[Show abstract][Hide abstract] ABSTRACT: Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although its clinical application is difficult.
In order to identify patients with ACOS, a cohort of well-characterized patients with COPD and up to one-year follow-up was analyzed. We evaluated the presence of specific characteristics associated to asthma in this COPD cohort, divided in major criteria (bronchodilator test greater than 400 ml and 15% and past medical history of asthma) and minor criteria (blood eosinophils greater than 5%, IgE>100 UI/ml, or two separate bronchodilator tests greater than 200 ml and 12%). We defined ACOS by the presence of one major criterion or two minor criteria. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between patients with and without criteria for ACOS.
Out of 831 COPD patients included,125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after one year. Patients with ACOS were predominantly male (81.6%), with symptomatic mild to moderate disease (67%), and receiving inhaled corticosteroids (63.2%). There were no significant differences in baseline characteristics, and only survival was worse in non-ACOS COPD patients after one-year of follow-up (p <0.05).
The proposed ACOS criteria are present in 15% of a cohort of COPD patients and these patients show better one-year prognosis than clinically similar COPD patients with no ACOS criteria.
[Show abstract][Hide abstract] ABSTRACT: The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in OHS patients, information regarding efficacy is limited.
We performed a large multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure.
Sequentially screened OHS patients with severe sleep apnea were randomized into the above-mentioned groups for a two-month follow-up. Arterial blood gases parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, six-minute walk distance (6-MWD), dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed.
In total, 221 patients were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, the spirometry and 6-MWD results improved more with NIV than CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP.
NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01405976.
American Journal of Respiratory and Critical Care Medicine 04/2015; 192(1). DOI:10.1164/rccm.201410-1900OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The modified Medical Research Council (mMRC) dyspnea, the Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by the GOLD initiative for assessing symptoms in COPD patients. However, there are no data on the prognostic value of these tools in terms of mortality.
To evaluate the prognostic value of the CAT and CCQ scores and compare with modified Medical Research Council (mMRC) dyspnea.
We analyzed the ability of these tests to predict mortality in an observational cohort of 768 COPD patients (82% males; FEV1 60%) from the CHAIN study, a multicenter observational Spanish cohort who were monitored annually for a mean follow-up time of 38 months.
Subjects who died (n=73; 9.5%) had higher CAT (14 vs. 11, p=0.022), CCQ (1.6 vs. 1.3, p=0.033), and mMRC dyspnea scores (2 vs. 1, p<0.001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥17 and CCQ scores >2.5 provided a similar sensitivity than mMRC dyspnea scores ≥2 to predict all-cause mortality.
The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with chronic obstructive pulmonary disease, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification.
ClinicalTrials.gov Identifier: NCT01122758.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the outcomes of standard automated perimetry (SAP) in patients with obstructive sleep apnea (OSA).
Eighty OSA patients and 111 age-matched controls were consecutively and prospectively enrolled. One eye per subject was randomly selected. All participants underwent at least one reliable SAP (24-2 SITA Standard algorithm). The peripapillary retinal nerve fiber layer thickness (RNFL) was measured with spectral-domain optical coherence tomography (OCT). Patients with OSA were classified into three groups according to the apnea/hypopnea index: mild, moderate, or severe OSA. Parameters of SAP and OCT were compared between healthy controls and OSA patients. Correlation of apnea/hypopnea index with OCT and SAP measurements were calculated.
Mean age, best-corrected visual acuity, and central corneal thickness were similar between groups. Intraocular pressure, however, was lower in the OSA group. Mean deviation of SAP was -0.23 ± 0.8 dB in the control group and -1.74 ± 2.8 dB in the OSA group (P < 0.001). Thickness of RNFL measured with OCT did not differ significantly between groups. Patients with OSA showed reduced sensitivity at most points tested by white-on-white perimetry compared with healthy individuals. The threshold values were more depressed in the peripheral visual field. The apnea/hypopnea index was related to the SAP indices: Pearson correlations were -0.432 with mean deviation, 0.467 with pattern standard deviation, and -0.416 with the visual field index (P < 0.001).
Patients with OSA exhibited reduced retinal sensitivity measured with SAP compared with healthy controls.
