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Effects of combined training on metabolic profile, lung function, stress and quality of life in sedentary adults: A study protocol for a randomized controlled trial.
Ferreira, JP, Duarte-Mendes, P, Teixeira, AM, Silva, FM
PloS one. 2022;(2):e0263455
Abstract
BACKGROUND Both physical inactivity and sedentary behavior are considered modifiable risk factors for chronic diseases and all-cause mortality. Adult office-workers spend most of their working day in sedentary behaviors, so they are particularly at high risk of developed chronic diseases (e.g., cardiovascular diseases, metabolic disorders like diabetes mellitus, …). It seems important to promote behavioral changes that could prevent or delay metabolic disease development. Evidence supports the use of exercise programs, however, to date there are several knowledge gaps and inconsistencies in the literature regarding the effects of Combined Training (i.e., aerobic plus resistance training) in sedentary healthy adults. This paper outlines an RCT designed to evaluate the effects of a 16-week combined training program on biochemical and immune markers of metabolic disease, lung function, salivary stress hormones and subjective quality of life (primary outcomes), as well as on body composition and physical fitness (secondary outcomes) in sedentary middle-aged office-workers. Furthermore, we aimed to assess the associations between the changes promoted by the exercise program and the different variables studied. METHODS AND DESIGN This is a single-blinded two-arm RCT with parallel groups. A minimum of healthy 40 office-workers aged 40-64 years will be recruited to engage in a 16-week intervention study. After baseline assessments, participants will be randomized to one of the two groups: (1) combined training group or (2) control group. Baseline assessments will be repeated after 8 weeks of intervention (mid-testing) and upon completion of the intervention (post-testing). DISCUSSION This RCT involves a multi-disciplinary approach and seems to be a relevant contribution to understanding the potential role of combined training in improving the metabolic profile, lung function, stress, and quality of life in adults. The results can provide important insights for clinical recommendations and for the optimization of strategies to prevent metabolic disorders in adults with sedentary jobs. TRIAL REGISTRATION This trial is registered with ClinicalTrials.gov (registration number: NCT04868240; date of registration April 30, 2021).
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Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19.
Nairz, M, Sahanic, S, Pizzini, A, Böhm, A, Tymoszuk, P, Mitterstiller, AM, von Raffay, L, Grubwieser, P, Bellmann-Weiler, R, Koppelstätter, S, et al
Scientific reports. 2022;(1):3677
Abstract
The CovILD study is a prospective, multicenter, observational cohort study to systematically follow up patients after coronavirus disease-2019 (COVID-19). We extensively evaluated 145 COVID-19 patients at 3 follow-up visits scheduled for 60, 100, and 180 days after initial confirmed diagnosis based on typical symptoms and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We employed comprehensive pulmonary function and laboratory tests, including serum concentrations of IgG against the viral spike (S) glycoprotein, and compared the results to clinical data and chest computed tomography (CT). We found that at the 60 day follow-up, 131 of 145 (90.3%) participants displayed S-specific serum IgG levels above the cut-off threshold. Notably, the highly elevated IgG levels against S glycoprotein positively correlated with biomarkers of immune activation and negatively correlated with pulmonary function and the extent of pulmonary CT abnormalities. Based on the association between serum S glycoprotein-specific IgG and clinical outcome, we generated an S-specific IgG-based recovery score that, when applied in the early convalescent phase, accurately predicted delayed pulmonary recovery after COVID-19. Therefore, we propose that S-specific IgG levels serve as a useful immunological surrogate marker for identifying at-risk individuals with persistent pulmonary injury who may require intensive follow-up care after COVID-19.
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Gut Microbiota, in the Halfway between Nutrition and Lung Function.
Espírito Santo, C, Caseiro, C, Martins, MJ, Monteiro, R, Brandão, I
Nutrients. 2021;(5)
Abstract
The gut microbiota is often mentioned as a "forgotten organ" or "metabolic organ", given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a "good" microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut-lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.
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Probiotics: A potential immunomodulator in COVID-19 infection management.
Singh, K, Rao, A
Nutrition research (New York, N.Y.). 2021;:1-12
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Abstract
COVID-19 caused by SARS-CoV-2 is an ongoing global pandemic. SARS-CoV-2 affects the human respiratory tract's epithelial cells, leading to a proinflammatory cytokine storm and chronic lung inflammation. With numerous patients dying daily, a vaccine and specific antiviral drug regimens are being explored. Probiotics are live microorganisms with proven beneficial effects on human health. While probiotics as nutritional supplements are long practiced in different cuisines across various countries, the emerging scientific evidence supports the antiviral and general immune-strengthening health effects of the probiotics. Here, we present an overview of the experimental studies published in the last 10 years that provide a scientific basis for unexplored probiotics as a preventive approach to respiratory viral infections. Based on collated insights from these experimental data, we identify promising microbial strains that may serve as lead prophylactic and immune-boosting probiotics in COVID-19 management.
