Effectiveness of CPAP vs. Noninvasive Ventilation Based on Disease Severity in Obesity Hypoventilation Syndrome and Concomitant Severe Obstructive Sleep Apnea.

RATIONALE: Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity. OBJECTIVE: To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups. METHODS: Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI)≥30events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45-49.9 or ≥50mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model. RESULTS: 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups. CONCLUSION: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2.

Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study).

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with cardiovascular events (CVEs), although recent randomized controlled trials have not demonstrated that long-term continuous positive airway pressure (CPAP) prevents CVEs. Our objective was to determine the effect of CPAP on older adults with moderate OSA regarding CVE reduction. METHODS: An observational and multicenter study of a cohort of older adults (> 70 years of age) diagnosed with moderate OSA (apnea-hypopnea index 15.0-29.9 events/h) was conducted. Two groups were formed: (1) CPAP treatment and (2) standard of care. The primary endpoint was CVE occurrence after OSA diagnosis. Association with CPAP treatment was assessed by propensity score matching and inverse weighting probability. Secondary endpoints were incidence of CVE separately and time to first CVE. RESULTS: A total of 614 patients were included. After matching, 236 older adults (111 men, mean age 75.9 ± 4.7 years) with a follow-up of 47 months (interquartile range: 29.6-64.0 months) were considered for primary and secondary endpoint evaluations. Forty-one patients presented at least 1 CVE (17.4%): 20 were in the standard-of-care group (16.9%) and 21 were in the CPAP group (17.8%), with a relative risk of 1.05 (95% confidence interval [CI], 0.60-1.83; P = .43) for CPAP treatment. Inverse probability weighting of the initial 614 patients determined an adjusted relative risk of 1.24 (95% CI, 0.79-1.96; P = .35) for CPAP treatment. No statistical differences were found in secondary endpoint analyses. CONCLUSIONS: CPAP should not be prescribed to reduce CVE probability in older adults with moderate OSA. CITATION: López-Padilla D, Terán-Tinedo J, Cerezo-Lajas A, et al. Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study). J Clin Sleep Med. 2022;18(2):553-561.

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS. METHODS: In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a P value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea. RESULTS: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO2 and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98; P = .003 for PaO2, and 1.07; 95% confidence interval 1.03 to 1.12; P = .001 for body mass index). In separate analyses, body mass index and PaO2 were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype. CONCLUSIONS: This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976. CITATION: Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome. J Clin Sleep Med. 2022;18(4):983-992.

[All Roads Lead to Rome: Results of Non-Invasive Respiratory Therapies Applied in a Tertiary-Care Hospital Without an Intermediate Care Unit During the COVID-19 Pandemic]. / Todos los caminos llevan a Roma: resultados de las terapias respiratorias no invasivas aplicadas en un centro terciario sin Unidad de Cuidados Intermedios durante la pandemia de COVID-19.

Introduction: Non-invasive respiratory therapies (NRT) were widely used in the first wave of the COVID-19 pandemic in different settings, depending on availability. The objective of our study was to present 90-day survival and associated factors in patients treated with NRT in a tertiary hospital without an Intermediate Respiratory Care Unit. The secondary objective was to compare the outcomes of the different therapies. Methods: Observational study of patients treated with NRT outside of an intensive care or intermediate respiratory care unit setting, diagnosed with COVID-19 and acute respiratory distress syndrome by radiological criteria and SpO2/FiO2 ratio. A multivariate logistic regression model was developed to determine independently associated variables, and the outcomes of high flow nasal cannula and continuous positive airway pressure were compared. Results: In total, 107 patients were treated and 85 (79.4%) survived at 90 days. Before starting NRT, the mean SpO2/FiO2 ratio was 119.8 ± 59.4. A higher SOFA score was significantly associated with mortality (OR 2,09; 95% CI 1.34-3.27), while self-pronation was a protective factor (OR 0.23; 95% CI 0.06-0.91). High flow nasal cannula was used in 63 subjects (58.9%), and continuous positive airway pressure in 41 (38.3%), with no differences between them. Conclusion: Approximately 4 out of 5 patients treated with NRT survived to 90 days, and no significant differences were found between high flow nasal cannula and continuous positive airway pressure.

