Rafael Golpe

Clinical Heterogeneity among Patients with Obesity Hypoventilation Syndrome: Therapeutic Implications

Background: Obesity hypoventilation syndrome (OHS) can be treated with noninvasive positive pressure ventilation (NIPPV). Once clinical stability is achieved, continuous positive airway pressure (CPAP) can be recommended in many cases. However, some patients respond only partially to CPAP and NIPPV is a better option for them. Objectives: To assess treatment effectiveness in 2 groups of patients: those who could be switched to CPAP after polysomnographic titration and those who required NIPPV. Methods: A prospective study of 24 OHS patients was conducted, 11 were treated with CPAP and 13 with NIPPV. Morning and evening arterial blood gases were measured. Daytime and overnight oximetric recordings were performed. A post hoc analysis compared both groups. Results: Neither group exhibited deterioration on morning-to-evening blood gases. All patients in the CPAP group presented SaO2 of less than 90% (CT90%) for <15% of the time on nocturnal and daytime recordings. In the NIPPV group, 8 patients had either daytime or nocturnal CT90% ≧15%. There were no intergroup differences regarding age, body mass index, Epworth scale values or PaO2/PaCO2 prior to treatment. FVC in the NIPPV group was lower than in the CPAP group (p = 0.01). Apnea-hypopnea index was higher (56 ± 23 vs. 36 ± 23, p = 0.049) and baseline CT90% was lower (76 ± 19% vs. 92 ± 14%, p = 0.03) in the CPAP group. Conclusions: Two patient subtypes can be identified. Those controlled with CPAP have better spirometry and a significantly higher apnea-hypopnea index. None of these patients showed daytime hypoxemia and all exhibited satisfactory overnight oxygenation. However, 61% of the NIPPV group had suboptimal oximetry results. Nocturnal/diurnal oximetries should be made to assess treatment efficacy in stable OHS patients who fail to achieve good control with CPAP.

Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma

We aimed to evaluate the accuracy of baseline exhaled nitric oxide fraction (FeNO) to recognise individuals with difficult-to-treat asthma who have the potential to achieve control with a guideline-based stepwise strategy. 102 consecutive patients with suboptimal asthma control underwent stepwise increase in the treatment with maximal fluticasone/salmeterol combination dose for 1 month. Then, those who remained uncontrolled received oral corticosteroids for an additional month. With this approach, 53 patients (52%) gained control. Those who achieved control were more likely to have positive skin results (60.4% versus 34%; p = 0.01), positive bronchodilator test (57.1% versus 35.8%; p = 0.02) and peak expiratory flow variability ≥20% (71.1% versus 49.1%; p = 0.04). Conversely, depression was more frequent in those who remained uncontrolled (18.4 % versus 43.4 %; p = 0.01). An FeNO value ≥30 ppb demonstrated a sensitivity of 87.5% (95% CI 73.9–94.5%) and a specificity of 90.6% (95% CI 79.7–95.9%) for the identification of responsive asthmatics. The current results suggest that FeNO can identify patients with difficult-to-treat asthma and the potential to respond to high doses of inhaled corticosteroids or systemic steroids.

Distribución de fenotipos clínicos en pacientes con enfermedad pulmonar obstructiva crónica por humo de biomasa y por tabaco

INTRODUCTION Exposure to biomass smoke is a risk factor for chronic obstructive pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has different characteristics to COPD caused by tobacco smoke. OBJECTIVE To determine clinical differences between these two types of the disease. METHODS Retrospective observational study of 499 patients with a diagnosis of COPD due to biomass or tobacco smoke. The clinical variables of both groups were compared. RESULTS There were 122 subjects (24.4%) in the biomass smoke group and 377 (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males was higher (91.2% vs 41.8%, P<.0001) and the age was lower (70.6 vs 76.2 years, P<.0001). Body mass index and FEV1% values were higher in the biomass group (29.4±5.7 vs 28.0±5.1, P=.01, and 55.6±15.6 vs 47.1±17.1, P<.0001, respectively). The mixed COPD-asthma phenotype was more common in the biomass group (21.3% vs 5%, P<.0001), although this difference disappeared when corrected for gender. The emphysema phenotype was more common in the tobacco group (45.9% vs 31.9%, P=.009). The prevalence of the chronic bronchitis and exacerbator phenotypes, the comorbidity burden and the rate of hospital admissions were the same in both groups. CONCLUSION Differences were observed between COPD caused by biomass and COPD caused by tobacco smoke, although these may be attributed in part to uneven gender distribution between the groups.

Obesity-Hypoventilation Syndrome: Increased Risk of Death over Sleep Apnea Syndrome

Aim To study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS. Material and methods Two retrospective cohorts of OHS and OSAS were matched 1:2 according to sex, age (±10 year) and length of time since initiation of CPAP/NIV therapy (±6 months). Results Three hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7±4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11–3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14–3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO2 < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS. Conclusion Mortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.

Differential Effect of Modified Medical Research Council Dyspnea, COPD Assessment Test, and Clinical COPD Questionnaire for Symptoms Evaluation Within the New GOLD Staging and Mortality in COPD

OBJECTIVE The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea. METHODS We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months. RESULTS Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC 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. CONCLUSIONS The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, 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. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Haemodynamic effects of non‐invasive ventilation in patients with obesity‐hypoventilation syndrome

Background and objective:  Although it has been reported that pulmonary hypertension is more frequent in patients with obesity‐hypoventilation syndrome than in patients with ‘pure’ obstructive sleep apnoea syndrome, little is known about the haemodynamic repercussions of this entity. The aim was to describe the haemodynamic status, as assessed by echocardiography and 6‐min walk test (6MWT), of patients with a newly diagnosed, most severe form of obesity‐hypoventilation syndrome, and to evaluate the impact of non‐invasive ventilation in these patients.

Prognostic Value of Walk Distance, Work, Oxygen Saturation, and Dyspnea During 6-Minute Walk Test in COPD Patients

BACKGROUND: Distance walked during the 6-min walk test (6MWT) predicts mortality in COPD. The body weight of the patient affects the work required to walk. Calculated work during the 6MWT (6MWT work) may account for differences in walk distance resulting from change in body weight. Thus, 6MWT work might be a better predictor of mortality than distance walked. This study was designed to test this hypothesis and to assess if other variables measured during the 6MWT, like continuous oximetry recording, offered additional prognostic information. METHODS: This was a retrospective analysis of prospectively collected data; 104 COPD patients were studied. 6MWT was performed in all cases. 6MWT work was calculated as body weight (in kg) × distance walked (in m). Receiver operating characteristic curves were used to assess the value of variables to predict mortality. Additional analysis was performed using Kaplan-Meier survival plots and Cox proportional hazards regression models. RESULTS: Mean follow-up was 590 ± 472 d. Eleven subjects (10.6%) died. 6MWT work was not better than distance walked to predict mortality (area under the curve 0.77 for 6MWT work vs 0.80 for distance; difference 0.03, 95% CI −0.05 to 0.12, P = .45). Subjects who died had more dyspnea (measured using the Borg scale) after the 6MWT (8.5 vs 4.0, P < .001), lower baseline SpO2 (85% vs 93%, P = .001), worse oxygen saturation during the 6MWT (mean SpO2 while walking 74.0% vs 86.6%, P = .02) and walked less distance (255 m vs 480 m, P = .001). On multivariate analysis, only 6MWT distance and dyspnea after the test correlated independently with mortality (P = .005 for both variables). CONCLUSIONS: 6MWT work was not more useful than 6MWT distance to predict mortality. The study confirms that 6MWT distance and dyspnea on exertion are key elements in prognostic evaluation in COPD, while the value of exercise oxygen desaturation is less clear.

Prevalence of persistent blood eosinophilia: relation to outcomes in patients with COPD

The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD) remains controversial. To evaluate the prevalence and stability of a high level of blood eosinophils (≥300 cells·μL–1) and its relationship to outcomes, we determined blood eosinophils at baseline and over 2 years in 424 COPD patients (forced expiratory volume in 1 s (FEV1) 60% predicted) and 67 smokers without COPD from the CHAIN cohort, and in 308 COPD patients (FEV1 60% predicted) in the BODE cohort. We related eosinophil levels to exacerbations and survival using Cox hazard analysis. In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE cohort had persistently elevated blood eosinophils at all three visits. A significant proportion (43.8%) of patients had counts that oscillated above and below the cut-off points, while the rest had persistent eosinophil levels <300 cells·μL–1. A similar eosinophil blood pattern was observed in controls. Exacerbation rates did not differ in patients with and without eosinophilia. All-cause mortality was lower in patients with high eosinophils compared with those with values <300 cells·μL–1 (15.8% versus 33.7%; p=0.026). In patients with COPD, blood eosinophils ≥300 cells·μL–1 persisting over 2 years was not a risk factor for COPD exacerbations. High eosinophil count was associated with better survival. The stability of blood eosinophils ≥300 cells per μL is low in COPD patients and it does not confer a poor prognosis http://ow.ly/TwGX30etVIy

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.

Multiple pulmonary nodules in a patient with Crohn's disease.

Crohn’s disease (CD) can be associated with respiratory involvement. Multiple pulmonary nodules are an infrequent finding in patients with CD. When they are found, histology usually shows sterile necrobiotic nodules, which are spherical aggregates of neutrophils, which frequently cavitate. We report a patient with inactive CD treated with mesalazine, who presented with multiple pulmonary nodules. Transthoracic biopsy of one of the nodules disclosed a benign, nongranulomatous inflammatory lymphoid infiltration. The radiographic abnormalities responded well to oral prednisone. Focal, nongranulomatous lymphoid infiltration thus must be considered in the differential diagnosis of multiple pulmonary nodules in patients with CD.