Exertional hypoxemia in stable COPD is common and predicted by circulating proadrenomedullin.
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.


BACKGROUND
ISRCTN Register; No.: ISRCTN99586989; URL: www.controlled-trials.com.
Department of Pneumology, University Hospital, Basel, Switzerland. Electronic address: Daiana.Stolz@usb.ch.
Daiana
D
Stolz
Department of Pneumology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
Wim
W
Boersma
Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Cà Granda, Milan, Italy.
Francesco
F
Blasi
Department of Pneumology, University of Liege, Liege, Belgium.
Renaud
R
Louis
Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Belgrade, Serbia.
Branislava
B
Milenkovic
University Thessaly Medical School, Larissa, Greece.
Kostantinos
K
Kostikas
Erasmus MC, Rotterdam and Amphia Hospital Breda, Breda, The Netherlands.
Joachim G
JG
Aerts
Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Gernot
G
Rohde
Department of Microbiology, Hospital Universitari Germans Trais i Pujol, Badalona, Spain.
Alicia
A
Lacoma
Department of Pneumology, University Hospital, Basel, Switzerland.
Janko
J
Rakic
Department of Pneumology, University Hospital, Basel, Switzerland.
Lucas
L
Boeck
Department of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Cà Granda, Milan, Italy.
Paola
P
Castellotti
Department of Pneumology, University Hospital, Basel, Switzerland.
Andreas
A
Scherr
Department of Microbiology, Hospital Universitari Germans Trais i Pujol, Badalona, Spain.
Alicia
A
Marin
Clinical Diagnostics Division, Thermo Scientific Biomarkers, BRAHMS GmbH, Hennigsdorf, Germany.
Sabine
S
Hertel
Clinical Diagnostics Division, Thermo Scientific Biomarkers, BRAHMS GmbH, Hennigsdorf, Germany.
Sven
S
Giersdorf
Pneumology Department, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERES, Barcelona, Spain.
Antoni
A
Torres
Department of Pneumology, Medizinische Hochschule, Hannover, Germany.
Tobias
T
Welte
Department of Pneumology, University Hospital, Basel, Switzerland.
Michael
M
Tamm
D053607:Adrenomedullin / Q000096:biosynthesis / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D005082:Physical Exertion / Q000502:physiology*; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000096:biosynthesis / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin