Changes in lower limb muscle function and muscle mass following exercise-based interventions in patients with chronic obstructive pulmonary disease: A review of the English-language literature.

Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting. Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures. This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass. PUBMED and PEDro databases were searched. In all, 70 studies ( n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised. Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated. Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured. Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients. Which intervention(s) is (are) best for which subgroup of patients remains currently unknown. Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients.

Body mass index and chronic airflow limitation in a worldwide population-based study.

Nutritional status has been associated with clinical outcome in chronic airflow limitation (CAL), but epidemiological studies are scarce. We aimed to assess the relationship between body mass index (BMI) and CAL, taking into account confounding factors. 18,606 participants (49% male, 21% smokers, mean age: 55.8 ± 11.2 years, mean BMI: 26.7 ± 5.5 kg/m(2)) of the BOLD initiative from 26 sites in 23 countries were included. CAL was defined as post-bronchodilator forced expiratory volume in the first second/forced vital capacity < lower limit of normal. Low and obese BMI were defined as <21 kg/m(2) and ≥30 kg/m(2), respectively. Multivariate logistic regression analysis controlled for confounders age, sex and smoking, and meta-analysis of between-site heterogeneity and clustering. Prevalence of low and obese BMI, smoking history and prevalence of CAL were highly variable between sites. After adjustment for confounders, the meta-analysis of all sites showed that compared to subjects without CAL, low BMI was more frequent, (adjusted odds ratio (OR): 2.23 (95% confidence interval: 1.75, 2.85)) and conversely, obesity was less frequent in subjects with CAL (adjusted OR: 0.78 (0.65, 0.94)). In a worldwide population sample, CAL was associated with lower BMI, even after adjusting for confounding factors age, gender, smoking and between-site heterogeneity. These results indicate a CAL-specific association with body composition.

Measurement properties of the Timed Up & Go test in patients with COPD.

We aimed to investigate the construct validity of the Timed Up & Go (TUG) test in chronic obstructive pulmonary disease (COPD), to identify characteristics related to an abnormal TUG time and to examine the responsiveness of the TUG to pulmonary rehabilitation (PR). TUG time was assessed before and after comprehensive PR in 500 COPD patients, and compared cross-sectionally in 100 non-COPD subjects. Physical health outcomes, mental health outcomes, symptom-related outcomes and multidimensional indices were assessed in COPD patients only. Good convergent and discriminant validity was demonstrated by fair-to-moderate correlation with physical health outcomes, symptom-related outcomes and multidimensional indices ( rs = 0.18-0.70) and by little correlation with mental health outcomes ( rs = 0.21-0.26). COPD patients had a worse TUG time than non-COPD subjects, demonstrating known-groups validity. A TUG time of 11.2 seconds had good sensitivity (0.75) and specificity (0.83) for identifying patients with a baseline 6-minute walk distance <350 m. TUG time improved after PR ( p < 0.0001) and a change of 0.9-1.4 seconds was identified as clinically important. The TUG is valid and responsive in COPD. An abnormal result is indicative of poor health outcomes. This simple test provides valuable information and can be adopted in clinical and research settings.

The Impact of Long COVID-19 on Mental Health: Observational 6-Month Follow-Up Study.

