The effect of an integrated palliative care intervention on quality of life and acute healthcare use in patients with COPD: Results of the COMPASSION cluster randomized controlled trial.

BACKGROUND: COPD causes high morbidity and mortality, emphasizing the need for palliative care. AIM: To assess the effectiveness of palliative care in patients with COPD. DESIGN: Cluster randomized controlled trial (COMPASSION study; Netherlands Trial Register (NTR): NL7644, 07-04-2019). Healthcare providers within the intervention group were trained to implement palliative care components into routine COPD care. Patients completed questionnaires at baseline, after 3 and 6 months; medical records were assessed after 12 months. The primary outcome was quality of life (FACIT-Pal). Secondary outcomes were anxiety, depression, spiritual well-being, satisfaction with care, acute healthcare use, documentation of life-sustaining treatment preferences and place of death. Generalized linear mixed modelling was used for analyses. SETTING: Eight hospital regions in the Netherlands. PARTICIPANTS: Patients hospitalized for an acute exacerbation of COPD and positive ProPal-COPD score. RESULTS: Of 222 patients included, 106 responded to the questionnaire at 6 months. Thirty-six of 98 intervention patients (36.7%) received the intervention. Intention-to-treat-analysis showed no effect on the primary outcome (adjusted difference: 1.09; 95% confidence interval: -5.44 to 7.60). In the intervention group, fewer intensive care admissions for COPD took place (adjusted odds ratio: 0.21; 95% confidence interval: 0.03-0.81) and strong indications were found for fewer hospitalizations (adjusted incidence rate ratio: 0.69; 95% confidence interval: 0.46-1.03). CONCLUSIONS: We found no evidence that palliative care improves quality of life in patients with COPD. However, it can potentially reduce acute healthcare use. The consequences of the COVID-19 pandemic led to suboptimal implementation and insufficient power, and may have affected some of our findings.

Efficacy of once-daily, single-inhaler, fixed-dose combination of mometasone/indacaterol/glycopyrronium in patients with asthma with or without persistent airflow limitation: Post hoc analysis from the IRIDIUM study.

BACKGROUND: A novel, once-daily, fixed-dose combination of mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) delivered via Breezhaler® is the first inhaled corticosteroid/long-acting ꞵ2-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) therapy approved for the maintenance treatment of asthma in adults inadequately controlled on ICS/LABA combination. In patients with asthma and persistent airflow limitation (PAL), maximal treatment, especially with combination is suggested. This post hoc analysis of data from the IRIDIUM study assessed the efficacy of MF/IND/GLY in asthma patients with and without PAL. METHODS: Patients with post-bronchodilator FEV1 ≤80% of predicted and FEV1/FVC ratio of ≤0.7 were categorised as PAL subgroup and the remaining as the non-PAL subgroup. Lung function parameters (FEV1, PEF, and FEF25%-75%) and annualised asthma exacerbations rates were evaluated in both subgroups across the treatment arms: once-daily high-dose MF/IND/GLY (160/150/50 µg), high-dose MF/IND (320/150 µg) and twice-daily high-dose fluticasone/salmeterol (FLU/SAL; 500/50 µg). RESULTS: Of the 3092 randomised patients, 64% (n = 1981) met the criteria for PAL. Overall, there was no evidence of treatment difference between PAL and non-PAL subgroups (interaction P-value for FEV1, FEF25%-75%, PEF, moderate or severe exacerbations, severe exacerbations and all exacerbations were 0.42, 0.08, 0.43 0.29, 0.35 and 0.12, respectively). In the PAL subgroup, high-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL improved trough FEV1 (mean difference: 102 mL [P < 0.0001] and 137 mL [P < 0.0001]) and reduced moderate or severe (16% and 32%), severe (25% and 39%) and all exacerbations (19% and 38%), respectively. CONCLUSIONS: Once-daily fixed-dose MF/IND/GLY was efficacious in asthma patients with and without persistent airflow limitation.

Chronic non-invasive ventilation for chronic obstructive pulmonary disease.

