Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Low-Dose Morphine Does Not Cause Sleepiness in COPD: A Secondary Analysis of a Randomized Trial.

RATIONALE: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality and daytime function have not been rigorously investigated. OBJECTIVES: Determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. METHODS: Pre-specified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained -release morphine versus placebo over four weeks commencing at 8mg or 16mg/day with blinded up-titration over two weeks to a maximum of 32mg/day. Primary outcomes for these analyses were week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) responses on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire (LSEQ) scores (end of weeks 1 and 4), KSS and ESS beyond week-1 and associations between breathlessness, morphine, and questionnaire scores. MEASUREMENTS AND MAIN RESULTS: 156 people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (∆ESS [95%CI] versus placebo: 8mg group: -0.59 [-1.99, 0.81], p=0.41; 16mg group: -0.72 [-2.33, 0.9], p=0.38; ∆KSS versus placebo: 8mg group: 0.11 [-0.7, 0.9], p=0.78; 16mg group: -0.41 [-1.31, 0.49], p=0.37). This neutral effect persisted at later timepoints. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also had improvement in LSEQ domain scores including perceived sleep quality and daytime function. CONCLUSIONS: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.

European Respiratory Society clinical practice guideline on symptom management for adults with serious respiratory illness.

Respiratory symptoms are ubiquitous and impair health-related quality of life in people with respiratory disease. This European Respiratory Society (ERS) task force aimed to provide recommendations for symptomatic treatment in people with serious respiratory illness. The ERS task force comprised 16 members, including representatives of people with serious respiratory illness and informal caregivers. Seven questions were formulated, six in the PICO (Population, Intervention, Comparison, Outcome) format, which were addressed with full systematic reviews and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One question was addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. To treat symptoms in people with serious respiratory illness, the task force suggests the use of graded exercise therapy (conditional recommendation, low certainty of evidence); and suggests the use of a multicomponent services, handheld fan and breathing techniques (conditional recommendations, very low certainty of evidence). The task force suggests not to use opioids (conditional recommendation, very low certainty of evidence); and suggests either administering or not administering supplemental oxygen therapy (conditional recommendation, low certainty of evidence). The task force suggests that needs assessment tools may be used as part of a comprehensive needs assessment, but do not replace patient-centred care and shared decision making (conditional recommendation, low certainty of evidence). The low certainty of evidence, modest impact of interventions on patient-centred outcomes, and absence of effective strategies to ameliorate cough highlight the need for new approaches to reduce symptoms and enhance wellbeing for individuals who live with serious respiratory illness.

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

The impact of regular, low-dose, sustained-release morphine for chronic breathlessness on caregiver burden: An exploratory analysis of the BEAMS trial.

BACKGROUND: Chronic breathlessness adversely impacts people with chronic obstructive pulmonary disease and their caregivers (family and friends), who may, in turn, experience significant burden due to their caregiving role. Sustained-release morphine may reduce chronic breathlessness in some patients, which may have an impact on caregivers' perceived burden. AIM: To explore the impact on caregiver burden of active treatment of people with chronic breathlessness (modified Medical Research Council (mMRC) ⩾ 3) and chronic obstructive pulmonary disease (COPD) with regular, low-dose, sustained-release morphine within a multi-site, double-blind, randomised, placebo-controlled trial. DESIGN: Exploratory analysis of self-reported caregiver burden at baseline and end of week 3 in a randomised, double-blind, placebo-controlled study. Caregiver measures included: demographics and perceived burden (Zarit Burden Interview 12-item short-form questionnaire). Patient measures included: worst breathlessness and FitBitR-measures. SETTING/PARTICIPANTS: All consenting caregivers of trial patient participants in a multi-site study recruiting from palliative care and respiratory services. RESULTS: Caregivers (n = 49; 59% women; median age 68 years [IQR 50-75]) reported median baseline caregiver burden 12 [IQR 5-17], with 53% reporting high burden (⩾13). Eighty-four percent of caregivers reported no change in burden. In people whose worst breathlessness improved, caregiver burden moved in the same direction, though the correlation was not significant (rs = 0.25, p = 0.17). Conversely, caregiver burden worsened as patients' minutes lightly active increased, with the correlation being significant (rs = 0.56, p = 0.04). CONCLUSIONS: Caregivers reported high levels of caregiver burden, but patients' response to treatment in terms of their symptom and function may influence change in caregiver burden over a three-week period.

