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OBJECTIVE: People with advanced chronic obstructive pulmonary disease (COPD) have substantial palliative care needs, but uncertainty exists around appropriate identification of patients for palliative care referral.We conducted a Delphi study of international experts to identify consensus referral criteria for specialist outpatient palliative care for people with COPD. METHODS: Clinicians in the fields of respiratory medicine, palliative and primary care from five continents with expertise in respiratory medicine and palliative care rated 81 criteria over three Delphi rounds. Consensus was defined a priori as ≥70% agreement. A criterion was considered 'major' if experts endorsed meeting that criterion alone justified palliative care referral. RESULTS: Response rates from the 57 panellists were 86% (49), 84% (48) and 91% (52) over first, second and third rounds, respectively. Panellists reached consensus on 17 major criteria for specialist outpatient palliative care referral, categorised under: (1) 'Health service use and need for advanced respiratory therapies' (six criteria, eg, need for home non-invasive ventilation); (2) 'Presence of symptoms, psychosocial and decision-making needs' (eight criteria, eg, severe (7-10 on a 10 point scale) chronic breathlessness); and (3) 'Prognostic estimate and performance status' (three criteria, eg, physician-estimated life expectancy of 6 months or less). CONCLUSIONS: International experts evaluated 81 potential referral criteria, reaching consensus on 17 major criteria for referral to specialist outpatient palliative care for people with COPD. Evaluation of the feasibility of these criteria in practice is required to improve standardised palliative care delivery for people with COPD.
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Aim: Heritability of cough has not yet been studied. We aimed to evaluate if individuals with cough are more likely to have offspring who develop cough, and if these associations differ by type of cough (productive/nonproductive). Methods: The RHINESSA Generation Study (Respiratory Health In Northern Europe, Spain and Australia) includes 7155 parents (initially aged 30-54) answering detailed questionnaires in 2000 and 2010, and 8176 offspring ≥20â years answering similar questionnaires in 2012-2019. Chronic cough was categorised as productive or nonproductive (dry) cough. Associations between parental and offspring cough were analysed using mixed-effects logistic regression, adjusting for offspring age, sex, body mass index, smoking history, education level, current asthma, rhinitis, nocturnal gastroesophageal reflux; parent sex and smoking history; centre and family. Results: Among parents with nonproductive cough, 11% of their offspring reported nonproductive cough, compared with 7% of offspring to parents without nonproductive cough, adjusted odds ratio (aOR) 1.59 (95% confidence interval 1.20-2.10). Among parents with productive cough, 14% of their offspring reported productive cough, compared with 11% of offspring to parents without productive cough, aOR 1.34 (1.07-1.67). No associations were found between parent productive cough-offspring nonproductive cough, nor between parent nonproductive cough-offspring productive cough. Conclusions: Parents with chronic cough are more likely to have offspring with chronic cough independent of parental asthma, suggesting cough to be a separate heritable trait. The type of cough is important, as the nonproductive cough in parent associates only with nonproductive cough in offspring, and the same applied for productive cough.
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RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO
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Analgésicos Opioides , Dispneia , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Dispneia/tratamento farmacológico , Dispneia/etiologia , Esquema de Medicação , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria. RESEARCH DESIGN AND METHODS: We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits. RESULTS: 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (-0.029 to 0.031), PCO2 -0.08 (-0.65 to 0.49) kPa, and PO2 0.04 (-1.71 to 1.78) kPa, with similar values for all sub-group analyses. CONCLUSION: These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid-base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.
