Rod Fontenette CAT September Antiinflammatory Effects of Long

							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