European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease.

There is increased awareness of palliative care needs in people with COPD or interstitial lung disease (ILD). This European Respiratory Society (ERS) task force aimed to provide recommendations for initiation and integration of palliative care into the respiratory care of adult people with COPD or ILD. The ERS task force consisted of 20 members, including representatives of people with COPD or ILD and informal caregivers. Eight questions were formulated, four in the Population, Intervention, Comparison, Outcome format. These were addressed with full systematic reviews and application of Grading of Recommendations Assessment, Development and Evaluation for assessing the evidence. Four additional questions were addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. The following definition of palliative care for people with COPD or ILD was agreed. A holistic and multidisciplinary person-centred approach aiming to control symptoms and improve quality of life of people with serious health-related suffering because of COPD or ILD, and to support their informal caregivers. Recommendations were made regarding people with COPD or ILD and their informal caregivers: to consider palliative care when physical, psychological, social or existential needs are identified through holistic needs assessment; to offer palliative care interventions, including support for informal caregivers, in accordance with such needs; to offer advance care planning in accordance with preferences; and to integrate palliative care into routine COPD and ILD care. Recommendations should be reconsidered as new evidence becomes available.

Prognosis after Intensive Care for COPD Exacerbation in Relation to Long-Term Oxygen Therapy: A Nationwide Cohort Study.

Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p < 0.001) and one-year mortality (70% vs. 43%; p < 0.001). Multivariable logistic and Cox regression models adjusted for age, sex and SAPS3 score confirmed higher mortality in LTOT, odds ratio for 30-day mortality was 1.8 ([95% confidence interval] 1.5-2.3) and hazard ratio for one-year mortality was 1.8 (1.6-2.0). In summary, although need for LTOT is a negative prognostic marker for survival after AECOPD requiring intensive care, a majority of patients with LTOT survived the AECOPD and 30% were alive after one year.

Breathlessness across generations: results from the RHINESSA generation study.

BACKGROUND: Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations. METHODS: We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings. RESULTS: A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring. CONCLUSION: Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored.

Cancer risk in severe alpha-1-antitrypsin deficiency.

BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits. METHODS: A longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analysed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease. RESULTS: The median follow-up time was 17 years (interquartile range 11 years) for the whole study population. The incidence rates of hepatic and non-hepatic cancer per 1000 person-years were 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0), respectively, for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1), respectively, for the controls. The adjusted hazard ratios for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5), respectively, in the PiZZ individuals compared with the controls. CONCLUSION: These results suggest that individuals with severe AATD may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.

Multiple drivers of large-scale lichen decline in boreal forest canopies.

Thin, hair-like lichens (Alectoria, Bryoria, Usnea) form conspicuous epiphyte communities across the boreal biome. These poikilohydric organisms provide important ecosystem functions and are useful indicators of global change. We analyse how environmental drivers influence changes in occurrence and length of these lichens on Norway spruce (Picea abies) over 10 years in managed forests in Sweden using data from >6000 trees. Alectoria and Usnea showed strong declines in southern-central regions, whereas Bryoria declined in northern regions. Overall, relative loss rates across the country ranged from 1.7% per year in Alectoria to 0.5% in Bryoria. These losses contrasted with increased length of Bryoria and Usnea in some regions. Occurrence trajectories (extinction, colonization, presence, absence) on remeasured trees correlated best with temperature, rain, nitrogen deposition, and stand age in multinomial logistic regression models. Our analysis strongly suggests that industrial forestry, in combination with nitrogen, is the main driver of lichen declines. Logging of forests with long continuity of tree cover, short rotation cycles, substrate limitation and low light in dense forests are harmful for lichens. Nitrogen deposition has decreased but is apparently still sufficiently high to prevent recovery. Warming correlated with occurrence trajectories of Alectoria and Bryoria, likely by altering hydration regimes and increasing respiration during autumn/winter. The large-scale lichen decline on an important host has cascading effects on biodiversity and function of boreal forest canopies. Forest management must apply a broad spectrum of methods, including uneven-aged continuous cover forestry and retention of large patches, to secure the ecosystem functions of these important canopy components under future climates. Our findings highlight interactions among drivers of lichen decline (forestry, nitrogen, climate), functional traits (dispersal, lichen colour, sensitivity to nitrogen, water storage), and population processes (extinction/colonization).

