Q:

5/23/2013
A patient of ours was seen by his Pediatrician who had prescribed two different inhaled steroids to be taken together. He was switched from Symbicort 80mcg to a combination of Flovent 44mcg 2 puffs twice a day and Qvar 40 mcg 2 puffs twice a day. Is there any literature that documents the benefits of this Asthma regime? Thank you for your time.

A:

Thank you for your inquiry.

The rationale behind the combined use of fluticasone CFC and beclomethasone HFA is based upon the fact that small airways inflammation in asthma is related to poor outcomes. A large portion of our lung consists of airways less than 2 micron in diameter, and many inhaled corticosteroids (including fluticasone HFA), because of their particle size (greater than 2 micron), do not reach the small airways. On the other hand, beclomethasone HFA has a particle size which is smaller and allows it to penetrate the small airways.

However, in most instances, as you can see by the abstract copied below, the addition of beclomethasone HFA is usually to assist in the management of a patient who is not controlled on a combination drug consisting of a long-acting bronchodilator and inhaled corticosteroid. This is because no such combination drug has a corticosteroid that is capable of penetrating to the small airways. Thus, the addition of beclomethasone HFA would allow for coverage of the small airways in addition to the large airways (which is being treated by the steroid in the combination product). It is unusual to stop a combination drug, start a large particle corticosteroid inhaler, and add a small particle steroid inhaler at the same time.

However, as noted above, because of the additional coverage, there is scientific rationale behind using a combination of a large particle inhaled corticosteroid and a small particle inhaled corticosteroid when asthma is not controlled by the use of one or the other of these two agents.

In addition to the research article abstract copied below, there is a nice recent review of this issue in the Journal of Allergy and Clinical Immunology. An abstract of this review is also copied for you below.

Thank you again for your inquiry and we hope this response is helpful to you.

J Asthma. 2005 May;42(4):257-63.
Hydrofluoroalkane-134A beclomethasone or chlorofluorocarbon fluticasone: effect on small airways in poorly controlled asthma.
Thongngarm T, Silkoff PE, Kossack WS, Nelson HS.
Source
Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, 1400 Jackson St., Denver, CO 80206, USA.
Abstract
Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

J Allergy Clin Immunol. 2013 Mar;131(3):646-57. doi: 10.1016/j.jaci.2012.12.1567. Epub 2013 Feb 4.
Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review.
van der Wiel E, ten Hacken NH, Postma DS, van den Berge M.
Source
Department of Pulmonary Medicine and Tuberculosis and the GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology