Asthma, Rhinitis, Other Respiratory Diseases
Effect of HFA-flunisolide on peripheral lung inflammation in asthma,☆☆

https://doi.org/10.1067/mai.2003.1612Get rights and content

Abstract

Background: New hydrofluoroalkane (HFA) formulations of glucocorticoids have been shown to effectively control asthma. HFA glucocorticoids are deposited across all sizes of airways, including the small ones. However, it is not clear whether they can suppress peripheral airway inflammation. Objective: We sought to determine whether HFA-flunisolide could suppress peripheral inflammation in asthma. Methods: Twelve patients with mild to moderate asthma received HFA-flunisolide for 6 weeks. Transbronchial and endobronchial biopsy specimens were obtained before and after treatment, and spirometry was performed. Changes in inflammatory cells (eosinophils, neutrophils, lymphocytes, macrophages, basophils) and IL-5 and eotaxin were measured by using immunocytochemistry and in situ hybridization. Results: Lung function significantly improved after treatment (P < .05). HFA-flunisolide significantly reduced eosinophils, IL-5, and eotaxin in both peripheral and central airways (P < .01). Neutrophils significantly increased after treatment in peripheral and central airways (P < .05). The numbers of lymphocytes remained unchanged. Conclusions: These results show that HFA-flunisolide effectively suppressed eosinophilic inflammation in peripheral and central airways. These changes were accompanied by improvement in lung function. (J Allergy Clin Immunol 2003;112:58-63.)

Section snippets

Study design

This was a single-center, open-label study in adult asthmatic patients to evaluate the effect of a small-particle, inhaled steroid (flunisolide HFA) on peripheral lung inflammation. The study was carried out in full compliance with FDA Guidelines for Good Clinical Practices and was approved by the institutional review board. Patients who met the inclusion and exclusion criteria underwent a baseline bronchoscopy when transbronchial and endobronchial lung biopsy specimens were obtained. Patients

Patient demographics

Twelve asthmatic patients were included in the study. Half of the patients were men; 11 of the patients were white. The mean age was 33 years (range, 22 to 41 years). The male patients had a mean weight of 98.9 kg and a mean height of 180 cm. The female patients had a mean weight of 66.3 kg and a mean height of 164 cm. All 12 patients completed the study, and no serious adverse events were reported.

Effect of HFA-flunisolide on parameters of lung function

At baseline, the mean FEV1 (3.02 L) was 78.7% of the predicted value, the mean FVC (4.4 L) was

Discussion

New HFA formulations of inhaled corticosteroids have been proven to be effective in treating asthma.22, 23 These formulations have a smaller particle size than the older CFC formulations and are capable of reaching the peripheral zones of the lung.18, 19, 20 Although all structures in the bronchi are involved in the inflammatory process underlying asthma, the small airways, defined as those <2 mm in diameter, have been understudied because of the difficulty in obtaining biopsy specimens from

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    Supported by Forest Laboratories, New York. Hans-Peter Hauber is a recipient of a GSK/CLA/CIHR scholarship.

    ☆☆

    Reprint requests: Qutayba Hamid, MD, PhD, Meakins-Christie Laboratories, 3626 St Urbain St, Montreal, Quebec H2X 2P2, Canada.

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