Applying the Rome Proposal on Exacerbations of Chronic Obstructive Pulmonary Disease: Does Comorbid Chronic Heart Failure Matter?

Background: Chronic heart failure (CHF) is a common comorbidity among patients with chronic obstructive pulmonary disease (COPD). Both exacerbations of COPD (ECOPDs) and exacerbations of CHF (ECHFs) display worsening of breathlessness at rest (BaR) and breathlessness at physical activity (BaPA). Comorbid CHF may have an impact on the vital signs assessed, when the Rome proposal (adopted by GOLD 2023) is applied on ECOPDs. Thus, the aim of the present study was to investigate the impact of comorbid CHF on ECOPDs severity, particularly focusing on the influence of comorbid CHF on BaR and BaPA. Methods: We analysed data on COPD symptoms collected from the telehealth study The eHealth Diary. Patients with COPD (n = 43) and patients with CHF (n = 41) were asked to daily monitor BaR and BaPA, employing a digital pen and scales for BaR and BaPA (from 0 to 10). Twenty-eight patients of the COPD patients presented with comorbid CHF. Totally, 125 exacerbations were analysed. Results: Exacerbations in the group with COPD patients and comorbid CHF were compared to the group with COPD patients without comorbid CHF and the group with CHF patients. Compared with GOLD 2022, the GOLD 2023 (the Rome proposal) significantly downgraded the ECOPD severity. Comorbid CHF did not interfere significantly on the observed difference. Comorbid CHF did not worsen BaR scores, assessed at inclusion and at the symptom peak of the exacerbations. Conclusion: In the present study, we find no evidence that comorbid CHF would interfere significantly with the parameters included in the Rome proposal (GOLD 2023). We conclude that the Rome proposal can be safely applied even on COPD patients with very advanced comorbid CHF.

The Exacerbation of Chronic Obstructive Pulmonary Disease: Which Symptom is Most Important to Monitor?

Background: GOLD 2023 defines an exacerbation of COPD (ECOPD) by a deterioration of breathlessness at rest (BaR), mucus and cough. The severity of an ECOPD is determined by the degree of BaR, ranging from 0 to 10. However, it is not known which symptom is the most important one to detect early of an ECOPD, and which symptom that predicts future ECOPDs best. Thus, the purpose of the present study was to find out which symptom is the most important one to monitor. Methods: We analysed data on COPD symptoms from the telehealth study The eHealth Diary. Frequent exacerbators (n = 27) were asked to daily monitor BaR and breathlessness at physical activity (BaPA), mucus and cough, employing a digital pen and symptom scales (0-10). Twenty-seven patients with 105 ECOPDs were analysed. The association between symptom development and the occurrence of exacerbations was evaluated using the Andersen-Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors. Results: According to the criteria proposed by GOLD 2023, 42% ECOPDs were mild, 48% were moderate and 5% were severe, while 6% were undefinable. Mucus and cough improved over study time, while BaR and BaPA deteriorated. Mucus appeared earliest, which was the most prominent feature of the average exacerbation, and worsening of mucus increased the risk for a future ECOPD. There was a 58% increase in the risk of exacerbation per unit increase in mucus score. Conclusion: This study suggests that mucus worsening is the most important COPD symptom to monitor to detect ECOPDs early and to predict future risk för ECOPDs. In the present study, we also noticed a pronounced difference between GOLD 2022 and 2023. Hence, GOLD 2023 defined the ECOPD severity much lower than GOLD 2022 did.

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement.

INTRODUCTION: This post hoc analysis of the "Early MAXimization of bronchodilation for improving COPD stability" (EMAX) trial investigated whether patients achieving early clinically important improvement (CII) sustained longer-term improvements and lower risk of clinically important deterioration (CID). METHODS: Patients were randomized to umeclidinium/vilanterol, umeclidinium, or salmeterol for 24 weeks. The patient-reported outcomes (PROs) Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms, St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) were assessed. CII, defined as attaining minimum clinically important differences (MCID) in ≥2 PROs, was assessed at Weeks 4, 12 and 24. CID was defined as a deterioration in CAT, SGRQ, TDI by the MCID and/or a moderate/severe exacerbation from Day 30. RESULTS: Of 2425 patients, 50%, 53% and 51% achieved a CII at Weeks 4, 12 and 24, respectively. Patients with a CII at Week 4 versus those without had significantly greater odds of achieving a CII at Weeks 12 and 24 (odds ratio: 5.57 [95% CI: 4.66, 6.66]; 4.09 [95% CI: 3.44, 4.86]). The risk of a CID was higher in patients who did not achieve a CII at Week 4 compared with patients who did (hazard ratio [95% CI]: 2.09 [1.86, 2.34]). Patients treated with umeclidinium/vilanterol versus either monotherapy had significantly greater odds of achieving CII at Weeks 4, 12 and 24. CONCLUSION: Achieving a CII at Week 4 was associated with longer-term improvement in PROs and a reduced risk of deterioration. Further research is required to investigate the importance of an early response to treatment on the long-term disease course.

Age-Dependent Associations Between 25-Hydroxy Vitamin D Levels and COPD Symptoms: Analysis of SPIROMICS.

INTRODUCTION: Age and vitamin D levels may affect symptom burden in chronic obstructive pulmonary disease (COPD). We used the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) to determine independent associations between vitamin D levels and COPD symptoms in different age strata. METHODS: Serum 25-hydroxy (OH)-vitamin D levels were modeled continuously and categorically (<20 ng/ml versus ≥20 ng/ml). Stratifying by age group (middle-age: 40-64 years old and older: >65 years old), multivariable modeling was performed to identify relationships between 25-OH-vitamin D levels and the COPD Assessment Test (CAT), the modified Medical Research Council score (mMRC), the St George's Respiratory Questionnaire (SGRQ) total and subdomain scores, the Veterans' Specific Activity Questionnaire, and the 6-minute walk test distance. RESULTS: InIn the middle-aged group, each 5 ng/ml higher 25-OH-vitamin D level was independently associated with more favorable CAT score (-0.35 [-0.67 to -0.03], P=0.03), total SGRQ (-0.91 [-1.65 to -0.17]; P=0.02), and the SGRQ subdomains (Symptoms:-1.07 [-1.96 to -0.18], P=0.02; Impact: -0.77 [-1.53 to -0.003], P=0.049; Activity: -1.07 [-1.96 to -0.18], P=0.02). These associations persisted after the addition of comorbidity score, reported vitamin D supplementation, outdoor time, or season of blood draw to models. No associations were observed between 25-OH-vitamin D levels and symptom scores in the older age group. DISCUSSION: When controlled for clinically relevant covariates, higher 25-OH-vitamin D levels are associated with more favorable respiratory-specific symptoms and quality-of-life assessments in middle-age but not older COPD individuals. Study of the role of vitamin D supplementation in the symptom burden of younger COPD patients is needed.

COPD Patients' Experience of Long-Term Domestic Oxygen-Enriched Nasal High Flow Treatment: A Qualitative Study.

Little is known about chronic obstructive pulmonary disease (COPD) patients experience with home-based health treatments, which are currently rapidly evolving. A previous randomized controlled trial investigated the use of long-term oxygen enriched high flow nasal cannula (HFNC) treatment at home. The aim of this study was to explore COPD patients' experience using home HFNC treatment. Patients in this qualitative study were included from the previous RCT. All patients used long-term oxygen therapy and HFNC, the latter as a primarily nocturnal add-on. Data were collected using semi-structured interviews focused on four themes: 'Description of daily use', 'Experienced changes', 'Treatment benefits and disadvantages' and 'User-friendliness'. The interviewer played an encouraging, non-normative neutral facilitator role in order to give the participants possibility to explain themselves as fully as possible. Participants were recruited until themes were saturated. A total of 12 patients (5 males, 7 females) and 8 relatives participated. Six themes were identified as important to patient adherence: Perceived lower work of breathing; reduced symptoms; improved quality of sleep; increased activity of daily living; feeling safe; technology use. The results increase our knowledge of patient experience of using HFNC for home treatment, which improved the patients' experience through reducing symptoms and increase the activity of daily living. Furthermore, they substantiate the necessity of perceived usefulness and ease of use as important factors for adherence to treatment.

Current evidence for COPD management with dual long-acting muscarinic antagonist/long-acting ß2-agonist bronchodilators.

