Chest
Volume 146, Issue 2, August 2014, Pages 328-338
Journal home page for Chest

Original Research
COPD
Exertional Hypoxemia in Stable COPD Is Common and Predicted by Circulating Proadrenomedullin

https://doi.org/10.1378/chest.13-1967Get rights and content

BACKGROUND

The prevalence of exertional hypoxemia in unselected patients with COPD is unknown. Intermittent hypoxia leads to adrenomedullin (ADM) upregulation through the hypoxia-inducible factor-1 pathway. We aimed to assess the prevalence and the annual probability to develop exertional hypoxemia in stable COPD. We also hypothesized that increased ADM might be associated with exertional hypoxemia and envisioned that adding ADM to clinical variables might improve its prediction in COPD.

METHODS

A total of 1,233 6-min walk tests and circulating proadrenomedullin (proADM) levels from 574 patients with clinically stable, moderate to very severe COPD enrolled in a multinational cohort study and followed up for 2 years were concomitantly analyzed.

RESULTS

The prevalence of exertional hypoxemia was 29.1%. In a matrix derived from a fitted-multistate model, the annual probability to develop exertional hypoxemia was 21.6%. Exertional hypoxemia was associated with greater deterioration of specific domains of health-related quality of life, higher severe exacerbation, and death annual rates. In the logistic linear and conditional Cox regression multivariable analyses, both FEV1% predicted and proADM proved independent predictors of exertional hypoxemia (P < .001 for both). Adjustment for comorbidities, including cardiovascular disorders, and exacerbation rate did not influence results. Relative to using FEV1% predicted alone, adding proADM resulted in a significant improvement of the predictive properties (P = .018). Based on the suggested nonlinear nomogram, patients with moderate COPD (FEV1% predicted = 50%) but high proADM levels (> 2 nmol/L) presented increased risk (> 30%) for exertional desaturation.

CONCLUSIONS

Exertional desaturation is common and associated with poorer clinical outcomes in COPD. ADM improves prediction of exertional desaturation as compared with the use of FEV1% predicted alone.

TRIAL REGISTRY

ISRCTN Register; No.: ISRCTN99586989; URL: www.controlled-trials.com

Section snippets

Study Design and Ethics

Conducted in 11 centers in eight European countries, the Predicting Outcome Using Systemic Markers in Severe Exacerbations of COPD (PROMISE-COPD) study evaluated variables potentially identifying poor outcomes in patients with moderate to very severe COPD. Such disease was defined as postbronchodilator FEV1/FVC < 70% and FEV1 < 80% predicted (ie, GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade II-IV airway obstruction); COPD exacerbation was defined as an acute change from

Results

The study design according to the CONSORT guidelines and patient disposition is summarized in Figure 1. Sixty-four patients were excluded from the analysis because of unavailable lowest oxygen saturation during 6MWT at baseline. The clinical characteristics (sex; race; BMI, airflow obstruction, dyspnea, exercise capacity [BODE] index; and 6-min walk distance [6MWD]) of these patients did not differ from the analysis cohort (P = not significant for all, data not shown). Thus, of 638 patients in

Discussion

We used data of a multinational, longitudinal cohort study to assess the prevalence and the annual probability to develop exertional hypoxemia among unselected, stable patients with moderate to very severe COPD followed up during a median time of 2 years. We found that exertional hypoxemia is present in almost one-third of the patients, with a prevalence ranging from one out of six patients in GOLD stage II to one out of two patients in GOLD stage IV. The cumulative HR of exertional hypoxemia

Acknowledgments

Author contributions: All authors take responsibility for the integrity of the work as a whole, from inception to published article.

D. S. and M. T. contributed to conceiving and designing the study and collected and analyzed study data; D. S. and S. H. contributed to conducting statistical analyses; W. B., F. B., R. L., B. M., K. K., J. G. A., G. R., J. R., L. B., A. S., A. M., A. T., T. W., and M. T. contributed to collecting study data; and D. S., W. B., F. B., R. L., B. M., K. K., J. G. A.,

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    FUNDING/SUPPORT: PROMISE-COPD was an investigator-initiated study primarily funded by the Clinic of Pulmonary Medicine and Respiratory Cell Research of the University Hospital Basel, Switzerland and by the Swiss National Foundation [Grant PP00-P3_128412/1]. Thermo Scientific Biomarkers (formerly BRAHMS AG), Hennigsdorf, Germany, provided all reagents for those analyses gratis and, through an unrestricted research grant, funded all costs of transporting blood samples to the central biomarker testing facility at University Hospital Basel.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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