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1.
Dev Cell ; 57(1): 112-145.e2, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1587971

ABSTRACT

The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing and genetic lineage tracing have revealed novel cell types and enriched functional properties of existing cell types in lung. The time has come to take a new census. Initiated by members of the NHLBI-funded LungMAP Consortium and aided by experts in the lung biology community, we synthesized current data into a comprehensive and practical cellular census of the lung. Identities of cell types in the normal lung are captured in individual cell cards with delineation of function, markers, developmental lineages, heterogeneity, regenerative potential, disease links, and key experimental tools. This publication will serve as the starting point of a live, up-to-date guide for lung research at https://www.lungmap.net/cell-cards/. We hope that Lung CellCards will promote the community-wide effort to establish, maintain, and restore respiratory health.


Subject(s)
Lung/cytology , Lung/physiology , Cell Differentiation/genetics , Databases as Topic , Humans , Lung/metabolism , Regeneration/genetics , Single-Cell Analysis/methods
2.
Int J Mol Sci ; 22(22)2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1524026

ABSTRACT

The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.


Subject(s)
COVID-19/complications , Immunomodulation/physiology , Mesenchymal Stem Cell Transplantation , Regeneration/physiology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Lung/pathology , Lung/physiology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/therapy , SARS-CoV-2/isolation & purification
3.
Med Sci Monit ; 27: e933381, 2021 Nov 14.
Article in English | MEDLINE | ID: covidwho-1488859

ABSTRACT

BACKGROUND Little is known of the changes in lung radiographic characteristics over time in patients recovering from COVID-19. This study analyzed the clinical features and temporal lung radiographic changes in patients with moderate and severe COVID-19 pneumonia who did not require invasive mechanical ventilation during the acute and convalescent periods. MATERIAL AND METHODS The data of 25 patients with COVID-19 pneumonia from January 29, 2020, to November 24, 2020, who did not require invasive mechanical ventilation and who were followed up were retrospectively collected. The 25 patients were divided into severe and moderate groups. Clinical characteristics and computed tomography (CT) manifestations were compared. A total of 121 consecutive thin-slice CT scans were collected at 4 weeks, 2 months, and 5 months after admission to evaluate lung abnormalities in the patients. The CT score was used to assess disease severity. RESULTS The severe group had a lower rate of nucleic acid conversion within 10 days of admission and higher D-dimer, creatine kinase, and lactate dehydrogenase values. In the severe group, hospital stay was longer and hospitalization costs were higher. The average CT score of the severe group peaked in the second week, while the moderate group peaked in the first week and then decreased over time. There were no statistically significant differences in the average CT score between the 2 groups at the 5-month follow-up. CONCLUSIONS The pulmonary lesions of patients recovering from COVID-19 and who do not require invasive mechanical ventilation were gradually absorbed and resolved over time.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/pathology , Lung/diagnostic imaging , Lung/physiology , Tomography, X-Ray Computed/methods , Adult , Case-Control Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
4.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477960

ABSTRACT

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.


Subject(s)
COVID-19/pathology , Lung/physiology , Regeneration , COVID-19/virology , Epigenomics , Fibrosis , Humans , Immune System/metabolism , MicroRNAs/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction
5.
Cells ; 10(10)2021 09 29.
Article in English | MEDLINE | ID: covidwho-1444117

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.


Subject(s)
COVID-19/blood , COVID-19/therapy , Lung/physiology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Regeneration/physiology , Animals , COVID-19/drug therapy , Cell Differentiation , Cell- and Tissue-Based Therapy , Culture Media , Extracellular Vesicles , Humans , Inflammation , Mice , Mice, SCID , Phenotype , Pneumonia/blood , Pneumonia/immunology , Pneumonia/therapy , Respiratory Distress Syndrome , SARS-CoV-2 , Thromboembolism/blood , Thromboembolism/immunology , Thromboembolism/therapy
6.
Respir Res ; 22(1): 255, 2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1440932

ABSTRACT

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.


