Chest
Volume 124, Issue 1, July 2003, Pages 57-62
Journal home page for Chest

Clinical Investigations
Asthma
Lack of Long-term Adverse Adrenal Effects From Inhaled Triamcinolone: Lung Health Study II

https://doi.org/10.1378/chest.124.1.57Get rights and content

Study objectives

Inhaled corticosteroids (ICS) are widely used in the treatment of COPD. One of the potential adverse effects of their use is the development of adrenal suppression. Our study aimed to determine the effects of ICS on adrenal function over 3 years of use in patients with COPD.

Methods

Two hundred twenty-one subjects were recruited from the 1,116 patients already enrolled in Lung Health Study II and were randomized to receive either triamcinolone, 1,200 μg, or placebo daily. Basal cortisol levels and cortisol levels at 30 min and 60 min following cosyntropin injection were measured at study entry and after 1 year and 3 years of participation.

Results

Basal cortisol levels in the placebo group were higher than in those receiving active drug at all time points and rose through the study period. There was no suppression of cortisol levels after cosyntropin stimulation at any study point in any subgroup.

Conclusion

Use of inhaled triamcinolone, 1,200 μg/d, over 3 years does not suppress baseline adrenal function or diminish adrenal responsiveness to cosyntropin stimulation.

Section snippets

Materials and Methods

In LHS II, 1,116 participants at 10 clinical centers in North America were recruited. Individuals participating (n = 1,018) and screened (n = 98) in the first LHS10 and who were smoking or had recently quit (less than 2 years) comprised the study group. Other inclusion criteria included age between 40 years and 69 years and the presence of obstruction as defined by an FEV1/FVC ratio < 0.70 and an FEV1 between 30% and 90% of predicted. Candidates were excluded if they had used an inhaled or oral

Results

Two hundred twenty-one participants entered the ancillary study of adrenal function, with 106 assigned to the active drug, and 115 assigned to placebo. Both treatment groups were similar with regard to age, gender, race, and baseline pulmonary function. Of the enrolled participants who had baseline measurements of adrenal function prior to initiation of treatment with ICS, 89% underwent repeat testing at year 1 and 85% at year 3 (Table 1). Baseline characteristics of both the enrolled

Discussion

Systemic side effects have been variably reported from the use of inhaled corticosteroids in asthma and COPD. Differences in doses employed, potency, and effectiveness of respiratory delivery between the various formulations of inhaled corticosteroids and in duration of use have contributed to this variability in reported systemic toxicity. LHS II provided an opportunity to study the systemic effects of a moderate dose of inhaled triamcinolone in patients with COPD in whom adherence to a

Appendix

The principal investigators and senior staff of the clinical and coordinating centers, the National Heart, Lung, and Blood Institute, and members of the Safety and Data Monitoring Board are as follows: Case Western Reserve University, Cleveland, OH (M.D. Altose, MD, Principal Investigator; S. Redline, MD, Co-Principal Investigator; C.D. Deitz, PhD; K.J. Quinlan); Henry Ford Hospital, Detroit, MI (M.S. Eichenhorn, MD, Principal Investigator; W.A. Conway, Jr., MD, Co-Principal Investigator; R.L.

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    Citation Excerpt :

    No differences in the proportion of noncompliant participants reporting slow healing were noted between treatment groups in either age category. In an ancillary study19 to LHS II involving a subset of 221 participants in 5 of the 10 centers, the HPA axis was evaluated at baseline, year 1, and year 3. The development of significantly impaired adrenal function was rare (1.8%),19 and no consistent or meaningful differences were noted between the presence or absence of bruising vs change in basal or stimulated morning serum cortisol level, irrespective of whether analyses were performed in all participants or were restricted to only the good compliers.

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Supported under a cooperative agreement with the National Institutes of Health (NHLBI-5U01-HL50267-05). Triamcinolone and placebo, as well as support for the ancillary safety studies on bone density and adrenal function, were provided by Rhône-Poulenc Rorer (now Aventis).

Dr. Wise consulted for Aventis regarding new drug development in September and October of 2000 and received $2,000 compensation.

Dr. Scanlon is currently providing research support for institutional review board-approved protocols (some investigator initiated, some company initiated) from various companies, including Aventis.

Dr. Bailey is participating in an Aventis drug study in progress, a phase III double-blind, parallel-group, multicenter, placebo-controlled study to determine the effectiveness of ciclesonide to reduce oral corticosteroid use in patients with severe persistent asthma.

A complete list of LHS participants is given in the Appendix

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