US hospital database analysis of invasive aspergillosis in the chronic obstructive pulmonary disease non-traditional host

Abstract

Objectives:

Invasive aspergillosis (IA) is reported increasingly in non-traditional hosts, typically patients with chronic obstructive pulmonary disease (COPD). Objectives were to describe the excess burden of IA in COPD, including mortality, resource utilization, and costs, as well as to examine the impact of initial antifungal selection on clinical and economic outcomes.

Methods:

This retrospective cohort study used national data from 2005 to 2008, from the Premier Perspective hospital database. IA was identified using proxy ICD-9 codes based on published algorithms. The COPD + IA patient cohort was analyzed using descriptive statistics. Excess resource utilization was analyzed by matching cases (COPD + IA) and controls (COPD patients without aspergillosis) on demographic and clinical variables. Multivariate analyses were used to assess the impact of initial antifungal drug selection on outcomes in COPD + IA.

Results:

In total, 475 COPD + IA patients were identified (mean age 69 years, 50% male, 76% Caucasian). COPD + IA cases had significantly higher costs, length of stay, intensive care unit (ICU) stay, and mortality compared to COPD controls (all p < 0.01). On average, antifungal therapy was initiated on hospital day 6, with mean length of therapy 15 days, and one-third of patients were in the ICU when antifungal treatment was initiated. Most commonly used antifungals were voriconazole, fluconazole, and caspofungin. Patients receiving fluconazole as the initial antifungal, an agent inactive against moulds, had almost two times greater mortality (p = 0.016), two additional hospital days (p = 0.002), and 25% greater costs (p = 0.007), compared to patients receiving voriconazole first-line. Findings were consistent in sub-analyses including ICU patients.

Limitations:

‘Invasive’ form of aspergillosis was identified using proxy ICD-9 codes based on published literature. Additional limitations stem from the study's non-randomized, retrospective design that is typical with any database analyses.

Conclusions:

COPD + IA patients had significantly higher mortality, resource utilization, and costs versus COPD controls. Treatment with an agent active against Aspergillus was associated with better survival and reduced economic burden, therefore this potential etiology of pneumonia should be considered when contemplating antifungal therapy in COPD patients.

Key words::

• Antifungals
• Chronic obstructive pulmonary disease
• Hospital database analysis
• Invasive aspergillosis
• Non-traditional host
• Outcomes
• Resource utilization

MeSH terms::

• Antifungal agents
• Chronic obstructive
• Invasive pulmonary aspergillosis
• Mycoses
• Pulmonary disease
• Voriconazole

Transparency

Declaration of funding

This research and preparation of this manuscript were funded by Pfizer Inc.

Declaration of financial/other relationships

D.P., X.G., and J.S. were employees of Pharmerit North America, who were paid consultants to Pfizer in connection with this research and the development of this manuscript. M.T. and M.F. were employed by Pfizer Inc, the manufacturer of antifungal agents.

The work was performed at Pharmerit North America LLC, Bethesda, MD, USA, and was sponsored by Pfizer Inc.

Acknowledgments

All authors contributed to project design and methodology, review and interpretation of results, manuscript writing and revisions, and approved the final manuscript. D.A. Patel and X. Gao conducted the programming and statistical analysis.

Editorial assistance was provided by Dean Clarke and Cath Bryant at Complete Medical Communications, and was funded by Pfizer Inc.