Subject(s)
COVID-19/physiopathology , Hospitalization/trends , Lung/physiology , Respiratory Mechanics/physiology , Spirometry/trends , Survivors , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/therapy , Female , Humans , Lung Diseases/diagnosis , Lung Diseases/physiopathology , Lung Diseases/therapy , Male , Middle Aged , Patient Discharge/trends , Respiratory Function Tests/methods , Respiratory Function Tests/trends , Spirometry/methods , Young Adult
7.
Cells ; 10(10)2021 09 24.
Article in English | MEDLINE | ID: covidwho-1438525

ABSTRACT

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.


Subject(s)
Biotechnology/methods , Diploidy , Lung/cytology , Regenerative Medicine/methods , Respiratory Tract Infections/therapy , Animals , Biological Specimen Banks , COVID-19 Vaccines , Cell Line , Cell- and Tissue-Based Therapy , History, 20th Century , History, 21st Century , Humans , Lung/physiology , Regeneration , Regenerative Medicine/history , SARS-CoV-2 , Stem Cell Transplantation , Stem Cells/cytology , Transplantation, Homologous
8.
Mar Drugs ; 19(1)2020 Dec 24.
Article in English | MEDLINE | ID: covidwho-1389434

ABSTRACT

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.


Subject(s)
COVID-19/drug therapy , Lung/drug effects , Polysaccharides/pharmacology , SARS-CoV-2 , Animals , COVID-19/immunology , Humans , Lung/physiology , Lung Diseases/drug therapy , Polysaccharides/therapeutic use , Virus Diseases/drug therapy
9.
Sci Adv ; 6(48)2020 11.
Article in English | MEDLINE | ID: covidwho-1388431

ABSTRACT

Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries is critical to avoid mortality, therapeutic targeting of this process requires a greater understanding of endothelial repair mechanisms. Here, we demonstrate that lung endothelium possesses substantial regenerative capacity and lineage tracing reveals that native endothelium is the source of vascular repair after influenza injury. Ablation of chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF2) (Nr2f2), a transcription factor implicated in developmental angiogenesis, reduced endothelial proliferation, exacerbating viral lung injury in vivo. In vitro, COUP-TF2 regulates proliferation and migration through activation of cyclin D1 and neuropilin 1. Upon influenza injury, nuclear factor κB suppresses COUP-TF2, but surviving endothelial cells ultimately reestablish vascular homeostasis dependent on restoration of COUP-TF2. Therefore, stabilization of COUP-TF2 may represent a therapeutic strategy to enhance recovery from pathogens, including H1N1 influenza and SARS-CoV-2.


Subject(s)
COUP Transcription Factor II/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Influenza A Virus, H1N1 Subtype , Lung/cytology , Lung/physiology , Orthomyxoviridae Infections/metabolism , Regeneration/genetics , Animals , COUP Transcription Factor II/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Disease Models, Animal , Female , Gene Knockout Techniques , HEK293 Cells , Humans , Male , Mice , Mice, Transgenic , Orthomyxoviridae Infections/virology , Transfection
12.
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1389392

ABSTRACT

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.


Subject(s)
Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/physiology , Lung Diseases/physiopathology , Lung/physiology , Alveolar Epithelial Cells/cytology , Animals , COVID-19/physiopathology , Humans , Immunity, Innate , Ions/metabolism , Lung/anatomy & histology , Lung Diseases/etiology , Lung Diseases/pathology , Pulmonary Surfactant-Associated Proteins/metabolism , Regeneration
13.
Cells ; 10(7)2021 06 26.
Article in English | MEDLINE | ID: covidwho-1389304

ABSTRACT

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.


Subject(s)
Lab-On-A-Chip Devices , Lung Diseases/pathology , Lung/physiology , Regeneration/physiology , Respiratory Mucosa/cytology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Cells, Cultured , Extracellular Matrix/physiology , Humans , Lung/cytology , Lung/pathology , Lung Diseases/physiopathology , Lung Diseases/therapy , Models, Biological , Respiratory Mucosa/pathology , Respiratory Mucosa/physiology , SARS-CoV-2/pathogenicity , Tissue Culture Techniques/instrumentation , Tissue Culture Techniques/methods
14.
Transfus Apher Sci ; 60(6): 103237, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1366698

ABSTRACT

SARS-CoV-2 attaches to the angiotensin-converting enzyme 2 (ACE-2) receptor on human cells. The virus causes hypercytokinemia, capillary leak, pulmonary edema, acute respiratory distress syndrome, acute cardiac injury, and leads to death. Mesenchymal stem cells (MSCs) are ACE-2 negative cells; therefore, can escape from SARS-CoV-2. MSCs prevent hypercytokinemia and help the resolution of the pulmonary edema and other damages occurred during the course of COVID-19. In addition, MSCs enhance the regeneration of the lung and other tissues affected by SARS-CoV-2. The case series reported beneficial effect of MSCs in COVID-19 treatment. However, there are some concerns about the safety of MSCs, particularly referring to the increased risk of disseminated intravascular coagulation, and thromboembolism due to the expression of TF/CD142. Prospective, randomized, large scale studies are needed to reveal the optimum dose, administration way, time, efficacy, and safety of MSCs in the COVID-19 treatment.


Subject(s)
COVID-19 , Lung/physiology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Regeneration , SARS-CoV-2/metabolism , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Humans , Peptidyl-Dipeptidase A/metabolism , Prospective Studies , Risk Factors , Thromboembolism/blood , Thromboembolism/etiology , Thromboplastin/biosynthesis
15.
Respir Investig ; 59(6): 871-875, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1364443

ABSTRACT

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.


Subject(s)
Lung/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Radiographic Image Enhancement/methods , Radiography, Thoracic/methods , Aged , Asthma/diagnosis , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Drug Combinations , Fluticasone/therapeutic use , Formoterol Fumarate/therapeutic use , Glycopyrrolate/analogs & derivatives , Glycopyrrolate/therapeutic use , Humans , Indans/therapeutic use , Lung/physiology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/therapeutic use , Spirometry , Tiotropium Bromide/therapeutic use , Treatment Outcome
16.
Respir Res ; 22(1): 222, 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1344107

ABSTRACT

The COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed "long COVID". However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.


Subject(s)
COVID-19/complications , Dyspnea/physiopathology , Exercise Tolerance/physiology , Lung/physiology , Phenotype , Physical Exertion/physiology , Adult , Aged , COVID-19/epidemiology , COVID-19/physiopathology , Dyspnea/epidemiology , Female , Humans , Male , Middle Aged , Oxygen Consumption/physiology , Walk Test/methods
17.
Front Biosci (Landmark Ed) ; 26(6): 135-148, 2021 05 30.
Article in English | MEDLINE | ID: covidwho-1281062

ABSTRACT

The human body is colonized from the birth by a large number of microorganisms. This will constitute a real "functional microbial organ" that is fundamental for homeostasis and therefore for health in humans. Those microorganisms. The microbial populations that colonize humans creating a specific ecosystem they have been collectively referred to as "human microbiota" or "human normal microflora". The microbiota play an important pathophysiological role in the various locations of the human body. This article focuses on one of the most important, that is the enteric microbiota. The composition (quantitative and qualitative) of microbes is analyzed in relation to age and environment during the course of human life. It also highlights eubiosis and dysbiosis as key terms for its role in health and disease. Finally, it analyzes its bi-directional relationship with the microbiota of the lungs, skin and that of the brain, and consequently for the whole central and peripheral nervous system for the maintenance of health in the human body.


Subject(s)
Bacteria/metabolism , Gastrointestinal Microbiome/physiology , Health Status , Homeostasis/physiology , Bacteria/classification , Brain/physiology , Cytokines/metabolism , Gastrointestinal Tract/physiology , Humans , Lung/physiology , Population Dynamics
18.
Curr Opin Pharmacol ; 59: 85-94, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275237

ABSTRACT

There is an urgent need for better treatment of lung diseases that are a major cause of morbidity and mortality worldwide. This urgency is illustrated by the current COVID-19 health crisis. Moderate-to-extensive lung injury characterizes several lung diseases, and not only therapies that reduce such lung injury are needed but also those that regenerate lung tissue and repair existing lung injury. At present, such therapies are not available, but as a result of a rapid increase in our understanding of lung development and repair, lung regenerative therapies are on the horizon. Here, we discuss existing targets for treatment, as well as novel strategies for development of pharmacological and cell therapy-based regenerative treatment for a variety of lung diseases and clinical studies. We discuss how both patient-relevant in vitro disease models using innovative culture techniques and other advanced new technologies aid in the development of pulmonary regenerative medicine.


