Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids

doi:10.1016/S0091-6749(98)70383-5

Journal of Allergy and Clinical Immunology

Volume 101, Issue 2, February 1998, Pages 188-195

https://doi.org/10.1016/S0091-6749(98)70383-5 Get rights and content

Abstract

Background: Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being.

Objective: We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 μg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler.

Results: Mean change from baseline in asthma quality-of-life scores was significantly greater (p ≤ 0.006) after 12 weeks of treatment with salmeterol compared with placebo (“as-needed” albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV₁ (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001).

Conclusion: Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy. (J Allergy Clin Immunol 1998;101:185-95.)

Section snippets

Patients

Male or female patients (G12 years of age) were eligible for enrollment if they met the criteria for asthma as defined by the American Thoracic Society,¹⁷ had an average daytime or nighttime symptom score of 1 on a 0 to 3 point scale over a 2-week screening period, used a short-acting bronchodilator on a daily basis, and used a fixed dose of inhaled corticosteroid that was within package insert guidelines (i.e., beclomethasone dipropionate, 252 to 840 μg/day; flunisolide, 1000 to 2000 μg/day;

RESULTS

Five hundred eighty-one patients were eligible for entry into the study and entered the screening period. Five hundred six patients were randomized and evenly distributed between the two treatment groups with respect to patient demographics and pulmonary function at the screening visit (Table I).Seventy-two (14%) patients did not complete the 12-week treatment period; however, the majority of these patients were withdrawn because of failure to return or protocol violations. Withdrawal because

DISCUSSION

The results of this study demonstrate that the addition of salmeterol to the treatment regimen of patients with symptoms while taking inhaled corticosteroids results in significant improvements in asthma-specific quality of life. These results support previous studies in which traditional clinical outcome measures were used to show the efficacy of salmeterol in patients also treated with inhaled corticosteroids.2, 3, 4, 5 Symptomatic patients treated with salmeterol experienced significantly

Acknowledgements

The Salmeterol Quality of Life Study Group was composed of: C. Agcaoili, MD, Redwood City, Calif.; G. Bensch, MD, Stockton, Calif.; B. Bowers, PharmD, Research Triangle Park, N.C.; D. Broide, MD, San Diego, Calif.; B. Buchanan, MD, Spokane, Wash.; P. Carvalho, MD, Boise, Idaho; T. Chestnut, MD, Spokane, Wash.; B. E. Chipps, MD, Sacramento, Calif.; R. O. Crapo, MD, Salt Lake City, Utah; B. W. Cromar, MD, Wenatchee, Wash.; H. H. Davis, MD, Cheyenne, Wyo.; D. Elkayam, MD, Bellingham, Wash.; R.

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Cited by (50)

Activity limitation and exertional dyspnea in adult asthmatic patients: What do we know?
2016, Respiratory Medicine
Citation Excerpt :
The administration of long-acting bronchodilator has also shown no effect on exercise capacity assessed by CPET [48,50]. However, in two studies assessing quality of life, the activity limitation domain of the Asthma Quality of Life Questionnaire has been shown to be significantly improved after treatment with salmeterol [51,52]. Concerning the potential relationship between anti-inflammatory agents and activity, only one study was found.
Limitation of activity is the most cited symptom described by uncontrolled asthma patients. Assessment of activity limitation can be undertaken through several ways, more or less complex, subjective or objective. Yet little is known about the link between patients sensations and objective measurements.
The present review reports the current knowledge regarding activity limitation and symptom perception (i.e., exertional dyspnea) in adult patients with asthma. This work is based on references indexed by PubMed, irrespective of the year of publication.
Overall, patients with stable asthma do not have a more sedentary lifestyle than healthy subjects. However, during a cycle ergometric test, the maximal load is reduced when FEV1, FVC and muscle strengths are decreased. Additionally, during the six-minute walking test, mild asthma patients walk less than healthy subjects even if the minimal clinically important difference is not reached.
The major complaint of asthma patients when exercising is dyspnea that is mainly related to the inspiratory effort and also to dynamic hyperinflation in some circumstances. Finally, the administration of bronchodilator does not improve the ventilatory pattern and the exercise capacity of asthma patients and little is known on its effect on exertional dyspnea.
The present review allows to conclude that until now there is no gold standard test allowing the objective assessment of “activity limitation and exertional dyspnea” in asthma patients.
The reply
2010, American Journal of Medicine
Quality of Life Outcomes After Functional Endoscopic Sinus Surgery
2010, Otolaryngologic Clinics of North America
Long-acting Beta-Agonists with and without Inhaled Corticosteroids and Catastrophic Asthma Events
2010, American Journal of Medicine
Citation Excerpt :
The search identified approximately 6500 articles, of which 211 were potentially relevant trials. Of these, 10 individual trials met the inclusion criteria.20-29 GlaxoSmithKline provided additional pooled trial data for long-acting β-agonists with and without concomitant inhaled corticosteroids.9
It is unclear whether long-acting β-agonists with concomitant inhaled corticosteroids increase asthma-related intubations and deaths. We pooled data on long-acting β-agonists with variable and concomitant inhaled corticosteroids to evaluate the risk for catastrophic asthma events.
We conducted searches of electronic databases, the US Food and Drug Administration website, clinical-trials registries, and selected references through December 2008. We analyzed randomized controlled trials in patients with asthma, which lasted at least 3 months, evaluated long-acting β-agonists compared with placebo or long-acting β-agonists with inhaled corticosteroids compared with corticosteroids alone, and included at least 1 catastrophic event, defined as asthma-related intubation or death.
In pooled trial data that included 36,588 participants, long-acting β-agonists increased catastrophic events 2-fold (Peto odds ratio [OR] 2.10; 95% confidence interval [CI], 1.37-3.22). Statistically significant increases were seen for long-acting β-agonists with variable corticosteroids compared with placebo (OR 1.83; 95% CI, 1.14-2.95) and for concomitant treatment with corticosteroids compared with corticosteroids alone (OR 3.65; 95% CI, 1.39-9.55). Similar increases in risk were seen for variable and concomitant corticosteroid use, salmeterol and formoterol, and children and adults. When the analysis was restricted to trials with controlled corticosteroid use, given as part of the study intervention, concomitant treatment still increased catastrophic events compared with corticosteroids alone (OR 8.19; 95% CI, 1.10-61.18).
Long-acting β-agonists increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant inhaled corticosteroids.
Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review
2009, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
Forty studies [3,18–51,104–108] were selected with a total of more than 40,000 asthmatics (Table 1). Nine studies included children and adolescents [19,31,38,42–44,49–51] and 31 adolescents and adults [3,18,20–30,32–37,39–41,45–48,104–108]. Twenty-eight studies were ≤12 weeks of duration, and twelve >12 weeks (range 4–56 weeks).
Safety of long-acting beta agonists (LABA) has been questioned and recent evidence suggested a detrimental effect on asthma control as well as an increased risk of death.
To evaluate the safety of regular use of LABA compared with placebo or LABA added to inhaled corticosteroids (ICS) compared with ICS in persistent asthma.
Randomized studies from MEDLINE, EMBASE, and Cochrane Controlled Trials Register were identified. Additionally, AstraZeneca, GlaxoSmithKline, Novartis and FDA clinical trials databases were searched. Primary outcomes were asthma exacerbations (AE) requiring systemic corticosteroids or hospitalization, life-threatening exacerbations and asthma-related deaths.
We identified 92 randomized clinical trials with 74,092 subjects. LABA (as monotherapy) reduced exacerbations requiring corticosteroids (Relative Risk [RR] = 0.80; 95% CI, 0.73–0.88), without detrimental effects on hospitalizations or life-threatening episodes. Contrarily, LABA showed a significant increase in asthma-related deaths (Relative Risk = 3.83; 95% CI, 1.21–12.14). Subgroup analysis suggests that children, patients receiving salmeterol, and a duration of treatment >12 weeks are associated with a higher risk of serious adverse effects; also there was a protective effect of concomitant use of ICS. On the other hand, combination of LABA/ICS reduced exacerbations (RR = 0.73; 95% CI, 0.67–0.79), and hospitalizations (RR = 0.58, 95% CI, 0.45–0.74). Combined therapy was also equivalent to ICS in terms of life-threatening episodes and asthma-related deaths. Again, children and use of salmeterol were associated with an increased risk of some severe outcomes as compared with adults and formoterol users, respectively.
This review reinforced the international recommendations in terms of the use of LABA remains the preferred add-on therapy to ICS for patients whose disease cannot adequately controlled with ICS, and that LABA cannot be prescribed as a monotherapy. Nevertheless, in spite of the protective effect of the ICS, children and salmeterol use still show an increased risk of non-fatal serious adverse events.
Exercise-induced asthma is associated with impaired quality of life amon children with asthma in Japan
2009, Allergology International
Asthma is the most common chronic diseases in school-aged children in Japan. It is important to consider health-related quality of life (QoL) among children with chronic diseases when treatment decisions are made.
A school-based survey was conducted in randomly selected public schools in Tokyo by using a KINDL® questionnaire for evaluating QoL and the international study of asthma and allergy on childhood (ISAAC) questionnaire, which is designed for comparing the asthma prevalence in various countries, from May to June in 2005. We recruited approximately 10% of the total children 6–7-years-old and 13–14-years-old living in Tokyo for sampling.
Response rate of this questionnaire was 86% (22,645 children) in the 6–7-year-old group and 64% (12,879 children) in the 13–14-year-old group. Comparing asthmatics with non-asthmatics in the same age, QoL of children with asthma was significantly impaired. The severity of QoL of children with asthma was significantly impaired. QoL of children with exercise-induced asthma (EIA) were more significantly impaired than ones without EIA and showed lower scores in the categories of physical functioning, emotional and school activities than those without EIA. Of note, QoL was more impaired in the EIA-positive group among severe asthmatics, suggesting that QoL of children with even severe asthma could be improved when EIA is appropriately controlled.
Existence of EIA among asthmatic children most strongly impairs their QoL. We should be more cautious about the management of EIA.

