103 results found
Raby KL, Michaeloudes C, Tonkin J, et al., 2023, Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD, Frontiers in Immunology, Vol: 14, Pages: 1-14, ISSN: 1664-3224
The airway epithelium comprises of different cell types and acts as a physical barrier preventing pathogens, including inhaled particles and microbes, from entering the lungs. Goblet cells and submucosal glands produce mucus that traps pathogens, which are expelled from the respiratory tract by ciliated cells. Basal cells act as progenitor cells, differentiating into different epithelial cell types, to maintain homeostasis following injury. Adherens and tight junctions between cells maintain the epithelial barrier function and regulate the movement of molecules across it. In this review we discuss how abnormal epithelial structure and function, caused by chronic injury and abnormal repair, drives airway disease and specifically asthma and chronic obstructive pulmonary disease (COPD). In both diseases, inhaled allergens, pollutants and microbes disrupt junctional complexes and promote cell death, impairing the barrier function and leading to increased penetration of pathogens and a constant airway immune response. In asthma, the inflammatory response precipitates the epithelial injury and drives abnormal basal cell differentiation. This leads to reduced ciliated cells, goblet cell hyperplasia and increased epithelial mesenchymal transition, which contribute to impaired mucociliary clearance and airway remodelling. In COPD, chronic oxidative stress and inflammation trigger premature epithelial cell senescence, which contributes to loss of epithelial integrity and airway inflammation and remodelling. Increased numbers of basal cells showing deregulated differentiation, contributes to ciliary dysfunction and mucous hyperproduction in COPD airways. Defective antioxidant, antiviral and damage repair mechanisms, possibly due to genetic or epigenetic factors, may confer susceptibility to airway epithelial dysfunction in these diseases. The current evidence suggests that a constant cycle of injury and abnormal repair of the epithelium drives chronic airway inflammation and r
Pham DD, Lee J-H, Kwon H-S, et al., 2023, WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study., Ann Allergy Asthma Immunol
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Abubakkar-Waziri H, Kalaiarasan G, Wawman R, et al., 2023, SARS-CoV2 in public spaces in West London UK during COVID-19 pandemic, BMJ Open Respiratory Research, Vol: 10, ISSN: 2052-4439
Background: Spread of SARS-CoV2 by aerosol is considered an important mode of transmission over distances >2 m, particularly indoors.Objectives: We determined whether SARS-CoV2 could be detected in the air of enclosed/semi-enclosed public spaces.Methods and analysis: Between March 2021 and December 2021 during the easing of COVID-19 pandemic restrictions after a period of lockdown, we used total suspended and size-segregated particulate matter (PM) samplers for the detection of SARS-CoV2 in hospitals wards and waiting areas, on public transport, in a university campus and in a primary school in West London.Results: We collected 207 samples, of which 20 (9.7%) were positive for SARS-CoV2 using quantitative PCR. Positive samples were collected from hospital patient waiting areas, from hospital wards treating patients with COVID-19 using stationary samplers and from train carriages in London underground using personal samplers. Mean virus concentrations varied between 429 500 copies/m3 in the hospital emergency waiting area and the more frequent 164 000 copies/m3 found in other areas. There were more frequent positive samples from PM samplers in the PM2.5 fractions compared with PM10 and PM1. Culture on Vero cells of all collected samples gave negative results.Conclusion: During a period of partial opening during the COVID-19 pandemic in London, we detected SARS-CoV2 RNA in the air of hospital waiting areas and wards and of London Underground train carriage. More research is needed to determine the transmission potential of SARS-CoV2 detected in the air.
Shah PL, Orton CM, Grinsztejn B, et al., 2023, Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care, LANCET RESPIRATORY MEDICINE, Vol: 11, Pages: 415-424, ISSN: 2213-2600
Chen X-Y, Chen K-Y, Feng P-H, et al., 2023, YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome, BIOMEDICINE & PHARMACOTHERAPY, Vol: 159, ISSN: 0753-3322
Wu X, Abubakar-Waziri H, Fang F, et al., 2023, Modeling for understanding of coronavirus disease-2019 (COVID-19) spread and design of an isolation room in a hospital, Physics of Fluids, Vol: 35, Pages: 1-9, ISSN: 1070-6631
We have modeled the transmission of coronavirus 2019 in the isolation room of a patient suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Royal Brompton Hospital in London. An adaptive mesh computational fluid dynamics model was used for simulation of three-dimensional spatial distribution of SARS-CoV-2 in the room. The modeling set-up is based on data collected in the room during the patient stay. Many numerical experiments have been carried out to provide an optimal design layout of the overall isolation room. Our focus has been on (1) the location of the air extractor and filtration rates, (2) the bed location of the patient, and (3) consideration of the health and safety of the staff working in the area.
Kumar P, Kalaiarasan G, Bhagat RK, et al., 2022, Active air monitoring for understanding the ventilation and infection risks of SARS-CoV-2 transmission in public indoor spaces, Atmosphere, Vol: 13, Pages: 1-24, ISSN: 2073-4433
Indoor, airborne, transmission of SARS-CoV-2 is a key infection route. We monitored fourteen different indoor spaces in order to assess the risk of SARS-CoV-2 transmission. PM2.5 and CO2 concentrations were simultaneously monitored in order to understand aerosol exposure and ventilation conditions. Average PM2.5 concentrations were highest in the underground station (261 ± 62.8 μgm−3), followed by outpatient and emergency rooms in hospitals located near major arterial roads (38.6 ± 20.4 μgm−3), the respiratory wards, medical day units and intensive care units recorded concentrations in the range of 5.9 to 1.1 μgm−3. Mean CO2 levels across all sites did not exceed 1000 ppm, the respiratory ward (788 ± 61 ppm) and the pub (bar) (744 ± 136 ppm) due to high occupancy. The estimated air change rates implied that there is sufficient ventilation in these spaces to manage increased levels of occupancy. The infection probability in the medical day unit of hospital 3, was 1.6-times and 2.2-times higher than the emergency and outpatient waiting rooms in hospitals 4 and 5, respectively. The temperature and relative humidity recorded at most sites was below 27 °C, and 40% and, in sites with high footfall and limited air exchange, such as the hospital medical day unit, indicate a high risk of airborne SARS-CoV-2 transmission.
Frankenberg Garcia J, Rogers A, Mak J, et al., 2022, Mitochondrial transfer regulates bioenergetics in healthy and COPD airway smooth muscle, American Journal of Respiratory Cell and Molecular Biology, Vol: 67, Pages: 471-481, ISSN: 1044-1549
Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress-induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.
Tonkin J, Rogers A, Orton CM, et al., 2022, Relating ciliary dysfunction to clinical phenotypes in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Orton CM, Tonkin J, Chan L, et al., 2022, Metered Cryospray improves patient-reported outcome measures at 6-months post-treatment, in patients with COPD with chronic bronchitis, in a randomised, sham-controlled trial, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Michaeloudes C, Abubakar-Waziri H, Lakhdar R, et al., 2022, Molecular mechanisms of oxidative stress in asthma, Molecular Aspects of Medicine, Vol: 85, ISSN: 0098-2997
The lungs are exposed to reactive oxygen species oxygen (ROS) produced as a result of inhalation of oxygen, as well as smoke and other air pollutants. Cell metabolism and the NADPH oxidases (Nox) generate low levels of intracellular ROS that act as signal transduction mediators by inducing oxidative modifications of histones, enzymes and transcription factors. Redox signalling is also regulated by localised production and sensing of ROS in mitochondria, the endoplasmic reticulum (ER) and inside the nucleus. Intracellular ROS are maintained at low levels through the action of a battery of enzymatic and non-enzymatic antioxidants. Asthma is a heterogeneous airway inflammatory disease with different immune endotypes; these include atopic or non-atopic Th2 type immune response associated with eosinophilia, or a non-Th2 response associated with neutrophilia. Airway remodelling and hyperresponsiveness accompany the inflammatory response in asthma. Over-production of ROS resulting from infiltrating immune cells, particularly eosinophils and neutrophils, and a concomitant impairment of antioxidant responses lead to development of oxidative stress in asthma. Oxidative stress is augmented in severe asthma and during exacerbations, as well as by air pollution and obesity, and causes oxidative damage of tissues promoting airway inflammation and hyperresponsiveness. Furthermore, deregulated Nox activity, mitochondrial dysfunction, ER stress and/or oxidative DNA damage, resulting from exposure to irritants, inflammatory mediators or obesity, may lead to redox-dependent changes in cell signalling. ROS play a central role in airway epithelium-mediated sensing, development of innate and adaptive immune responses, and airway remodelling and hyperresponsiveness. Nonetheless, antioxidant compounds have proven clinically ineffective as therapeutic agents for asthma, partly due to issues with stability and in vivo metabolism of these compounds. The compartmentalised nature of ROS product
Chung KF, Dixey P, Abubakar-Waziri H, et al., 2022, Characteristics, phenotypes, mechanisms and management of severe asthma, CHINESE MEDICAL JOURNAL, Vol: 135, Pages: 1141-1155, ISSN: 0366-6999
Hoda U, Pavlidis S, Bansal AT, et al., 2022, Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort, Clinical and Translational Medicine, Vol: 12, ISSN: 2001-1326
Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively.
Chen R, Michaeloudes C, Liang Y, et al., 2022, ORMDL3 regulates cigarette smoke-induced endoplasmic reticulum stress in airway smooth muscle cells, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 149, Pages: 1445-+, ISSN: 0091-6749
Kermani N, Song W-J, Badi Y, et al., 2021, Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma, Respiratory Research, Vol: 22, ISSN: 1465-9921
BackgroundPatients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells.MethodsWe examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels.ResultsACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes.ConclusionLevels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.
Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” Asthma diagnosis and its severity requires systematic assessment of the underlying causative factors including suboptimal adherence to treatments and inhaler technique, comorbidities, risk factors and triggers. This is followed by asthma phenotyping using blood eosinophil counts and the fractional level of nitric oxide (FeNO) in exhaled breath to enable treatment with targeted anti-Type 2 inflammation-directed antibodies. Deeper molecular phenotyping of type 2 and non-type 2 airway inflammatory processes and elucidation of better selective biomarkers will lead to further precision medicine approaches linking mechanisms to treatable traits and biomarkers.
Michaeloudes C, Li X, Mak JCW, et al., 2021, Study of Mesenchymal Stem Cell-Mediated Mitochondrial Transfer in In Vitro Models of Oxidant-Mediated Airway Epithelial and Smooth Muscle Cell Injury, IN VITRO MODELS FOR STEM CELL THERAPY, Vol: 2269, Pages: 93-105, ISSN: 1064-3745
Haji G, Wiegman C, Michaeloudes C, et al., 2020, Mitochondrial dysfunction in airways and quadriceps muscle of patients with Chronic Obstructive Pulmonary Disease, Respiratory Research, Vol: 21, ISSN: 1465-9921
BackgroundMitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD.MethodsBronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function.ResultsDecreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression.ConclusionsMitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs.
Orton CM, Garner JL, Shah TA, et al., 2020, Metered Cryospray Modulates Bronchial Epithelial Gene Expression in Patients with Chronic Obstructive Pulmonary Disease, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Michaeloudes C, Bhavsar PK, Mumby S, et al., 2020, Role of metabolic reprogramming in pulmonary innate immunity and Its impact on lung diseases, Journal of Innate Immunity, Vol: 12, Pages: 1-16, ISSN: 1662-811X
Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.
Garcia JF, Xu B, Hui C, et al., 2019, REGULATION OF MITOCHONDRIAL TRANSFER BETWEEN AIRWAY SMOOTH MUSCLE CELLS (ASMCS): RELEVANCE TO COPD, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 0040-6376
Garcia JF, Mak J, Xu B, et al., 2019, Regulation of mitochondrial transfer between airway smooth muscle cells: relevance to COPD, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Garcia JF, Michaeloudes C, Xu B, et al., 2019, Mechanisms of Mitochondrial Transfer in Health and Disease, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Tsang J, Xu B, Xie J, et al., 2019, Effect of Corticosteroids on Metabolic Gene Expression in Airway Smooth Muscle Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Bhavsar PK, 2018, Role of humoral defense in severe asthma, American Journal of Respiratory and Critical Care Medicine, Vol: 197, Pages: 1369-1371, ISSN: 1073-449X
Mullegama R, Pavlidis S, Chung KF, et al., 2017, CLINICAL AND TRANSCRIPTOMIC PROFILES OF SEVERE ASTHMATICS WITH HIGH OR LOW EXPRESSION OF THE GLUCOCORTICOID RECEPTOR AND IMPORTIN-7, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A40-A41, ISSN: 0040-6376
Dhesi SS, Chung KF, Michaeloudes C, et al., 2017, THE EFFECT OF LONG ACTING BETA-AGONISTS ON GLUCOCORTICOID RECEPTOR AND IMPORTIN-7 NUCLEAR TRANSLOCATION IN AIRWAY SMOOTH MUSCLE CELLS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A55-A55, ISSN: 0040-6376
Lo C-Y, Michaeloudes C, Bhavsar PK, et al., 2017, Reduced suppressive effect of beta(2)-adrenoceptor agonist on fibrocyte function in severe asthma, RESPIRATORY RESEARCH, Vol: 18, ISSN: 1465-993X
BackgroundPatients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function.MethodsNon-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram.ResultsSalmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface β2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased β2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation.ConclusionsFibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids.
Michaeloudes C, Bhavsar PK, Mumby S, et al., 2017, Dealing with Stress: Defective Metabolic Adaptation in Chronic Obstructive Pulmonary Disease Pathogenesis, Annals of the American Thoracic Society, Vol: 14, Pages: S374-S382, ISSN: 2329-6933
The mitochondrion is the main site of energy production and ahub of key signaling pathways. It is also central in stress-adaptiveresponse due to its dynamic morphology and ability to interactwith other organelles. In response to stress, mitochondria fuseinto networks to increase bioenergetic efficiency and protectagainst oxidative damage. Mitochondrial damage triggerssegregation of damaged mitochondria from the mitochondrialnetwork through fission and their proteolytic degradation bymitophagy. Post-translational modifications of themitochondrial proteome and nuclear cross-talk lead toreprogramming of metabolic gene expression to maintain energyproduction and redox balance. Chronic obstructive pulmonarydisease (COPD) is caused by chronic exposure to oxidativestress arising from inhaled irritants, such as cigarette smoke.Impaired mitochondrial structure and function, due tooxidative stress–induced damage, may play a key role incausing COPD. Deregulated metabolic adaptation maycontribute to the development and persistence of mitochondrialdysfunction in COPD. We discuss the evidence for deregulatedmetabolic adaptation and highlight important areas forinvestigation that will allow the identification of moleculartargets for protecting the COPD lung from the effects ofdysfunctional mitochondria.
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