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.

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.

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort.

BACKGROUND: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. METHODS AND FINDINGS: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. CONCLUSION: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age.

Prospective comparison of non-invasive risk markers of major cardiovascular events in COPD patients.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients. The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients. METHODS: CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables. The predictive power of each parameter was explored using CV events as the main outcome. RESULTS: During a median follow up of 65 months (ICR: 36-100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%). A total of 35 CV deaths occurred during that period. Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events. Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19-1.46, p < 001). CONCLUSIONS: In COPD patients attending pulmonary clinics, CAC was the best independent non-invasive predictor of CV events. This tool may help evaluate the risk for a CV event in patients with COPD. Larger studies should reproduce and validate these findings.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

Differences in cardiopulmonary exercise test results by American Thoracic Society/European Respiratory Society-Global Initiative for Chronic Obstructive Lung Disease stage categories and gender.

BACKGROUND: The American Thoracic Society (ATS)/European Respiratory Society (ERS)-Global Initiative for Chronic Obstructive Lung Disease (GOLD) has developed a new staging system based on the degree of airflow obstruction. Its validity to predict exercise capacity as an outcome has not been extensively studied. We hypothesized that exercise performance measured by cardiopulmonary exercise test (CPET) results should decline significantly with each disease stage, independent of gender. METHODS: We examined 453 consecutive incremental CPET and pulmonary function tests performed in patients who had been referred to a single respiratory physiology laboratory in a tertiary care hospital. They were divided into a control group (normal lung function) and ATS/ERS-GOLD stages 1 to 4. We measured anthropometrics, peak work (in watts), peak oxygen uptake (in liters per kilogram per minute and percent predicted), breathing reserve (in percent predicted), and arterial blood gas response. We compared these results between different stages and genders. RESULTS: The mean (+/- SD) age for the entire group was 64 +/- 11 years, the mean FEV(1) was 66 +/- 28%, and the mean body mass index (BMI) was 27.2 +/- 5.82 kg/m(2). Patients in stage 4 were significantly younger (p < 0.001) and had a lower BMI (p < 0.02) compared to those in stages 1 to 3. There was a significant reduction in exercise capacity for patients at every stage except for those in stage 1, who had values similar to those of the control group. Women had better lung function and exercise capacity than men, but the difference disappeared when adjusted by COPD stages. CONCLUSIONS: The ATS/ERS-GOLD staging system can be used to indicate differences in exercise capacity in patients with COPD stages 2 to 4 and to normalize apparent gender disparities. The value of differentiating stage 1 patients requires further studies with different outcomes.

Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD.

BACKGROUND: Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited information relating levels of systemic inflammatory markers with symptoms and physiologic changes during an exacerbation METHODS: We measured dyspnea using the visual analog scale, pulmonary function tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene B(4) (LTB4), tumor necrosis factor-alpha, and secretory leukocyte protease inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge (recovery). RESULTS: Dyspnea was present in all patients. Inspiratory capacity improved faster than FEV(1). Compared to recovery, there was a significant increase in the mean (+/- SD) hospital admission plasma levels of IL-6 (6.38 +/- 0.72 to 2.80 +/- 0.79 pg/mL; p = 0.0001), IL-8 (8.18 +/- 0.85 to 3.72 +/- 0.85 pg/mL; p = 0.002), and LTB4 (8,675 +/- 1,652 to 2,534 +/- 1,813 pg/mL; p = 0.003), and the percentages of segmented neutrophils (79 to 69%; p < 0.02) and band forms (7.3 to 1.0%; p < 0.01) in peripheral blood, with no changes in TNF-alpha and SLPI. There were significant correlations between changes in IL-6 (r = 0.61; p = 0.01) and IL-8 (r = 0.56; p = 0.04) with changes in dyspnea and levels of IL-6 (r = -0.51; p = 0.04) and TNF-alpha (r = -0.71; p < 0.02) with changes in FEV(1.) CONCLUSIONS: Hospitalized patients with ECOPDs experience significant changes in systemic cytokine levels that correlate with symptoms and lung function. An ECOPD represents not only a worsening of airflow obstruction but also increased systemic demand in a host with limited ventilatory reserve.

Cough and phlegm are important predictors of health status in smokers without COPD.

STUDY OBJECTIVES: The health-related quality of life of smokers without COPD and that of ex-smokers has not been defined. If abnormal, the role of small airways disease and that of cough and phlegm have never been evaluated. Therefore, the aim of the study was to explore whether the differences in quality of life between smokers and ex-smokers could be explained by cough and phlegm, differences in pulmonary function tests, or exercise capacity. DESIGN: Observational, prospective. SETTING: Pulmonary and Critical Care Division, COPD Center at St. Elizabeth's Medical Center. POPULATION: In 36 smokers, 21 ex-smokers (stopped smoking for > 20 years), 19 never-smokers with normal FVC and FEV(1) values, and 41 patients with COPD (FEV(1) 38 +/- 11% predicted [mean +/- SD]), the St. George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and a 6-min walk distance (6MWD) were performed. RESULTS: The total SGRQ scores were worse in current smokers (15 +/- 15) than in ex-smokers (6 +/- 4) or never-smokers (4 +/- 3) [p < 0.05]. As expected, the worst score was seen in COPD (50 +/- 15). After correcting for cough and phlegm, the difference in SGRQ scores between smokers and ex-smokers disappeared. In current and ex-smokers, the SGRQ score was associated with the exposure to pack-years smoking history (r = 0.45, p < 0.01, and r = 0.83, p < 0.0001, respectively) but independent of lung function or exercise parameters (6MWD). CONCLUSIONS: In smokers without COPD, the abnormal SGRQ score is due to the noxious effect of cigarette smoke, resulting in cough and phlegm, independent of its physiologic effects.

Dermatomiositis juvenil: experiencia clínica y epidemiológica / Juvenile dermatomyositis: clinical and epidemiologic experience

Se estudiaron en forma retrospectiva 27 casos con diagnóstico de Dermatomiositis Juvenil (DMJ) de un total de 1.307 pacientes con enfermedades del tejido conectivo; 19 de los cuales cumplieron con los criterios diagnósticos de Bohan y Peters. El sexo femenino fue el más frecuentemente afectado; el 52,63% de los casos presentaron los primeros síntomas entre los 5 y 9 años; lesiones en piel, debilidad en miembros inferiores y fiebre fueron los motivos de consulta más frecuentes. La Aldolasa y la LDH fueron las enzimas musculares que se elevaron en el mayor número de casos. La electromiografía fue más sensible que la biopsia muscular en el diagnóstico de la enfermedad. Considerando las características epidemiológicas y clínicas encontradas en nuestro estudio, sugerimos que éstas sirvan como pautas para el diagnóstico certero de la DMJ en Venezuela