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Pathogenesis-directed therapy of 2019 novel coronavirus disease.
Stratton, CW, Tang, YW, Lu, H
Journal of medical virology. 2021;(3):1320-1342
Abstract
The 2019 novel coronavirus disease (COVID-19) now is considered a global public health emergency. One of the unprecedented challenges is defining the optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID-19. The optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of COVID-19, there have been many prepublications and publications reviewing the therapy of COVID-19 as well as many prepublications and publications reviewing the pathogenesis of SARS-CoV-2. However, there have been no comprehensive reviews that link COVID-19 therapies to the pathogenic mechanisms of SARS-CoV-2. To link COVID-19 therapies to pathogenic mechanisms of SARS-CoV-2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID-19, SARS-CoV-2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune-based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID-19 therapies with pathogenic mechanisms of SARS-CoV-2 has resulted in six major therapeutic goals for COVID-19 therapy based on the pathogenic mechanisms of SARS-CoV-2. These goals are listed below: 1. The first goal is identifying COVID-19 patients that require both testing and therapy. This is best accomplished with a COVID-19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. Whether a symptomatic respiratory illness is COVID-19, influenza, or another respiratory pathogen, an oxygen saturation less than 90% means that the patient requires medical assistance. 2. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory-directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID-19. 3. The third goal is to reduce the viral load of SARS-CoV-2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS-CoV-2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS-CoV-2. These are post-Covid-19 plasma with a high neutralizing antibody titer against SARS-CoV-2 or intravenous remdesivir; both options require hospitalization. 4. The fourth goal is to identify and address the hyperinflammation phase often seen in hospitalized COVID-19 patients. Currently, fever with an elevated C-reactive protein is useful for diagnosing this hyperinflammation syndrome. Low-dose dexamethasone therapy currently is the best therapeutic approach. 5. The fifth goal is to identify and address the hypercoagulability phase seen in many hospitalized COVID-19 patients. Patients who would benefit from anticoagulation therapy can be identified by a marked increase in d-dimer and prothrombin time with a decrease in fibrinogen. To correct this disseminated intravascular coagulation-like phase, anticoagulation therapy with low molecular weight heparin is preferred. Anticoagulation therapy with unfractionated heparin is preferred in COVID-19 patients with acute kidney injuries. 6. The last goal is prophylaxis for persons who are not yet infected. Potential supplements include vitamin D and zinc. Although the data for such supplements is not extremely strong, it can be argued that almost 50% of the population worldwide has a vitamin D deficiency. Correcting this deficiency would be beneficial regardless of any impact of COVID-19. Similarly, zinc is an important supplement that is important in one's diet regardless of any effect on SARS-CoV-2. As emerging therapies are found to be more effective against the SARS-CoV-2 pathogenic mechanisms identified, they can be substituted for those therapies presented in this review.
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The importance of airway and lung microbiome in the critically ill.
Martin-Loeches, I, Dickson, R, Torres, A, Hanberger, H, Lipman, J, Antonelli, M, de Pascale, G, Bozza, F, Vincent, JL, Murthy, S, et al
Critical care (London, England). 2020;(1):537
Abstract
During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances.Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology.The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity.In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.
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Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment.
Martín Giménez, VM, Inserra, F, Tajer, CD, Mariani, J, Ferder, L, Reiter, RJ, Manucha, W
Life sciences. 2020;:117808
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Abstract
COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.
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MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19.
Bilezikian, JP, Bikle, D, Hewison, M, Lazaretti-Castro, M, Formenti, AM, Gupta, A, Madhavan, MV, Nair, N, Babalyan, V, Hutchings, N, et al
European journal of endocrinology. 2020;(5):R133-R147
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The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.
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Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.
Jevnikar, Z, Östling, J, Ax, E, Calvén, J, Thörn, K, Israelsson, E, Öberg, L, Singhania, A, Lau, LCK, Wilson, SJ, et al
The Journal of allergy and clinical immunology. 2019;(2):577-590
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Abstract
BACKGROUND Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. OBJECTIVE We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. METHODS An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. RESULTS Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β. CONCLUSIONS Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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Interactions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases.
Chellappan, DK, Sze Ning, QL, Su Min, SK, Bin, SY, Chern, PJ, Shi, TP, Ee Mei, SW, Yee, TH, Qi, OJ, Thangavelu, L, et al
Chemico-biological interactions. 2019;:108732
Abstract
BACKGROUND The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases. METHODS Relevant published studies, literature and reports were searched from accessible electronic databases and related institutional databases. We used keywords, viz; microbiome, microbiota, microbiome drug delivery and respiratory disease. Selected articles were carefully read through, clustered, segregated into subtopics and reviewed. FINDINGS The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage, bacteria-derived lipid vesicles and microbe-derived extracellular vesicles. This review highlights the relationships between microbiota and different types of respiratory diseases, the importance of microbiota towards human health and diseases, including the role of novel microbiome drug delivery systems in targeting various respiratory diseases.