Lung Diffusing Capacity Improves the Prognostic Validity of the GOLD Spirometric Staging in COPD

Casanova, Ciro; Gonzalez-Dávila, Enrique; de Torres, Juan P.; Cabrera, Carlos; Cosio, Borja G.; O’Donnel, Denis E.; Martínez-Gonzalez, Cristina; Solanes, Ingrid; Fuster, Antonia; Gotera, Carolina; Marin, Alicia; Amado, Carlos; Iscar, Marta; Marin, José M.; Neder, José Alberto; Feu, Nuria; Soriano, Joan B.; López-Campos, José Luis; Divo, Miguel; Peces-Barba, Germán; Celli, Bartolomé R.

doi:10.1016/j.arbres.2025.05.004

Archivos de Bronconeumología

ISSN: 0300-2896

Archivos de Bronconeumologia is an international journal that publishes original studies whose content is based upon results of research initiatives dealing with several aspects of respiratory medicine including epidemiology, respiratory physiology, pathophysiology of respiratory diseases, clinical management, thoracic surgery, pediatric lung diseases, respiratory critical care, respiratory allergy and translational research. Other types of articles such as editorials, reviews, and different types of letters are also published in the journal. Additionally, the journal expresses the voice of the following scientific societies: the Spanish Respiratory Society of Pneumology and Thoracic Surgery (SEPAR; https://www.separ.es/), the Latin American Thoracic Society (ALAT; https://alatorax.org/), and the Iberian American Association of Thoracic Surgery (AIACT; http://www.aiatorax.com/).

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Enrique Gonzalez-DávilabJuan P. de TorrescCarlos CabreradBorja G. CosioeDenis E. O’DonnelfCristina Martínez-GonzalezgIngrid SolaneshAntonia FusteriCarolina GoterajAlicia MarinkCarlos AmadolMarta IscargJosé M. MarinmJosé Alberto NederfNuria FeunJoan B. SorianooJosé Luis López-CamposoMiguel DivopGermán Peces-BarbajBartolomé R. Cellip

a Pulmonary Department, Research Unit, Hospital Universitario Nuestra Señora de La Candelaria, Universidad de La Laguna, Spain

b Department of Mathematics, Statistics and Operations Research, IMAULL Institute, University of La Laguna, Tenerife, Spain

c Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain

d Pulmonary Department Hospital Universitario de Gran Canaria, Las Palmas de Gran Canaria, Spain

e Department of Respiratory Medicine, Hospital Son Espases-IdISBa-CIBERES, Palma de Mallorca, Spain1

f Division of Respirology, Department of Medicine, Queen's University, Kingston, ON, Canada

g Pulmonary Department, Hospital Universitario Central de Asturias, ISPA, Universidad de Oviedo, Oviedo, Spain

h Pulmonary Department, Hospital Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain

i Pulmonary Department, Hospital Son Llátzer, Mallorca, Spain

j Pulmonary Department, Fundación Jimenez Díaz, Madrid, Spain1

k Pulmonary Department, Hospital Vall's de Hebrón, Barcelona, Spain

l Pulmonary Department, Hospital Marqués de Valdecilla, IDIVAL, UNICAN, Santander, Spain

m Pulmonary Department, Hospital Universitario Miguel Servet, Zaragoza, Spain

n Pulmonary Department, Hospital Universitario Reina Sofia, IMIBIC, UCO, Córdoba, Spain

o Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain1

p Pulmonary and Critical Care Department, Brigham and Women's Hospital, Boston, MA, USA

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Figures (9)

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Tables (4)

Table 1. Baseline characteristics of the COPD patients included in the study, stratified by vital status.

Table 2. Cox proportional univariate analysis of baseline variables associated with all-cause and respiratory-related mortality at 5 and 10 years.

Table 3. Cox proportional multivariate survival analysis of baseline variables associated with all-cause (3a) and respiratory-related (3b) mortality.

Table 4. Ten years mortality combining GOLD stages and DLco value <50% predicted.

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Abstract

Rationale

The lung diffusing capacity for carbon monoxide (DLco), a metric of gas transfer, provides physiological information distinct from spirometry. While DLco independently predicts mortality in COPD, its integration into the GOLD spirometric staging (% FEV1) to improve risk assessment, remains unexplored.

Objectives

To determine if DLco enhances the predictive power of GOLD spirometric classification for all-cause and respiratory mortality.

Methods

We followed 469 patients (mean age 64 years, 58% FEV1) with complete lung function tests in the Spanish multicenter CHAIN study for up to 10 years, with mortality as the main outcome. Patients were dichotomized based on DLco impairment (<50% cutoff). A Cox proportional hazard model evaluated the added value of DLco to GOLD FEV1 spirometric staging for all-cause and respiratory mortality. Validation of the results was conducted in the Kingston COPD Canadian cohort (N=300 patients).

Results

Over time, 184 (39.2%) patients died, 84 (17.9%) from respiratory causes. Adjusted analyses showed DLco<50% independently predicted all-cause [HR=1.83 (95%CI 1.32–2.54, p<0.001)] and respiratory [HR=2.27 (95%CI 1.43–3.60, p<0.001)] mortality. Incorporating DLco<50% increased mortality risk compared to FEV1 alone, particularly in GOLD stages 3 and 4, where survival time decreased by 1.23 years (p=0.002) and 1.25 years (p=0.004) for all-cause and respiratory deaths, respectively. These findings were validated in the Canadian cohort.

Conclusions

Adding DLco to FEV1 enhances the prognostic accuracy of the GOLD spirometric severity classification, especially for patients in GOLD stages 3–4 at higher risk of adverse outcomes.

ClinicalTrials.gov Identifier: NCT01122758.

Keywords:

COPD

Carbone monoxide diffusing capacity

Lung function

GOLD

Mortality

Graphical abstract