Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience

Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts.MethodsCOPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated.ResultsIn total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality – 33% and 22% respectively.ConclusionsAn important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice. (AU)

Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience.

INTRODUCTION: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. METHODS: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. RESULTS: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. CONCLUSIONS: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice.

Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients.

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP treatment to identify potential specific disease candidates. Fasting morning plasma exosomes isolated from 12 adult patients with polysomnographically-diagnosed OSA were analyzed before and after 12 months of adherent CPAP therapy (mean ≥ 6 h/night) (OSAT). Exosomes were characterized by flow cytometry, transmission electron microscopy, and nanoparticle tracking analysis. Endothelial cell barrier integrity, wound healing, and tube formation were also performed. Multi-omics analysis for exosome cargos was integrated. Exosomes derived from OSAT improved endothelial permeability and dysfunction as well as significant improvement in tube formation compared with OSA. Multi-omic approaches for OSA circulating exosomes included lipidomic, proteomic, and small RNA (miRNAs) assessments. We found 30 differentially expressed proteins (DEPs), 72 lipids (DELs), and 13 miRNAs (DEMs). We found that the cholesterol metabolism (has04979) pathway is associated with lipid classes in OSA patients. Among the 12 subjects of OSA and OSAT, seven subjects had complete comprehensive exosome cargo information including lipids, proteins, and miRNAs. Multi-omic approaches identify potential signature biomarkers in plasma exosomes that are responsive to adherent OSA treatment. These differentially expressed molecules may also play a mechanistic role in OSA-induced morbidities and their reversibility. Our data suggest that a multi-omic integrative approach might be useful in understanding how exosomes function, their origin, and their potential clinical relevance, all of which merit future exploration in the context of relevant phenotypic variance. Developing an integrated molecular classification should lead to improved diagnostic classification, risk stratification, and patient management of OSA by assigning molecular disease-specific therapies.

Visual Performance at All Distances and Patient Satisfaction With a New Aspheric Inverted Meniscus Intraocular Lens.

PURPOSE: To evaluate visual performance, spectacle independence, and quality of vision of new intraocular lenses (IOLs) for presbyopia correction with an aspheric inverted meniscus optical design (ArtIOLs; Voptica SL) in patients undergoing bilateral cataract surgery. METHODS: In this prospective study, 60 eyes from 30 patients implanted bilaterally with Art40 and Art70 IOLs were included. These new IOLs were designed with an inverted meniscus shape to improve the peripheral performance and with aspheric surfaces to induce different amounts of negative spherical aberration in each IOL model. Distance-corrected and uncorrected through-focus visual acuities and contrast sensitivity were measured 1 to 3 months after surgery. Twenty-eight patients answered Patient Reported Spectacle Independence (PRSIQ) and Quality of Vision (QoV) questionnaires. RESULTS: Mean monocular (Art40 and Art70) and binocular (Art40/70) corrected distance visual acuities (CDVA) were zero logMAR (20/20). Binocular uncorrected distance visual acuity (UDVA) at far, intermediate (66 cm), and near (40 cm) distances was 0.00 ± 0.01, 0.01 ± 0.03, and 0.09 ± 0.09 logMAR, respectively. Spectacle independence was achieved by 24 (85.7%) patients for far and intermediate vision and 20 patients (71.4%) for near vision. The number of patients never reporting experiencing glare, halos, and starbursts was 28, 27, and 26 (100%, 96.4%, and 92.9%), respectively. CONCLUSIONS: The binocular combination of two ArtIOLs models (Art40 and Art70) significantly extended the depth of focus up to at least 40 cm. This combination resulted in a full range of vision with a high level of spectacle independence and without the compromise of halos or dysphotopsias. [J Refract Surg. 2023;39(9):582-588.].

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome.