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Artérias , Gasometria , Oxigênio , Veias , Humanos , Gasometria/métodos , Oxigênio/sangue , Artérias/fisiopatologia , Concentração de Íons de Hidrogênio , Dióxido de Carbono/sangue , Equilíbrio Ácido-Base , Hipercapnia/sangue , Hipercapnia/fisiopatologia , Hipercapnia/diagnóstico , Desequilíbrio Ácido-Base/sangue , Desequilíbrio Ácido-Base/diagnóstico , Desequilíbrio Ácido-Base/fisiopatologia , Valor Preditivo dos TestesRESUMO
INTRODUCTION: Home oxygen therapy is one of the few interventions that can improve survival in patients with chronic obstructive pulmonary disease (COPD) when administered appropriately, although it may cause side effects and be an unnecessary burden for some patients. AREAS COVERED: This narrative review summarizes the current literature on the assessment of hypoxemia, different types of home oxygen therapy, potential beneficial and adverse effects, and emerging research on home oxygen therapy in COPD. A literature search was performed using MEDLINE and EMBASE up to January 2024, with additional articles being identified through clinical guidelines. EXPERT OPINION: Hypoxemia is common in patients with more severe COPD. Long-term oxygen therapy is established to prolong survival in patients with chronic severe resting hypoxemia. Conversely, in the absence of chronic severe resting hypoxemia, home oxygen therapy has an unclear or conflicting evidence base, including for palliation of breathlessness, and is generally not recommended. However, beneficial effects in some patients cannot be precluded. Evidence is emerging on the optimal daily duration of oxygen use, the role of high-flow and auto-titrated oxygen therapy, improved informed decision-making, and telemonitoring. Further research is needed to validate novel oxygen delivery systems and monitoring tools and establish long-term effects of ambulatory oxygen therapy in COPD.
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Serviços de Assistência Domiciliar , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Oxigenoterapia/efeitos adversos , Hipóxia/terapia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Disability, resulting from altered interactions between individuals and their environment, is a worldwide issue causing inequities and suffering. Many diseases associated with breathlessness cause disability but the relationship between disability and the severity of breathlessness itself is unknown.This study evaluated associations between disability using the WHO's Disability Assessment Schedule (WHODAS) 2.0 and levels of long-term breathlessness limiting exertion. METHODS: This population-based, cross-sectional online survey (n=10 033) reflected the most recent national census (2016) by age, sex, state/territory of residence and rurality. Assessments included self-reported disability (WHODAS 2.0 12-item (range 12 (no disability) to 60 (most severe disability)) assessed in 6 domains) and long-term breathlessness limiting exertion (modified Medical Research Council (mMRC) breathlessness scale; 0-4 (4-most severe)). Days in the last month affected by breathlessness were reported. RESULTS: Of respondents (52% women; mean age 45), mean total disability score was 20.9 (SD 9.5). 42% (n=4245) had mMRC >0 (mMRC1 31% (n=3139); mMRC2 8% (n=806); mMRC3,4 3% (n=300)). Every level of long-term breathlessness limiting exertion was associated with greater levels of disability (total p <0.001; each domain p <0.001). The most compromised domains were Mobility and Participation.In the last 30 days, people with severe breathlessness (mMRC 3-4): experienced disability (20 days); reduced activities/work (10 days); and completely forwent activities (another 5 days). CONCLUSIONS: Disability should be in the definition of persistent breathlessness as it is systematically associated with long-term breathlessness limiting exertion in a grade-dependent, multidimensional manner. Disability should be assessed in people with long-term breathlessness to optimise their social well-being and health.
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Avaliação da Deficiência , Pessoas com Deficiência , Dispneia , Humanos , Dispneia/epidemiologia , Dispneia/etiologia , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Pessoas com Deficiência/estatística & dados numéricos , Idoso , Índice de Gravidade de Doença , Adulto Jovem , Autorrelato , AdolescenteRESUMO
RATIONALE: Knowledge regarding prevalence and shared and unique characteristics of Restrictive spirometric pattern (RSP) and Preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs. OBJECTIVES: To investigate shared and unique features for RSP and PRISm. METHODS: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50 - 64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score (CACS). Odds ratios (OR) with 95% confidence intervals (CI) were calculated using adjusted logistic regression. RSP was defined as FEV1/FVC≥0.70 and FVC<80%. PRISm was defined as FEV1/FVC≥0.70 and FEV1<80%. A local reference equation was applied. MEASUREMENTS AND RESULTS: The prevalence of RSP and PRISm were 5.1% (95% CI 4.9 - 5.4) and 5.1% (95% CI 4.8 - 5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease (IHD), bronchial wall thickening, interstitial lung abnormalities (ILA), and bronchiectasis. Emphysema was uniquely linked to PRISm (OR 1.69, 1.36-2.10) vs 1.10 (0.84-1.43) for RSP. CACS≥300 was related to PRISm, but not among among never-smokers. CONCLUSIONS: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not. 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/).
