Santiago Carrizo

Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study.

BACKGROUND The effect of obstructive sleep apnoea-hypopnoea as a cardiovascular risk factor and the potential protective effect of its treatment with continuous positive airway pressure (CPAP) is unclear. We did an observational study to compare incidence of fatal and non-fatal cardiovascular events in simple snorers, patients with untreated obstructive sleep apnoea-hypopnoea, patients treated with CPAP, and healthy men recruited from the general population. METHODS We recruited men with obstructive sleep apnoea-hypopnoea or simple snorers from a sleep clinic, and a population-based sample of healthy men, matched for age and body-mass index with the patients with untreated severe obstructive sleep apnoea-hypopnoea. The presence and severity of the disorder was determined with full polysomnography, and the apnoea-hypopnoea index (AHI) was calculated as the average number of apnoeas and hypopnoeas per hour of sleep. Participants were followed-up at least once per year for a mean of 10.1 years (SD 1.6) and CPAP compliance was checked with the built-in meter. Endpoints were fatal cardiovascular events (death from myocardial infarction or stroke) and non-fatal cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, coronary artery bypass surgery, and percutaneous transluminal coronary angiography). FINDINGS 264 healthy men, 377 simple snorers, 403 with untreated mild-moderate obstructive sleep apnoea-hypopnoea, 235 with untreated severe disease, and 372 with the disease and treated with CPAP were included in the analysis. Patients with untreated severe disease had a higher incidence of fatal cardiovascular events (1.06 per 100 person-years) and non-fatal cardiovascular events (2.13 per 100 person-years) than did untreated patients with mild-moderate disease (0.55, p=0.02 and 0.89, p<0.0001), simple snorers (0.34, p=0.0006 and 0.58, p<0.0001), patients treated with CPAP (0.35, p=0.0008 and 0.64, p<0.0001), and healthy participants (0.3, p=0.0012 and 0.45, p<0.0001). Multivariate analysis, adjusted for potential confounders, showed that untreated severe obstructive sleep apnoea-hypopnoea significantly increased the risk of fatal (odds ratio 2.87, 95%CI 1.17-7.51) and non-fatal (3.17, 1.12-7.51) cardiovascular events compared with healthy participants. INTERPRETATION In men, severe obstructive sleep apnoea-hypopnoea significantly increases the risk of fatal and non-fatal cardiovascular events. CPAP treatment reduces this risk.

Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea The Overlap Syndrome

RATIONALE Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) (overlap syndrome) are more likely to develop pulmonary hypertension than patients with either condition alone. OBJECTIVES To assess the relation of overlap syndrome to mortality and first-time hospitalization because of COPD exacerbation and the effect of continuous positive airway pressure (CPAP) on these major outcomes. METHODS We included 228 patients with overlap syndrome treated with CPAP, 213 patients with overlap syndrome not treated with CPAP, and 210 patients with COPD without OSA. All were free of heart failure, myocardial infarction, or stroke. Median follow-up was 9.4 years (range, 3.3-12.7). End points were all-cause mortality and first-time COPD exacerbation leading to hospitalization. MEASUREMENTS AND MAIN RESULTS After adjustment for age, sex, body mass index, smoking status, alcohol consumption, comorbidities, severity of COPD, apnea-hypopnea index, and daytime sleepiness, patients with overlap syndrome not treated with CPAP had a higher mortality (relative risk, 1.79; 95% confidence interval, 1.16-2.77) and were more likely to suffer a severe COPD exacerbation leading to hospitalization (relative risk, 1.70; 95% confidence interval, 1.21-2.38) versus the COPD-only group. Patients with overlap syndrome treated with CPAP had no increased risk for either outcome compared with patients with COPD-only. CONCLUSIONS The overlap syndrome is associated with an increased risk of death and hospitalization because of COPD exacerbation. CPAP treatment was associated with improved survival and decreased hospitalizations in patients with overlap syndrome.

Lung cancer in patients with chronic obstructive pulmonary disease-- incidence and predicting factors.

RATIONALE Little is known about the clinical factors associated with the development of lung cancer in patients with chronic obstructive pulmonary disease (COPD), although airway obstruction and emphysema have been identified as possible risk factors. OBJECTIVES To explore incidence, histologic type, and factors associated with development of lung cancer diagnosis in a cohort of outpatients with COPD attending a pulmonary clinic. METHODS A cohort of 2,507 patients without initial clinical or radiologic evidence of lung cancer was followed a median of 60 months(30–90). At baseline, anthropometrics, smoking history, lung function,and body composition were recorded. Time to diagnosis and histologic type of lung cancer was then registered. Cox analysis was used to explore factors associated with lung cancer diagnosis. MEASUREMENTS AND MAIN RESULTS A total of 215 of the 2,507 patients with COPD developed lung cancer (incidence density of 16.7 cases per 1,000 person-years). The most frequent type was squamous cell carcinoma (44%). Lung cancer incidence was lower in patients with worse severity of airflow obstruction. Global Initiative for Chronic Obstructive Lung Disease Stages I and II, older age, lower body mass index,and lung diffusion capacity of carbon monoxide less than 80%were associated with lung cancer diagnosis. CONCLUSIONS Incidence density of lung cancer is high in outpatients with COPD and occurs more frequently in older patients with milder airflow obstruction (Global Initiative for Chronic Obstructive Lung Disease Stages I and II) and lower body mass index. A lung diffusion capacity of carbon monoxide less than 80% is associated with cancer diagnosis. Squamous cell carcinoma is the most frequent histologic type. Knowledge of these factors may help direct efforts for early detection of lung cancer and disease management.

