step 2, step 1 plus inhaled corticosteroids [ICS]; step 3, step 2 plus long-acting beta agonists [LABAs]; and step 4, step 3 plus leukotriene antagonists ). Age, sex, and exposure to tobacco smoke were included in the study as covariates.
Fifteen percent of the patients who were studied had the Arg/Arg genotype and 38% had the Gly/Gly genotype. Those with the Arg/Arg genotype demonstrated a significant overall increased hazard for asthma exacerbations. They pointed out recent data showing worsened lung function in those homozygous for the Arg/Arg genotype at the 16 codon location, termed the ADRB2 gene. Of interest, an increased risk for the Arg/Arg genotype was only seen in those patients in the step 3 severity level with the British Thoracic Society guideline criteria (ie, those being treated with ICS, LABAs, and as-needed short-acting beta agonists [SABAs]). Increased risk for asthma exacerbations was not seen in patients with more severe asthma, who were treated with the same medications with the addition of leukotriene modifiers. This finding is interesting, and at present with no plausible explanation. A possible protective effect of leukotriene modifiers may offer an explanation. It is also noteworthy that those patients with the Arg/Arg genotype not taking salmeterol also had an increased risk for exacerbations; however, this did not reach statistical significance (P = .092). The study authors acknowledged that the lack of statistical significance may be due to the fact that the study design was not statistically powered to detect this difference. They concluded that the Arg/Arg genotype at the 16 codon location predisposes patients with asthma to an increased risk for asthma exacerbations, particularly those who are exposed to regular salmeterol. They suggested the need for further study in this area.
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