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There are no known estimates of the prevalence, severity and impacts from breathlessness in low- and middle-income countries. This study aimed to explore the prevalence, severity, self-attributed underlying conditions and impacts of breathlessness limiting exertion in community-dwelling adults in India. This exploratory, population-based online survey recruited a pre-planned sample of 3,000 adult respondents stratified by age, sex and rurality (quotas as per the 2011 Indian National Census). Measures included: demographics; breathlessness limiting exertion (modified Medical Research [mMRC] scale); health-related quality of life (EQ-5D-5L); and disability (World Health Organisation's Disability Assessment Schedule 2.0 12-item questionnaire [WHODAS-12]). Respondents (n = 3,046) had a mean age of 38 years (SD 15); 57% were male, 59% lived in rural areas and 33% had completed 12th grade. Breathlessness limiting exertion (mMRC ≥1) was reported by 44%, mostly attributed to poor nutrition (28%), lung conditions excluding tuberculosis (17%) or anaemia (13%). Compared to those without breathlessness, a higher proportion of people with breathlessness (mMRC ≥1) reported problems across all EQ-5D-5L dimensions. Most people reporting breathlessness (81%) indicated the symptom had adversely affected their normal activities. Disability scores (WHODAS-12 total and individual domains) increased as breathlessness worsened. To conclude, in India, conservative estimates indicate 626 million people live with breathlessness of whom 52 million people live with severe breathlessness. The symptom is associated with poorer health-related quality of life and marked disability, including reduced ability to perform daily activities.
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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.
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Qualidade de Vida , Humanos , Europa (Continente) , Adulto , Sociedades Médicas , Oxigenoterapia , Terapia por Exercício , Analgésicos Opioides/uso terapêutico , Medicina Baseada em Evidências , Pneumologia/normas , Assistência Centrada no Paciente , Avaliação das NecessidadesRESUMO
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/).
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Background: Small-bore chest drains are now the most common drains for treating pleural effusion (PE), but knowledge on complications is limited especially in malignant PE and empyema. We aimed to evaluate rate of complications of ultrasound guided small bore chest drains [6-10 French (F)] by PE etiology. Methods: Retrospective cohort study of 484 chest drains inserted in 330 adults in a Swedish department 2018-2020. Rate of complications (blockage, dislocation, infection, or misplacement) and repeat intervention (new drain within 2 weeks or surgery) was analyzed by effusion type (organ failure, parapneumonic, malignant, empyema, other, unknown), age, sex, seniority of radiologist, and bore size using multivariable logistic regression. Results: Most inserted drains (73.3%) were 6 F. The rate of repeat intervention was substantially higher in malignant PE [25.5%; adjusted odds ratio (aOR) 3.3; 95% confidence interval (CI): 1.6-6.8] and empyema (56.4%; aOR 11.9; 95% CI: 4.8-29.4) compared to other aetiologies (range, 9.5-17.8%). Surgery as complication occurred in empyema in 23.0% of cases (aOR 10.6; 95% CI: 1.4-79.4). The rate of repeat intervention in simple PE (parapneumonic or due to organ failure) was low (range, 9.5-12.5%). Conclusions: A single small-bore chest drain (6-10 F) was successful in the vast majority of simple PEs, but had high complication rates in empyema with frequent need of additional drains or surgery. These findings support use of larger drains and early consultation with a thoracic surgeon in empyema.
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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.
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Anemia , Cardiopatias , Masculino , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Sobrepeso , Estudos Transversais , Dispneia/diagnóstico , Dispneia/epidemiologia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , ObesidadeRESUMO
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.
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Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness. Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64â years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations. Results: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1â s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13). Conclusion: This large population-based study of men and women aged 50-64â years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.
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BACKGROUND: Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. RESEARCH QUESTION: How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiologic responses in people with chronic airflow limitation (CAL)? STUDY DESIGN AND METHODS: An analysis was done of people aged ≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output, rate of oxygen uptake, and minute ventilation at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy people; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. RESULTS: We included 330 participants (44% women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV1/FVC, 57.3% ± 8.2%; FEV1, 75.6% ± 17.9% predicted. Abnormally low exercise capacity (peak rate of oxygen uptake < lower limit of normal) was present in 26%. Relative to peak power output, rate of oxygen uptake, and minute ventilation, abnormally high breathlessness was present in 26%, 25%, and 18% of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiologic abnormalities during CPET. INTERPRETATION: Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness.