Lung cancer in chronic obstructive pulmonary disease patients, it is not just the cigarette smoke.

PURPOSE OF REVIEW: An important association has been described between chronic obstructive pulmonary disease (COPD) and lung cancer, where different mechanisms have been proposed. There is no unique cause for this association, as COPD is by itself a heterogeneous disease, in which their classical phenotypes (i.e., emphysema and chronic bronchitis) each play an important role in lung cancer development. We will discuss recent evidence that links these two diseases and specific characteristics found in lung cancers from patients with COPD. RECENT FINDINGS: Molecular studies have found specific gene expressions (reduction and overexpression) in lung tumors from patients with COPD, which likely predispose to increased methylation during lung carcinogenesis, and are associated with aggressiveness. Recent evidence suggests that lung cancer risk is higher in individuals with long telomeres, and that this effect takes place well in advance of diagnosis. Lung cancer is likely to develop in areas of the lung with greater emphysema and the severity of the latter is associated with larger and more aggressive tumors. SUMMARY: Clinical and molecular studies have found that lung cancers that develop in patients with COPD and/or emphysema appear to be more aggressive and have a distinct molecular profile when compared with tumors from patients without an underlying lung disease. This could have important implications when deciding on personalized treatments.

Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score.

RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for lung cancer (LC) and represent a potential target to improve the diagnostic yield of screening programs. OBJECTIVES: To develop a predictive score for LC risk for patients with COPD. METHODS: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) and the Pittsburgh Lung Screening Study (PLuSS) databases were analyzed. Only patients with COPD on spirometry were included. By logistic regression we determined which factors were independently associated with LC in PLuSS and developed a COPD LC screening score (COPD-LUCSS) to be validated in P-IELCAP. MEASUREMENTS AND MAIN RESULTS: By regression analysis, age greater than 60, body mass index less than 25 kg/m(2), pack-years history greater than 60, and emphysema presence were independently associated with LC diagnosis and integrated into the COPD-LUCSS, which ranges from 0 to 10 points. Two COPD-LUCSS risk categories were proposed: low risk (scores 0-6) and high risk (scores 7-10). In comparison with low-risk patients, in both cohorts LC risk increased 3.5-fold in the high-risk category. CONCLUSIONS: The COPD-LUCSS is a good predictor of LC risk in patients with COPD participating in LC screening programs. Validation in two different populations adds strength to the findings.

Improving selection criteria for lung cancer screening. The potential role of emphysema.

RATIONALE: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity. OBJECTIVES: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion. METHODS: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema. MEASUREMENTS AND MAIN RESULTS: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%. CONCLUSIONS: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.

COPD comorbidities network.

Multimorbidity frequently affects the ageing population and their co-existence may not occur at random. Understanding their interactions and that with clinical variables could be important for disease screening and management.In a cohort of 1969 chronic obstructive pulmonary disease (COPD) patients and 316 non-COPD controls, we applied a network-based analysis to explore the associations between multiple comorbidities. Clinical characteristics (age, degree of obstruction, walking, dyspnoea, body mass index) and 79 comorbidities were identified and their interrelationships quantified. Using network visualisation software, we represented each clinical variable and comorbidity as a node with linkages representing statistically significant associations.The resulting COPD comorbidity network had 428, 357 or 265 linkages depending on the statistical threshold used (p≤0.01, p≤0.001 or p≤0.0001). There were more nodes and links in COPD compared with controls after adjusting for age, sex and number of subjects. In COPD, a subset of nodes had a larger number of linkages representing hubs. Four sub-networks or modules were identified using an inter-linkage affinity algorithm and their display provided meaningful interactions not discernible by univariate analysis.COPD patients are affected by larger number of multiple interlinked morbidities which clustering pattern may suggest common pathobiological processes or be utilised for screening and/or therapeutic interventions.

Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE.

BACKGROUND: The Global Obstructive Lung Disease (GOLD) 2011 revision recommends the multidimensional assessment of COPD including comorbidities and has developed a disease categories system (ABCD) attempting to implement this strategy. The added value provided by quantifying comorbidities and integrating them to multidimensional indices has not been explored. OBJECTIVE: Compare the prognostic value of the GOLD ABCD categories versus the BMI, Obstruction, Dyspnea, Exercise (BODE) index, and explore the added prognostic value of comorbidities evaluation to this multidimensional assessment. METHODS: From the patients who have been enrolled in the BODE study, we selected the most recent ones who had the available information needed to classify them by the ABCD GOLD categories. Cox proportional hazards ratios for all-cause mortality were performed for GOLD categories and BODE index. The added value of the comorbidity Copd cO-morbidity TEst (COTE) index was also explored using receiver operating curves (ROC) values. RESULTS: 707 patients were followed for 50±30 months including all degrees of airway limitation and BODE index severity. ABCD GOLD predicted global mortality (HR: 1.47; 95% CI 1.28 to 1.70) as did the BODE index (HR: 2.02; 95% CI 1.76 to 2.31). Area under the curve (AUC) of ROC for ABCD GOLD was 0.68; (95% CI 0.64 to 0.73) while for the BODE index was 0.71 (95% CI 0.67 to 0.76). The C statistics value was significantly higher for the observed difference. Adding the COTE index to the BODE index improved its AUC to 0.81 (95% CI 0.77 to 0.85), (χ(2)=40.28, p<0.001). CONCLUSIONS: In this population of COPD patients, the BODE index had a better survival prediction than the ABCD GOLD categories. Adding the COTE to the BODE index was complimentary and significantly improved outcome prediction.

Disease progression in young patients with COPD: rethinking the Fletcher and Peto model.

Chronic obstructive pulmonary disease (COPD), although frequent in older individuals, can also occur at younger age; this latter population has not been well described. We reviewed the functional progression of 1708 patients with COPD attending pulmonary clinics. Those with three or more annual spirometries were divided into those who, at enrolment, were ≤ 55 (n = 103) or ≥ 65 (n = 463) years of age (younger and older COPD, respectively). Baseline and annual changes in lung function (forced expiratory volume in 1 s (FEV1)) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) score were recorded and compared between both groups. Severity distribution by Global Initiative for Chronic Obstructive Lung Disease and BODE scores were similar in both groups, except for mild obstruction, which was higher in the younger group. Mean FEV1 decline was 38.8 and 40.6 mL · year(-1), while BODE scores increased 0.19 and 0.23 units per year, for younger and older COPD, respectively. Both groups had similar proportion of FEV1 rapid decliners (42% and 46%, respectively). The severity distribution and progression of disease in younger patients with COPD is similar to that of patients of older age. This observation suggests that younger individuals presenting with COPD develop the disease from an already compromised pulmonary and systemic status, complementing the model of steeper decline of lung function proposed by Fletcher and Peto.

[Highlights 56th SEPAR Congress]. / Highlights del 56° Congreso SEPAR.

The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 56th congress in Granada from 8 to 10 June 2023. The SEPAR congress has established itself as the leading scientific meeting for specialists in medicine and respiratory care, reaching a record of participation this year with 2600 attendees. Our society thus demonstrates its leadership in the management of respiratory diseases, as well as its growth and progress in order to achieve excellence. In this review, we offer a summary of some notable issues addressed in six selected areas of interest: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), tuberculosis and respiratory infections, pulmonary circulation, and respiratory nursing.

Relationship between pediatric asthma and psychosocial status of caregivers.

OBJECTIVE: To determine the relationship between psychosocial caregiver disorders and childhood asthma. STUDY DESIGN: We performed a matched case-control study with asthmatic children (6-14 years of age) from two different clinics in Zaragoza, Spain, between 2010 - 2016. Clinical data were collected from medical records and psychosocial disorders were assessed by interviewing the caregiver using validated questionnaires (Goldberg, CES-D, SF-12, PSS and SPIN). General analysis of cases and controls was performed using McNemar, Chi2 and Wilcoxon nonparametric tests. A logistic regression model to predict more severe asthma, adjusted by caregiver psychosocial disorders was performed. RESULTS: 208 children were evaluated (104 cases). Mean age was 9.7 ± 2.4 years, with a male predominance (62.5%). Anxiety, social phobia, depression, acute and chronic psychological disorders, and poor quality of life related to mental health were significantly more prevalent in caregivers of asthmatic children (p<0.05). On multivariate analysis, all of the above disorders significantly increased the risk of uncontrolled asthma, where anxiety, acute psychological disorders, and chronic psychological disorders were the most significant (OR 8.54, 95%CI 3.46-21.05, p<0.001; OR 6.05, 95%CI 2.39-15.28, p<0.001; and OR 4.86, 95%CI 1.97-12.02, p=0.001, respectively). CONCLUSION: The prevalence of psychosocial disorders in caregivers of asthmatic children is high, when compared to caregivers of healthy children. The presence of anxiety, social phobia, depression, and poor quality of life is associated with an increased risk of worse controlled asthma. Perhaps, early detection and treatment of these disorders could positively impact childhood asthma control.

Prevalence and burden of bronchiectasis in a lung cancer screening program.

INTRODUCTION: The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program. METHODS: 3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period. RESULTS: The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p<0.001). The occurrence of false positives was higher in subjects with bronchiectasis (26%vs17%;p = 0.003). During follow-up, new nodules were more common among subjects with bronchiectasis (17%vs.12%; p = 0.008). The total number of false positives during follow-up was 29(17.06%) for patients with bronchiectasis vs. 88(12.17%) for controls (p = 0.008).The incidence rate of lung cancer during follow-up was 6.8/1000 and 5.1/1000 person-years for each group respectively (p = 0.62). CONCLUSIONS: Bronchiectasis are common among current and former smokers undergoing lung cancer screening with LDCT. The presence of bronchiectasis is associated with greater incidence of new nodules and false positives on baseline and follow-up screening rounds. This leads to an increase need of diagnostic tests, although the lung cancer occurrence is not different.

Emphysema phenotypes and lung cancer risk.

BACKGROUND: To assess the relationship between lung cancer and emphysema subtypes. OBJECTIVE: Airflow obstruction and emphysema predispose to lung cancer. Little is known, however, about the lung cancer risk associated with different emphysema phenotypes. We assessed the risk of lung cancer based on the presence, type and severity of emphysema, using visual assessment. METHODS: Seventy-two consecutive lung cancer cases were selected from a prospective cohort of 3,477 participants enrolled in the Clínica Universidad de Navarra's lung cancer screening program. Each case was matched to three control subjects using age, sex, smoking history and body mass index as key variables. Visual assessment of emphysema and spirometry were performed. Logistic regression and interaction model analysis were used in order to investigate associations between lung cancer and emphysema subtypes. RESULTS: Airflow obstruction and visual emphysema were significantly associated with lung cancer (OR = 2.8, 95%CI: 1.6 to 5.2; OR = 5.9, 95%CI: 2.9 to 12.2; respectively). Emphysema severity and centrilobular subtype were associated with greater risk when adjusted for confounders (OR = 12.6, 95%CI: 1.6 to 99.9; OR = 34.3, 95%CI: 25.5 to 99.3, respectively). The risk of lung cancer decreases with the added presence of paraseptal emphysema (OR = 4.0, 95%CI: 3.6 to 34.9), losing this increased risk of lung cancer when it occurs alone (OR = 0.7, 95%CI: 0.5 to 2.6). CONCLUSIONS: Visual scoring of emphysema predicts lung cancer risk. The centrilobular phenotype is associated with the greatest risk.

Clinical Features of Smokers With Radiological Emphysema But Without Airway Limitation.

BACKGROUND: The clinical characteristics of patients with emphysema but without airway limitations remain unknown. The goal of this study was to compare the clinical features of current and former smokers without airflow limitation who have radiologic emphysema on chest CT scans vs a control group of current and ex-smokers without emphysema. METHODS: Subjects enrolled had anthropometric characteristics recorded, provided a medical history, and underwent low-dose chest CT scanning. The following parameters were also evaluated: pulmonary function tests including diffusion capacity for carbon monoxide (Dlco), the modified Medical Research Council dyspnea score, COPD assessment test (CAT), and 6-min walk test (6MWT). A comparison was conducted between those with and without CT-confirmed emphysema. RESULTS: Of the 203 subjects, 154 had emphysema, and 49 did not. Adjusted group comparisons revealed that a higher proportion of patients with emphysema according to low-dose chest CT scanning had an abnormal Dlco value (< 80%) (46% vs 19%; P = .02), a decrease in percentage of oxygen saturation > 4% during the 6MWT (8.5% vs 0; P = .04), and an altered quality of life (CAT score ≥ 10) (32% vs 14%; P = .01). A detailed analysis of the CAT questionnaire items revealed that more patients with emphysema had a score ≥ 1 in the "chest tightness" (P = .05) and "limitation when doing activities at home" (P < .01) items compared with those with no emphysema. They also experienced significantly more exacerbations in the previous year (0.19 vs 0.04; P = .02). CONCLUSIONS: A significant proportion of smokers with emphysema according to low-dose chest CT scanning but without airway limitation had alterations in their quality of life, number of exacerbations, Dlco values, and oxygen saturation during the 6MWT test.

Lung cancer screening in patients with chronic obstructive pulmonary disease.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development.

OBJECTIVES: Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development. MATERIALS AND METHODS: Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (<0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer. RESULTS: After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor. CONCLUSION: In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.

Is COPD a Progressive Disease? A Long Term Bode Cohort Observation.

BACKGROUND: The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades. OBJECTIVE: Explore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up. METHODS: Patients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a "survival selection" bias. The proportion of patients that had a change (improvement or worsening) in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade. RESULTS: A total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and 11% of non survivors had an improvement of at least one GOLD grade. Seventy one percent of survivors and non-survivors remained in the same GOLD grade. Those that improved had a greater degree of airway obstruction at baseline. CONCLUSIONS: In this selected population of COPD patients, a high proportion of patients remained in the same spirometric GOLD grade or improved in a long-term follow-up. These findings suggest that once diagnosed, COPD is usually a non-progressive disease.

Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT.

BACKGROUND: A major drawback of lung cancer screening programs is the high frequency of false-positive findings on computed tomography (CT). We investigated the accuracy of selective 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan in assessing radiologically indeterminate lung nodules detected in lung cancer screening. METHODS: FDG PET/CT was performed to characterize 64 baseline lung nodules >10mm and 36 incidence nodules detected on low-dose CT screening in asymptomatic current or former smokers (83 men, age range 40-83 years) at high risk for lung cancer. CT images were acquired without intravenous contrast. Nodules were analyzed by size, density, and metabolic activity and visual scored on a 5-point scale for FDG uptake. Nodules were classified as negative for malignancy when no FDG uptake was observed, or positive when focal uptake was observed in the visual analysis, and the maximum standardized uptake value (SUVmax) was measured. Final diagnosis was based on histopathological evaluation or at least 24 months of follow-up. RESULTS: A total of 100 nodules were included. The prevalence of lung cancer was 1%. The sensitivity, specificity, NPV and PPV of visual analysis to detect malignancy were 84%, 95%, 91%, and 91%, respectively, with an accuracy of 91% (AUC 0.893). FDG PET/CT accurately detected 31 malignant tumors (diameters 9-42mm, SUVmax range 0.6-14.2) and was falsely negative in 6 patients. With SUVmax thresholds for malignancy of 1.5, 2, and 2.5, specificity was 97% but sensitivity decreased to 65%, 49%, and 46% respectively, and accuracy decreased to 85%, 79%, and 78% respectively (AUC 0.872). CONCLUSIONS: The visual analysis of FDG PET/CT scan is highly accurate in characterizing indeterminate pulmonary nodules detected in lung cancer screening with low-dose CT. Semi-quantitative analysis does not improve the accuracy of FDG PET/CT over that obtained with a qualitative method for lung nodule characterization.

Lung cancer screening: fourteen year experience of the Pamplona early detection program (P-IELCAP).

INTRODUCTION AND OBJECTIVES: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain. METHODOLOGY: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) is actively screening participants for lung cancer using LDCT since year 2000 following the IELCAP protocol, including spirometric assessments. Men and women, ≥40 years of age, current or former smokers with a tobacco history of ≥10 pack-years are included. Results are compared to those from other European trials. RESULTS: A total of 2989 participants were screened until March 2014 (73% male). A median of 2 (IQR 1-3) annual screening rounds were performed. Sixty lung cancers were detected in 53 participants (73% in StageI). Adenocarcinoma was the most frequent. The lung cancer prevalence and incidence proportion was 1.0% and 1.4%, respectively, with an annual detection rate of 0.41. The estimated 10-year survival rate among individuals with lung cancer was 70%. Chronic obstructive pulmonary disease and emphysema are important lung cancer predictors. CONCLUSIONS: The experience in Spain's longest lung cancer screening program is comparable to what has been described in the rest of Europe, and confirms the feasibility and efficacy of lung cancer screening using LDCT.

Comorbidity Distribution, Clinical Expression and Survival in COPD Patients with Different Body Mass Index.

Rationale: Contrary to the general population, in patients with chronic obstructive pulmonary disease (COPD) a low body mass index (BMI) is associated with excess mortality, while obesity appears protective (obesity paradox). We hypothesized that BMI is associated with a distinct number and expression of comorbidities in patients with COPD. The type of comorbidity may relate to mortality variability. Objectives and Methods: We followed 1659 COPD patients for a median of 51 months [IQR 27-77] with detailed comorbidity records and tracking pulmonary function, exercise capacity, dyspnea, health status, and cause of death. The cohort was categorized into the 5 National Heart Lung and Blood Institute (NHLBI) BMI groups with determination made about each group's relationship to specific comorbidities, clinical parameters and risk for death. Results: Whereas osteoporosis, substance abuse, abdominal aortic aneurism and peripheral arterial disease were more prevalent in patients with low BMI, metabolic and cardiac problems were more frequent in those with high BMI. The BMI was inversely related to the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC)(FEV1 %), BODE (Body mass index, airway Obstruction, Dyspnea, Exercise capacity) index and hyperinflation, had a "U" shape with dyspnea and the St. George's Respiratory Questionaire (SGRQ) score and an inverse "U" with exercise capacity. The crude mortality rate was 60%, 43%, 37%, 36% and 28% from the lowest to highest BMI groups (p<.0001). More respiratory deaths were observed in the lowest BMI group even though they had a lower number of comorbidities. Conclusions: Different BMI categories are associated with distinct clinical expressions of COPD and comorbidity patterns. The relationship between BMI and mortality in patients with COPD remains an unresolved paradox.