Daiana Stolz1, Wim Boersma2, Francesco Blasi3, Renaud Louis4, Branislava Milenkovic5, Kostantinos Kostikas6, Joachim G Aerts7, Gernot Rohde8, Alicia Lacoma9, Janko Rakic10, Lucas Boeck10, Paola Castellotti3, Andreas Scherr10, Alicia Marin9, Sabine Hertel11, Sven Giersdorf11, Antoni Torres12, Tobias Welte13, Michael Tamm10. 1. Department of Pneumology, University Hospital, Basel, Switzerland. Electronic address: Daiana.Stolz@usb.ch. 2. Department of Pneumology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands. 3. Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Cà Granda, Milan, Italy. 4. Department of Pneumology, University of Liege, Liege, Belgium. 5. Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Belgrade, Serbia. 6. University Thessaly Medical School, Larissa, Greece. 7. Erasmus MC, Rotterdam and Amphia Hospital Breda, Breda, The Netherlands. 8. Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands. 9. Department of Microbiology, Hospital Universitari Germans Trais i Pujol, Badalona, Spain. 10. Department of Pneumology, University Hospital, Basel, Switzerland. 11. Clinical Diagnostics Division, Thermo Scientific Biomarkers, BRAHMS GmbH, Hennigsdorf, Germany. 12. Pneumology Department, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERES, Barcelona, Spain. 13. Department of Pneumology, Medizinische Hochschule, Hannover, Germany.
Abstract
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.
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.
Authors: A Apostolou; T Kerenidi; A Michopoulos; K I Gourgoulianis; M Noutsias; A E Germenis; M Speletas Journal: Herz Date: 2016-12-01 Impact factor: 1.443
Authors: Jyotshna Mandal; Bijaya Malla; Rudi Steffensen; Luigi Costa; Adrian Egli; Marten Trendelenburg; Francesco Blasi; Kostantinos Kostikas; Tobias Welte; Antoni Torres; Renaud Louis; Wim Boersma; Branislava Milenkovic; Joachim Aerts; Gernot G U Rohde; Alicia Lacoma; Katharina Rentsch; Michael Roth; Michael Tamm; Daiana Stolz Journal: Respir Res Date: 2015-12-18