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Spirometry reference values differ by race/ethnicity, which is controversial. We evaluated the effect of race-specific references on prevalence of lung function impairment and its relation to breathlessness and mortality in the US population. Population-based analysis of the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Race/ethnicity was analyzed as black, white, or other. Reference values for forced expiratory volume in one second (FEV ) and forced vital capacity (FVC) were calculated for each person using the Global Lung Initiative (GLI)-2012 equations for (1) white; (2) black; and (3) other/mixed people. Outcomes were prevalence of lung function impairment (< lower limit of normal [LLN]), moderate/severe impairment (< 50%pred); exertional breathlessness; and mortality until 31 December, 2015. We studied 14,123 people (50% female). Compared to those for white, black reference values identified markedly fewer cases of lung function impairment (FEV ) both in black people (9.3% vs. 36.9%) and other non-white (1.5% vs. 9.5%); and prevalence of moderate/severe impairment was approximately halved. Outcomes by impairment differed by reference used: white (best), other/mixed (intermediate), and black (worst outcomes). Black people with FEV  ≥ LLN but < LLN had 48% increased rate of breathlessness and almost doubled mortality, compared to blacks ≥ LLN . White references identified people with good outcomes similarly in black and white people. Findings were similar for FEV and FVC. Compared to using a common reference (for white) across the population, race-specific spirometry references did not improve prediction of breathlessness and prognosis, and may misclassify lung function as normal despite worse outcomes in black people.

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.

Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting. Four versions of the CCI were compared and evaluated by disease-specific experts. We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing. This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.

The fact that we all need oxygen to survive might make the benefit of supplemental oxygen in hypoxemia seem obvious. It is not. Long-term oxygen therapy was the first treatment to improve prognosis in patients with chronic obstructive pulmonary disease (COPD) and chronic severe hypoxemia. 1 , 2 However, the question of whether long-term oxygen therapy is beneficial in moderate hypoxemia has been floating in the air. The literature on the efficacy of long-term oxygen therapy requires no librarian. The current indications for its use are based on two unblinded, randomized trials that were conducted in the 1970s and involved a total . . .

IntroductionBreathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear.MethodsThis population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.ResultsWe included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.ConclusionBreathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

Abstract Rationale Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from breathlessness, deconditioning, and reduced health-related quality of life (HRQL) despite best medical management. Opioids may relieve breathlessness at rest and on exertion in COPD. Objectives We aimed to estimate the efficacy and safety of opioids on refractory breathlessness, exercise capacity, and HRQL in COPD. Methods This was a systematic review and metaanalysis using Cochrane methodology. We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase up to 8 September, 2014 for randomized, double-blind, placebo-controlled trials of any opioid for breathlessness, exercise capacity, or HRQL that included at least one participant with COPD. Effects were analyzed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random effect models. Measurements and Main Results A total of 16 studies (15 crossover trials and 1 parallel-group study, 271 participants, 95% with severe COPD) were included. There were no serious adverse effects. Breathlessness was reduced by opioids overall: SMD, −0.35 (95% CI, −0.53 to −0.17; I  2, 48.9%), by systemic opioids (eight studies, 118 participants): SMD, −0.34 (95% CI, −0.58 to −0.10; I  2, 0%), and less consistently by nebulized opioids (four studies, 82 participants): SMD, −0.39 (95% CI, −0.71 to −0.07; I  2, 78.9%). The quality of evidence was moderate for systemic opioids and low for nebulized opioids on breathlessness. Opioids did not affect exercise capacity (13 studies, 149 participants): SMD, 0.06 (95% CI, −0.15 to 0.28; I  2, 70.7%). HRQL could not be analyzed. Findings were robust in sensitivity analyses. Risk of study bias was low or unclear. Conclusions Opioids improved breathlessness but not exercise capacity in severe COPD.