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnoea (OSA) is defined as the presence of more than five events of complete obstruction (apnoea) or partial obstruction (hypopnea) of the pharynx [apnoea–hypopnaea index (AHI) >5] per hour of sleep. Among adults, more than 24% of men and 9% of women suffer from OSA each night . When a patient with OSA presents daytime sleepiness that affects work or social activity, OSA syndrome is diagnosed. Almost all patients with OSA snore and experience unrefreshed sleep but tend not to consult their general practitioner (GP) regarding this symptomatology.This article is protected by copyright. All rights reserved.
Journal of Internal Medicine 08/2014; 276(6). DOI:10.1111/joim.12300 · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The forced expiratory volume at first second (FEV1) during spirometry reflects the severity of Chronic Obstructive Pulmonary Disease (COPD) and is known to be an important prognostic factor. It is uncertain whether the response to short-acting bronchodilators may predict long-term outcomes such as hospitalizations and mortality.
We retrospectively studied a total of 1203 consecutive COPD patients without significant co-morbidities during a mean (±SD) of 69±39 months of follow-up. At baseline the subjects were classified as those with positive or negative bronchodilator test (BDT) and also in quartiles of absolute bronchodilator response to 400 μg of salbutamol. Hospital visits and mortality were the end points.
A positive bronchodilator test was observed in 332 (27.6%) of the patients. There were 73 (21.9%) deaths in patients with a positive BDT versus 253 (28.7%) in those with a negative BDT (p=0.04). In adjusted Cox regression analysis a positive BDT was significantly associated with a prolonged time to first hospitalization. After stratifying the population by quartiles of response to BDT, a dose-response relationship was observed with the best outcomes in the quartile with highest level of airflow reversibility, even after controlling for age, sex, BMI, smoking status and baseline postbronchodilator FEV1
In a large population of well characterized COPD patients without significant comorbidities, those demonstrating higher levels of reversibility at baseline presented better long-term outcomes even after controlling for other known prognostic factors.
Respiratory Medicine 08/2014; 108(8). DOI:10.1016/j.rmed.2014.05.006 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610).
EPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines.
EPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects.
BMC Pulmonary Medicine 07/2014; 14(1):114. DOI:10.1186/1471-2466-14-114 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion.
This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea–hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox’s proportional regression analyses after adjusting for relevant confounders.
In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02–1.41). The closest association was shown in patients <65 years in both the AHI (continuous log-transformed AHI, HR, 1.87; 95% CI, 1.1–3.2; upper vs lower AHI tertile, HR, 3.98; 95% CI, 1.14–3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23–2.4; upper vs lower TSat90 tertile: HR, 14.4; 95% CI, 1.85–111.6).
OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.
Sleep Medicine 07/2014; 15(7). DOI:10.1016/j.sleep.2014.01.020 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary and Sleep MedicineSESSION TYPE: Slide PresentationPRESENTED ON: Saturday, March 22, 2014 at 09:00 AM - 10:00 AMPURPOSE: Intermittent hypoxia and increase sympathetic activity during apnea episodes may cause systemic inflammation via down-regulation of regulatory T-cell (Treg cells). This may contribute to premature atherosclerosis leading to an increase in the size of arterial intima-media thickness (IMT). To evaluate the relationship between Treg plasma cells and intima-media thickness (IMT) in non-OSA and OSA patients without comorbidities
During a 10 months period, we enrolled 100 adults (age range: 20 to 55) among those referred for sleep study due to suspected OSA. Exclusion criteria were: history of tobacco or alcohol consumption, hypertension, dyslipidemia, diabetes, cardiovascular, cerebrovascular, renal, neuromuscular, inflammatory or autoimmune chronic diseases. OSA diagnosis was made on the basis of an apnea/hypopnea index (AHI) > 5. IMT was assessed in common carotid arteries by high-resolution B-mode ultrasonography. By flow-cytometry analysis, CD+CD25+Foxp3+ cells as were acquired (BD Pharmigen) and identified as Treg cells.
Non-OSA subjects (n = 30) were younger (41 ± 8 vs 45 ± 8 years, p = 0.02) and had a lower body mass index (26.4 ± 3.8 vs 30.1 ± 5.5 kg/m2, p < 0.001) than OSA patients (n = 70). IMT was 0.53 ± 0.08 (95 percentile: 0.65 mm) and 0.66 ± 0.12 mm respectively (p<0.001). Abnormal IMT (> 0.65 mm) was identified in 41% of OSA group. In multivariate linear regression analyses, age, BMI and baseline systolic blood pressure but not AHI, were related with IMT. Treg cells represent 7.5 ± 1.6% of all CD3 (lymphocytes) in non-OSA subjects and 6.7 ± 1.4 % in OSA patients. IMT and Treg cells were significantly related (r = -0.29, p =0.007).
