The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV                         1                         /FVC Ratio in tiotropium safety and performance in respimat participants

Peter M.A. Calverley; Achim Mueller; Andrew Fowler; Norbert Metzdorf; Robert A. Wise

doi:10.1513/AnnalsATS.201703-194OC

The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants

Peter M.A. Calverley, Achim Mueller, Andrew Fowler, Norbert Metzdorf, Robert A. Wise

School of Medicine

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Rationale: There is continuing debate about whether to define airflow obstruction by a post-bronchodilator ratio of forced expiratory volume in 1 second (FEV ₁ ) and forced vital capacity (FVC) below 0.70, or by ratio values falling below the age-dependent lower limit of normal (LLN) derived from general population data. Objectives: To determine whether using the LLN criterion affects the classification and outcomes of patients previously defined as having chronic obstructive pulmonary disease by the fixed FEV ₁ /FVC ratio. Methods: We applied the LLN definition to pooled data from the Tiotropium Safety and Performance in Respimat study that used the fixed FEV ₁ /FVC ratio for the clinical diagnosis of chronic obstructive pulmonary disease. Results: A total of 17,072 patients were analyzed; of these, 1,807 (10.6%) patients had a ratio greater than or equal to LLN. Patients with a ratio greater than or equal to LLN had similar risks of death from any cause and fatal major adverse cardiovascular (CV) event as those below LLN. Patients with a ratio below LLN had a significantly lower risk of major adverse CV events (hazard ratio = 0.69; 95% confidence interval [CI] = 0.55-0.86; P = 0.001), and had significantly greater risks of moderate to severe exacerbation (rate ratio = 1.48; 95% CI = 1.36-1.61; P < 0.0001) and severe exacerbation (rate ratio = 2.01; 95% CI = 1.68-2.40; P < 0.0001) when compared with patients greater than or equal to LLN. Study outcomes by treatment arm (5 μg tiotropium Respimat vs. 18 μgHandiHaler) were comparable. Conclusions: Using the LLN to define airflow obstruction would have excluded patients in the Tiotropium Safety and Performance in Respimat study with a higher risk of nonfatal major adverse CV events and a lower risk of exacerbation; study outcomes by treatment arm (2.5 μg/5 μg tiotropium Respimat vs. 18 μg HandiHaler) remained similar.

Original language	English (US)
Pages (from-to)	200-208
Number of pages	9
Journal	Annals of the American Thoracic Society
Volume	15
Issue number	2
DOIs	https://doi.org/10.1513/AnnalsATS.201703-194OC
State	Published - Feb 2018

Keywords

Airflow obstruction
Disease exacerbation
Mortality
Tiotropium

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

Access to Document

10.1513/AnnalsATS.201703-194OC

Cite this

Calverley, P. M. A., Mueller, A., Fowler, A., Metzdorf, N., & Wise, R. A. (2018). The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants Annals of the American Thoracic Society, 15(2), 200-208. https://doi.org/10.1513/AnnalsATS.201703-194OC

The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants . / Calverley, Peter M.A.; Mueller, Achim; Fowler, Andrew et al.
In: Annals of the American Thoracic Society, Vol. 15, No. 2, 02.2018, p. 200-208.

Research output: Contribution to journal › Article › peer-review

Calverley, PMA, Mueller, A, Fowler, A, Metzdorf, N & Wise, RA 2018, ' The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants ', Annals of the American Thoracic Society, vol. 15, no. 2, pp. 200-208. https://doi.org/10.1513/AnnalsATS.201703-194OC

Calverley PMA, Mueller A, Fowler A, Metzdorf N, Wise RA. The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants Annals of the American Thoracic Society. 2018 Feb;15(2):200-208. doi: 10.1513/AnnalsATS.201703-194OC

Calverley, Peter M.A. ; Mueller, Achim ; Fowler, Andrew et al. / The effect of defining chronic obstructive pulmonary disease by the lower limit of normal of FEV ₁ /FVC Ratio in tiotropium safety and performance in respimat participants In: Annals of the American Thoracic Society. 2018 ; Vol. 15, No. 2. pp. 200-208.

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abstract = " Rationale: There is continuing debate about whether to define airflow obstruction by a post-bronchodilator ratio of forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) below 0.70, or by ratio values falling below the age-dependent lower limit of normal (LLN) derived from general population data. Objectives: To determine whether using the LLN criterion affects the classification and outcomes of patients previously defined as having chronic obstructive pulmonary disease by the fixed FEV 1 /FVC ratio. Methods: We applied the LLN definition to pooled data from the Tiotropium Safety and Performance in Respimat study that used the fixed FEV 1 /FVC ratio for the clinical diagnosis of chronic obstructive pulmonary disease. Results: A total of 17,072 patients were analyzed; of these, 1,807 (10.6%) patients had a ratio greater than or equal to LLN. Patients with a ratio greater than or equal to LLN had similar risks of death from any cause and fatal major adverse cardiovascular (CV) event as those below LLN. Patients with a ratio below LLN had a significantly lower risk of major adverse CV events (hazard ratio = 0.69; 95% confidence interval [CI] = 0.55-0.86; P = 0.001), and had significantly greater risks of moderate to severe exacerbation (rate ratio = 1.48; 95% CI = 1.36-1.61; P < 0.0001) and severe exacerbation (rate ratio = 2.01; 95% CI = 1.68-2.40; P < 0.0001) when compared with patients greater than or equal to LLN. Study outcomes by treatment arm (5 μg tiotropium Respimat vs. 18 μgHandiHaler) were comparable. Conclusions: Using the LLN to define airflow obstruction would have excluded patients in the Tiotropium Safety and Performance in Respimat study with a higher risk of nonfatal major adverse CV events and a lower risk of exacerbation; study outcomes by treatment arm (2.5 μg/5 μg tiotropium Respimat vs. 18 μg HandiHaler) remained similar.",

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