[Highlights of the 55th SEPAR Congress]. / Highlights del 55.° Congreso SEPAR.

The 55th SEPAR Congress was held in Pamplona from 2 to 4 of June 2022. Once again, it was the referral scientific meeting for specialists in pulmonology, thoracic surgery, nursing, physiotherapy, paediatric respiratory diseases and other disciplines involved in respiratory care. The Spanish Society of Pulmonology and Thoracic Surgery showed its national and international leadership in the management of respiratory diseases, which was reflected in a program with an excellent content and a high scientific level. In this review, we offer a summary of some notable aspects covered in six selected areas of interest: pulmonary vascular diseases, non-invasive mechanical ventilation and sleep disorders, asthma, chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), and interventional pulmonolgy and lung transplant.

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.

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.

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.

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.

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.

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients.

RATIONALE: Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality. METHODS: At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65±8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48-119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality. RESULTS: PsD was lower in COPD patients than in controls (40.5 vs 42.5, p=0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV1%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02-1.12, p=0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94-0.99, p=0.023) were the variables independently associated with all-cause mortality. CONCLUSIONS: In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.

Low-Blood Lymphocyte Number and Lymphocyte Decline as Key Factors in COPD Outcomes: A Longitudinal Cohort Study.

BACKGROUND: Smokers with and without chronic obstructive pulmonary disease (COPD) are at risk of severe outcomes like exacerbations, cancer, respiratory failure, and decreased survival. The mechanisms for these outcomes are unclear; however, there is evidence that blood lymphocytes (BL) number might play a role. OBJECTIVE: The objective of this study is to investigate the relationship between BL and their possible decline over time with long-term outcomes in smokers with and without COPD. METHODS: In 511 smokers, 302 with COPD (COPD) and 209 without COPD (noCOPD), followed long term, we investigated whether BL number and BL decline over time might be associated with long-term outcomes. Smokers were divided according to BL number in high-BL (≥1,800 cells/µL) and low-BL (<1,800 cells/µL). Clinical features, cancer incidence, and mortality were recorded during follow-up. BL count in multiple samples and BL decline over time were calculated and related to outcomes. RESULTS: BL count was lower in COPD (1,880 cells/µL) than noCOPD (2,300 cells/µL; p < 0.001). 43% of COPD and 23% of noCOPD had low-BL count (p < 0.001). BL decline over time was higher in COPD than noCOPD (p = 0.040). 22.5% of the whole cohort developed cancer which incidence was higher in low-BL subjects and in BL decliners than high-BL (31 vs. 18%; p = 0.001) and no decliners (32 vs. 19%; p = 0.002). 26% in the cohort died during follow-up. Furthermore, low-BL count, BL decline, and age were independent risk factors for mortality by Cox regression analysis. CONCLUSION: BL count and BL decline are related to worse outcomes in smokers with and without COPD, which suggests that BL count and decline might play a mechanistic role in outcomes deterioration. Insights into mechanisms inducing the fall in BL count could improve the understanding of COPD pathogenesis and point toward new therapeutic measures.

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex.

BACKGROUND: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression. RESEARCH QUESTION: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? STUDY DESIGN AND METHODS: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time. RESULTS: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039). INTERPRETATION: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers.

BACKGROUND: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. METHODS: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. RESULTS: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06-3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02-1.05) and higher % of sleep time with O2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00-1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01-1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01-1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01-1.07). CONCLUSIONS: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence.

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients.

RATIONALE: Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality. METHODS: At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65±8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48-119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality. RESULTS: PsD was lower in COPD patients than in controls (40.5 vs 42.5, p=0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV1%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02-1.12, p=0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94-0.99, p=0.023) were the variables independently associated with all-cause mortality. CONCLUSIONS: In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.

Somatotypes trajectories during adulthood and their association with COPD phenotypes.

RATIONALE: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. OBJECTIVES: We hypothesised that somatotype changes - as a surrogate of adiposity - from early adulthood follow different trajectories to reach distinct phenotypes. METHODS: Using the validated Stunkard's Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. MEASUREMENTS AND MAIN RESULTS: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m-2) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m-2). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and D LCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), D LCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. CONCLUSIONS: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.

Upper airway and systemic inflammation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment.We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h-1), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay.In PHAL, CD4+ T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p<0.05). The AHI correlated with CD4+, IL-6 and IL-8 in PHAL (all p-values <0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery.In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found.