Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD

Abstract

Background

Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old) outpatients with acute Anthonisen type 1 exacerbations.

Trial registration

NCT0656747.

Methods

Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease) trial (MAESTRAL) database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT) and 8 weeks posttherapy.

Results

The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation, mild or moderate (vs extreme) sleep disturbances, lower body temperature at exacerbation, forced expiratory volume in 1 second <30%, lower body mass index, concomitant systemic corticosteroids for the current exacerbation, maintenance long-acting β₂-agonist and long-acting anticholinergic treatments, and positive sputum culture at EOT.

Conclusion

Several bacteriological, historical, treatment-related factors were identified as predictors of early (EOT) and later (8 weeks posttherapy) clinical failure in this older outpatient population with moderate-to-severe chronic obstructive pulmonary disease. These patients should be closely monitored and sputum cultures considered before and after treatment.

Keywords:

• AECOPD
• clinical failure
• prognostic factor
• long-term outcome
• poor outcome

Acknowledgments

This study was supported by Bayer HealthCare, Germany. Editorial assistance was provided by Highfield Communication, Oxford, UK, sponsored by Bayer HealthCare. The authors thank Mr Feng Zhan, inVentive Health, US, for his invaluable support in the bootstrapping and logistic regression analyses.

Author contributions

Robert Wilson, Antonio Anzueto, Marc Miravitlles, Pierre Arvis, and Sanjay Sethi contributed to the study design, data analysis and interpretation, and review and approval of the manuscript preparation. Robert Wilson is the guarantor of this publication. Daniel Haverstock and Mila Trajanovic contributed to statistical analysis and interpretation, and data analysis and interpretation, respectively, and contributed to review and approval of the manuscript preparation. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

Sanjay Sethi has received lecture, consulting fees, and research funds from Bayer, GlaxoSmithKline, Merck, and Sharp & Dohme. Antonio Anzueto has participated as a speaker in scientific meetings or courses organized and financed by various pharmaceutical companies including AstraZeneca, Boehringer Ingelheim, Bayer, Pfizer, GlaxoSmithKline, and Novartis. Antonio Anzueto has been a consultant for AstraZeneca, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Novartis, and Bayer. He has also been the principal investigator for research grants for the University of Texas Health Science Center (San Antonio, TX, USA) that received payment for participating in a multicenter clinical trial sponsored by: GlaxoSmithKline, Bayer, Eli Lilly, and National Institutes of Health. Marc Miravitlles has received speaker fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Bayer Schering, Novartis, Talecris-Grifols, Takeda-Nycomed, Merck, Sharp & Dohme, and Novartis, and consulting fees from Boehringer Ingelheim, Pfizer, GlaxoSmithKline, AstraZeneca, Bayer Schering, Novartis, Almirall, Merck, Sharp & Dohme, Talecris-Grifols, and Takeda-Nycomed. Robert Wilson has received honoraria for taking part in advisory boards and presenting at meetings from Almirall, Aperion Advisors LLC, AstraZeneca, Athena Medical PR, Bayer HealthCare, Forest Laboratories (Bronchiectasis symposium), Genactis Ltd, Opticom International, Penn Technology Partnership, Resolutions Group, Rivervest, Transave, VacZine Analytics, and Wyeth Pharmaceuticals. Pierre Arvis is a full-time employee of Bayer HealthCare. Daniel Haverstock is a full-time employee of Bayer HealthCare Pharmaceuticals. Mila Trajanovic is a full-time employee of Bayer Inc. and holds stocks of the company. The authors report no other conflicts of interest in this work.