BACKGROUND: Chronic non-invasive ventilation (NIV) is increasingly being used to treat people with COPD who have respiratory failure, but the evidence supporting this treatment has been conflicting. OBJECTIVES: To assess the effects of chronic non-invasive ventilation at home via a facial mask in people with COPD, using a pooled analysis of IPD and meta-analysis. SEARCH METHODS: We searched the Cochrane Airways Register of Trials, MEDLINE, Embase, PsycINFO, CINAHL, AMED, proceedings of respiratory conferences, clinical trial registries and bibliographies of relevant studies. We conducted the latest search on 21 December 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing chronic NIV for at least five hours per night for three consecutive weeks or more (in addition to standard care) versus standard care alone, in people with COPD. Studies investigating people initiated on NIV in a stable phase and studies investigating NIV commenced after a severe COPD exacerbation were eligible, but we reported and analysed them separately. The primary outcomes were arterial blood gases, health-related quality of life (HRQL), exercise capacity (stable COPD) and admission-free survival (post-exacerbation COPD). Secondary outcomes for both populations were: lung function, COPD exacerbations and admissions, and all-cause mortality. For stable COPD, we also reported respiratory muscle strength, dyspnoea and sleep efficiency. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. After inclusion of a study, we requested the IPD. We analysed continuous and time-to-event data using linear- and cox-regression mixed-effect models with a random effect on study level. We analysed dichotomous IPD using generalised estimating equations. We adjusted all models for age and sex. We assessed changes in outcomes after three and 12 months.  We also conducted a meta-analysis on aggregated trial data. MAIN RESULTS: We included 14 new RCTs in this review update, in addition to the seven previously included. Seventeen studies investigated chronic NIV in stable COPD and four studies investigated chronic NIV commenced after a severe COPD exacerbation. Three studies compared NIV to sham continuous positive airway pressure (2 to 4 cmH2O). Seven studies used a nasal mask, one study used an oronasal mask and eight studies used both interfaces. Five studies did not report the interface. The majority of trials (20/21) were at high risk of performance bias due to an unblinded design. We considered 11 studies to have a low risk of selection bias and 13 to have a low risk of attrition bias. We collected and analysed the IPD from 13 stable COPD studies (n = 778, 68% of the participants included) and from three post-exacerbation studies (n = 364, 96% of the participants included). In the stable COPD group, NIV probably results in a minor benefit on the arterial partial pressure of oxygen (PaO2) after three months (adjusted mean difference (AMD) 0.27 kPa, 95% CI 0.04 to 0.49; 9 studies, 271 participants; moderate-certainty evidence), but there was little to no benefit at 12 months (AMD 0.09 kPa, 95% CI -0.23 to 0.42; 3 studies, 171 participants; low-certainty evidence). The arterial partial pressure of carbon dioxide (PaCO2) was reduced in participants allocated to NIV after three months (AMD -0.61 kPa, 95% CI -0.77 to -0.45; 11 studies, 475 participants; high-certainty evidence) and persisted up to 12 months (AMD -0.42 kPa, 95% CI -0.68 to -0.16; 4 studies, 232 participants; high-certainty evidence).  Exercise capacity was measured with the 6-minute walking distance (minimal clinical important difference: 26 m). There was no clinically relevant effect of NIV on exercise capacity (3 months: AMD 15.5 m, 95% CI -0.8 to 31.7; 8 studies, 330 participants; low-certainty evidence; 12 months: AMD 26.4 m, 95% CI -7.6 to 60.5; 3 studies, 134 participants; very low-certainty evidence). HRQL was measured with the Severe Respiratory Insufficiency and the St. Georges's Respiratory Questionnaire and may be improved by NIV, but only after three months (3 months: standardised mean difference (SMD) 0.39, 95% CI 0.15 to 0.62; 5 studies, 259 participants; very low-certainty evidence; 12 months: SMD 0.15, 95% CI -0.13 to 0.43; 4 studies, 200 participants; very low-certainty evidence). Lastly, the risk for all-cause mortality is likely reduced by NIV (adjusted hazard ratio (AHR) 0.75, 95% CI 0.58 to 0.97; 3 studies, 405 participants; moderate-certainty evidence). In the post-exacerbation COPD group, there was little to no benefit on the PaO2 after three months, but there may be a slight decrease after 12 months (3 months: AMD -0.10 kPa, 95% CI -0.65 to 0.45; 3 studies, 234 participants; low-certainty evidence; 12 months: -0.27 kPa, 95% CI -0.86 to 0.32, 3 studies; 170 participants; low-certainty evidence). The PaCO2 was reduced by NIV at both three months (AMD -0.40 kPa, 95% CI -0.70 to -0.09; 3 studies, 241 participants; moderate-certainty evidence) and 12 months (AMD -0.52 kPa, 95% CI -0.87 to -0.18; 3 studies, 175 participants; high-certainty evidence). NIV may have little to no benefit on HRQL (3 months: SMD 0.25, 95% CI -0.01 to 0.51; 2 studies, 219 participants; very low-certainty evidence; 12 months: SMD 0.25, 95% -0.06 to 0.55; 2 studies, 164 participants; very low-certainty evidence). Admission-free survival seems improved with NIV (AHR 0.71, 95% CI 0.54 to 0.94; 2 studies, 317 participants; low-certainty evidence), but the risk for all-cause mortality does not seem to improve (AHR 0.97, 95% CI 0.74 to 1.28; 2 studies, 317 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Regardless of the timing of initiation, chronic NIV improves daytime hypercapnia. In addition, in stable COPD, survival seems to be improved and there might be a short term HRQL benefit. In people with persistent hypercapnia after a COPD exacerbation, chronic NIV might prolong admission-free survival without a beneficial effect on HRQL. In stable COPD, future RCTs comparing NIV to a control group receiving standard care might no longer be warranted, but research should focus on identifying participant characteristics that would define treatment success. Furthermore, the optimal timing for initiation of NIV after a severe COPD exacerbation is still unknown.