STUDY OBJECTIVES: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual, also known as overlap syndrome (OVS), is associated with higher cardiovascular risk and mortality than either OSA or COPD alone. However, the underlying mechanisms remain unclear. We hypothesized that patients with OVS have elevated systemic inflammatory biomarkers relative to patients with either disease alone, which could explain greater cardiovascular risk observed in OVS. METHODS: We included 255 participants in the study, 55 with COPD alone, 100 with OSA alone, 50 with OVS, and 50 healthy controls. All participants underwent a home sleep study, spirometry, and a blood draw for high-sensitivity C-reactive protein and total blood count analysis. In a randomly selected subset of 186 participants, inflammatory protein profiling was performed using Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assays. Biomarker level differences across groups were identified using a mixed linear model. RESULTS: Levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and granulocyte colony stimulating factor (G-CSF) were higher in participants with OVS and COPD compared with healthy controls and participants with OSA. Furthermore, participants with OVS had higher circulating levels of leukocytes and neutrophils than those with COPD, OSA, and controls. CONCLUSIONS: COPD and OVS are associated with higher systemic inflammation relative to OSA and healthy controls. This work proposes the potential utilization of interleukin 6, granulocyte colony stimulating factor, and high-sensitivity C-reactive protein as screening biomarkers for COPD in patients with OSA. Inflammatory pathways may not fully explain the higher cardiovascular risk observed in OVS, indicating the need for further investigation. CITATION: Sanchez-Azofra A, Gu W, Masso-Silva JA, et al. Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome. J Clin Sleep Med. 2023;19(8):1447-1456.

Non-indigenous aquatic fauna in transitional waters from the Spanish Mediterranean coast: A comprehensive assessment.

Understanding drivers of spatial variation in non-indigenous species (NIS) is a key goal in invasion biology, but comprehensive assessments providing high-resolution data are extremely scarce. Anthropogenic modifications to transitional waters facilitate the invasion of NIS where they cause both ecological and economic important damage. By screening validated data sources, we conducted a comprehensive assessment of non-indigenous aquatic fauna in Spanish Mediterranean transitional waters (30 sites), as well as assessed introduction pathways, native regions, NIS assemblage patterns and temporal introduction rate. One hundred and twenty-nine NIS were inventoried, with 72 % established and more than half listed before 1980. Two intentional (release, escape) and two unintentional (contaminant, stowaway) introduction pathways were dominant. Recorded NIS originated mostly from North America and Asia. A clear nested pattern in NIS assemblages was observed across sites, suggesting secondary spread from the most invaded waters placed in the northern regions. Our updated inventory should be pivotal for designing prevention protocols and informing specific management plans on non-indigenous fauna in transitional waters.

A horizon scan exercise for aquatic invasive alien species in Iberian inland waters.

As the number of introduced species keeps increasing unabatedly, identifying and prioritising current and potential Invasive Alien Species (IAS) has become essential to manage them. Horizon Scanning (HS), defined as an exploration of potential threats, is considered a fundamental component of IAS management. By combining scientific knowledge on taxa with expert opinion, we identified the most relevant aquatic IAS in the Iberian Peninsula, i.e., those with the greatest geographic extent (or probability of introduction), severe ecological, economic and human health impacts, greatest difficulty and acceptability of management. We highlighted the 126 most relevant IAS already present in Iberian inland waters (i.e., Concern list) and 89 with a high probability of being introduced in the near future (i.e., Alert list), of which 24 and 10 IAS, respectively, were considered as a management priority after receiving the highest scores in the expert assessment (i.e., top-ranked IAS). In both lists, aquatic IAS belonging to the four thematic groups (plants, freshwater invertebrates, estuarine invertebrates, and vertebrates) were identified as having been introduced through various pathways from different regions of the world and classified according to their main functional feeding groups. Also, the latest update of the list of IAS of Union concern pursuant to Regulation (EU) No 1143/2014 includes only 12 top-ranked IAS identified for the Iberian Peninsula, while the national lists incorporate the vast majority of them. This fact underlines the great importance of taxa prioritisation exercises at biogeographical scales as a step prior to risk analyses and their inclusion in national lists. This HS provides a robust assessment and a cost-effective strategy for decision-makers and stakeholders to prioritise the use of limited resources for IAS prevention and management. Although applied at a transnational level in a European biodiversity hotspot, this approach is designed for potential application at any geographical or administrative scale, including the continental one.

Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis.

BACKGROUND: Atherosclerosis is a common comorbidity of obstructive sleep apnoea (OSA) patients, caused by the interaction of dyslipidaemia and systemic inflammation. The OSA pro-inflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermittent hypoxia (IH) and an activation signal provided by soluble stimulus present in plasma. Our objectives were to study oxidised low-density lipoprotein (oxLDL) expression in OSA patients with or without early subclinical atherosclerosis (eSA) as well as its contribution to NLRP3 activation and tissue factor (TF) release. METHODS: We analysed oxLDL, key components of the NLRP3 inflammasome cascade and TF in plasma and monocytes from OSA patients and non-apnoeic subjects, with or without eSA as determined by increased carotid intima-media thickness without the appearance of atherosclerotic plaques. The oxLDL contribution to NLRP3 inflammasome activation was assessed using in vitro models. RESULTS: High levels of oxLDL were identified in plasma from OSA patients, particularly in those with eSA, as well as an overexpression of NLRP3 cascade components and TF. Furthermore, in vitro models showed that both oxLDL and plasma from OSA patients with eSA act synergistically with IH as a priming and activation signal of NLRP3 that enhances the inflammatory response, pyroptosis and TF release. CONCLUSIONS: OSA patients with eSA exhibit NLRP3 activation by IH and the presence of oxLDL capable of releasing TF, constituting a pathway for the interaction between dyslipidaemia and systemic inflammation in the development of atherosclerotic lesions.

Comorbidities and mortality risk in adults younger than 50 years of age with chronic obstructive pulmonary disease.

RATIONALE AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown. METHODS: We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the "Young" and "Old" COPD groups. RESULTS: The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjusting for age, sex, and pack-years, the prevalence of subjects with at least one comorbidity was 31% for controls, 77% for the Young, and 86% for older COPD patients. Compared to controls, "Young" COPDs' had a nine-fold increased mortality risk (p < 0.0001). "Comorbidomes" differed between Young and Old COPD groups, with tuberculosis, substance use, and bipolar disorders being distinct comorbidities associated with increased mortality risk in the Young COPD group. CONCLUSIONS: Young COPD patients carry a higher comorbidity prevalence and mortality risk compared to non-obstructed control subjects. Young COPD differed from older COPD patients by the behavioral-related comorbidities that increase their risk of premature death.

Chronic Bronchitis Affects Outcomes in Smokers without Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic bronchitis (CB) importantly affects outcomes in smokers with COPD, but the effects on smokers without COPD are less well known and less emphasized. The aim of our study was to investigate the possible effects of CB on clinical outcomes in smokers without COPD (noCOPD) and compare them with the effects in smokers with COPD (COPD). METHODS: For that purpose, we studied 511 smokers, 302 with and 209 without COPD, followed for 10 years in an academic COPD ambulatory setting. Chronic bronchitis was defined as the presence of cough and sputum production for at least 3 months in each of two consecutive years. All subjects underwent clinical and functional examination with spirometry, diffusion capacity (DLco), 6-min walking test (6MWT), mMRC Dyspnoea Scale, COPD Assessment Test (CAT), and recording of annual frequency of exacerbations. All-cause mortality during follow-up was recorded. RESULTS: 27% of noCOPD and 45% of COPD had CB. noCOPD with CB had lower FEV1 and DLco, worse 6MWT, more dyspnoea, a higher number of exacerbations and lower survival than noCOPD without CB. CB did not affect FEV1 decline in noCOPD but it significantly did in COPD. CONCLUSIONS: The presence of chronic bronchitis in smokers without COPD will significantly affect symptoms, quality of life, and survival, underlining the importance of recognizing the condition and managing it accordingly.

Symptomatic smokers without COPD have physiological changes heralding the development of COPD.

Background: COPD is a major health problem, mainly due to cigarette smoking. Most studies in COPD are dedicated to fully developed COPD in older subjects, even though development of COPD may start soon after smoking initiation. Therefore, there is a need to diagnose this "early disease" by detecting the initial events responsible for ultimate development of COPD. Methods: Measurement of maximum mid expiratory flow between 25 and 75% of vital capacity (MMEF) in a routine spirometry, which detects small airways disease, was used to investigate if MMEF abnormalities in smokers without COPD (noCOPD) would relate to respiratory symptoms and identify smokers that might progress to COPD. For this purpose we studied 511 smokers, 302 COPD and 209 noCOPD, followed long term with spirometry including MMEF, diffusing capacity of the lung for carbon monoxide (D LCO), 6-min walk test (6MWT), Medical Research Council Dyspnoea Scale and COPD Assessment Test. Three spirometries V1,V2 and V3 (5±2.5 and 10±4 years apart from V1) were performed to assess functional decline and development of COPD. Results: 65% of noCOPD had an abnormal MMEF (<80%) and 38% an abnormal D LCO. The NoCOPD with MMEF <80% group performed worse in the 6MWT (p=0.01), was more dyspnoeic (p=0.01) and had higher prevalence of chronic bronchitis than the noCOPD with MMEF>80% group (p=0.04). 21% of noCOPD with MMEF <80% and 2.7% with MMEF>80% developed COPD by V3 (p=0.0004). Conclusions: The MMEF, a functional test available in a routine spirometry, can detect early lung abnormalities and identify the subset of symptomatic smokers with pathological changes that might lead to COPD.

