Clinical session
Respiratory health, comorbidities and mortality
Speakers
Sine Voss Winter (Denmark), Mohammad Azizzadeh (Austria), Sam Bartlett-Pestell (UK), Josefin Sundh – (Sweden), Yu Liu (China), Sigrid Anna Aalberg Vikjord (Norway), Helene Backman (Sweden), Olivia Murrin (UK), Jonas Eriksson Ström (Sweden)
A preview of new insights into COPD and comorbidities
A wide range of comorbidities frequently coexist with the progressive respiratory condition chronic obstructive pulmonary disease (COPD).1 These comorbid conditions—such as cardiovascular disease, metabolic syndrome, osteoporosis, depression, anxiety, and lung cancer—can significantly impact the clinical course, prognosis, and quality of life of individuals with COPD. The presence of comorbidities often complicates diagnosis and treatment, increases healthcare utilization, and contributes to higher mortality rates.2 Understanding the interplay between COPD and its associated comorbidities is essential for developing comprehensive management strategies that address both the pulmonary and extrapulmonary aspects of the disease.
Here is a preview of the studies presented in this session:
Genetics and Thrombosis: A1 Antitrypsin Deficiency Under the Microscope
(Sine Woss Winther, Denmark)
α1-Antitrypsin deficiency is a genetic disorder that causes emphysema due to the loss of elastic fibres in the lungs, as well as liver cirrhosis. However, α1-antitrypsin deficiency also affects the coagulation cascade and may increase the risk of blood clot formation. A Danish cohort study revealed that individuals with α1-antitrypsin deficiency face significantly higher risks of pulmonary embolism, deep vein thrombosis, and venous thromboembolism.3 This association remained even after adjusting for known confounders such as sex, COPD, and age. Mortality from pulmonary embolism was also elevated in individuals with α1-antitrypsin deficiency. Although no cause-relationship can be established based on this observational cohort study, it was hypothesized that the deficiency may disrupt thrombin regulation and increase the risk of clot formation.
Metabolic Markers and Lung Function: The TyG Index
(Mohammad Azizzadeh, Austria)
The triglyceride-glucose (TyG) index is a marker of metabolic dysfunction.4 Data from the LEAD study highlighted the TyG index as a potential marker for restrictive lung impairment. At baseline, TyG was positively associated with age and was consistently higher in males than in females. Additionally, TyG levels were elevated in individuals with impaired lung function, as assessed by spirometry. Cross-sectional analysis showed that TyG was associated with a higher risk of impaired lung function. However, longitudinal data showed only borderline significance, prompting calls for further research. The TyG index may serve as an indicative marker of impaired lung function, similar to other indexes of metabolic dysfunction.
Silent cardiovascular risk in Small Airways Obstruction
(Sam Bartlett-Pestell, UK)
Isolated small airway obstruction (SAO) does not have a gold standard test. Typically, Forced Expiratory Flow between 25% and 75% of forced vital capacity (FEF25–75), the ratio of Forced Expiratory Flow in 3 seconds to forced vital capacity (FEV3/FVC), or the ratio of FEV3 to FEV6 (FEV3/FEV6), combined with a normal FEV1/FVC, is used to identify isolated SAO.5
Individuals with isolated SAO report higher scores on the St. George’s Respiratory Questionnaire, experience more breathlessness, and have more gas trapping compared to individuals without isolated SAO. Isolated SAO is associated with increased mortality,6 including cardiovascular mortality.7
However, the longitudinal association between SAO and cardiovascular disease is unknown, and this was the focus of Dr. Sam Bartlett-Pestell’s study. In the study, isolated SAO was defined as FEV3/FEV6 below the lower limit of normal, combined with an FEV1/FEV6 above the lower limit of normal. Bartlett-Pestell emphasized that FEV6 was used instead of FVC because FVC is likely underestimated in this population.
Using UK Biobank data, isolated SAO were linked to a 5% increased risk of cardiovascular disease, particularly in women and ever-smokers. These findings suggest that SAO may serve as an early warning sign for cardiovascular issues.
Real-World Swedish data (The PRAXIS Study): COPD and cardiovascular mortality
(Josefin Sundh, Sweden)
COPD patients are living longer, potentially with more cardiovascular comorbidities. In addition, treatments for cardiovascular diseases (CVD) have improved.
The aim of the presented study was to investigate the incidence of cardiovascular disease among COPD patients in two cohorts, one decade apart, and to explore 10-year cardiovascular mortality compared to other causes of death in this population.
Using two COPD cohorts (Cohort 1: starting in 2005; Cohort 2: starting in 2014), the researchers found stable rates of heart disease, cardiovascular, and respiratory mortality among COPD patients. However, stratified analysis by disease severity showed that cardiovascular mortality decreased significantly among patients with mild to moderate disease in the second cohort.
Cholesterol Paradox in COPD
(Yu Liu, China)
A NHANES-based study revealed a dual role for the non-HDL/HDL cholesterol ratio (NHHR): while a higher NHHR increased the risk of developing COPD, it was paradoxically associated with lower all-cause mortality among COPD patients.8 This finding underscores the complexity of lipid metabolism in chronic lung disease.
Socioeconomic disparities persist – even with universal healthcare
(Sigrid Anna Aalberg Vikjord, Norway)
Socioeconomic status (SES) is associated with COPD risk and outcomes.9 However, its impact on pre-COPD states with respiratory symptoms remains unclear. Norwegian researchers used data from the HUNT study to investigate lung function and mortality in relation to SES among COPD patients, individuals with pre-COPD, and the general population.