Background The Dyspnoea-12 (D12) and Multidimensional dyspnea profile (MDP) are commonly used instruments for assessing multiple dimensions of breathlessness but have not been validated in older people in the population. The aim of this study was to validate the D12 and MDP in 73-years old men in terms of the instruments’ underlying factor structures, internal consistency, and validity. Methods A postal survey was sent out to a population sample of 73-years old men ( n  = 1,193) in southern Sweden. The two-factor structures were evaluated with confirmatory factor analysis, internal consistency with Cronbach's alpha, and validity using Pearson´s correlations with validated scales of breathlessness, anxiety, depression, fatigue, physical/mental quality of life, body mass index (BMI), and cardiorespiratory disease. Results A total 684 men were included. Respiratory and cardiovascular disease were reported by 17% and 38%, respectively. For D12 and MDP, the proposed two-factor structure was not fully confirmed in this population. Internal consistency was excellent for all D12 and MDP domain scores (Cronbach's alpha scores > 0.92), and the instruments’ domains showed concurrent validity with other breathlessness scales, and discriminant validity with anxiety, depression, physical/mental quality of life, BMI, and cardiorespiratory disease. Conclusions In a population sample of 73-years old men, the D12 and MDP had good psychometrical properties in terms of reliability and validity, which supports that the instruments are valid for use in population studies of older men.

Cardiovascular drugs may improve survival in chronic obstructive pulmonary disease (COPD). However, previous studies did not account for major sources of bias, and drug effects have not been evaluated in severe COPD. To estimate the time-dependent effects of cardiovascular drugs on survival in oxygen-dependent COPD, accounting for immortal and immeasurable time bias. Prospective national study of patients starting long-term oxygen therapy for COPD in Sweden between 1 October 2005 and 30 June 2009. Effects on mortality were estimated using extended Cox regression adjusted for age, sex, PaO2, PaCO2, World Health Organization performance status, body mass index, comorbidity, and concomitant medications. Immortal and immeasurable time bias was addressed by analyzing all medications as time-dependent variables and accounting for hospitalized time, respectively. Time-dependent effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, antiplatelet drugs, [beta]-blockers, and statins on all-cause mortality were measured. Of the 2,249 included patients, 1,129 (50%) died under observation. No patient was lost to follow-up. The adjusted time-dependent model was compatible with reduced mortality for antiplatelet drugs (hazard ratio [HR], 0.86; 95% CI, 0.75-0.99; P = 0.030) and trends for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (HR, 0.90; 95% CI, 0.79-1.04; P = 0.166) and statins (HR, 0.86; 95% CI, 0.72-1.03; P = 0.105), whereas [beta]-blockers increased mortality (HR, 1.19; 95% CI, 1.04-1.37; P = 0.010). This study supports that antiplatelet drugs improve survival and [beta]-blockers decrease survival in oxygen-dependent COPD.

Breathlessness is prevalent in the general population and may be associated with adverse health outcomes. This study aimed to evaluate the association of breathlessness with Chronic Obstructive Pulmonary Disease (COPD) events, cardiac events and all-cause mortality from middle-age throughout life. Breathlessness was measured in 699, 55-year old men residing in Malmö, Sweden using modified Medical Research Council (mMRC). COPD events (hospitalisation, death or diagnosis) cardiac events and all-cause mortality was assessed using The Swedish Causes of Death Register and Hospital Discharge Register. Data was analyzed using Cox- and competing risks (Fine-Gray) regression analysis. 695 (99%) of 699 participants died and four emigrated during follow up. Eighty-seven (12%) had mMRC = 1 and 19 (3%) had mMRC≥2. Breathlessness was associated with COPD events; adjusted Sub-Hazard Ratio 2.1 (95% CI, 1.2-3.6) for mMRC = 1 and 7.5 (2.6-21.7) for mMRC ≥ 2 but not associated with cardiac events when adjusting for competing events and confounding. Breathlessness was associated increased all- cause mortality (Hazard Ratios of 1.4 (1.1-1.7) (mMRC = 1) and 3.4 (2.1-5.6) (mMRC ≥ 2)). Breathlessness is associated with increased risk of COPD events and increase in all-cause mortality from age 55 until death.