Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.

BACKGROUND: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort. METHODS: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found. RESULTS: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients. CONCLUSIONS: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.

Combined Exercise Training and Nutritional Interventions or Pharmacological Treatments to Improve Exercise Capacity and Body Composition in Chronic Obstructive Pulmonary Disease: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that is associated with significant morbidity, mortality, and healthcare costs. The burden of respiratory symptoms and airflow limitation can translate to reduced physical activity, in turn contributing to poor exercise capacity, muscle dysfunction, and body composition abnormalities. These extrapulmonary features of the disease are targeted during pulmonary rehabilitation, which provides patients with tailored therapies to improve the physical and emotional status. Patients with COPD can be divided into metabolic phenotypes, including cachectic, sarcopenic, normal weight, obese, and sarcopenic with hidden obesity. To date, there have been many studies performed investigating the individual effects of exercise training programs as well as nutritional and pharmacological treatments to improve exercise capacity and body composition in patients with COPD. However, little research is available investigating the combined effect of exercise training with nutritional or pharmacological treatments on these outcomes. Therefore, this review focuses on exploring the potential additional beneficial effects of combinations of exercise training and nutritional or pharmacological treatments to target exercise capacity and body composition in patients with COPD with different metabolic phenotypes.

Precision Medicine for More Oxygen (P4O2)-Study Design and First Results of the Long COVID-19 Extension.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40-65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3-6 and 12-18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient's home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3-6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.

The role of diet and nutrition in the management of COPD.

In 2014, the European Respiratory Society published a statement on nutritional assessment and therapy in COPD. Since then, increasing research has been performed on the role of diet and nutrition in the prevention and management of COPD. Here, we provide an overview of recent scientific advances and clinical implications. Evidence for a potential role of diet and nutrition as a risk factor in the development of COPD has been accumulating and is reflected in the dietary patterns of patients with COPD. Consuming a healthy diet should, therefore, be promoted in patients with COPD. Distinct COPD phenotypes have been identified incorporating nutritional status, ranging from cachexia and frailty to obesity. The importance of body composition assessment and the need for tailored nutritional screening instruments is further highlighted. Dietary interventions and targeted single or multi-nutrient supplementation can be beneficial when optimal timing is considered. The therapeutic window of opportunity for nutritional interventions during and recovering from an acute exacerbation and hospitalisation is underexplored.

Identifying risk factors for COPD and adult-onset asthma: an umbrella review.

BACKGROUND: COPD and adult-onset asthma (AOA) are the most common noncommunicable respiratory diseases. To improve early identification and prevention, an overview of risk factors is needed. We therefore aimed to systematically summarise the nongenetic (exposome) risk factors for AOA and COPD. Additionally, we aimed to compare the risk factors for COPD and AOA. METHODS: In this umbrella review, we searched PubMed for articles from inception until 1 February 2023 and screened the references of relevant articles. We included systematic reviews and meta-analyses of observational epidemiological studies in humans that assessed a minimum of one lifestyle or environmental risk factor for AOA or COPD. RESULTS: In total, 75 reviews were included, of which 45 focused on risk factors for COPD, 28 on AOA and two examined both. For asthma, 43 different risk factors were identified while 45 were identified for COPD. For AOA, smoking, a high body mass index (BMI), wood dust exposure and residential chemical exposures, such as formaldehyde exposure or exposure to volatile organic compounds, were amongst the risk factors found. For COPD, smoking, ambient air pollution including nitrogen dioxide, a low BMI, indoor biomass burning, childhood asthma, occupational dust exposure and diet were amongst the risk factors found. CONCLUSIONS: Many different factors for COPD and asthma have been found, highlighting the differences and similarities. The results of this systematic review can be used to target and identify people at high risk for COPD or AOA.

CT Scan-Derived Muscle, But Not Fat, Area Independently Predicts Mortality in COVID-19.