The data showed that lower SES correlates with reduced lung function and higher mortality across all groups, including those with pre-COPD symptoms. Additionally, people with low SES had approximately 3.4 years of lung function loss at age 45 and about 7 additional years at age 75 compared to individuals with higher education.
Interestingly, there were no differences in the rate of decline over time. Furthermore, a socioeconomic gradient was observed in mortality rates, which was more pronounced in the COPD population.
In conclusion, the study demonstrated a clear socioeconomic gradient in lung function levels but no difference in the speed of decline over time. Moreover, the impact of SES on mortality was more significant in individuals with COPD than in those with pre-COPD or in the general population. These findings call for targeted public health interventions and improved health literacy, even in high-income countries.
Lung Function Trajectories and Mortality Risk
(Helena Backman, Sweden)
Using longitudinal spirometry data, Helene Backman presented findings from a study investigating the trajectories of FEV1 and FEV1/VC among adults with airway obstruction and their association with all-cause mortality.10
The data, derived from a clinical sub-cohort of the Obstructive Lung Diseases in Northern Sweden (OLIN) studies, revealed that rapidly declining FEV1 or starting with low FEV1 trajectories are associated with increased mortality. Smoking and obesity emerged as key risk factors, reinforcing the importance of early intervention and lifestyle modification.
Multimorbidity: COPD and Rheumatoid Arthritis – A Deadly Duo
(Olivia Murrin, UK)
COPD often co-occurs with rheumatoid arthritis (RA) and other inflammatory diseases.11
Data from the UK highlighted that patients with both COPD and RA experience the worst outcomes in terms of mortality and hospitalizations. Genetic links and shared risk factors suggest a need for integrated care strategies and early identification of at-risk individuals.
Troponin Levels in COPD: A Cardiovascular Signal?
(Jonas Eriksson Ström, Sweden)
There is substantial evidence of elevated troponin levels in stable COPD patients without known cardiovascular disease (CVD).12 The study presented by Jonas Eriksson Ström, aimed to investigate the association between troponin I and COPD, and to further explore the influence of coronary artery disease (CAD).
Contrary to previous studies, Swedish SCAPIS data found no association between troponin I levels and COPD in patients without known CVD. Researchers suggest that elevated troponin may reflect undiagnosed heart conditions rather than COPD itself, particularly in mild to moderate cases.
Take-aways
This session underscored the multifaceted nature of COPD, emphasizing the importance of metabolic markers, socioeconomic context, and comorbidity management. As COPD patients live longer, understanding and addressing these interconnected risks will be critical to improving outcomes and tailoring therapies.
Emil Bojsen-Møller
Medical Advisor, Chiesi Nordic
References
- Global Initiative for Chronic Obstructive Lung Disease (GOLD) – Global Strategy for Prevention, Diagnosis and Management of COPD [Internet]. 2023. Available from: https://goldcopd.org/2023-gold-report-2/
- Divo M, Cote C, De Torres JP, Casanova C, Marin JM, Pinto-Plata V, et al. Comorbidities and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2012 July 15;186(2):155–61.
- Riis J, Nordestgaard BG, Afzal S. α1-Antitrypsin Z allele and risk of venous thromboembolism in the general population. J Thromb Haemost. 2022;20(1):115-125. doi:10.1111/jth.15556
- Khan SH, Sobia F, Niazi NK, Manzoor SM, Fazal N, Ahmad F. Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetol Metab Syndr. 2018 Dec;10(1):74.
- Hogg JC, Paré PD, Hackett TL. The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease. Physiological Reviews. 2017 Apr;97(2):529–52.
- Quintero Santofimio V, Knox-Brown B, Potts J, Bartlett-Pestell S, Feary J, Amaral AFS. Small Airways Obstruction and Mortality. CHEST. 2024 Oct;166(4):712–20.
- Knox-Brown B, Patel J, Potts J, Ahmed R, Aquart-Stewart A, Barbara C, et al. The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study. Respir Res. 2023 May 23;24(1):137.
- Zhong Y, Zhou K, Li S, Zhang R, Wang D. Association Between the Non-High-Density Lipoprotein Cholesterol-to-High-Density Lipoprotein Cholesterol Ratio (NHHR) and Mortality in Patients with COPD: Evidence From the NHANES 1999-2018. Int J Chron Obstruct Pulmon Dis. 2025 Mar 28;20:857-868. doi: 10.2147/COPD.S508481. PMID: 40171052; PMCID: PMC11960475.
- Lowe KE, Make BJ, Crapo JD, Kinney GL, Hokanson JE, Kim V, et al. Association of low income with pulmonary disease progression in smokers with and without chronic obstructive pulmonary disease. ERJ Open Res. 2018 Oct;4(4):00069–2018.
- Backman H, Blomberg A, Lundquist A, et al. Lung Function Trajectories and Associated Mortality among Adults with and without Airway Obstruction. Am J Respir Crit Care Med. 2023;208(10):1063-1074. doi:10.1164/rccm.202211-2166OC
- Murrin O, Mounier N, Voller B, Tata L, Gallego-Moll C, Roso-Llorach A, et al. A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data. eBioMedicine. 2025 Mar;113:105584.
- Nilsson U, Van Fleteren LEGW. Troponin as a biomarker for mortality in stable COPD. Eur Respir J. 2020 Feb;55(2):1902447.
17088 10.10.2025