Allergologia et Immunopathologia

Allergologia et Immunopathologia

Volume 40, Issue 2, March–April 2012, Pages 100-103
Allergologia et Immunopathologia

Original article
Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma

https://doi.org/10.1016/j.aller.2011.11.001Get rights and content

Abstract

Background

Cell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity.

Study objectives

To evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids.

Methods

Eighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens.

Results

There was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group.

Conclusion

Patients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study.

Introduction

Asthma is a variable and chronic inflammatory disease of the airways. The inflammatory disorder underlying asthma arises from the interaction of various cells including eosinophils, mast cells and T lymphocytes.1 Thus, anti-inflammatory therapy, in the form of inhaled corticosteroids, is key in the management of persistent asthma.2 As the prevalence of asthma has been increasing, so has the use of inhaled corticosteroids, and at higher doses than previously prescribed early in its introduction.

Recent studies have shown that inhaled corticosteroids have systemic effects on bone metabolism,3, 4, 5, 6, 7, 8 hypothalamus–pituitary adrenal axis,9, 10, 11, 12, 13, 14, 15 on linear growth,16, 17, 18 and cataracts.19, 20, 21 Oral corticosteroids have an even more potent effect on these parameters, and additionally have been shown to suppress cell mediated immunity, increasing an individual's susceptibility of acquiring an opportunistic infection.22, 23, 24, 25, 26, 27, 28, 29, 30, 31

It is unclear at this time whether high dose inhaled corticosteroids also suppress cell mediated immunity. Studies addressing this issue have been conflicting thus far.32, 33, 34 Currently there are no data to suggest increased incidence or course of fungal, viral or bacterial infections with the use of inhaled corticosteroids. However, there are rare cases that have been reported of reactivation of tuberculosis or viral infections associated with the use of inhaled corticosteroids.35, 36, 37 The US Food and Drug Administration has instructed the manufacturers of oral, injectable and inhaled corticosteroids to include the warning about the possible risk of tuberculosis and viral infections with the use of these agents.38 However, the American Academy of Allergy and Immunology issued a position statement, stating that this warning is unwarranted.39

The objective of our current study was to evaluate if there is a correlation between high dose inhaled corticosteroids and suppression of cell mediated immunity in asthmatics. This was accomplished by determining if there was a statistically significant higher incidence of impaired cellular immunity (as reflected in anergy or lower cumulative skin test scores to DTH testing) in patients with asthma who have already been receiving high dose inhaled fluticasone for >6 months compared to an age-matched control asthma population not on high dose inhaled corticosteroids.

Section snippets

Study design

Eighteen volunteers with asthma between the ages of 42 and 67 were recruited for this cross-sectional study. Informed consent was obtained from each subject prior to entry into the study and the protocol was approved by the local Institutional Review Board (IRB B, VA Promise No. 0035). Exclusion criteria included subjects who have received systemic corticosteroids or immunosupressants in the past 6 months, patients with chronic diseases that may influence cell mediated immunity (autoimmune

Statistical analysis

The non-parametric Wilcoxon rank sum test and the parametric t test were both used to compute p values for comparing means between the inhaled corticosteroid group (group A) and the albuterol only (group B) in total skin test score for candida and tetanus individually, total skin test score for candida plus tetanus, as well as difference in incidence of anergy. A statistically significant result was defined as p < 0.05. Means ± SEM are reported.

Results

Eighteen volunteer subjects completed this study. Subjects ranged in age from 42 to 67 years (mean, 57.11 ± 6.6). One subject in the study was lost to follow up. There were no significant adverse events experienced in the 18 subjects who completed the study. The most common complaint was mild pruritis at the site of skin testing.

Table 1, Table 2 depict the sum of mean orthogonal diameters for candida and tetanus skin test score individually as well as for the candida plus tetanus total skin test

Discussion

Inhaled corticosteroids have been demonstrated to have adverse effects on bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and cataracts, like systemic corticosteroids, but to a lesser degree. However, studies evaluating whether inhaled corticosteroids impair cell mediated immunity have been conflicting and inconclusive thus far. An early study by Levy et al. found no suppression of cell mediated immunity in children with asthma treated with lower dose inhaled

Funding

Research conducted at VA Greater Los Angeles Healthcare System; Los Angeles, CA. Research non-funded and approved by local IRB Board.

Conflicts of interest

Dr. Lee and Dr. Klaustermeyer have no conflicts of interest to disclose.

Acknowledgement

The authors would like to thank Jeffrey Gornbein, DrPH, SBCC for statistical computation support.

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