38 results found
Finney L, Glanville N, Farne H, et al., 2021, Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 510-519.e5, ISSN: 0091-6749
Background: The mechanisms underlying altered susceptibility and propensity to severe Coronavirus disease 2019 (COVID-19) disease in at-risk groups such as patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Inhaled corticosteroids (ICS) are widely used in COPD but the extent to which these therapies protect or expose patients to risk of severe COVID-19 is unknown. Objective: The aim of this study was to evaluate the effect of ICS upon pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2.Methods: We evaluated the effect of ICS administration upon pulmonary ACE2 expression in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration. Mice deficient in the type I interferon-α/β receptor (Ifnar1−/−) and exogenous interferon-β administration experiments were used to study the functional role of type-I IFN signalling in ACE2 expression. We compared sputum ACE2 expression in patients with COPD stratified according to use or non-use of ICS.ResultsICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous interferon-β administration and Ifnar1−/− mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect. ICS administration attenuated expression of ACE2 in COPD airway epithelial cell cultures and in mice with elastase-induced COPD-like changes. COPD patients taking ICS also had reduced sputum expression of ACE2 compared to non-ICS users.Conclusion: ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2. This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.
Soni S, Garner J, O'Dea K, et al., 2021, Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD, American Journal of Physiology: Lung Cellular and Molecular Physiology, Vol: 320, Pages: L73-L83, ISSN: 1040-0605
Despite advances in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD but their association to COPD disease severity remains unknown. We analysed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from sixty-two patients with mild to very severe COPD (51% male; mean age: 65.9 years). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, exercise testing) and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF (leukocyte, PMN (polymorphonuclear leukocyte i.e. neutrophil), monocyte, epithelial and platelet MVs) and plasma (leukocyte, PMN, monocyte and endothelial MVs), and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including FEV1, mMRC dyspnoea score, 6-minute walk test, hyperinflation and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically-relevant disease severity indices. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.
Farne H, Kumar K, Ritchie AI, et al., 2020, Repurposing existing drugs for the treatment of COVID-19, Annals of the American Thoracic Society, Vol: 17, Pages: 1186-1194, ISSN: 1546-3222
The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by SARS-CoV-2 viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist, thus development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and anti-inflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date only dexamethasone and remedesivir have been shown to be effective, but several other promising candidates are in trials.
Ritchie AI, Brill SE, Vlies BH, et al., 2020, Targeted retreatment of incompletely recovered COPD exacerbations with ciprofloxacin: a double-blind, randomised, placebo-controlled, multicentre phase III trial, American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 549-557, ISSN: 1073-449X
RATIONALE: COPD exacerbations are prone to non-recovery but there are no data about the effectiveness of retreatment on these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. METHODS: This multi-centre randomised double-blind placebo-controlled trial studied retreatment with oral ciprofloxacin 500mg or matched placebo twice daily for 7 days in patients with GOLD stage II - IV COPD with persistent symptoms and/or serum C-reactive protein (CRP) ≥8mg/L initiated 14 (+/- 3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period. RESULTS: Of 826 patients screened at 4 centres, 144 eligible participants with incomplete recovery were randomised to receive ciprofloxacin (n=72) or placebo (n=72). 57% of patients in the ciprofloxacin group had experienced 1 or more exacerbations, compared to 53% in the placebo group. The median time to the next exacerbation was 32.5 days (IQR 13-50) in the placebo arm and 34 days (IQR 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio = 1.07, 95% CI 0.68-1.68; p=0.76). No significant differences were seen in quality of life scores or lung function between treatment groups. CONCLUSION: In patients with persistent symptoms and/or raised CRP 14 days following a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared to placebo. This suggests that non-recovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with anti-inflammatory therapy.
Singanayagam A, Loo S-L, Calderazzo MA, et al., 2019, Antiviral immunity is impaired in COPD patients with frequent exacerbations, American Journal of Physiology: Lung Cellular and Molecular Physiology, Vol: 317, Pages: L893-L903, ISSN: 1040-0605
Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro RV-infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate anti-microbial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.
Singanayagam A, Glanville N, Cuthbertson L, et al., 2019, Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease, Science Translational Medicine, Vol: 11, Pages: 1-13, ISSN: 1946-6234
Bacterial infection commonly complicates inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). The mechanisms of increased infection susceptibility and how use of the commonly prescribed therapy inhaled corticosteroids (ICS) accentuates pneumonia risk in COPD are poorly understood. Here, using analysis of samples from patients with COPD, we show that ICS use is associated with lung microbiota disruption leading to proliferation of streptococcal genera, an effect that could be recapitulated in ICS-treated mice. To study mechanisms underlying this effect, we used cellular and mouse models of streptococcal expansion with Streptococcus pneumoniae, an important pathogen in COPD, to demonstrate that ICS impairs pulmonary clearance of bacteria through suppression of the antimicrobial peptide cathelicidin. ICS impairment of pulmonary immunity was dependent on suppression of cathelicidin because ICS had no effect on bacterial loads in mice lacking cathelicidin (Camp-/-) and exogenous cathelicidin prevented ICS-mediated expansion of streptococci within the microbiota and improved bacterial clearance. Suppression of pulmonary immunity by ICS was mediated by augmentation of the protease cathepsin D. Collectively, these data suggest a central role for cathepsin D/cathelicidin in the suppression of antibacterial host defense by ICS in COPD. Therapeutic restoration of cathelicidin to boost antibacterial immunity and beneficially modulate the lung microbiota might be an effective strategy in COPD.
Finney LJ, Padmanaban V, Todd S, et al., 2019, Validity of the diagnosis of pneumonia in hospitalised patients with COPD., ERJ Open Research, Vol: 5, Pages: 1-8, ISSN: 2312-0541
Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia are two of the most common reasons for acute hospital admissions. Acute exacerbations and pneumonia present with similar symptoms in COPD patients, representing a diagnostic challenge with a significant impact on patient outcomes. The objectives of this study were to compare the prevalence of radiographic consolidation with the discharge diagnoses of hospitalised COPD patients. Methods: COPD patients admitted to three UK hospitals over a 3-year period were identified. Participants were included if they were admitted with an acute respiratory illness, COPD was confirmed by spirometry and a chest radiograph was performed within 24 h of admission. Pneumonia was defined as consolidation on chest radiograph reviewed by two independent observers. Results: There were 941 admissions in 621 patients included in the final analysis. In 235 admissions, consolidation was present on chest radiography and there were 706 admissions without consolidation. Of the 235 admissions with consolidation, only 42.9% had a discharge diagnosis of pneumonia; 90.7% of patients without consolidation had a discharge diagnosis of COPD exacerbation. The presence of consolidation was associated with increased rate of high-dependency care admission, increased mortality and prolonged length of stay. Inhaled corticosteroid use was associated with recurrent pneumonia. Conclusions: Pneumonia is underdiagnosed in patients with COPD. Radiographic consolidation is associated with worse outcomes and prolonged length of stay. Incorrect diagnosis could result in inappropriate use of inhaled corticosteroids. Future guidelines should specifically address the diagnosis and management of pneumonia in COPD.
Finney LJ, Belchamber KBR, Fenwick PS, et al., 2019, Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 1496-1507, ISSN: 1073-449X
Rationale Human rhinovirus (HRV) is a common cause of COPD exacerbations. Secondary bacterial infection is associated with more severe symptoms and delayed recovery. Alveolar macrophages clear bacteria from the lung and maintain lung homeostasis through cytokine secretion. These processes are defective in COPD. The effect of HRV on macrophage function is unknown. Objectives To investigate the effect of HRV on phagocytosis and cytokine response to bacteria by alveolar macrophages and monocyte derived macrophages (MDM) in COPD and healthy controls. Methods Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV 16 (multiplicity of infection 5), polyI:C 30μg/ml, interferon (IFN)-β 10μg/ml, IFN-γ 10μg/ml or medium control for 24 hours. Phagocytosis of fluorescently-labelled Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8, TNF and IL-10 release was measured by ELISA. Main Results HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n=37) and 18% in alveolar macrophages (n=20) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM. There was no effect in healthy controls. Phagocytosis of H. influenzae was impaired by polyI:C but not IFN-β or IFN-γ. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by polyI:C, IFN-β and IFN-γ. Conclusions HRV impairs phagocytosis of bacteria in COPD which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/IFN pathway which may prevent resolution of inflammation leading to prolonged exacerbations in COPD.
Finney LJ, 2019, Is it safe to prescribe benzodiazepines or opioids for dyspnoea in interstitial lung disease?, BREATHE, Vol: 15, Pages: 137-139, ISSN: 1810-6838
Calderazzo MA, Trujillo-Torralbo M-B, Finney LJ, et al., 2019, Inflammation and infections in unreported chronic obstructive pulmonary disease exacerbations, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 2019, Pages: 823-832, ISSN: 1176-9106
Purpose: COPD patients often do not report acute exacerbations to healthcare providers – unreported exacerbations. It is not known whether variances in symptoms, airway obstruction, aetiology and inflammatory responses account for differences in reporting of COPD exacerbations. The aims of the study were to compare symptoms, lung function changes, aetiology and inflammatory markers between exacerbations that were reported to healthcare providers or treated, with those that were unreported and untreated.Patients and methods: We recruited a cohort of COPD patients and collected clinical data and blood and airway samples when stable and during acute exacerbations. Virological and bacterial analyses were carried out and inflammatory markers measured.Results: We found no differences in symptoms, lung function, incidence of infection and inflammatory markers between reported and unreported exacerbations. Subjects who reported all exacerbations had higher BODE scores, lower FEV1 and more exacerbations compared with those who did not.Conclusion: The failure to report exacerbations is not related to the severity, aetiology or inflammatory profile of the exacerbation. Patients with less severe COPD and less frequent exacerbations are less likely to report exacerbations. The decision to report an exacerbation is not an objective marker of exacerbation severity and therefore studies that do not count unreported exacerbations will underestimate the frequency of clinically significant exacerbations. A better understanding of the factors that determine non-reporting of exacerbations is required to improve exacerbation reporting.
Garner J, Garner S, Hardie R, et al., 2019, Evaluation of a Low Cost, Re-Useable, Bronchoscopy Biosimulator with Ventilated Lungs: The Bronchoscopy BioSim, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Donaldson GC, Finney L, Wiseman D, et al., 2019, Comparison of Paper and Tablet Based App Diary Cards in COPD Patients, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney L, Donaldson GC, Wiseman DJ, et al., 2019, Activity Monitoring in COPD: A Feasibility Study, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wiseman DJ, Kamal F, Finney L, et al., 2019, Respiratory Syncytial Virus (RSV) Detection Is Associated with an Increased Inflammatory Response in Stable (non-Exacerbating) Chronic Obstructive Pulmonary Disease (COPD) Patients, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney L, Fenwick PS, Kemp S, et al., 2019, Interferon Response to Human Rhinovirus Is Impaired in Alveolar Macrophages but Not Bronchial Epithelial Cells in Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney LJ, Belchamber KBR, Kemp SV, et al., 2018, HUMAN RHINOVIRUS IMPAIRS THE INNATE IMMUNE RESPONSE TO BACTERIA IN MACROPHAGES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A9-A9, ISSN: 0040-6376
Finney L, Belchamber K, Fenwick P, et al., 2018, Human rhinovirus impairs macrophage innate immune responses to bacteria via the interferon pathway in COPD, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Tregoning JS, Mallia P, Webber J, et al., 2018, Role of airway glucose in bacterial infections in chronic obstructive pulmonary disease, Journal of Allergy and Clinical Immunology, Vol: 142, Pages: 815-823.e6, ISSN: 0091-6749
BackgroundPatients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear.ObjectivesThe aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection.MethodsWe measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function. Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations. Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined.ResultsSputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD. In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values. There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load. Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro.ConclusionsAirway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations. Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD. This has important implications for the development of nonantibiotic therapeutic strategies for the prev
Singanayagam A, Glanville N, Girkin J, et al., 2018, Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations, Nature Communications, Vol: 9, Pages: 1-16, ISSN: 2041-1723
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.
Xu H, Finney L, Wedzicha J, et al., 2018, Features of the Common Cold that Would Lead to an Exacerbation of Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney LJ, Belchamber K, Kemp S, et al., 2017, HUMAN RHINOVIRUS IMPAIRS PHAGOCYTOSIS OF HAEMOPHILUS INFLUENZAE IN ALVEOLAR MACROPHAGES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A112-A112, ISSN: 0040-6376
Donaldson GC, Allinson JP, Finney L, et al., 2017, Not All Treated COPD Exacerbations Are Associated With A Raised C-Reactive Protein, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney LJ, Belchamber KBR, Mallia P, et al., 2016, HUMAN RHINOVIRUS IMPAIRS THE INNATE IMMUNE RESPONSE TO BACTERIA IN MONOCYTE DERIVED MACROPHAGES FROM PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE, British Thoracic Society Winter Meeting 2016, Publisher: BMJ PUBLISHING GROUP, Pages: A2-A2, ISSN: 0040-6376
Finney LJ, Belchamber KBR, Edwards MR, et al., 2016, Rhinovirus Impairs Phagocytosis Of Bacteria By Monocyte Derived Macrophages In Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney L, Elkin S, Todd S, et al., 2015, LATE-BREAKING ABSTRACT: Microbiology and radiology of pneumonia in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Coleman M, Finney LJ, Komrower D, et al., 2015, Markers to differentiate between Kaposi's sarcoma and tuberculous pleural effusions in HIV-positive patients, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 19, Pages: 144-150, ISSN: 1027-3719
Finney LJ, Toussaint M, Calderazzo M, et al., 2015, Bacterial Load In Stable And Exacerbated COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Calderazzo M, Trujillo-Torralbo M, Finney LJ, et al., 2015, Relationship Between Viral Colds And COPD Exacerbations, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Finney L, Berry M, Singanayagam A, et al., 2014, Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease, LANCET RESPIRATORY MEDICINE, Vol: 2, Pages: 919-932, ISSN: 2213-2600
Finney LJ, Ritchie A, Pollard E, et al., 2014, Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 9, Pages: 1119-1132, ISSN: 1176-9106
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.