Long-acting inhaled bronchodilator medications are recommended as initial maintenance therapy for many patients with COPD. These medications include long-acting muscarinic antagonists (LAMA) and long-acting ß2-agonists (LABA). Combinations of long-acting bronchodilator agents (LAMA/LABA) and inhaled corticosteroids combined with LABA (ICS/LABA) are also used as initial or follow-up therapy in patients with more severe symptoms or at risk of COPD exacerbations. This review summarizes the position of LAMA/LABA combinations in treatment recommendations, and the evidence supporting their placement relative to LAMA monotherapy and ICS/LABA combination therapy, as well as differences within the LAMA/LABA class. Most studies show that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment. There are fewer studies comparing the impact of different medication classes on patients' risk of exacerbations; however, the available evidence suggests that LAMA/LABA treatment and LAMA monotherapy lead to a similar reduction in exacerbation risk, while the effect of LAMA/LABA compared with ICS/LABA remains unclear. The incidence of adverse events is similar with LAMA/LABA and LAMA alone. There is a lower risk of pneumonia with LAMA/LABA compared with ICS/LABA. This evidence supports the use of LAMA/LABA combinations as an initial maintenance therapy option for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations, and as follow-up treatment in patients with uncontrolled symptoms or exacerbations on bronchodilator monotherapy.

GOLD assessment of COPD severity in the Clinical Practice Research Datalink (CPRD).

PURPOSE: To evaluate availability of spirometry and symptom data in the Clinical Practice Research Datalink (United Kingdom) to assess COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 definition and comparing it with an algorithm used in other studies. METHODS: This was a descriptive, noninterventional, secondary database cohort study of patients with COPD aged 40 years or older, who initiated treatment with specific COPD medications. Patients were classified according to COPD severity (1) in GOLD 2016 "ABCD" categories based on symptoms (Medical Research Council dyspnea grade, COPD Assessment Test, breathlessness), percent predicted FEV1, and exacerbation history and (2) as mild, moderate, severe, or very severe based on treatment and exacerbation history. RESULTS: The study included 63 900 patients with COPD aged 40 years or older that were new users of 1 or more COPD medication of interest. Percent predicted FEV1 was available for 80.9% of patients; symptoms for 75.6% of patients. Classification into GOLD 2016 ABCD categories was possible for 75.6% of the patients. The GOLD 2016 ABCD definition classified more patients under the high-risk categories (22.1%, A; 18.8%, B; 21.3%, C; 37.9%, D) than did the adapted algorithm (7.9%, mild; 48.6%, moderate; 42.1%, severe; 1.4%, very severe). CONCLUSION: Using our adaptation of the GOLD 2016 COPD severity classification, the information in the Clinical Practice Research Datalink allowed us to ascertain COPD severity in approximately 75% of patients with COPD. Algorithms that include medication use tend to misclassify patients with the extreme COPD severity categories.

The association between objectively measured physical activity and morning symptoms in COPD.

PURPOSE: The morning is the most bothersome period for COPD patients. Morning symptom severities in different Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages are not well studied. Furthermore, factors that are associated with morning symptoms, especially the associations with objectively measured physical activity, are also not well described. MATERIALS AND METHODS: The aim of this cross-sectional observational study was to assess morning symptom severity in GOLD A, B, C and D patients, according to the definitions of the GOLD 2015 statement. Morning symptoms were assessed with the PRO-Morning COPD Symptoms Questionnaire. Differences in morning symptom severity between different COPD stages were assessed with a one-way analysis of variance followed by post hoc analyses. The association between dyspnea severity (assessed with the modified Medical Research Council scale), health status, airflow limitation, lung hyperinflation, anxiety and depression, inflammatory parameters, exacerbations, objectively measured physical activity parameters retrieved from accelerometry and morning symptom severity was evaluated using linear regression analysis. RESULTS: Eighty patients were included (aged 65.6±8.7 years, forced expiratory volume in 1 second [FEV1] % predicted 55.1±16.9). Mean (±SD) morning symptom score was 19.7 (±11.7). Morning symptom severity was significantly different between COPD stages: mean (±SD) score in GOLD A was 9.7 (±7.2), in GOLD B 19.8 (±10.7), in GOLD C 8.6 (±9.3) and in GOLD D 23.8 (±11.2) (p<0.001). Lower health status, more symptoms, increased anxiety and depression, less physical activity (all p<0.001) and lower FEV1 (p=0.03) were associated with an increased morning symptom severity. CONCLUSION: Patients with overall more symptomatic COPD have significant higher morning symptom scores. Morning symptom severity was associated with important clinical outcomes: lower health status, more symptoms, increased anxiety and depression, fewer steps a day, less time in moderate and vigorous physical activity with bouts of at least 10 minutes and lower FEV1. The data suggest that morning symptoms should be carefully assessed in addition to assessment by general COPD-specific questionnaires, especially in those with more symptomatic COPD. More research is needed on potential therapies to improve morning symptoms; this study shows potential targets for intervention.