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^☆: From ^aAllergy & Asthma Medical Group and Research Center, APC, San Diego; ^bAllergy and Asthma Medical Group of Diablo Valley, Inc., Walnut Creek and Clinical Research Division, Danville; ^cAllergy Associates, Chico; ^dAllergy Research Foundation, Los Angeles; and ^eGlaxo Wellcome Inc., Research Triangle Park.

^☆☆: *Members of the Salmeterol Quality-of-Life Study Group are listed in the acknowledgments.

^★: Supported by a grant from Glaxo Wellcome, Inc.

^★★: Reprint requests: James P. Kemp, MD, Allergy & Asthma Medical Group and Research Center, APC, 9610 Granite Ridge Drive, Suite B, San Diego, CA 92123.

^♢: 1/1/86894

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Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids☆,☆☆,★,★★,♢

Abstract

Section snippets

Patients

RESULTS

DISCUSSION

Acknowledgements

Lancet

Respir Med

J Clin Epidemiol

Global initiative for asthma

Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma

JAMA

A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma

N Engl J Med

A twelve month comparison of salmeterol with salbutamol in asthmatic patients

Eur Respir J

A four-week comparison of salmeterol and terbutaline in asthmatic patients [abstract]

Eur Respir J

Salmeterol and sustained release theophylline: a comparison in asthmatic patients [abstract]

Allergy

Measuring quality of life in asthma

Am Rev Respir Dis

Comparison of performance of four instruments in evaluating the effects of salmeterol on asthma quality of life

Eur Respir J

Sensitivity of quality of life domains and constructs to longitudinal change in a clinical trial comparing salmeterol with placebo in asthmatics

Qual Life Res