BACKGROUND: The psychological impact of COVID-19 can be substantial. However, knowledge about long-term psychological outcomes in patients with COVID-19 is scarce. OBJECTIVE: In this longitudinal, observational study, we aimed to reveal symptoms of posttraumatic stress disorder (PTSD) and symptoms of anxiety and depression up to 6 months after the onset of COVID-19-related symptoms in patients with confirmed COVID-19 and persistent complaints. To demonstrate the impact in nonhospitalized patients, we further aimed to compare these outcomes between nonhospitalized and hospitalized patients. METHODS: Demographics, symptoms of PTSD (Trauma Screening Questionnaire [TSQ] ≥6 points) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS] ≥8 points) were assessed at 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID-19 peer support groups. RESULTS: Data from 239 patients with confirmed COVID-19 (198/239, 82.8% female; median age: 50 [IQR 39-56] years) were analyzed. At the 3-month follow-up, 37.2% (89/239) of the patients had symptoms of PTSD, 35.6% (85/239) had symptoms of anxiety, and 46.9% (112/239) had symptoms of depression, which remained high at the 6-month follow-up (64/239, 26.8%, P=.001; 83/239, 34.7%, P=.90; 97/239, 40.6%, P=.08, respectively; versus the 3-month follow-up). TSQ scores and HADS anxiety and depression scores were strongly correlated at the 3- and 6-month follow-ups (r=0.63-0.71, P<.001). Symptoms of PTSD, anxiety, and depression were comparable between hospitalized (n=62) and nonhospitalized (n=177) patients. CONCLUSIONS: A substantial percentage of patients with confirmed COVID-19 and persistent complaints reported symptoms of PTSD, anxiety, or depression 3 and 6 months after the onset of COVID-19-related symptoms. The prevalence rates of symptoms of PTSD, anxiety, and depression were comparable between hospitalized and nonhospitalized patients and merely improved over time. Health care professionals need to be aware of these psychological complications and intervene on time in post-COVID-19 patients with persistent complaints. TRIAL REGISTRATION: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.

Understanding and Being Understood: Information and Care Needs of 2113 Patients With Confirmed or Suspected COVID-19.

To become a proactive and informed partner in postacute coronavirus disease 2019 (COVID-19) management, patients need to have the knowledge, skills, and confidence to self-manage COVID-19-related health challenges. Due to several restrictions and consequently social isolation, online platforms and forums where people can share information and experiences became more popular and influential. Therefore, this study aimed to identify perceived information needs and care needs of members of 2 Facebook groups for patients with COVID-19 and persistent complaints in the Netherlands and Belgium and patients with COVID-19 who registered at a website of the Lung Foundation Netherlands. Besides demographics and clinical characteristics, the degree of satisfaction with care during and after the infection as well as satisfaction with available information were assessed. Open text fields revealed specific information needs which were summarized. Patients with confirmed or suspected COVID-19 perceive various unmet needs varying from specific information needs (eg, information about permanent lung damage) to general needs (eg, being heard and understood). These data lead to several recommendations to improve care for patients with COVID-19 and justify further development of online platforms specifically addressing these unmet needs.

External Validation Of The Updated ADO Score In COPD Patients From The Birmingham COPD Cohort.

Background: Reviews suggest that the ADO score is the most discriminatory prognostic score for predicting mortality among chronic obstructive pulmonary disease (COPD) patients, but a full evaluation and external validation within primary care settings is critical before implementation. Objectives: To validate the ADO score in prevalent and screen-detected primary care COPD cases at 3 years and at shorter time periods. Patients and methods: One thousand eight hundred and ninety-two COPD cases were recruited between 2012 and 2014 from 71 United Kingdom general practices as part of the Birmingham COPD Cohort study. Cases were either on the practice COPD register or screen-detected. We validated the ADO score for predicting 3-year mortality with 1-year and 2-year mortality as secondary endpoints using discrimination (area-under-the-curve (AUC)) and calibration plots. Results: One hundred and fifty-four deaths occurred within 3 years. The ADO score was discriminatory for predicting 3-year mortality (AUC= 0.74; 95% CI: 0.69-0.79). Similar performance was found for 1- (AUC= 0.73; 0.66-0.80) and 2-year mortality (0.72; 0.67-0.76). The ADO score showed reasonable calibration for predicting 3-year mortality (calibration slope 0.95; 0.70-1.19) but over-predicted in cases with higher predicted risks of mortality at 1 (0.79; 0.45-1.13) and 2-year (0.79; 0.57-1.01) mortality. Discussion: The ADO score showed promising discrimination in predicting 3-year mortality in a primary care population including screen-detected cases. It may need to be recalibrated if it is used to provide risk predictions for 1- or 2-year mortality since, in these time-periods, over-prediction was evident, especially in cases with higher predicted mortality risks.

Personalized medicine for patients with COPD: where are we?

Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD.

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale.

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration.

The patient with a complex chronic respiratory disease: a specialist of his own life?

INTRODUCTION: The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

Risk of community-acquired pneumonia in chronic obstructive pulmonary disease stratified by smoking status: a population-based cohort study in the United Kingdom.

BACKGROUND: Smoking increases the risk of community-acquired pneumonia (CAP) and is associated with the development of COPD. Until now, it is unclear whether CAP in COPD is due to smoking-related effects, or due to COPD pathophysiology itself. OBJECTIVE: To evaluate the association between COPD and CAP by smoking status. METHODS: In total, 62,621 COPD and 191,654 control subjects, matched by year of birth, gender and primary care practice, were extracted from the Clinical Practice Research Datalink (2005-2014). Incidence rates (IRs) were estimated by dividing the total number of CAP cases by the cumulative person-time at risk. Time-varying Cox proportional hazard models were used to estimate the hazard ratios (HRs) for CAP in COPD patients versus controls. HRs of CAP by smoking status were calculated by stratified analyses in COPD patients versus controls and within both subgroups with never smoking as reference. RESULTS: IRs of CAP in COPD patients (32.00/1,000 person-years) and controls (6.75/1,000 person-years) increased with age and female gender. The risk of CAP in COPD patients was higher than in controls (HR 4.51, 95% CI: 4.27-4.77). Current smoking COPD patients had comparable CAP risk (HR 0.92, 95% CI: 0.82-1.02) as never smoking COPD patients (reference), whereas current smoking controls had a higher risk (HR 1.23, 95% CI: 1.13-1.34) compared to never smoking controls. CONCLUSION: COPD patients have a fourfold increased risk to develop CAP, independent of smoking status. Identification of factors related with the increased risk of CAP in COPD is warranted, in order to improve the management of patients at risk.

Domain-specific cognitive impairment in patients with COPD and control subjects.

Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls.

Sputum microbiology predicts health status in COPD.

BACKGROUND: Spontaneous sputum production occurs in a subset of COPD patients; however, its clinical relevance has not been established. Differences in health status and clinical outcomes between patients with and without positive sputum cultures are unknown. OBJECTIVE: To compare clinical characteristics and health status of spontaneous sputum producers with a positive culture (SC+) and negative culture (SC-) with nonsputum producers (NP) in a cohort of COPD patients referred for pulmonary rehabilitation. METHODS: In total, 518 clinically stable patients with mild-to-very severe COPD were recruited (mean age: 64.1±9.1 years, 55.6% males, forced expiratory volume in 1 second 48.6%±20.0% predicted). Health status was measured using COPD Assessment Test, St George's Respiratory Questionnaire, and the Clinical COPD Questionnaire. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Exercise capacity was measured using the 6-minute walking distance. Spontaneously expectorated sputum was cultured for microbiology. RESULTS: Almost one-third of patients spontaneously produced sputum (n=164, 31.7%). Despite comparable lung function, SC+ reported more frequent exacerbations than NP (≥2 exacerbations <1 year: 43 [81.1%] vs 179 [50.6%], P<0.001). COPD Assessment Test total score and the Clinical COPD Questionnaire total score were significantly worse in SC+ than NP (23.9±6.1 vs 21.1±6.7, P=0.012; 3.1±1.0 vs 2.5±1.0, P=0.002; respectively). Hospital Anxiety and Depression Scale-D score was significantly higher in SC+ than NP (8.7±4.1 vs 7.2±4.3, P=0.046). CONCLUSION: Spontaneous sputum production is common in COPD. Particularly, patients with positive cultures have worse health status and more symptoms of depression. Impact on disease progression and long-term outcomes remain to be established. CLINICAL TRIAL REGISTRATION: NTR3416, registered at www.trialregister.nl.