Down regulation of Treg cells but not AHI is associated with subclinical atherosclerosis suggesting different epigenetic adaptations to apnea episodes in OSA.
The effect of nocturnal intermittent hypoxia and increase sympathetic activity is not homogeneous among all patients with OSA. It seems that a subset of patients exhibit an increased risk of subclinical atherosclerosis associated with a down-regulation of regulatory T-cells. This subgroup of patients probably represents a particular phenotypic presentation of OSA that merits a specific treatment. Supported by ISCIII grant PI12/02175 and SEPAR-2014DISCLOSURE: The following authors have nothing to disclose: Marta Marin-Oto, Teresa Martin, Javier Godino, Marta Andres, Victoria Gil, Jose MarinNo Product/Research Disclosure Information.
[Show abstract][Hide abstract] ABSTRACT: FEV1 is universally used as a measure of severity in COPD. Current thresholds are based on expert opinion and not on evidence.
We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.
We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS). Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.
A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%). Overall 975 (28.1%) patients died at 5 years. The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%. Survival at 5 years was 0.89 for patients with FEV1≥70 vs. 0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74). The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001). Prognostic reliability is maintained at 1, 3, 5, and 10 years. In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.
The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%. These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs.
PLoS ONE 02/2014; 9(2):e89866. DOI:10.1371/journal.pone.0089866 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT RATIONALE:
The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was proposed for assessing health status in COPD, but little is known about its longitudinal changes.
To evaluate one-year CAT variability in stable COPD patients and relate its variations to changes in other disease markers.
We evaluated the following variables in smokers with and without COPD at baseline and after one year: CAT score, age, gender, smoking status, pack-years history, BMI, modified Medical Research Council (MMRC) scale, 6MWD, lung function, BODE index, hospital admissions, Hospital and Depression Questionnaire, and the Charlson comorbidity score. In COPD patients we explored the association of CAT scores and its one-year changes with the studied parameters.
824 smokers with COPD and 126 without were evaluated at baseline, and 441 smokers with COPD and 66 without one year later. At 1 year, CAT scores for COPD patients were similar (±4 points) in 56%, higher in 27%, and lower in 17%. Interestingly, MMRC scores were similar (± 1 point) in 46% of patients, worse in 36% and better in 18% at 1 year. One-year CAT changes were best predicted by changes in MMRC scores (β coefficient 0.47, p<0.001). A similar behavior was found for CAT and MMRC in smokers without COPD.
One-year longitudinal data shows variability in CAT scores among stable COPD patients, similar to what happened to MMRC that was the best predictor of one-year CAT changes. Further longitudinal studies should confirm the long-term CAT variability and it clinical applicability.
[Show abstract][Hide abstract] ABSTRACT: Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD).
To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only.
We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data.
At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722).
In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index.
Respiratory research 01/2014; 15(1):3. DOI:10.1186/1465-9921-15-3 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sleep in chronic obstructive pulmonary disease (COPD) is commonly associated with oxygen desaturation, which may exceed the degree of desaturation during maximum exercise, both subjectively and objectively impairing sleep quality. The mechanisms of desaturation include hypoventilation and ventilation to perfusion mismatching. The consequences of this desaturation include cardiac arrhythmias, pulmonary hypertension and nocturnal death, especially during acute exacerbations. Coexistence of COPD and obstructive sleep apnoea (OSA), referred to as overlap syndrome, has been estimated to occur in 1% of the general adult population. Overlap patients have worse sleep-related hypoxaemia and hypercapnia than patients with COPD or OSA alone. OSA has a similar prevalence in COPD as in a general population of similar age, but oxygen desaturation during sleep is more pronounced when the two conditions coexist. Management of sleep-related problems in COPD should particularly focus on minimising sleep disturbance via measures to limit cough and dyspnoea; nocturnal oxygen therapy is not generally indicated for isolated nocturnal hypoxaemia. Treatment with continuous positive airway pressure alleviates hypoxaemia, reduces hospitalisation and pulmonary hypertension, and improves survival.
European Respiratory Review 09/2013; 22(129):365-75. DOI:10.1183/09059180.00003213