Subject(s)
Lung Diseases/therapy , Lung/physiology , Regeneration , Animals , Humans , Stem Cell Transplantation , Stem Cells
19.
BMJ Open Respir Res ; 8(1)2021 05.
Article in English | MEDLINE | ID: covidwho-1247381

ABSTRACT

INTRODUCTION: Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing and its intensity as a physical activity are not well understood. METHODS: We compared cardiorespiratory parameters while completing components of Singing for Lung Health sessions, with treadmill walking at differing speeds (2, 4 and 6 km/hour). RESULTS: Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced acute physiological responses that were consistent with moderate intensity activity (metabolic equivalents: median 4.12, IQR 2.72-4.78), with oxygen consumption, heart rate and volume per breath above those seen walking at 4 km/hour. Minute ventilation was higher during singing (median 22.42 L/min, IQR 16.83-30.54) than at rest (11 L/min, 9-13), lower than 6 km/hour walking (30.35 L/min, 26.94-41.11), but not statistically different from 2 km/hour (18.77 L/min, 16.89-21.35) or 4 km/hour (23.27 L/min, 20.09-26.37) walking. CONCLUSIONS: Our findings suggest the acute metabolic demands of singing are comparable with walking at a moderately brisk pace, hence, physical effects may contribute to the health and well-being benefits attributed to singing participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers and physical performance impacts when used as a training modality is encouraged. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT04121351).


Subject(s)
Cardiorespiratory Fitness/physiology , Heart Rate/physiology , Lung/physiology , Oxygen Consumption/physiology , Singing/physiology , Walking/physiology , Adult , Exercise Test , Female , Healthy Volunteers , Humans , Male , Metabolic Flux Analysis/methods , Music , Physical Exertion/physiology , Respiratory Function Tests/methods , Warm-Up Exercise
20.
Elife ; 102021 03 15.
Article in English | MEDLINE | ID: covidwho-1196112

ABSTRACT

Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug-repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug-repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug-gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug-repurposing opportunities that could improve lung function.


Chronic respiratory disorders like asthma affect around 600 million people worldwide. Although these illnesses are widespread, they can have several different underlying causes, making them difficult to treat. Drugs that work well on one type of respiratory disorder may be completely ineffective on another. Understanding the biological and environmental factors that cause these illnesses will allow them to be treated more effectively by tailoring therapies to each patient. Reduced lung function is a factor in respiratory disorders and it can have many genetic causes. Studying the genes of patients with reduced lung function can reveal the genes involved, some of which may already be targets of existing drugs for other illnesses. So, could a patient's genetics be used to repurpose existing drugs to treat their respiratory disorders? Reay et al. combined three methods to link genetics and biological processes to the causes of reduced lung function. The results reveal several factors that could lead to new treatments. In one example, reduced lung function showed a link to genes associated with high blood sugar. As such, treatments used in diabetes might help improve lung function in some patients. Reay et al. also developed a scoring system that could predict the efficacy of a treatment based on a patient's genetics. The study suggests that COVID-19 infection could be affected by blood sugar levels too. Chronic respiratory disorders are a critical issue worldwide and have proven difficult to treat, but these results suggest a way to identify new therapies and target them to the right patients. The findings also support a connection between lung function and blood sugar levels. This implies that perhaps existing diabetes treatments ­ including diet and lifestyle changes aimed at reducing or limiting blood sugar ­ could be repurposed to treat respiratory disorders in some patients. The next step will be to perform clinical trials to test whether these therapies are in fact effective.


Subject(s)
Drug Repositioning/methods , Hyperglycemia/genetics , Lung Diseases/drug therapy , Lung Diseases/genetics , Blood Glucose/metabolism , Causality , Databases, Genetic , Genome-Wide Association Study/methods , Humans , Hyperglycemia/metabolism , Hyperglycemia/physiopathology , Lung/drug effects , Lung/physiology , Lung/physiopathology , Lung Diseases/metabolism , Lung Diseases/physiopathology , Multifactorial Inheritance , Phenotype , Polymorphism, Single Nucleotide , Respiratory Function Tests/methods , Transcriptome
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