Inhaled Glucocorticoids

Our understanding of the role and complexity of T cells in asthma exacerbations, the pathogenesis of asthma, and other airway and interstitial diseases, and factors inducing pathologic responses versus immune tolerance, continues to evolve. Castro and colleagues studied "asthma exacerbations," defined by falls in PEF (25%) and FEV₁ (15%) induced by withdrawal of inhaled corticosteroids. Thirteen of 25 asthmatics studied experienced an exacerbation defined by these criteria. Although both groups of subjects with asthma (exacerbating and nonexacerbating) experienced an increase in eosinophils present in bronchial biopsies, an increase in airway T cells (both CD4⁺ and CD8⁺) was observed only in subjects with asthma with an exacerbation defined by these physiologic criteria, accompanied by an increase in CCL5 in airway epithelium without activation of nuclear transcription factor NF- ${kappa}$ B. This pattern of immunologic responses was suggested to resemble that occurring after viral infection, rather than a classic Th2-driven eosinophilic response, and indicates a role for airway T cells in mediating asthma exacerbations.

One potential explanation for apparently refractory symptoms and airway dysfunction, particularly in clinical practice, is poor treatment adherence. Krishnan and colleagues evaluated this using a range of measures, including an electronic medication monitor, in 60 adults who had been discharged after an episode of acute severe asthma. Poor adherence (< 50% doses taken) was present in one half of the population studied when an assessment was made at 1 week. When present, it was associated with significantly worse symptom control. Perhaps the most important message of this study was that poor adherence was best detected using the electronic medication monitor; self-reported adherence, canister weight, and pill count all had a low sensitivity for detecting poor adherence.

A novel approach to management of patients with severe asthma and persistent eosinophilic airway inflammation is the use of the long-acting corticosteroid triamcinalone. ten Brink and colleagues showed that 2 weeks after an intramuscular injection of 120 mg of triamcinalone, all patients with refractory symptoms and eosinophilic airway inflammation, despite high-dose inhaled and sometimes oral corticosteroid, had an improvement in symptoms, improved FEV₁, and a reduction in the sputum eosinophil count. The study participants were apparently compliant with inhaled and oral treatment before entry into the study, suggesting that intramuscular triamcinolone might have additional properties. However, this management approach might be particularly useful in high-risk patients with poor treatment adherence and persistent eosinophilic airway inflammation.

The use of high-dose inhaled corticosteroids brings into focus the potential adverse effects of therapy and the importance of careful study of systemic toxicity. A good example of the latter is the thorough assessment of adrenal function and bone metabolism after escalating doses of fluticasone and mometasone described by Fardon and colleagues. This study showed approximately equivalent effects of fluticasone and mometasone on a microgram basis on overnight urinary cortisol–creatinine ratio and other markers. These findings are not consistent with the view that mometasone has negligible systemic bioavailability.

Citations 1-4 of 4 total displayed.

Corticosteroid Use after Hospital Discharge among High-risk Adults with Asthma

Jerry A. Krishnan, Kristin A. Riekert, Jonathan V. McCoy, Dana Y. Stewart, Spencer Schmidt, Arjun Chanmugam, Peter Hill, and Cynthia S. Rand
Am. J. Respir. Crit. Care Med. 170: 1281 -1285. First published online as doi:10.1164/rccm.200403-409OC [Abstract] [Full text]

Adrenal Suppression with Dry Powder Formulations of Fluticasone Propionate and Mometasone Furoate

Tom C. Fardon, Daniel K. C. Lee, Kay Haggart, Lesley C. McFarlane, and Brian J. Lipworth
Am. J. Respir. Crit. Care Med. 170: 960 -966. First published online as doi:10.1164/rccm.200404-500OC [Abstract] [Full text]

"Refractory" Eosinophilic Airway Inflammation in Severe Asthma: Effect of Parenteral Corticosteroids

Anneke ten Brinke, Aeilko H. Zwinderman, Peter J. Sterk, Klaus F. Rabe, and Elisabeth H. Bel
Am. J. Respir. Crit. Care Med. 170: 601 -605. First published online as doi:10.1164/rccm.200404-440OC [Abstract] [Full text]

Asthma Exacerbations after Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway

Mario Castro, Sharon R. Bloch, Michelle V. Jenkerson, Steve DeMartino, Daniel L. Hamilos, Rebecca B. Cochran, Xueping E. Liang Zhang, Haochuan Wang, Joseph P. Bradley, Kenneth B. Schechtman, and Michael J. Holtzman
Am. J. Respir. Crit. Care Med. 169: 842 -849. First published online as doi:10.1164/rccm.200208-960OC [Abstract] [Full text]

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