BACKGROUND: COVID-19 has demonstrated a highly variable disease course, from asymptomatic to severe illness and eventually death. Clinical parameters, as included in the 4C Mortality Score, can predict mortality accurately in COVID-19. Additionally, CT scan-derived low muscle and high adipose tissue cross-sectional areas (CSAs) have been associated with adverse outcomes in COVID-19. RESEARCH QUESTION: Are CT scan-derived muscle and adipose tissue CSAs associated with 30-day in-hospital mortality in COVID-19, independent of 4C Mortality Score? STUDY DESIGN AND METHODS: This was a retrospective cohort analysis of patients with COVID-19 seeking treatment at the ED of two participating hospitals during the first wave of the pandemic. Skeletal muscle and adipose tissue CSAs were collected from routine chest CT-scans at admission. Pectoralis muscle CSA was demarcated manually at the fourth thoracic vertebra, and skeletal muscle and adipose tissue CSA was demarcated at the first lumbar vertebra level. Outcome measures and 4C Mortality Score items were retrieved from medical records. RESULTS: Data from 578 patients were analyzed (64.6% men; mean age, 67.7 ± 13.5 years; 18.2% 30-day in-hospital mortality). Patients who died within 30 days demonstrated lower pectoralis CSA (median, 32.6 [interquartile range (IQR), 24.3-38.8] vs 35.4 [IQR, 27.2-44.2]; P = .002) than survivors, whereas visceral adipose tissue CSA was higher (median, 151.1 [IQR, 93.6-219.7] vs 112.9 [IQR, 63.7-174.1]; P = .013). In multivariate analyses, low pectoralis muscle CSA remained associated with 30-day in-hospital mortality when adjusted for 4C Mortality Score (hazard ratio, 0.98; 95% CI, 0.96-1.00; P = .038). INTERPRETATION: CT scan-derived low pectoralis muscle CSA is associated significantly with higher 30-day in-hospital mortality in patients with COVID-19 independently of the 4C Mortality Score.

Pulmonary function three to five months after hospital discharge for COVID-19: a single centre cohort study.

Some COVID-19 survivors suffer from persistent pulmonary function impairment, but the extent and associated factors are unclear. This study aimed to characterize pulmonary function impairment three to five months after hospital discharge and the association with disease severity. Survivors of COVID-19 after hospitalization to the VieCuri Medical Centre between February and December 2020 were invited for follow-up, three to five months after discharge. Dynamic and static lung volumes, respiratory muscle strength and diffusion capacity were measured. The cohort comprised 257 patients after a moderate (n = 33), severe (n = 151) or critical (n = 73) COVID-19 infection with a median follow-up of 112 days (interquartile range 96-134 days). The main sequelae included reduced diffusion capacity (36%) and reduced maximal expiratory pressure (24%). Critically ill patients were more likely to have reduced diffusion capacity than moderate (OR 8.00, 95% CI 2.46-26.01) and severe cases (OR 3.74, 95% CI 1.88-7.44) and lower forced vital capacity (OR 3.29, 95% CI 1.20-9.06) compared to severe cases. Many COVID-19 survivors, especially after a critical disease course, showed pulmonary function sequelae, mainly DLCO impairments, three to five months after discharge. Monitoring is needed to investigate the persistence of these symptoms and the longer-term implications of the COVID-19 burden.

Update on the Etiology, Assessment, and Management of COPD Cachexia: Considerations for the Clinician.

Cachexia is a commonly observed but frequently neglected extra-pulmonary manifestation in patients with chronic obstructive pulmonary disease (COPD). Cachexia is a multifactorial syndrome characterized by severe loss of body weight, muscle, and fat, as well as increased protein catabolism. COPD cachexia places a high burden on patients (eg, increased mortality risk and disease burden, reduced exercise capacity and quality of life) and the healthcare system (eg, increased number, length, and cost of hospitalizations). The etiology of COPD cachexia involves a complex interplay of non-modifiable and modifiable factors (eg, smoking, hypoxemia, hypercapnia, physical inactivity, energy imbalance, and exacerbations). Addressing these modifiable factors is needed to prevent and treat COPD cachexia. Oral nutritional supplementation combined with exercise training should be the primary multimodal treatment approach. Adding a pharmacological agent might be considered in some, but not all, patients with COPD cachexia. Clinicians and researchers should use longitudinal measures (eg, weight loss, muscle mass loss) instead of cross-sectional measures (eg, low body mass index or fat-free mass index) where possible to evaluate patients with COPD cachexia. Lastly, in future research, more detailed phenotyping of cachectic patients to enable a better comparison of included patients between studies, prospective longitudinal studies, and more focus on the impact of exacerbations and the role of biomarkers in COPD cachexia, are highly recommended.

Physical and mental fatigue in people with non-communicable chronic diseases.

BACKGROUND: Fatigue is frequently reported in people with a non-communicable chronic disease. More insight in the nature of this symptom may enhance targeted treatment of fatigue. In this study, we aimed to gain more insight in the prevalence of different types of fatigue and in current prescribed treatment strategies to reduce fatigue in non-communicable chronic diseases. METHODS: People with non-communicable chronic diseases were contacted via public, non-profit, disease-specific health funds and patient associations and invited to complete a web-based survey. The survey included a general question about the experience ("Do you now or have you ever had complaints of fatigue?") and nature of fatigue (physically/mentally/combination), the Checklist Individual Strength-subscale subjective fatigue (CIS-Fatigue; 8-56 points), self-constructed questions for the distinction between physical and mental fatigue (both 3-21 points) and questions on prescribed treatments for fatigue. RESULTS: In total, 4199 participants (77% females) completed the online survey. 3945 participants (94.0%) reported experiencing fatigue, of which 64.4% reported a combination of both physical and mental fatigue. Median CIS-Fatigue score was 41 (32-48) points, with 68% of the participants reporting severe fatigue (≥36 points). Median scores for physical and mental fatigue were 15 (11-18) and 12 (8-16) points, respectively. In 55% of the participants, fatigue was only occasionally or never discussed with the healthcare professional, and only 23% of the participants were prescribed a treatment for fatigue. Participants often reported no effect or even an increase in fatigue after treatment. CONCLUSIONS: Findings indicate that both physical and mental fatigue are often experienced simultaneously in people with non-communicable chronic diseases, but can also occur separately. Fatigue is often only occasionally or never discussed, let alone treated, highlighting the need to raise awareness among healthcare professionals. Future studies are needed to gain more insight in underlying factors of fatigue in non-communicable chronic diseases, its impact on daily life and development and evaluation of targeted treatment strategies.Key messages:Both physical and mental fatigue are frequently present in people with non-communicable chronic diseases.Fatigue is often only occasionally or never discussed during consultation with the physician, highlighting the need to raise awareness among healthcare professionals for adequate screening and evaluating of fatigue in people with non-communicable chronic diseases.Only less than a quarter of the people with non-communicable chronic diseases who reported to experience fatigue were prescribed a treatment for fatigue, which was often experienced as ineffective.

Physical and mental health profile of patients with the early-onset severe COPD phenotype: A cross-sectional analysis.

BACKGROUND & AIM: Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD. METHODS: This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1 s (FEV1) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV1%predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups. RESULTS: Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p = 0.029). In line with a large difference in FEV1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p < 0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1 m, p = 0.001, and 25.9%predicted, p < 0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups. CONCLUSION: Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD.

Nutrition as a modifiable factor in the onset and progression of pulmonary function impairment in COPD: a systematic review.

CONTEXT: Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD. OBJECTIVE: The association of dietary intake and nutrient status with COPD risk and onset, as well as pulmonary function decline (change in forced expiratory volume in 1 second, forced vital capacity, or the ratio of the former to the latter) in patients with COPD was investigated in this systematic review. DATA SOURCES: The PubMed database was searched by combining terms of pulmonary function or COPD with diet, nutrient status, or nutritional supplementation. DATA EXTRACTION: Original studies and systematic reviews and meta-analyses were included. Articles obtained were independently screened for relevance on the bases of title and abstract by 2 researchers. Eventually, 89 articles were included in the analysis. RESULTS: The unhealthy Western-style diet is associated with an increased risk of COPD and an accelerated decline of pulmonary function. Intake of fruit, vegetables, dietary fibers, vitamins C and E, polyphenols, and ß-carotene were individually associated with lower COPD risk, whereas consumption of processed meat was associated with higher COPD risk. Data on the effect of dietary quality on pulmonary function decline in patients with COPD are limited and inconsistent. Strong evidence for beneficial effects on pulmonary function decline was found only for vitamin D supplementation. CONCLUSION: Considering the increasing burden of COPD, more attention should be given to dietary quality as a modifiable factor in disease development and progression in patients with COPD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021240183.

Fatigue in patients with chronic disease: results from the population-based Lifelines Cohort Study.

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5-1.7] with one chronic disease to 5.5 [4.5-6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5-1.6] to 4.9 [3.9-6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach.

Alterations in plasma hyaluronic acid in patients with clinically stable COPD versus (non)smoking controls.

Hyaluronic acid (HA) is a key component of the extracellular matrix. HA and its metabolism are suggested to be altered in the lungs of patients with chronic obstructive pulmonary disease (COPD). The present study explored systemic HA, and its metabolic regulators, in patients with clinically stable COPD and smoking and non-smoking controls. Furthermore, associations of HA with acute exacerbations (AECOPD), airway-related hospitalizations, systemic inflammation and cardiovascular risk were studied. In total, 192 patients with moderate to very severe COPD [aged 62.3 y (± SD 7.0)], 84 smoking controls [aged 61.8 y (± 5.7)], and 107 non-smoking controls [aged 60.1 y (± 7.0)] were included. Plasma HA was reduced in patients with COPD compared to non-smoking controls (p = 0.033), but was comparable after adjusting for age and sex. Expression of HAS-3 did not differ between groups, but was substantially less detectable in more patients with COPD than (non)smoking controls (p < 0.001). Expression of HYAL-2 was enhanced in patients with COPD versus smoking (p = 0.019) and non-smoking (p < 0.001) controls, also in the age- and sex- adjusted model (p < 0.001). Plasma HA was not associated with AECOPD, airway-related hospitalizations in the previous year, or systemic inflammation in COPD. Arterial pulse wave velocity explained some of the variance (< 10%) in plasma HA (p = 0.006). Overall, these results indicate that expression of HYAL-2, but not plasma HA nor HAS-3, is enhanced in patients with COPD compared to (non)smoking controls. Furthermore, HA was not associated with clinical outcomes, yet, cardiovascular risk might play a role in its systemic regulation in stable COPD.

Resveratrol for patients with chronic obstructive pulmonary disease: hype or hope?

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with a high prevalence of extrapulmonary manifestations and, frequently, cardiovascular comorbidity. Resveratrol is a food-derived compound with anti-inflammatory, antioxidant, metabolic and cardioprotective potential. Therefore, resveratrol might improve the pulmonary as well as extrapulmonary pathology in COPD. In this review, we will evaluate knowledge on the effects of resveratrol on lung injury, muscle metabolism and cardiovascular risk profile and discuss if resveratrol is a hype or hope for patients with COPD. RECENT FINDINGS: Experimental models of COPD consistently show decreased inflammation and oxidative stress in the lungs after resveratrol treatment. These beneficial anti-inflammatory and antioxidant properties of resveratrol can indirectly also improve both skeletal and respiratory muscle impairment in COPD. Recent clinical studies in non-COPD populations show improved mitochondrial oxidative metabolism after resveratrol treatment, which could be beneficial for both lung and muscle impairment in COPD. Moreover, preclinical studies suggest cardioprotective effects of resveratrol but results of clinical studies are inconclusive. SUMMARY: Resveratrol might be an interesting therapeutic candidate to counteract lung and muscle impairments characteristic to COPD. However, there is no convincing evidence that resveratrol will significantly decrease the cardiovascular risk in patients with COPD.

The effect of acute and 7-days dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD. METHODS: This double-blind, randomized cross-over placebo controlled trial included 20 mild-to-moderate COPD patients (66.6 ± 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 ± 3 kg/m2) but high prevalence of abdominal obesity (83.3%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (∼8 mmol/day) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated. RESULTS: Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure. CONCLUSION: Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients.

Normal Weight but Low Muscle Mass and Abdominally Obese: Implications for the Cardiometabolic Risk Profile in Chronic Obstructive Pulmonary Disease.

BACKGROUND: It is well established that low muscle mass affects physical performance in chronic obstructive pulmonary disease (COPD). We hypothesize that combined low muscle mass and abdominal obesity may also adversely influence the cardiometabolic risk profile in COPD, even in those with normal weight. The cardiometabolic risk profile and the responsiveness to 4 months high-intensity exercise training was assessed in normal-weight patients with COPD with low muscle mass stratified by abdominal obesity. METHODS: This is a cross-sectional study including 81 clinically stable patients with COPD (age 62.5 ± 8.2 years; 50.6% males; forced expiratory volume in 1 second 55.1 ± 19.5 percentage predicted) with fat-free mass index <25th percentile eligible for outpatient pulmonary rehabilitation. Body composition, blood biomarkers, blood pressure, physical activity level, dietary intake, and physical performance were assessed at baseline and in a subgroup after 4 months of exercise training. RESULTS: Mean body mass index was 22.7 ± 2.7 kg/m2, and 75% of patients had abdominal obesity. Abdominally obese patients had higher glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), branched chain amino acids and a higher prevalence of metabolic syndrome compared with those without abdominal obesity. Exercise training improved cycling endurance time and quadriceps strength, but did not yield a clinically meaningful improvement of the cardiometabolic risk profile. Triglycerides showed a significant decrease, while the HOMA-IR increased. CONCLUSION: Abdominal obesity is highly prevalent in normal-weight patients with COPD with low muscle mass who showed an increased cardiometabolic risk compared with patients without abdominal obesity. This cardiometabolic risk profile was not altered after 4 months of exercise training.

Sarcopenia in Advanced COPD Affects Cardiometabolic Risk Reduction by Short-Term High-intensity Pulmonary Rehabilitation.

OBJECTIVES: Sarcopenia is common in chronic obstructive pulmonary disease (COPD) and may contribute to increased cardiometabolic risk. Interventions to reduce cardiometabolic risk in advanced COPD have been scarcely studied. We have investigated the cardiometabolic effect of a short-term high-intensity rehabilitation program in sarcopenic and nonsarcopenic patients with advanced COPD. DESIGN: Prospective observational study. SETTING: Inpatient 4-week short-term high-intensity pulmonary rehabilitation program at the University Clinic Golnik, Slovenia. PARTICIPANTS: 112 stable COPD patients (66 ± 8 years, 85% GOLD III/IV, 66% men). MEASUREMENTS: Blood biomarkers were assessed at baseline and after rehabilitation. Sarcopenia was assessed at baseline (skeletal muscle index <7.23 kg/m(2) for men and <5.67 kg/m(2) for women, as measured by whole-body dual energy X-ray absorptiometry. Insulin resistance (IR) was defined as homeostasis model assessment of insulin resistance (HOMA-IR) above 2.5. RESULTS: IR and sarcopenia were detected in 59% and 55% of patients, respectively. In contrast to sarcopenic patients, rehabilitation decreased HOMA-IR (2.8 to 1.9, P = .031), fat mass index (10.1 to 9.7 kg/m(2), P = .013), waist circumference (103 to 101 cm, P = .002), and low-density lipoprotein cholesterol (3.2 to 3.0 mmol/L, P = .034) in nonsarcopenic patients. A decrease in total cholesterol levels was observed in both groups. CONCLUSIONS: Sarcopenia affects the modification of cardiometabolic risk markers by short-term high-intensity pulmonary rehabilitation in advanced COPD patients.

A Multidimensional Risk Score to Predict All-Cause Hospitalization in Community-Dwelling Older Individuals With Obstructive Lung Disease.

BACKGROUND: Both respiratory and nonrespiratory hospitalizations are common and costly events in older individuals with obstructive lung disease. Prevention of any hospitalization in these individuals is essential. We aimed to construct a prediction model for all-cause hospitalization risk in community-dwelling older individuals with obstructive lung disease. METHODS: We studied 268 community-dwelling individuals with obstructive lung disease (defined as FEV1/FVC

The Prevalence of Metabolic Syndrome In Chronic Obstructive Pulmonary Disease: A Systematic Review.

Type 2 Diabetes Mellitus (T2DM) and cardiovascular diseases (CVD) are common in patients with chronic obstructive pulmonary disease (COPD). Prevention of these co-morbidities in COPD requires knowledge on their risk factors. Metabolic syndrome (MetS) predisposes to the development of T2DM and CVD but its prevalence in COPD remains unclear. The aim of this review was to assess the prevalence of MetS and its components in COPD patients compared to controls and to investigate the contribution of clinical characteristics to MetS prevalence. We systematically searched PubMed and EMBASE for original studies in COPD that have investigated the prevalence of MetS and its components. In total, 19 studies involving 4208 COPD patients were included. The pooled MetS prevalence was 34%. Compared to controls, the prevalence was higher in COPD (10 studies, 32% and 30%, p = 0.001). The three most prevalent components in both COPD and controls were arterial hypertension (56% and 51%), abdominal obesity (39% and 38%) and hyperglycemia (44% and 47%). Compared to COPD patients without MetS, those with MetS had higher body mass index (BMI) (29.9 and 24.6 kg/m(2), p < 0.001), higher forced expiratory volume in 1 second (FEV1) % predicted (54 and 51, p < 0.001) and were more frequently female (31% and 25%, p = 0.011). In conclusion, the prevalence of MetS in COPD patients is high and hypertension, abdominal obesity and hyperglycemia are the most prevalent components. Further studies are needed to evaluate the impact of lifestyle factors and medications on MetS in COPD.