Prediction of risk of COPD exacerbations by the BODE index.

OBJECTIVES This study assesses the power of the BODE index, a multidimensional grading system that predicts mortality, to predict subsequent exacerbations in patients with COPD. DESIGN Prospective cohort study. PATIENTS AND INTERVENTIONS A total of 275 COPD patients were followed every 6 months up to 8 years (median of 5.1 years). Baseline clinical variables were recorded and the BODE index was calculated. We investigated the prognostic value of BODE quartiles (scores 0-2, 3-4, 5-6 and 7-10) for both the number and severity of exacerbations requiring ambulatory treatment, emergency room visit, or hospitalization. RESULTS The annual rate of COPD exacerbations was 1.95 (95% CI, 0.90-2.1). The mean time to a first exacerbation was inversely proportional to the worsening of the BODE quartiles (7.9 yrs, 5.7 yrs, 3.4 yrs and 1.3 yrs for BODE scores of 0-2, 3-4, 5-6 and 7-10, respectively). Similarly, the mean time to a first COPD emergency room visit was 6.7 yrs, 3.6 yrs, 2.0 yrs and 0.8 yrs for BODE quartiles (all p<0.05). Using ROC curves, the BODE index was a better predictor of exacerbation than the FEV(1) alone (p<0.01). CONCLUSIONS The BODE index is a better predictor of the number and severity of exacerbations in COPD than FEV(1) alone.

Tongue‐Base Suspension in Conjunction with Uvulopalatopharyngoplasty for Treatment of Severe Obstructive Sleep Apnea: Long‐Term Follow‐Up Results

Objectives/Hypothesis: To evaluate the usefulness of tongue‐base suspension (TBS) in addition to uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea syndrome (OSAS).

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), (χ2=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.

Prognostic assessment in COPD: health related quality of life and the BODE index.

RATIONALE COPD is a debilitating disease with increasing mortality worldwide. The BODE index evaluates disease severity and the St Georges Respiratory Questionnaire (SGRQ) measures health status. OBJECTIVE To identify the relationship between BODE index and the SGRQ and to test the predictive value of both tools against survival. METHODS Open cohort study of 1398 COPD patients (85% male) followed for up to 10 years. MEASUREMENTS AND MAIN RESULTS At the time of the inclusion, clinical data, forced spirometry and 6 min walking distance were determined and BODE index and SGRQ were calculated. Vital status and cause of death were documented at the end of follow-up. RESULTS The cohorts mean of FEV1% predicted was 46 ± 18%, BODE index was 3.6 ± 2.5, and SGRQ% total score was 49 ± 20. The SGRQ scores increased progressively as severity of COPD increased by BODE quartiles. The correlation between SGRQ and BODE index was good (r = 0.58, p < 0.0001). Both tests correlated with COPD survival (BODE = -0.4 vs. SGRQ = -0.20, p < 0.0001). The area under the curve (AUC) for the BODE index was 0.77 vs. 0.66 for the SGRQ % total score (p < 0.001). CONCLUSIONS Health status as measured by SGRQ worsens with disease severity evaluated by the BODE index. Both tools predict mortality and provide complimentary information in the evaluation of patients with COPD.

A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations

PURPOSE This prospective, multicenter, double-blind, placebo-controlled study tested the hypothesis that noninvasive positive pressure ventilation reduces the need for endotracheal intubation in patients hospitalized in a pulmonary ward because of acute exacerbation of chronic obstructive pulmonary disease. MATERIALS AND METHODS Seventy-five consecutive patients with exacerbation (pH, 7.31 +/- 0.02; Pao(2), 45 +/- 9 mm Hg; Paco(2), 69 +/- 13 mm Hg) were randomly assigned to receive noninvasive ventilation or sham noninvasive ventilation during the first 3 days of hospitalization on top of standard medical treatment. RESULTS The need for intubation (according to predefined criteria) was lower in the noninvasive ventilation group (13.5% vs 34%, P < .01); in 31 patients with pH not exceeding 7.30, these percentages were 22% and 77%, respectively (P < .001). Arterial pH and Paco(2) improved in both groups, but changes were enhanced by noninvasive ventilation. Length of stay was lower in the noninvasive ventilation group (10 +/- 5 vs 12 +/- 6 days, P = .06). In-hospital mortality was similar in both groups. CONCLUSIONS These results demonstrate that noninvasive positive pressure ventilation, in a pulmonary ward, reduces the need for endotracheal intubation, particularly in the more severe patients, and leads to a faster recovery in patients with acute exacerbation of chronic obstructive pulmonary disease.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of −6 (95% CI −7.7 to −4.2) mm Hg versus −2.8 (95% CI −4.3 to −1.3) mm Hg, (p<0.001) and serum bicarbonate of −3.4 (95% CI −4.5 to −2.3) versus −1 (95% CI −1.7 to −0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. Trial registration number NCT01405976; results.

Protective Cardiovascular Effect of Sleep Apnea Severity in Obesity Hypoventilation Syndrome

BACKGROUND Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS. METHODS In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders. RESULTS The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile. CONCLUSIONS In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS. TRIAL REGISTRY Clinicaltrial.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.