Combination Therapy with a Long-Acting β-Agonist and a Leukotriene Antagonist in Moderate Asthma

Deykin, Aaron; Wechsler, Michael E.; Boushey, Homer A.; Chinchilli, Vernon M.; Kunselman, Susan J.; Craig, Timothy J.; DiMango, Emily; Fahy, John V.; Kraft, Monica; Leone, Frank T.; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Pesola, Gene R.; Peters, Stephen P.; Sorkness, Christine A.; Szefler, Stanley J.; Israel, Elliot

doi:10.1164/rccm.200601-112oc

Cited by 71 publications

(35 citation statements)

References 22 publications

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“…Leukotriene modifiers used as add-on therapy may reduce the dose of inhaled glucocorticosteroids required by patients with moderate to severe asthma [82], and may improve asthma control in patients whose asthma is not controlled with low or high doses of inhaled glucocorticosteroids [81,[83][84][85]. With the exception of one study that has demonstrated equivalence in preventing exacerbations [86], several studies have demonstrated that leukotriene modifiers are less effective than long-acting inhaled b 2 -agonists as addon therapy [87][88][89][90].…”

Section: Leukotriene Modifiersmentioning

confidence: 99%

Global strategy for asthma management and prevention: GINA executive summary

Bateman

Ss²,

Barnes³

et al. 2008

European Respiratory Journal

2,641

2,301

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Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled ''A Global Strategy for Asthma Management and Prevention'', first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that ''it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained,'' and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.

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Section: Leukotriene Modifiersmentioning

confidence: 99%

Global strategy for asthma management and prevention: GINA executive summary

Bateman

Ss²,

Barnes³

et al. 2008

European Respiratory Journal

2,641

2,301

View full text Add to dashboard Cite

show abstract

“…Data were derived from 995 subjects with asthma enrolled in nine clinical trials conducted by the ACRN that included at least one sputum induction as part of the study protocol (aggregated NCT00000577) (see Table E1 in the online supplement) (8,9,(16)(17)(18)(19)(20)(21). All subjects were between the ages of 12 and 70 years, met the criteria for persistent asthma as defined by the National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma (22), and were current nonsmokers with a lifetime history of smoking no greater than 10 pack-years.…”

Section: Methods Subjectsmentioning

confidence: 99%

A Large Subgroup of Mild-to-Moderate Asthma Is Persistently Noneosinophilic

McGrath

Icitovic

Boushey

et al. 2012

Am J Respir Crit Care Med

Self Cite

440

313

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Rationale: Airway eosinophilia is typical of asthma, and many controller treatments target eosinophilic disease. Asthma is clinically heterogeneous, however, and a subgroup of people with asthma do not have airway eosinophilia. The size of this subgroup is uncertain because prior studies have not examined repeated measures of sputum cytology to determine when people with asthma have intermittent versus persistent sputum eosinophila and when they are persistently noneosinophilic. Objectives: To determine the prevalence and clinical characteristics of the noneosinophilic asthma phenotype. Methods: We analyzed sputum cytology data from 995 subjects with asthma enrolled in clinical trials in the Asthma Clinical Research Network where they had undergone sputum induction and measures of sputum cytology, often repeatedly, and assessment of responses to standardized asthma treatments. Measurements and Main Results: In cross-sectional analyses, sputum eosinophilia (>2% eosinophils) was found in only 36% of subjects with asthma not taking an inhaled corticosteroid (ICS) and 17% of ICS-treated subjects with asthma; an absence of eosinophilia was noted frequently, even in subjects with asthma whose disease was suboptimally controlled. In repeated measures analyses of people with asthma not taking an ICS, 22% of subjects had sputum eosinophilia on every occasion (persistent eosinophilia); 31% had eosinophilia on at least one occasion (intermittent eosinophilia); and 47% had no eosinophilia on every occasion (persistently noneosinophilic). Two weeks of combined antiinflammatory therapy caused significant improvements in airflow obstruction in eosinophilic asthma, but not in persistently noneosinophilic asthma. In contrast, bronchodilator responses to albuterol were similar in eosinophilic and noneosinophilic asthma. Conclusions: Approximately half of patients with mild-to-moderate asthma have persistently noneosinophilic disease, a disease phenotype that responds poorly to currently available antiinflammatory therapy.Keywords: asthma; eosinophil; noneosinophilic; obesity; neutrophil Asthma is a common disease affecting people across the lifespan; the cost to US society is $56 billion annually (1). Airway eosinophilia is well-described in asthma (2-4), and currently available antiinflammatory treatments for asthma almost exclusively target eosinophilic airway inflammation (5, 6). Many people with asthma respond suboptimally to currently available eosinophil-directed treatments, however, most likely because they do not have airway eosinophilia (7-13).Increased attention is focusing on the clinical heterogeneity of asthma and the argument that failure to recognize and discover the underlying mechanisms of different asthma subtypes is a major limitation to progress (14). Continued uncertainly about the prevalence of eosinophilic versus noneosinophilic subtypes of asthma and about the relationship between airway eosinophilia and treatment responses relates to limitations in previous studies of these issues. The principal limitatio...

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“…A number of studies have reported that LTRAs used as add-on therapy decrease the need for ␤ 2 -agonists (Nathan et al, 1998;Noonan et al, 1998;Jarvis and Markham, 2000;Virchow et al, 2000;Keam et al, 2003;Vaquerizo et al, 2003;Deykin et al, 2007;Borderias et al, 2007) and that a positive association exists between a CysLTR antagonist and a ␤ 2 -agonist in controlling asthma symptoms, particularly in patients homozygous for the glycine-16 ␤ 2 AR polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the ␤ 2 AR (Lipworth et al, 2000). The response to ␤ 2 -agonist agonists is reduced in asthmatic airways, and this desensitization has been postulated to be due in part to inflammatory mediators such as cysteinyl LTs (Song et al, 1998;Milanese et al, 2005).…”

Section: Desensitization and Cross-talk Of Cyslt Receptorsmentioning

confidence: 99%