Effectiveness and implementation of palliative care interventions for patients with chronic obstructive pulmonary disease: A systematic review.

BACKGROUND: Although guidelines recommend palliative care for patients with chronic obstructive pulmonary disease, there is little evidence for the effectiveness of palliative care interventions for this patient group specifically. AIM: To describe the characteristics of palliative care interventions for patients with COPD and their informal caregivers and review the available evidence on effectiveness and implementation outcomes. DESIGN: Systematic review and narrative synthesis (PROSPERO CRD42017079962). DATA SOURCES: Seven databases were searched for articles reporting on multi-component palliative care interventions for study populations containing ⩾30% patients with COPD. Quantitative as well as qualitative and mixed-method studies were included. Intervention characteristics, effect outcomes, implementation outcomes and barriers and facilitators for successful implementation were extracted and synthesized qualitatively. RESULTS: Thirty-one articles reporting on twenty unique interventions were included. Only four interventions (20%) were evaluated in an adequately powered controlled trial. Most interventions comprised of longitudinal palliative care, including care coordination and comprehensive needs assessments. Results on effectiveness were mixed and inconclusive. The feasibility level varied and was context-dependent. Acceptability of the interventions was high; having someone to call for support and education about breathlessness were most valued characteristics. Most frequently named barriers were uncertainty about the timing of referral due to the unpredictable disease trajectory (referrers), time availability (providers) and accessibility (patients). CONCLUSION: Little high-quality evidence is yet available on the effectiveness and implementation of palliative care interventions for patients with COPD. There is a need for well-conducted effectiveness studies and adequate process evaluations using standardized methodologies to create higher-level evidence and inform successful implementation.

Functional respiratory imaging: heterogeneity of acute exacerbations of COPD.

Background: Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity. It contributes to the current persistent one-size-fits-all treatment. To replace this treatment by more personalized, precision medicine, new insights are required. We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs. Methods: The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution. Results: Forty seven patients were assessed. FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of -0.25±0.61 L, p≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p=0.02), and airway resistance. As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters. Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI. Conclusion: FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups. It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations.

Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD) (AECOPD), but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. METHODS: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state) at least 42 days later: inspiratory capacity (IC), body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. RESULTS: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L) and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01). Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01), and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01). CONCLUSION: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase.

