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Rod Fontenette CAT September 2009 Antiinflammatory Effects of Long-Acting B²-Agonists in Patients With Asthma. Chest. Anees Sindi, MBChB; David C. Todd, MD; and Parameswaran Nair, MD, PhD, FCCP. Chest. 2009 Jul;136(1):145-54 Background: Long-acting B²-agonists (LABAs) are recommended as add-on therapy to anti-inflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo anti-inflammatory effect of LABA are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo anti-inflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive anti- inflammatory effect. Methods: A systematic search was performed of online databases for randomized controlled trials evaluating the anti-inflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). The inclusion criteria included: (1) RCT design; (2) performed in adults or children with an established diagnosis of asthma; (3) comparing either salmeterol or formoterol with placebo or the combination of an ECS and a LABA; and (4) the primary outcome included a change in an inflammatory marker. Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. Results: The search strategy yielded 1,757 citations from the various electronic databases. In total, 1,641 citations were excluded after review of the title and abstract. Of the 116 potentially relevant articles, 32 studies with 1,105 participants satisfied the inclusion criteria. 729 participants were from studies that evaluated the anti- inflammatory effect of LABAs vs placebo. 376 participants were from studies that evaluated the synergistic effect of LABAs and ICSs vs ICSs alone. From this metaanalysis, it appears that LABA therapy does not appear to have any clinically important anti-inflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage. Discussion: In the Emergency Department (ED), patients with the chief complaint of shortness of breath or difficulty breathing with asthma in their past medical history is a common occurrence. Two to three percent of all Emergency Department patients have a chief complaint of respiratory distress in varying degree and asthma comprises a substantial portion of these patients. There are several factors that contribute to the exacerbation of their asthma symptoms. These factors range from poor compliance with medications to poor control of the underlying disease. Many times, patients present stating that they have tried their home Albuterol MDI and/or nebulizer and the symptoms have either persisted or gotten worse. This article sheds light on an important clinical question; “Should we in the ED start patients with acute asthma exacerbation on a long-acting B²-agonist to decrease the duration of symptoms and risk of recurrence?” This is an important question as many of our patients do not follow-up as recommended. Asthma affects approximately four to five percent of the U.S. population. It is the most common chronic disease of childhood affecting five to ten percent of children, and it is estimated to affect seven to ten percent of the elderly. The cost of asthma management in the United States rose from 6.2 billion dollars in 1990 to approximately 13.8 billion dollars in 2000. If patients with severe asthma could be started on a LABA in conjunction with their ICS, this would decrease patient’s visits to the ED and have a direct impact on the financial strain it places on healthcare. This makes since in theory; however, this study proves that there are no additive benefits of patients taking these medications in combination. I feel if patients are educated on the importance of taking their medications as prescribed and following-up with the physician managing their asthma this will decrease patient visits to the ED. I also feel the majority of patients we see in the ED with acute exacerbations have mild to moderate asthma and respond well to nebulizer therapy along with oral or IV corticosteroids, and are comfortable being discharged with prescriptions for an Albuterol MDI and a short course of oral steroids. With this metaanalysis proving that there are no additional benefits to adding LABAs to patients regimen, doing so will only increase out-of-pocket expenses for the patient and make it less likely they will be compliant with medications. This will also increase the likelihood of the patient returning to the ED for another acute exacerbation. Limitations: There was substantial heterogeneity among the studies in terms of duration and method for reporting data. Treatment duration varied among the studies from 1 to 52 weeks. It is plausible that shorter studies may show les of an anti- inflammatory effect, but this hypothesis could not be tested because there were too few studies to perform subgroup analysis according to study duration. The second limitation is that patients with airway inflammation induced by an allergen were excluded because this was not the focus of this study. MH- Administration, Inhalation MH- Adrenergic beta-Agonists/administration & dosage/*therapeutic use MH- Adult MH- Asthma/*drug therapy/metabolism/*pathology MH- Child MH- Drug Therapy, Combination MH- Glucocorticoids/administration & dosage MH- Humans MH- Inflammation/drug therapy/metabolism/pathology MH- Inflammation Mediators/metabolism MH- Receptors, Adrenergic, beta-2/*agonists
"Rod Fontenette CAT September Antiinflammatory Effects of Long"