Soluble RAGE in COPD, with or without coexisting obstructive sleep apnoea.

BACKGROUND: Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-inflammatory biomarker of COPD. We assessed sRAGE in patients with hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap. METHODS: Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers [HNS], 84 healthy smokers [HS], 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap). RESULTS: After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (- 12.5%, p = 0.005), COPD (- 14.8%, p < 0.001) and OSA-COPD overlap (- 12.3%, p = 0.02) compared with HNS. There were no differences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change significantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased significantly. CONCLUSIONS: The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD.

Peripheral Refraction and Contrast Detection Sensitivity in Pseudophakic Patients Implanted With a New Meniscus Intraocular Lens.

PURPOSE: To evaluate peripheral refraction and contrast detection sensitivity in pseudophakic patients implanted with a new type of inverted meniscus intraocular lens (IOL) (Art25; Voptica SL) that was designed to provide better peripheral optics. METHODS: One month after cataract surgery, in 87 eyes implanted with the Art25 IOL, peripheral contrast detection sensitivity was measured psychophysically at 40° visual angle, both horizontally and vertically, and compared with a control group of 51 eyes implanted with standard biconvex IOLs. Thirty-one eyes with the Art25 IOL and 28 eyes from the control group were randomly selected to also measure peripheral refraction using a scanning Hartmann-Shack wavefront sensor along 80° in the horizontal meridian. RESULTS: Most patients achieved emmetropia and good visual acuity, and no significant adverse events were observed after cataract surgery with Art25 IOLs. Peripheral contrast detection sensitivity was significantly better (P < .01) in the group with the Art25 IOL in both directions (7.78 ± 3.24 vs 5.74 ± 2.60 vertical, 10.98 ± 5.09 vs 7.47 ± 3.96 horizontal), which was in agreement with the optical quality improvement in the periphery due to a reduction of defocus (1.97 and 1.21 diopters [D] at 40° temporal and nasal sides) and astigmatism (1.17 and 0.37 D at 40° temporal and nasal sides) that was statistically significant (P < .01) from 20° of eccentricity. CONCLUSIONS: Patients implanted with a new inverted meniscus IOL present a reduced amount of peripheral defocus and astigmatism compared to patients implanted with standard biconvex IOLs. This improvement in optical quality leads to better contrast detection sensitivity measured at 40° of eccentricity. [J Refract Surg. 2022;38(4):229-234.].

Effectiveness of CPAP vs. Noninvasive Ventilation Based on Disease Severity in Obesity Hypoventilation Syndrome and Concomitant Severe Obstructive Sleep Apnea.

RATIONALE: Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity. OBJECTIVE: To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups. METHODS: Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI)≥30events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45-49.9 or ≥50mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model. RESULTS: 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups. CONCLUSION: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2.

Chest CT-assessed comorbidities and all-cause mortality risk in COPD patients in the BODE cohort.

BACKGROUND AND OBJECTIVE: The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic identification and relationship with all-cause mortality have not been explored. Furthermore, whether their CT-detected prevalence differs from clinical diagnosis is unknown. METHODS: The prevalence of 10 CT-assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT-determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all-cause mortality was analysed. A 'CT-comorbidome' graphically expressed the strength of their association with mortality risk. RESULTS: Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio [HR] 2.09; 95% CI 1.03-4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05-4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23-5.57, p = 0.010) were independently associated with all-cause mortality and helped define the 'CT-comorbidome'. CONCLUSION: This study of COPD patients shows that systematic detection of 10 CT-diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them.