Changes in ventilation-perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling.

Introduction: Severe exacerbations associated with chronic obstructive pulmonary disease (COPD) that require hospitalization significantly contribute to morbidity and mortality. Definitions for exacerbations are very broad, and it is unclear whether there is one predominant underlying mechanism that leads to them. Functional respiratory imaging (FRI) with modeling provides detailed information about airway resistance, hyperinflation, and ventilation-perfusion (V/Q) mismatch during and following an acute exacerbation. Materials and methods: Forty-two patients with COPD participating in a multicenter study were assessed by FRI, pulmonary function tests, and self-reported outcome measures during an acute exacerbation and following resolution. Arterial blood gasses and lung function parameters were measured. Results: A significant correlation was found between alveolar-arterial gradient and image-based V/Q (iV/Q), suggesting that iV/Q represents V/Q mismatch during an exacerbation (p<0.05). Conclusion: Recovery of an exacerbation is due to decreased (mainly distal) airway resistance (p<0.05). Improvement in patient-reported outcomes were also associated with decreased distal airway resistance (p<0.05), but not with forced expiratory volume. FRI is, therefore, a sensitive tool to describe changes in airway caliber, ventilation, and perfusion during and after exacerbation. On the basis of the fact that FRI increased distal airway resistance seems to be the main cause of an exacerbation, therapy should mainly focus on decreasing it during and after the acute event.

Real-life data on antibiotic prescription and sputum culture diagnostics in acute exacerbations of COPD in primary care.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are generally treated with optimization of bronchodilation therapy and a course of oral corticosteroids, mostly without antibiotics. The Dutch guidelines recommend prudent use of antibiotics, with amoxicillin or doxycycline as first choice. Here we evaluate adherence to these guidelines with regard to antibiotic prescription in AECOPD in primary care and the use of sputum cultures. METHODS: We retrospectively analyzed a longitudinal cohort of patients in three primary care practices in the north-eastern region of the Netherlands from 2009 to 2013 (n=36,172 subjects) participating in the Registration Network Groningen. Antibiotics prescribed for AECOPD -10/+28 days from the start date of corticosteroid courses were evaluated. In addition, we assessed regional data on the susceptibility of respiratory pathogens from COPD patients. RESULTS: We identified 1,297 patients with COPD. Of these, 616 experienced one or more exacerbations, resulting in a total of 1,558 exacerbations, for which 1,594 antibiotic courses were prescribed. The recommended antibiotics doxycycline and amoxicillin accounted for 56% of the prescribed antibiotics overall and for 35% in subsequent antibiotic courses. The alternative choices were not based on culture results because only in 67 AECOPD events (2.9%) sputum samples were taken. Regional data including 3,638 sputum samples showed that pathogens relevant in AECOPD were detected in 19% of cultures. CONCLUSION: Our study shows that guidelines regarding the prescription of antibiotics are poorly followed, particularly in recurrent exacerbations. Sputum cultures were performed in a small minority of cases. Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment.

(Cost-)effectiveness of self-treatment of exacerbations in patients with COPD: 2 years follow-up of a RCT.

BACKGROUND AND OBJECTIVE: Long-term effectiveness of action plans in patients with chronic obstructive pulmonary disease (COPD) is minimally investigated. We have evaluated the (cost-)effectiveness of a self-management programme with or without self-treatment of exacerbations after 2 years follow-up. METHODS: Self-management with or without self-treatment of exacerbations was randomly assigned to patients. All patients participated in four self-management meetings. Patients in the self-treatment group (STG) also learned to use an action plan to start a course of prednisolone and/or antibiotics in case of worsening of symptoms. Primary outcome was the duration and severity of exacerbations. RESULTS: Data of 70 COPD patients in the STG and 72 patients in the control group (CG) were analysed. Over 2 years, the median number of exacerbation days was significantly lower in the STG (50, IQR: 32-115) compared with the CG (82, IQR: 22-186) (P = 0.047), as was the mean symptom score of an exacerbation (STG: 43.4, IQR 27.2-68.6 vs CG: 55.9, IQR: 31.2-96.8) (P = 0.029). Also, patients in the STG visited the respiratory physician and emergency department less frequently than patients in the CG with incidence rate ratios of 1.52 (95% CI: 1.28-1.79) and 2.27 (95% CI: 1.11-4.62), respectively. Direct medical costs per patient over 2 years were €1078 lower in the STG. CONCLUSION: Self-treatment of exacerbations is beneficial in COPD patients without significant comorbidities because it reduces exacerbation duration, exacerbation severity and health-care utilization leading to considerable cost savings.

Bronchiectasis.

INTRODUCTION: Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions. RESULTS: We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery.

Volume-targeted versus pressure-targeted noninvasive ventilation in patients with chest-wall deformity: a pilot study.

BACKGROUND: Long-term noninvasive ventilation (NIV) is an effective treatment for patients with chronic respiratory failure due to chest-wall deformity, but it is unknown if the time required for the patient to adjust to long-term NIV depends on whether the NIV is volume-targeted or pressure-targeted. OBJECTIVE: To determine whether volume controlled or pressure controlled NIV is easier to implement in patients with chronic respiratory failure due to chest-wall deformity. METHODS: We randomized 16 ventilator-naïve patients to receive either volume-targeted or pressure-targeted nocturnal NIV. The primary outcome was the number of days needed to successfully establish NIV, defined as adequate adjustment and effective ventilation, as measured with overnight arterial blood gas measurement. RESULTS: Two patients did not tolerate volume NIV, and switched to pressure NIV. NIV was successfully established in both groups after a median 6.0 days. There were no significant differences between the groups at any time point in P(aCO(2)) or P(aO(2)) improvement, nor in changes over time. CONCLUSIONS: There was no significant difference in days needed to successfully establish volume NIV versus pressure NIV in patients with chest-wall deformity. However, two patients switched successfully from volume NIV to pressure NIV, which suggests that they preferred pressure NIV.

Copd.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Classically, it is thought to be a combination of emphysema and chronic bronchitis, although only one of these may be present in some people with COPD. The main risk factor for the development and deterioration of COPD is smoking. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of maintenance drug treatment in stable COPD? What are the effects of maintenance drug treatment in stable COPD? What are the effects of non-drug interventions in people with stable COPD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha(1) antitrypsin, antibiotics (prophylactic), anticholinergics (inhaled), beta(2) agonists (inhaled), corticosteroids (oral and inhaled), general physical activity enhancement, inspiratory muscle training, maintaining healthy weight, mucolytics, oxygen treatment (long-term domiciliary treatment), peripheral muscle strength training, psychosocial and pharmacological interventions for smoking cessation, pulmonary rehabilitation, and theophylline.

Quality of life in smokers: focus on functional limitations rather than on lung function?

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based solely on obstruction and does not capture physical functioning. The hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate better with quality of life than the level of airflow limitation was examined. AIM: To study the associations between quality of life in smokers and limitations in physical functioning (MRC dyspnoea scale) and, quality of life and airflow limitation (GOLD COPD stages). DESIGN: Cross-sectional study. SETTING: The city of IJsselstein, a small town in the centre of The Netherlands. METHOD: Male smokers aged 40-65 years without a prior diagnosis of COPD and enlisted with a general practice, participated in this study. Quality of life was assessed by means of a generic (SF-36) and a disease-specific, questionnaire (QOLRIQ). RESULTS: A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed adequate spirometry and completed the questionnaires. Limitations of physical functioning according to the MRC dyspnoea scale were found in 25.1% (99/395) of the participants and airflow limitation in 40.2% (159/395). The correlations of limitations of physical functioning with all quality-of-life components were stronger than the correlations of all quality-of-life subscales with the severity of airflow limitation. CONCLUSION: In middle-aged smokers the correlation of limitations of physical functioning (MRC dyspnoea scale) with quality of life was stronger than the correlation of the severity of airflow limitation with quality of life. Future staging systems of severity of COPD should capture this and not rely on forced expiratory volume in one second (FEV1) alone.