Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy

© 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Breathlessness is a cardinal symptom of chronic obstructive pulmonary disease (COPD). Long-term oxygen therapy (LTOT) is given to improve survival time in people with COPD and severe chronic hypoxaemia at rest. The efficacy of oxygen therapy for breathlessness and health-related quality of life (HRQOL) in people with COPD and mild or no hypoxaemia who do not meet the criteria for LTOT has not been established. Objectives: To determine the efficacy of oxygen versus air in mildly hypoxaemic or non-hypoxaemic patients with COPD in terms of (1) breathlessness; (2) HRQOL; (3) patient preference whether to continue therapy; and (4) oxygen-related adverse events. Search methods: We searched the Cochrane Airways Group Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, to 12 July 2016, for randomised controlled trials (RCTs). We handsearched the reference lists of included articles. Selection criteria: We included RCTs of the effects of non-invasive oxygen versus air on breathlessness, HRQOL or patient preference to continue therapy among people with COPD and mild or no hypoxaemia (partial pressure of oxygen (PaO2) > 7.3 kPa) who were not already receiving LTOT. Two review authors independently assessed articles for inclusion in the review. Data collection and analysis: Two review authors independently collected and analysed data. We assessed risk of bias by using the Cochrane 'Risk of bias tool'. We pooled effects recorded on different scales as standardised mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. Lower SMDs indicated decreased breathlessness and reduced HRQOL. We performed subanalyses and sensitivity analyses and assessed the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Main results: Compared with the previous review, which was published in 2011, we included 14 additional studies (493 participants), excluded one study and included data for meta-analysis of HRQOL. In total, we included in this review 44 studies including 1195 participants, and we included 33 of these (901 participants)in the meta-analysis. We found that breathlessness during exercise or daily activities was reduced by oxygen compared with air (32 studies; 865 participants; SMD -0.34, 95% CI -0.48 to -0.21; I2 = 37%; low-quality evidence). This translates to a decrease in breathlessness of about 0.7 points on a 0 to 10 numerical rating scale. In contrast, we found no effect of short-burst oxygen given before exercise (four studies; 90 participants; SMD 0.01, 95% CI -0.26 to 0.28; I2 = 0%; low-quality evidence). Oxygen reduced breathlessness measured during exercise tests (25 studies; 442 participants; SMD -0.34, 95% CI -0.46 to -0.22; I2 = 29%; moderate-quality evidence), whereas evidence of an effect on breathlessness measured in daily life was limited (two studies; 274 participants; SMD -0.13, 95% CI, -0.37 to 0.11; I2 = 0%; low-quality evidence). Oxygen did not clearly affect HRQOL (five studies; 267 participants; SMD 0.10, 95% CI -0.06 to 0.26; I2 = 0%; low-quality evidence). Patient preference and adverse events could not be analysed owing to insufficient data. Authors' conclusions: We are moderately confident that oxygen can relieve breathlessness when given during exercise to mildly hypoxaemic and non-hypoxaemic people with chronic obstructive pulmonary disease who would not otherwise qualify for home oxygen therapy. Most evidence pertains to acute effects during exercise tests, and no evidence indicates that oxygen decreases breathlessness in the daily life setting. Findings show that oxygen does not affect health-related quality of life

Safety of benzodiazepines and opioids in very severe respiratory disease: National prospective study

Objective: To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). Design: Population based longitudinal consecutive cohort study. Setting: Centres prescribing long term oxygen therapy in Sweden. Patients: 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. Main outcome measures: Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. Results: 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. Conclusions: Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease

Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months: follow-up of a longitudinal clinical study.

Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities (SQs) and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness

Bibloc and Monobloc Oral appliances in the Treatment of Obstructive Sleep apnoea : a Multicenter, Randomized, Blinded, Parallel-Group Trial

Introduction: The clinical benefit of bibloc over monobloc appliances has not been established in randomized trials treating obstructive sleep apnoea (OSA). We hypothesized that the two types of appliances are equally effective in treating moderate to severe OSA. Materials and methods: We performed a blinded, multicenter, randomized, controlled, prospective, parallel-group trial including patients aged 18 years or older who had moderate-to-severe OSA. Patients were randomly assigned to receive either a bibloc or a monobloc appliance with the intention to protrude the mandible 75% of the individual maximal protrusion capacity. At baseline a one-night respiratory polygraphy was done without any respiratory support. The polygraphy was iterated with the appliance in place at a 6-week follow-up. The primary outcome was the absolute change in the apnoea-hypopnea-index (AHI) from baseline to the 6-week follow-up, analysed in the per-protocol population. All patients who received an appliance were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02148510, and approved by Uppsala Regional Ethical Review Board, Sweden (#2014/021). Results: We recruited patients from three dental specialist clinics in Sweden; enrolment of 302 patients was done between March 2014 and April 2016; 146 randomized to bibloc and 156 to monobloc appliance. Twenty-three patients in the bibloc group and 17 in the monobloc group were withdrawn due to reasons like appliance could not be fitted, lack of compliance, adverse events or non-valid follow-up polygraphy i.e. a per-protocol group of 123 bibloc and 139 monobloc treated patients. The mean change of AHI from baseline to 6 weeks of treatment was -13.8 (95% CI -16.1 to -11.5; p < 0.001) in the bibloc group and -12.5 (95% CI -14.8 to -10.3; p < 0.001) in the monobloc group. The mean difference was not significant between the groups (-1.3 (95% CI -4.5 to 1.9). The most common adverse event in the orofacial region was upper airway infection followed by complains from various parts of the mouth, jaws and teeth. Conclusions: Bibloc and monobloc appliance treatment was equal in their effects in treating OSA as measured by at home polygraphic respiratory measures and the appliances were associated with a similar degree of adverse events. Acknowledgements: Funding from Uppsala-Örebro Regional Research Council and Vastmanland County Council, Sweden

Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease

Long-term oxygen therapy (LTOT) &gt;= 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease ( COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed