20 years of neuromuscular electrical stimulation in COPD.

Although a lung disease, COPD is also associated with extrapulmonary manifestations including, among others, limb muscle dysfunction. Limb muscle dysfunction is a key systemic consequence of COPD that impacts patients' physical activity, exercise tolerance, quality of life and survival. Deconditioning is the main mechanism underlying the development of limb muscle dysfunction in COPD, which can be partially improved with exercise. However, some patients may not be able to tolerate exercise because of incapacitating breathlessness or unwillingness to undertake whole-body exercise. Alternative training modalities that do not give rise to dyspnoea, such as neuromuscular electrical stimulation (NMES), are urged. Over the past 20 years, NMES in COPD has presented conflicting conclusions in meta-analysis. In this review, we try to understand the reason for this result by analysing possible biases and factors that brought conflicting conclusions. We discuss the population (the intervention group, but also the control group), the outcome measures, the frequency of stimulation, the rehabilitation protocol (i.e. NMES alone versus standard care/rehabilitation or NMES plus conventional exercise training versus conventional exercise training alone or NMES versus sham treatment) and the trial design. The main reason for this discrepancy is the lack of dedicated guidelines for NMES. Further research is urged to determine the optimal parameters for an NMES programme. Despite this, NMES appears to be an effective means of enhancing quadriceps strength and exercise capacity in COPD with the potential to break the vicious circle induced by the disease and COPD patients' lifestyle.

Network Pharmacology and Experimental Verification Reveal the Regulatory Mechanism of Chuanbeimu in Treating Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches. Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments. Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2. Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.

Efficacy of Acupuncture in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Purpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD. Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: -3.25; 95% CI: -3.73 to -2.78, P<0.001) and arterial blood gas (PaCO2: MD: -1.85; 95% CI: -2.74 to -0.95, P<0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P<0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: -0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: -0.60 to 193.98, P = 0.051), hospitalization duration (MD: -5.70; 95% CI: -11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: -0.19; 95% CI: -0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in "high" risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in "some concern" and 1 RCT assessing hospitalization duration was in "low" risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported. Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.

Addressing Barriers to Chronic Obstructive Pulmonary Disease (COPD) Care: Three Innovative Evidence-Based Approaches: A Review.

Chronic obstructive pulmonary disease (COPD) is a preventable yet widespread and profoundly debilitating respiratory condition, exerting substantial personal and global health ramifications alongside significant economic implications. The first objective of this literature review was to identify reviews the barriers to optimal COPD care, categorizing them into personal patient factors, professional awareness and knowledge, patient-professional relationships, and healthcare service models, including access to care that significantly impacts the quality of COPD management. The second objective was to introduce three approaches for enhancing COPD care outcomes: Self-Management Educational Programs, Health Qigong, and Telehealth service provision, each demonstrating positive effects on COPD patients' health status. These evidence-based interventions offer promising avenues for enhancing COPD care and patient outcomes. Integrating these approaches into comprehensive COPD management strategies holds potential for improving the well-being and quality of life of individuals living with this chronic condition.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study.

BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

"In their own words": delineating the contours of dyspnea invisibility in patients with advanced chronic obstructive pulmonary disease from quantitative discourse analysis.

BACKGROUND: Dyspnea conveys an upsetting or distressing experience of breathing awareness. It heavily weighs on chronic respiratory disease patients, particularly when it persists despite maximal treatment of causative abnormalities. The physical, psychological and social impacts of persistent dyspnea are ill-appreciated by others. This invisibility constitutes a social barrier and impedes access to care. This study aimed to better understand dyspnea invisibility in patients with chronic obstructive pulmonary disease (COPD) through quantitative discourse analysis. METHODS: We conducted a lexicometric analysis (lemmatization, descending hierarchical classification, multicomponent analysis, similarity analysis) of 11 patients' discourses (6 men, severe COPD; immediate postexacerbation rehabilitation) to identify semantic classes and communities, which we then confronted with themes previously identified using interpretative phenomenological analysis (IPA). RESULTS: Class#1 ("experience and need for better understanding"; 38.9% of semantic forms, 50% of patients) illustrates the gap that patients perceive between their experience and what others see, confirming the importance of dyspnea invisibility in patients' concerns. Class#2 ("limitations"; 28.7% of forms) and Class#3 (management"; 13.1% of forms) point to the weight of daily limitations in performing basic activities, of the need to accept or adapt to the constraints of the disease. These three classes matched previously identified IPA-derived themes. Class#4 ("hospitalization"; 18.2% of forms) points to the importance of interactions with the hospital, especially during exacerbations, which constitutes novel information. CONCLUSIONS: Lexicometry confirms the importance of dyspnea invisibility as a burden to COPD patients.

Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Multidisciplinary diagnosis and treatment model based on a retrospective cohort study: Pulmonary function and prognosis quality of life in severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worsening airflow limitation. OBJECTIVE: To explore pulmonary function rehabilitation, life quality and prognosis in patients with severe COPD. METHODS: Between February 2018 and August 2021, 150 patients with severe COPD cured in our hospital were arbitrarily assigned into the control group (n= 75) and study group (n= 75). The control group received routine treatment and the research group received multidisciplinary diagnosis and treatment. The body mass index, airflow obstruction, dyspnea and exercise (BODE), pulmonary function, the number of acute attacks, 6-minute walking distance (6MWD), Borg score and life quality were compared. RESULTS: There was no remarkable difference in BODE score before treatment (P> 0.05). During the 2- and 6-month following treatment, the BODE score of the study group was lower (P< 0.05). In the study group, FEV1 percentage of the predicted value, forced expiratory volume in one second (PPO-FEV1) and the percentage of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) in the first second were higher (P< 0.05). In the study group, there were fewer acute attacks (P< 0.05). After treatment, the 6MWD of the study group following 2- and 6-month treatment was higher (P< 0.05). The Borg scores of the study group at 2- and 6-months after treatment were lower (P< 0.05). There were no remarkable differences in the score of life quality before treatment (P> 0.05), however, the symptom score, activity score, influence score and total score of the study group were lower after the treatment (P< 0.05). CONCLUSION: The application of multidisciplinary diagnosis and treatment model can promote the rehabilitation of pulmonary function of patients with severe COPD, improve their prognosis, slow down the development of the disease and enhance their life quality.

The patient journey in Chronic Obstructive Pulmonary Disease (COPD): a human factors qualitative international study to understand the needs of people living with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common condition that causes irreversible airway obstruction. Fatigue and exertional dyspnoea, for example, have a detrimental impact on the patient's daily life. Current research has revealed the need to empower the patient, which can result in not only educated and effective decision-making, but also a considerable improvement in patient satisfaction and treatment compliance. The current study aimed to investigate the perspectives and requirements of people living with COPD to possibly explore new ways to manage their disease. METHODS: Adults with COPD from 8 European countries were interviewed by human factor experts to evaluate their disease journey through the gathering of information on the age, performance, length, and impact of diagnosis, symptoms progression, and family and friends' reactions. The assessment of present symptoms, services, and challenges was performed through a 90-min semi-structured interview. To identify possible unmet needs of participants, a generic thematic method was used to explore patterns, themes, linkages, and sequences within the data collected. Flow charts and diagrams were created to communicate the primary findings. Following analysis, the data was consolidated into cohesive insights and conversation themes relevant to determining the patient's unmet needs. RESULTS: The 62, who voluntarily accepted to be interviewed, were patients (61% females, aged 32-70 years) with a COPD diagnosis for at least 6 months with stable symptoms of different severity. The main challenges expressed by the patients were the impact on their lifestyle, reduced physical activity, and issues with their mobility. About one-fourth had challenges with their symptoms or medication including difficulty in breathing. Beyond finding a cure for COPD was the primary goal for patients, their main needs were to receive adequate information on the disease and treatments, and to have adequate support to improve physical activity and mobility, helpful both for patients and their families. CONCLUSIONS: These results could aid in the creation of new ideas and concepts to improve our patient's quality of life, encouraging a holistic approach to people living with COPD and reinforcing the commitment to understanding their needs.

The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics.

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased over the last decade and has emerged as the third leading cause of death worldwide. It is characterized by emphysema with prolonged airflow limitation. COPD patients are more susceptible to COVID-19 and increase the disease severity about four times. The most used drugs to treat it show numerous side effects, including immune suppression and infection. This review discusses a narrative opinion and critical review of COPD. We present different aspects of the disease, from cellular and inflammatory responses to cigarette smoking in COPD and signaling pathways. In addition, we highlighted various risk factors for developing COPD apart from smoking, like occupational exposure, pollutants, genetic factors, gender, etc. After the recent elucidation of the underlying inflammatory signaling pathways in COPD, new molecular targeted drug candidates for COPD are signal-transmitting substances. We further summarize recent developments in biomarker discovery for COPD and its implications for disease diagnosis. In addition, we discuss novel drug targets for COPD that could be explored for drug development and subsequent clinical management of cardiovascular disease and COVID-19, commonly associated with COPD. Our extensive analysis of COPD cause, etiology, diagnosis, and therapeutic will provide a better understanding of the disease and the development of effective therapeutic options. In-depth knowledge of the underlying mechanism will offer deeper insights into identifying novel molecular targets for developing potent therapeutics and biomarkers of disease diagnosis.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Role of thioredoxin in chronic obstructive pulmonary disease (COPD): a promising future target.

INTRODUCTION: Thioredoxin (Trx) is a secretory protein that acts as an antioxidant, redox regulator, anti-allergic, and anti-inflammatory molecule. It has been used to treat dermatitis and inflammation of the digestive tract. In the lungs, Trx has a significant anti-inflammatory impact. On the other hand, Chronic Obstructive Pulmonary Disease (COPD) is one of the significant causes of death in the developed world, with a tremendous individual and socioeconomic impact. Despite new initiatives and endless treatment trials, COPD incidence and death will likely escalate in the coming decades. AREAS COVERED: COPD is a chronic inflammatory disease impacting the airways, lung parenchyma, and pulmonary vasculature. Oxidative stress and protease-antiprotease imbalances are thought to be involved in the process. The most popular respiratory inflammatory and allergic disorders therapies are corticosteroids and ß-receptor agonists. These medications are helpful but have some drawbacks, such as infection and immunosuppression; thus, addressing Trx signalling treatments may be a viable COPD treatment approach. This review shall cover the pathophysiology of COPD, the pharmacognosy of anti-COPD drugs, including the assets and liabilities of each, and the role and mechanism of Trx in COPD treatment. EXPERT OPINION: Limited research has targeted the thioredoxin system as an anti-COPD drug. Spectating the increase in the mortality rates of COPD, this review article would be an interesting one to research.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

Knowledge of Vaccination Against Influenza and Pneumococcus in Patients with Chronic Obstructive Pulmonary Disease in an Integrated Care Program.

Purpose: To compare the level of knowledge in vaccination against influenza and pneumococcus of patients with chronic obstructive pulmonary disease (COPD) who are managed in an Integrated Care Program (ICP) with those who receive usual care (UC). Methods: A telephone survey of patients diagnosed with COPD registered in public care networks or private institutions was done. A descriptive and comparative analysis of the characteristics of the ICP and UC groups was carried out. The relationship between belonging to an ICP and the level of knowledge about vaccination was evaluated using Propensity Score Matching (PSM) and multivariate logistic and ordinal regression models. Results: Of 674 study participants, 27.2% were from the ICP group. ICP patients were older, more frequently men, from a higher socioeconomic stratum and a higher educational level (p<0.05). 75.5% of the patients in the ICP group had a high level of vaccination knowledge compared to 42.7% in the UC group (p<0.001). In the multivariate analysis, adjusting for sociodemographic variables, years of COPD diagnosis, and comorbidities, belonging to the ICP was associated with a higher probability of answering questions about vaccination correctly and having a high level of knowledge (OR 3.397, IC 95% 2.058-5.608, p<0.001). Conclusion: Patients with COPD managed in an ICP have a higher level of knowledge in vaccination against influenza and pneumococcus, compared to patients in usual care.

Real-World Treatment Patterns and Switching Following Moderate/Severe Chronic Obstructive Pulmonary Disease Exacerbation in Patients with Commercial or Medicare Insurance in the United States.

Purpose: There is limited literature regarding real-world treatment patterns of patients with COPD, particularly since the introduction of once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol in 2017. Here, we evaluated treatment patterns of patients with COPD before and after a COPD exacerbation. Patients and Methods: Retrospective, descriptive study using medical and pharmacy claims data and enrollment information from the Optum® Clinformatics® Data Mart database. Patients aged ≥40 years with ≥1 COPD exacerbation on or after September 18, 2017 were included. The index date was the last day of the first COPD exacerbation (ie day of visit for a moderate exacerbation or discharge date for a severe exacerbation). The baseline period was 12 months prior to index and the follow-up period (≥3 months) spanned from index until the earliest of health plan disenrollment, end of data availability (September 30, 2020), or death. Treatment patterns were evaluated during baseline and follow-up, with a focus on medication switching in the 90 days pre- and post-index. Results: COPD exacerbations were identified in 307,727 patients (125,942 severe; 181,785 moderate). Mean age at index was 72.8 years; 56.3% were female. Before and after first exacerbation, 37.7% and 48.2% of patients used ≥1 controller medication, respectively. In the 90 days pre-index, ICS, LABA, and LAMA medications were used by 27.5% of patients. Of these users, 64.3% remained on the same medication class, 21.7% discontinued, and 14.1% switched medication in the 90 days post-index. Among switchers, 44.0% switched to triple therapy. Most common switches were ICS/LABA to ICS/LABA/LAMA (20.7%) and LAMA to ICS/LABA/LAMA (16.4%). Conclusion: Many COPD exacerbations occur among patients not on controller medications. Although the percentage of patients receiving a controller medication increased following a first exacerbation, it remained below 50%. Of patients receiving controller medications pre-exacerbation, only a small proportion escalated to triple therapy post-exacerbation.

Lack of Clinical Control in COPD Patients Depending on the Target and the Therapeutic Option.

Introduction: According to the Global Initiative for chronic obstructive lung disease (GOLD), when a treatment is not achieving an appropriate response it should be switched taking into account the predominant treatable trait to target (dyspnea or exacerbations). The objective of the present study was to investigate the lack of clinical control according to the target and medication groups. Materials and Methods: This was a post-hoc analysis of the CLAVE study, an observational, cross-sectional, multicenter study which evaluated the clinical control, and related-factors, in a cohort of 4801 patients with severe chronic obstructive pulmonary disease (COPD). The primary endpoint was the percentage of uncontrolled patients defined as COPD Assessment Test (CAT) >16 or presence of exacerbations in the last 3 months despite receiving long-acting beta2-agonist (LABA) and/or long-acting antimuscarinic antagonist (LAMA) with or without inhaled corticosteroids (ICS). Secondary objectives included the description of sociodemographic and clinical characteristics of patients by therapeutic group and the identification of characteristics potentially associated with the lack of control of COPD including low adherence measured by the test to adherence to inhalers (TAI). Results: In the dyspnea pathway, lack of clinical control was of 25.0% of patients receiving LABA or LAMA in monotherapy, 29.5% by those with LABA + LAMA, 38.3% with LABA + ICS and 37.0% with triple therapy (LABA + LAMA + ICS). In the exacerbation pathway, percentages were 87.1%, 76.7%, 83.3%, and 84.1%, respectively. Low physical activity and high Charlson comorbidity index were independent factor of non-control in all therapeutic groups. Additional factors were lower post-bronchodilator FEV1 and poor adherence to inhalers. Conclusion: There are still room for improvement in COPD control. From the pharmacological perspective, every step in treatment have a pool of uncontrolled patients in which a step-up could be considered according to a trait to target strategy.

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.

Exercise Rehabilitation and Chronic Respiratory Diseases: Effects, Mechanisms, and Therapeutic Benefits.

Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.

Meditative movement for breathlessness in advanced COPD or cancer: a systematic review and meta-analysis.

The effect of meditative movement, which includes yoga, tai chi and qi gong, on breathlessness in advanced disease is unknown. This systematic review aims to comprehensively assess the evidence on the effect of meditative movement on breathlessness (primary outcome), health-related quality of life, exercise capacity, functional performance and psychological symptoms (secondary outcomes) in advanced disease. 11 English and Chinese language databases were searched for relevant trials. Risk of bias was assessed using the Cochrane tool. Standardised mean differences (SMDs) with 95% confidence intervals were computed. 17 trials with 1125 participants (n=815 COPD, n=310 cancer), all with unclear or high risk of bias, were included. Pooled estimates (14 studies, n=671) showed no statistically significant difference in breathlessness between meditative movement and control interventions (SMD (95% CI) 0.10 (-0.15-0.34); Chi2=30.11; I2=57%; p=0.45), irrespective of comparator, intervention or disease category. Similar results were observed for health-related quality of life and exercise capacity. It was not possible to perform a meta-analysis for functional performance and psychological symptoms. In conclusion, in people with advanced COPD or cancer, meditative movement does not improve breathlessness, health-related quality of life or exercise capacity. Methodological limitations lead to low levels of certainty in the results.

Conventional, Complementary and Alternative Medicines: Mechanistic Insights into Therapeutic Landscape of Chronic Obstructive Pulmonary Disease.

COPD (chronic obstructive pulmonary disease) is a major public health concern associated with significant morbidity and mortality worldwide. Current therapeutic guidelines for this disease recommend starting with an inhaled bronchodilator, stepping up to combination therapy as necessary, and/or adding inhaled corticosteroids as symptoms and airflow obstruction progress. However, no drug therapy exists to stop disease progression. The mechanistic definition underlying COPD pathogenesis remains poorly understood, it is generally accepted that oxidative stress and the altered immune response of low-grade airway inflammation are major factors contributing to COPD development. There are several potential therapeutic targets that are currently under investigation, including immune regulatory pathways in inflammation and lung-associated steroid resistance induced by oxidative stress signaling cascades. Patients with COPD have increased levels of inflammatory mediators, including lipid and peptide mediators, as well as a network of cytokines and chemokines that maintain inflammatory immune response and recruit circulating cells into the lungs. Many of these pro-inflammatory mediators are regulated by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs), such as p38 MAPK. Increased oxidative stress is a key driving mechanism in perpetuating inflammation and lung injury. Furthermore, many proteases that degrade elastin fibres are secreted by airway resident infiltrating immune cells in COPD patients. In this perspective, we discuss novel aspects of signaling pathway activation in the context of inflammation and oxidative stress, and the broad view of potential effective pharmacotherapies that target the underlying mechanistic disease process in COPD.