Long-term Noninvasive Ventilation in Obesity Hypoventilation Syndrome Without Severe OSA: The Pickwick Randomized Controlled Trial.

BACKGROUND: Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. RESEARCH QUESTION: Is NIV effective in OHS without severe OSA phenotype? STUDY DESIGN AND METHODS: In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups. RESULTS: Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. INTERPRETATION: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.

Cost-effectiveness of positive airway pressure modalities in obesity hypoventilation syndrome with severe obstructive sleep apnoea.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. OBJECTIVES: We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. METHODS: Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. RESULTS: In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. CONCLUSION: CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA. TRIAL REGISTRATION NUMBER: NCT01405976.

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial.

Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.Objectives: In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.Methods: At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV.Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.Conclusions: In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

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.

Ventilación mecánica no invasiva en pacientes con síndrome de obesidad-hipoventilación. Evolución a largo plazo y factores pronósticos / Noninvasive Mechanical Ventilation in Patients with Obesity Hypoventilation Syndrome. Long-term Outcome and Prognostic Factors

Introducción: Desde el punto de vista respiratorio, la obesidad se asocia con 2 enfermedades muy relacionadas: el síndrome de obesidad-hipoventilación (SOH) y el síndrome de apnea-hipopnea del sueño (SAHS). Se ha demostrado que el tratamiento con ventilación mecánica no invasiva durante el sueño produce una mejoría clínica y funcional en estos pacientes. Analizamos a largo plazo la supervivencia con este tratamiento, y la diferencia en la evolución entre pacientes con SOH con y sin SAHS asociado. Metodología: Estudio longitudinal, observacional, de una cohorte de pacientes diagnosticados de SOH e incluidos en un programa de ventilación domiciliaria a lo largo de 12 años, distribuidos en 2 grupos: SOH puro y SOH asociado a SAHS. La ventilación se llevó a cabo con ventiladores de presión positiva continua binivel. Durante el tiempo de seguimiento se monitorizó y comparó su situación clínica (síntomas, exacerbaciones e ingresos), gasométrica y funcional, así como su supervivencia. Resultados: Ochenta y tres pacientes fueron válidos para el análisis, 60 mujeres (72,3%) y 23 hombres (27,7%), con una media de supervivencia de 8,47 años. Cincuenta pacientes (60,2%) fueron incluidos en el grupo sin SAHS (SOH) y 33 (39,8%) en el grupo con SAHS (SOH-SAHS). La PaCO2 del grupo SOH era significativamente mayor que la del grupo SOH-SAHS (p < 0,01), y también presentaban más hospitalizaciones (p < 0,05). Existió una mejoría significativa en ambos grupos en FEV1 y FVC, y en los valores de PaCO2 y PaO2, sin diferencias entre los grupos. Mientras que no se apreciaron diferencias en la supervivencia relacionadas con el subgrupo diagnóstico, valores bajos de FVC sí constituían un factor predictivo de mortalidad. Conclusiones: El uso de ventilación domiciliaria en pacientes con SOH con o sin SAHS es un tratamiento eficaz que corrige las alteraciones gasométricas y funcionales y permite alcanzar tiempos prolongados de supervivencia

Introduction: Obesity is associated with 2 closely related respiratory diseases: obesity hypoventilation syndrome (OHS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). It has been shown that noninvasive ventilation during sleep produces clinical and functional improvement in these patients. The long-term survival rate with this treatment, and the difference in clinical progress in OHS patients with and without OSAHS are analyzed. Methodology: Longitudinal, observational study with a cohort of patients diagnosed with OHS, included in a home ventilation program over a period of 12 years, divided into 2 groups: pure OHS and OSAHS associated OHS. Bi-level positive airway pressure ventilation was administered. During the follow-up period, symptoms, exacerbations and hospitalizations, blood gas tests and pulmonary function tests, and survival rates were monitored and compared Results: Eighty-three patients were eligible for analysis, 60 women (72.3%) and 23 men (27.7%), with a mean survival time of 8.47 years. Fifty patients (60.2%) were included in the group without OSAHS (OHS) and 33 (39.8%) in the OSAHS-associated OHS group (OHS-OSAHS). PaCO2 in the OHS group was significantly higher than in the OHS-OSAHS group (P < .01). OHS patients also had a higher hospitalization rate (P < .05). There was a significant improvement in both groups in FEV1 and FVC, and no differences between groups in PaCO2 and PaO2 values. There were no differences in mortality between the 2 groups, but low FVC values were predictive of mortality. Conclusions: The use of mechanical ventilation in patients with OHS, with or without OSAHS, is an effective treatment for the correction of blood gases and functional alterations and can achieve prolonged survival rates

Noninvasive mechanical ventilation in patients with obesity hypoventilation syndrome. Long-term outcome and prognostic factors.

INTRODUCTION: Obesity is associated with 2 closely related respiratory diseases: obesity hypoventilation syndrome (OHS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). It has been shown that noninvasive ventilation during sleep produces clinical and functional improvement in these patients. The long-term survival rate with this treatment, and the difference in clinical progress in OHS patients with and without OSAHS are analyzed. METHODOLOGY: Longitudinal, observational study with a cohort of patients diagnosed with OHS, included in a home ventilation program over a period of 12 years, divided into 2 groups: pure OHS and OSAHS-associated OHS. Bi-level positive airway pressure ventilation was administered. During the follow-up period, symptoms, exacerbations and hospitalizations, blood gas tests and pulmonary function tests, and survival rates were monitored and compared. RESULTS: Eighty-three patients were eligible for analysis, 60 women (72.3%) and 23 men (27.7%), with a mean survival time of 8.47 years. Fifty patients (60.2%) were included in the group without OSAHS (OHS) and 33 (39.8%) in the OSAHS-associated OHS group (OHS-OSAHS). PaCO2 in the OHS group was significantly higher than in the OHS-OSAHS group (P<.01). OHS patients also had a higher hospitalization rate (P<.05). There was a significant improvement in both groups in FEV1 and FVC, and no differences between groups in PaCO2 and PaO2 values. There were no differences in mortality between the 2 groups, but low FVC values were predictive of mortality. CONCLUSIONS: The use of mechanical ventilation in patients with OHS, with or without OSAHS, is an effective treatment for the correction of blood gases and functional alterations and can achieve prolonged survival rates.

'Smoking genes': a genetic association study.

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).

Limitaciones del tratamiento actual: necesidades no cubiertas en el tratamiento de la EPOC / Limitations of current treatment: unmet needs in the treatment of COPD

En las 2 últimas décadas se ha despertado un considerable interés en el tratamiento de la enfermedad pulmonarobstructiva crónica (EPOC), y se ha pasado de una situación de nihilismo terapéutico a otra mucho más proactiva,plasmada en la aparición de diferentes guías y recomendaciones de sociedades científicas. Podemos distinguir3 peldaños fundamentales en el tratamiento: la prevención de la enfermedad, el tratamiento de sus síntomas, progresión y complicaciones, así como la recuperación de la función física de los pacientes mediante la rehabilitación respiratoria. En las 3 dimensiones se han producido considerables avances pero se detectan limitaciones y, por tanto, áreas de mejora. El tratamiento del tabaquismo es la mejor terapéutica para prevenir la enfermedad, pero, si bien se dispone de fármacos de moderada eficacia para la abstención puntual, no ocurre lo mismo a la hora de evitar recaídas. Además, razones de política sanitaria hacen que la mayoría de los pacientes con EPOC no accedan al tratamiento farmacológico del tabaquismo. En relación con el tratamiento de la enfermedad y sus complicaciones, éste se apoya en la utilización de broncodilatadores, capaces de mejorar síntomas, calidad de vida y, en mayor o menor medida, evitar exacerbaciones. Sin embargo, el tratamiento dirigido a las bases patogénicas de la enfermedad, que debería ser el tratamiento antiinflamatorio, continúa siendo una asignatura pendiente debido a losescasos resultados ofrecidos por los corticoides inhalados, que siempre deben utilizarse combinados con un broncodilatador(AU)

La aparición de nuevos antiinflamatorios, como el roflumilast, puede mejorar el manejo de los pacientes más graves y con repetidas exacerbaciones. Por último, aunque la rehabilitación respiratoria muestra una gran eficacia en la recuperación de la capacidad de ejercicio de los pacientes, son pocos los enfermos que pueden acceder a aquélla, y tal como ocurría con el tratamiento del tabaquismo, se detecta la necesidad de implementar suutilización a través de nuevos programas sencillos, eficaces y con apoyo de la administración sanitaria(AU)

In the last few years, considerable interest has been aroused in the treatment of chronic obstructive pulmonarydisease (COPD) and the dearth of therapeutic options has been replaced by a far more proactive treatmentapproach, reflected in the development of the various guidelines and recommendations of the scientific societies.There are three main steps in the treatment of COPD: prevention of the disease, treatment of its symptoms,progression and complications, and recovery of physical function through respiratory rehabilitation. Considerableadvances have been produced in these three dimensions, but limitations have been detected, indicating areas forimprovement. The most effective means to prevent the disease is smoking cessation. While there are moderatelyeffective drugs to help individuals quit, no drugs are available to prevent relapses. Moreover, due to healthpolicies, most patients with COPD do not receive drug treatment for smoking. The treatment of COPD and itscomplications is based on the use of bronchodilators, which improve symptoms and quality of life and, to agreater or lesser extent, prevent exacerbations. However, treatment aimed at the underlying pathogenic causesof the disease, which should be antiinflammatory treatment, remains an unresolved issue due to the discouragingresults obtained with inhaled corticosteroids, which should always be used in combination with a bronchodilator.The development of new antiinflammatory agents, such as roflumilast, could improve the management ofpatients with the most severe disease and repeated exacerbations. Lastly, although respiratory rehabilitation ishighly effective in helping patients recover their ability to exercise, few patients have access to this option. Aswith the treatment of smoking, there is a need to implement respiratory rehabilitation through simple andeffective programs and with the support of the health administration(AU)

[Limitations of current treatment: unmet needs in the treatment of COPD]. / Limitaciones del tratamiento actual: necesidades no cubiertas en el tratamiento de la EPOC.

In the last few years, considerable interest has been aroused in the treatment of chronic obstructive pulmonary disease (COPD) and the dearth of therapeutic options has been replaced by a far more proactive treatment approach, reflected in the development of the various guidelines and recommendations of the scientific societies. There are three main steps in the treatment of COPD: prevention of the disease, treatment of its symptoms, progression and complications, and recovery of physical function through respiratory rehabilitation. Considerable advances have been produced in these three dimensions, but limitations have been detected, indicating areas for improvement. The most effective means to prevent the disease is smoking cessation. While there are moderately effective drugs to help individuals quit, no drugs are available to prevent relapses. Moreover, due to health policies, most patients with COPD do not receive drug treatment for smoking. The treatment of COPD and its complications is based on the use of bronchodilators, which improve symptoms and quality of life and, to a greater or lesser extent, prevent exacerbations. However, treatment aimed at the underlying pathogenic causes of the disease, which should be antiinflammatory treatment, remains an unresolved issue due to the discouraging results obtained with inhaled corticosteroids, which should always be used in combination with a bronchodilator. The development of new antiinflammatory agents, such as roflumilast, could improve the management of patients with the most severe disease and repeated exacerbations. Lastly, although respiratory rehabilitation is highly effective in helping patients recover their ability to exercise, few patients have access to this option. As with the treatment of smoking, there is a need to implement respiratory rehabilitation through simple and effective programs and with the support of the health administration.