Research race-specific reference values and lung function impairment, breathlessness and prognosis: Analysis of NHANES 2007-2012.

BACKGROUND: 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. METHODS: 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 (FEV1) 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. RESULTS: We studied 14,123 people (50% female). Compared to those for white, black reference values identified markedly fewer cases of lung function impairment (FEV1) 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 FEV1 ≥ LLNblack but < LLNwhite had 48% increased rate of breathlessness and almost doubled mortality, compared to blacks ≥ LLNwhite. White references identified people with good outcomes similarly in black and white people. Findings were similar for FEV1 and FVC. CONCLUSION: 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.

Can birth weight predict offspring's lung function in adult age? Evidence from two Swedish birth cohorts.

BACKGROUND: Associations between birth weight (BW) and adult lung function have been inconsistent and limited to early adulthood. We aimed to study this association in two population-based cohorts and explore if BW, adjusted for gestational age, predicts adult lung function. We also tested adult lung function impairment according to the mis-match hypothesis-small babies growing big as adults. METHODS: We included 3495 individuals (aged 46.4 ± 5.4 years) from the Malmo Preventive Project (MPP), Sweden, born between 1921 and 1949, and 1401 young to middle-aged individuals (aged 28.6 ± 6.7 years) from the Malmo Offspring Study (MOS) with complete data on BW and gestational age. Adult lung function (forced vital capacity [FVC], forced expiratory volume in one second [FEV1] and the FEV1/FVC-ratio) were analysed as level of impairment (z-score), using multiple linear and logistic regressions. RESULTS: BW (z-score) did not predict adult lung function in MPP, whereas BW was a significant (p = 0.003) predictor of FEV1 following full adjustment in MOS. For every additional unit increase in BW, children were 0.77 (95% CI 0.65-0.92) times less likely to have impaired adult lung function (FEV1). Moreover, adults born with lower BW (< 3510 g) showed improved lung function (FEV1 and FEV1/FVC in MOS and MPP, respectively) if they achieved higher adult body weight. CONCLUSIONS: Adults born with lower birth weight, adjusted for gestational age, are more likely to have impaired lung function, seen in a younger birth cohort. Postnatal growth pattern may, however, compensate for low birth weight and contribute to better adult lung function.

Short-acting ß2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

BACKGROUND: In adults and adolescents with asthma, use of ≥3 short-acting ß2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population. METHODS: This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression. RESULTS: Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups). CONCLUSIONS: High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.

Comparing recalled versus experienced symptoms of breathlessness ratings: An ecological assessment study using mobile phone technology.

BACKGROUND AND OBJECTIVE: Recall of breathlessness is important for clinical care but might differ from the experienced (momentary) symptoms. This study aimed to characterize the relationship between momentary breathlessness ratings and the recall of the experience. It is hypothesized that recall is influenced by the peak (worst) and end (most recent) ratings of momentary breathlessness (peak-end rule). METHODS: This study used mobile ecological momentary assessment (mEMA) for assessing breathlessness in daily life through an application installed on participants' mobile phones. Breathlessness ratings (0-10 numerical rating scale) were recorded throughout the day and recalled each night and at the end of the week. Analyses were performed using regular and mixed linear regression. RESULTS: Eighty-four people participated. Their mean age was 64.4 years, 60% were female and 98% had modified Medical Research Council (mMRC) ≥ 1. The mean number of momentary ratings of breathlessness provided was 7.7 ratings/participant/day. Recalled breathlessness was associated with the mean, peak and end values of the day. The mean was most closely associated with the daily recall. Associations were strong for weekly values: peak breathlessness (beta = 0.95, r2  = 0.57); mean (beta = 0.91, r2  = 0.53); and end (beta = 0.67, r2  = 0.48); p < 0.001 for all. Multivariate analysis showed that peak breathlessness had the strongest influence on the breathlessness recalled at the end of the week. CONCLUSION: Over 1 week, recalled breathlessness is most strongly influenced by the peak breathlessness; over 1 day, it is mean breathlessness that participants most readily recalled.

Validation of the Dyspnoea-12 and Multidimensional Dyspnea profile among older Swedish men in the population.

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.

Lower workforce participation is associated with more severe persisting breathlessness.

