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Article ; Online: Drugs without benefits? Confronting the challenges of drug-induced interstitial lung disease.

Denneny, Emma K / Porter, Joanna C

2021 Volume 76, Issue 12, Page(s) 1172–1173

MeSH term(s)	Humans ; Lung ; Lung Diseases, Interstitial/chemically induced ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2021-08-05
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2021-217373
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Article ; Online: A Role for Steroids in COVID-19-associated Pneumonitis at Six-Week Follow-Up?

Denneny, Emma K / Garthwaite, Helen S / Heightman, Melissa J / Porter, Joanna C

Annals of the American Thoracic Society

2021 Volume 18, Issue 6, Page(s) 1082–1083

MeSH term(s)	Adrenal Cortex Hormones ; COVID-19 ; Follow-Up Studies ; Humans ; Lung Diseases, Interstitial ; Pneumonia/drug therapy ; SARS-CoV-2 ; Steroids/adverse effects
Chemical Substances	Adrenal Cortex Hormones ; Steroids
Language	English
Publishing date	2021-03-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202101-048LE
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Article: Lupus and the Lungs: The Assessment and Management of Pulmonary Manifestations of Systemic Lupus Erythematosus.

Amarnani, Raj / Yeoh, Su-Ann / Denneny, Emma K / Wincup, Chris

Frontiers in medicine

2021 Volume 7, Page(s) 610257

Abstract: Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout ...

Abstract	Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout the course of their disease. This can include disorders of the lung parenchyma (such as interstitial lung disease and acute pneumonitis), pleura (resulting in pleurisy and pleural effusion), and pulmonary vasculature [including pulmonary arterial hypertension (PAH), pulmonary embolic disease, and pulmonary vasculitis], whilst shrinking lung syndrome is a rare complication of the disease. Furthermore, the risks of respiratory infection (which often mimic acute pulmonary manifestations of SLE) are increased by the immunosuppressive treatment that is routinely used in the management of lupus. Although these conditions commonly present with a combination of dyspnea, cough and chest pain, it is important to consider that some patients may be asymptomatic with the only suggestion of the respiratory disorder being found incidentally on thoracic imaging or pulmonary function tests. Treatment decisions are often based upon evidence from case reports or small cases series given the paucity of clinical trial data specifically focused on pulmonary manifestations of SLE. Many therapeutic options are often initiated based on studies in severe manifestations of SLE affecting other organ systems or from experience drawn from the use of these therapeutics in the pulmonary manifestations of other systemic autoimmune rheumatic diseases. In this review, we describe the key features of the pulmonary manifestations of SLE and approaches to investigation and management in clinical practice.
Language	English
Publishing date	2021-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2020.610257
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Article ; Online: Investigating the role of platelets and platelet-derived transforming growth factor-β in idiopathic pulmonary fibrosis.

Chong, Deborah L W / Mikolasch, Theresia A / Sahota, Jagdeep / Rebeyrol, Carine / Garthwaite, Helen S / Booth, Helen L / Heightman, Melissa / Denneny, Emma K / José, Ricardo J / Khawaja, Akif A / Duckworth, Anna / Labelle, Myriam / Scotton, Chris J / Porter, Joanna C

American journal of physiology. Lung cellular and molecular physiology

2023 Volume 325, Issue 4, Page(s) L487–L499

Abstract: Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFβ1, although the role of these cells in ...

Abstract	Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFβ1, although the role of these cells in IPF is ill-defined. In this study, we investigated whether platelets, and specifically platelet-derived TGFβ1, mediate IPF disease progression. Patients with IPF and non-IPF patients were recruited to determine platelet reactivity, and separate cohorts of patients with IPF were followed for mortality. To study whether platelet-derived TGFβ1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1
MeSH term(s)	Humans ; Mice ; Animals ; Idiopathic Pulmonary Fibrosis/pathology ; Lung/pathology ; Transforming Growth Factor beta1/pharmacology ; Fibrosis ; Transforming Growth Factor beta ; Bleomycin/adverse effects ; Inflammation/pathology ; Transforming Growth Factors/adverse effects
Chemical Substances	Transforming Growth Factor beta1 ; Transforming Growth Factor beta ; Bleomycin (11056-06-7) ; Transforming Growth Factors (76057-06-2)
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00227.2022
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Article ; Online: Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

Mehta, Puja / Sanz-Magallón Duque de Estrada, Blanca / Denneny, Emma K / Foster, Kane / Turner, Carolin T / Mayer, Andreas / Milighetti, Martina / Platé, Manuela / Worlock, Kaylee B / Yoshida, Masahiro / Brown, Jeremy S / Nikolić, Marko Z / Nair, Arjun / Chain, Benjamin M / Noursadeghi, Mahdad / Chambers, Rachel C / Porter, Joanna C / Tomlinson, Gillian S

medRxiv

Abstract: Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad ... ...

Abstract	Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives: We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results: Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions: There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified.
Keywords	covid19
Language	English
Publishing date	2023-03-29
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.03.28.23287759
Database	COVID19

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Article ; Online: Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

Mehta, Puja / Sanz-Magallon Duque de Estrada, Blanca / Denneny, Emma K / Foster, Kane / Turner, Carolin T / Mayer, Andreas / Milighetti, Martina / Plate, Manuela / Worlock, Kaylee B / Yoshida, Masahiro / Brown, Jeremy S / Nikolic, Marko Z / Nair, Arjun / Chain, Benjamin M / Noursadeghi, Mahdad / Chambers, Rachel C / Porter, Joanna C / Tomlinson, Gillian S

medRxiv

Abstract	Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives: We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results: Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions: There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified.
Keywords	covid19
Language	English
Publishing date	2023-03-29
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.03.28.23287759
Database	COVID19

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Article ; Online: 'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19.

Mandal, Swapna / Barnett, Joseph / Brill, Simon E / Brown, Jeremy S / Denneny, Emma K / Hare, Samanjit S / Heightman, Melissa / Hillman, Toby E / Jacob, Joseph / Jarvis, Hannah C / Lipman, Marc C I / Naidu, Sindhu B / Nair, Arjun / Porter, Joanna C / Tomlinson, Gillian S / Hurst, John R

Thorax

2020 Volume 76, Issue 4, Page(s) 396–398

Abstract: Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and ... ...

Abstract	Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.
MeSH term(s)	Biomarkers/blood ; COVID-19/blood ; COVID-19/diagnosis ; Cross-Sectional Studies ; Diagnostic Imaging ; Female ; Hospitalization/trends ; Humans ; Lung/diagnostic imaging ; Male ; Middle Aged ; Pandemics ; SARS-CoV-2 ; Severity of Illness Index
Chemical Substances	Biomarkers
Keywords	covid19
Language	English
Publishing date	2020-11-10
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-215818
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Article: 'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19

Thorax

Abstract	Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #919095
Database	COVID19

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Article ; Online: Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).

Wild, Jim M / Porter, Joanna C / Molyneaux, Philip L / George, Peter M / Stewart, Iain / Allen, Richard James / Aul, Raminder / Baillie, John Kenneth / Barratt, Shaney L / Beirne, Paul / Bianchi, Stephen M / Blaikley, John F / Brooke, Jonathan / Chaudhuri, Nazia / Collier, Guilhem / Denneny, Emma K / Docherty, Annemarie / Fabbri, Laura / Gibbons, Michael A /

Gleeson, Fergus V / Gooptu, Bibek / Hall, Ian P / Hanley, Neil A / Heightman, Melissa / Hillman, Toby E / Johnson, Simon R / Jones, Mark G / Khan, Fasihul / Lawson, Rod / Mehta, Puja / Mitchell, Jane A / Platé, Manuela / Poinasamy, Krisnah / Quint, Jennifer K / Rivera-Ortega, Pilar / Semple, Malcolm / Simpson, A John / Smith, Djf / Spears, Mark / Spencer, LIsa G / Stanel, Stefan C / Thickett, David R / Thompson, A A Roger / Walsh, Simon Lf / Weatherley, Nicholas D / Weeks, Mark Everard / Wootton, Dan G / Brightling, Chris E / Chambers, Rachel C / Ho, Ling-Pei / Jacob, Joseph / Piper Hanley, Karen / Wain, Louise V / Jenkins, R Gisli

BMJ open respiratory research

2022 Volume 8, Issue 1

Abstract: Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and ...

Abstract	Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
MeSH term(s)	COVID-19/complications ; Humans ; Longitudinal Studies ; Lung Diseases, Interstitial/epidemiology ; Observational Studies as Topic ; Pandemics ; Prospective Studies ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2021-001049
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Article: Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis.

Gudmundsson, Eyjolfur / Zhao, An / Mogulkoc, Nesrin / van Beek, Frouke / Goos, Tinne / Brereton, Christopher J / Veltkamp, Marcel / Chapman, Robert / van Es, Hendrik W / Garthwaite, Helen / Gholipour, Bahareh / Heightman, Melissa / Nair, Arjun / Pontoppidan, Katarina / Savas, Recep / Ahmed, Asia / Vermant, Marie / Unat, Omer / Procter, Alex /

De Sadeleer, Laurens / Denneny, Emma / Wallis, Timothy / Duncan, Mark / Taylor, Magali / Verleden, Stijn / Janes, Sam M / Alexander, Daniel C / Wells, Athol U / Porter, Joanna / Jones, Mark G / Stewart, Iain / van Moorsel, Coline H M / Wuyts, Wim / Jacob, Joseph

ERJ open research

2023 Volume 9, Issue 2

Abstract: Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in ... ...

Abstract	Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Results: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). Interpretation: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.
Language	English
Publishing date	2023-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00637-2022
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