BACKGROUND: Not being able to work has negative health, social and financial consequences. Persisting breathlessness is prevalent in working-aged people. Is it associated with lower workforce participation? This study, using the South Australian Health Omnibus, aimed to explore associations between paid workforce participation and persisting breathlessness intensity, and economic impacts on income in people of working age. METHODS: This cross-sectional study conducted face-to-face interviews with a random sample of adults in South Australia (n = 8916). Questions included key demographic data, workforce participation and the presence and intensity of persisting breathlessness. Data from working-aged respondents (20-65 years of age) were standardised to the census for regression analyses. Work was coded to paid full- or part-time work or 'other'. Persisting breathlessness (more than three of the last six months) used the modified Medical Research Council breathlessness scale (aggregated to 0, 1, 2-4). Opportunity cost valuations compared annual income foregone by persisting breathlessness severity. RESULTS: Of people interviewed, 6,608 were working-aged (49.9% male; 67.5% had post-secondary qualifications; 70.9% were in paid full- or part-time work; and 1.7% had mMRC score 2-4). Workforce participation dropped in working aged people with increasing breathlessness: mMRC 0, 70.6%; mMRC 1, 51.7%; mMRC 2-4, 20.3%. In the regression model, people with the most severe breathlessness were much less likely to work (OR 0.14; 95% CI 0.09, 0.22). Annual income foregone by people with persisting breathlessness was AU$10.7 billion (AU$9.1b for full-time and AU$1.6b for part-time work; range AU$5.9b, AU$49.7b). CONCLUSION: Worsening persisting breathlessness is associated with lower workforce participation with direct financial consequences, greatest for older males.

Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial.

Importance: Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed. Objective: To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019. Interventions: People were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week's dose, or placebo. Main Outcomes and Measures: The primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days -3 to -1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day -1) to the mean step count from week 3 (from days 19 to 21). Results: Among the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -0.3 [95% CI, -0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, -0.3 [95%, CI, -1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -1453 [95% CI, -3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, -1312 [95% CI, -3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, -692 [95% CI, -2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, -1924 [95% CI, -47 699 to 921]). Conclusions and Relevance: Among people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness. Trial Registration: ClinicalTrials.gov Identifier: NCT02720822.

Sleeping-related distress in a palliative care population: A national, prospective, consecutive cohort.

BACKGROUND: Sleep, a multi-dimensional experience, is essential for optimal physical and mental wellbeing. Poor sleep is associated with worse wellbeing but data are scarce from multi-site studies on sleeping-related distress in palliative care populations. AIM: To evaluate patient-reported distress related to sleep and explore key demographic and symptom distress related to pain, breathing or fatigue. DESIGN: Australian national, consecutive cohort study with prospectively collected point-of-care data using symptoms from the Symptom Assessment Scale (SAS). SETTING/PARTICIPANTS: People (n = 118,117; 475,298 phases of care) who died while being seen by specialist palliative care services (n = 152) 2013-2019. Settings: inpatient (direct care, consultative); community (outpatient clinics, home, residential aged care). RESULTS: Moderate/severe levels of sleeping-related distress were reported in 11.9% of assessments, more frequently by males (12.7% vs 10.9% females); people aged <50 years (16.2% vs 11.5%); and people with cancer (12.3% vs 10.0% for other diagnoses). Sleeping-related distress peaked with mid-range Australia-modified Karnofsky Performance Status scores (40-60).Strong associations existed between pain-, breathing- and fatigue-related distress in people who identified moderate/severe sleeping-related distress, adjusted for age, sex and functional status. Those reporting moderate/severe sleeping-related distress were also more likely to experience severe pain-related distress (adjusted odds ratios [OR] 6.6; 95% confidence interval (CI) 6.3, 6.9); breathing-related distress (OR 6.2; 95% CI 5.8, 6.6); and fatigue-related distress (OR 10.4; 95% CI 9.99-10.8). CONCLUSIONS: This large, representative study of palliative care patients shows high prevalence of sleeping-related distress, with strong associations shown to distress from other symptoms including pain, breathlessness and fatigue.

Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.

Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness. METHODS: Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, 'as needed', immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0-100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms. RESULTS: Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference -0.15 mm (95% CI -4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation. CONCLUSION: No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine. TRIAL REGISTRATION NUMBER: ACTRN12609000806268.