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Article ; Online: Interstitial lung disease incidence and mortality in the UK and the European Union

Justin D. Salciccioli / Dominic C. Marshall / Richard Goodall / Conor Crowley / Joseph Shalhoub / Preya Patel / Philip L. Molyneaux

ERJ Open Research, Vol 8, Iss

an observational study, 2001–2017

2022 Volume 3

Abstract: Objective To compare the trends in age-standardised incidence and mortality from interstitial lung diseases (ILD) in the UK and the European Union (EU). Methods This was an observational study using data obtained from the Global Burden of Disease Study ... ...

Abstract	Objective To compare the trends in age-standardised incidence and mortality from interstitial lung diseases (ILD) in the UK and the European Union (EU). Methods This was an observational study using data obtained from the Global Burden of Disease Study on residents of the UK and of the 27 EU countries. The main outcome measures were ILD age-standardised incidence rates per 100 000 (ASIR), age-standardised death rates per 100 000 (ASDR) and mortality-to-incidence ratios (MIRs), which are presented for men and women separately for each country for the years 2001–2017. Trends were analysed using joinpoint regression analysis. Results In 2017, the median incidence of ILD was 7.22 (IQR 5.57–8.96) per 100 000 population for men and 4.34 (IQR 3.36–6.29) per 100 000 population for women. In 2017, the median ASDR attributed to ILD was 2.04 (IQR 1.13–2.71) per 100 000 population for men and 1.02 (0.68–1.37) per 100 000 population for women. There was an overall increase in ASDR during the observation period, with a median increase of +20.42% (IQR 5.44–31.40) for men and +15.44% (IQR −1.01–31.52) for women. Despite increases in mortality over the entire observation period, there were decreasing mortality trends in the majority of countries at the end of the observation period (75% for men and 86% for women). Conclusion Over the past two decades, there have been increases in the incidence and mortality of ILD in Europe. The most recent trends, however, demonstrate decreases in mortality from ILD in the majority of European countries for both men and women. These data support the ongoing improvements in the diagnosis and management of ILD.
Keywords	Medicine ; R
Subject code	331
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Genetics in Interstitial Lung Disease

Chad A. Newton / Philip L. Molyneaux / Justin M. Oldham

Frontiers in Medicine, Vol

2018 Volume 5

Abstract: Interstitial lung disease (ILD) comprises a heterogeneous group of diffuse parenchymal lung processes with overlapping clinical, radiographic, and histopathologic features. Among the most common and deadly ILDs are idiopathic pulmonary fibrosis (IPF) and ...

Abstract	Interstitial lung disease (ILD) comprises a heterogeneous group of diffuse parenchymal lung processes with overlapping clinical, radiographic, and histopathologic features. Among the most common and deadly ILDs are idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP). As the name implies, the cause of IPF remains elusive, but a variety of genetic and infectious risk factors have been identified. CHP results from chronic inhalation of an organic antigen, usually of avian or mold origin, and may occur in patients with a genetic predisposition. While IPF is treated with anti-fibrotic compounds, CHP is generally treated by suppression of the immune system and elimination of the causative antigen. Despite advances in our understanding of IPF and CHP, there exists substantial variability in the diagnosis and treatment of these disease processes. Furthermore, IPF and CHP natural history and treatment response remain far from uniform, leaving it unclear which patients derive the most benefit from disease-specific therapy. While clinical prediction models have improved our understanding of outcome risk in patients with various forms of ILD, recent advances in genomic technology provides a valuable opportunity to begin understanding the basis for outcome variability. Such advances will ultimately allow for the incorporation of genomic markers into risk stratification and clinical decision-making. In this piece, we highlight recent advances in our understanding of the genomic factors that influence susceptibility and outcome risk among patients with IPF and CHP. Genomic modalities used to identify these genomic markers include genome-wide association studies, analyses of gene expression, drug–gene interaction testing, telomere length determination, telomerase mutation analysis, and studies of the lung microbiome. We then identify gaps in knowledge that should be addressed to help facilitate the incorporation of these genomic technologies into ILD clinical practice.
Keywords	idiopathic pulmonary fibrosis ; hypersensitivity pneumonitis ; interstitial lung disease ; idiopathic interstitial pneumonia ; genomics ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

Francesco Amati / Anna Stainer / Marco Mantero / Andrea Gramegna / Edoardo Simonetta / Giulia Suigo / Antonio Voza / Anoop M. Nambiar / Umberto Cariboni / Justin Oldham / Philip L. Molyneaux / Paolo Spagnolo / Francesco Blasi / Stefano Aliberti

International Journal of Molecular Sciences, Vol 23, Iss 977, p

2022 Volume 977

Abstract: Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis ... ...

Abstract	Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
Keywords	microbiome ; interstitial lung diseases ; treatable traits ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease

Karim Boustani / Poonam Ghai / Rachele Invernizzi / Richard J. Hewitt / Toby M. Maher / Quan-Zhen Li / Philip L. Molyneaux / James A. Harker

ERJ Open Research, Vol 8, Iss

2022 Volume 1

Abstract: Background Fibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore ... ...

Abstract	Background Fibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD, and assessed association with disease severity and outcome. Methods Bronchoalveolar lavage (BAL) fluid was collected from a cohort of fILD patients and total BAL antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 122 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls. Results A subset of patients with fILD but not healthy controls had a local autoimmune signature in their BAL that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased BAL total IgA and IgG1 while subjects with CHP had increased BAL IgA, IgG1 and IgG4. In patients with CHP, increased BAL total IgA was associated with reduced survival probability. Conclusion Airway autoantibodies that are not present systemically identify a group of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PAciFy Cough—a multicentre, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of pulmonary Fibrosis Cough

Zhe Wu / Winston Banya / Nazia Chaudhuri / Ira Jakupovic / Toby M. Maher / Brijesh Patel / Lisa G. Spencer / Muhunthan Thillai / Alex West / John Westoby / Marlies Wijsenbeek / Jaclyn Smith / Philip L. Molyneaux

Trials, Vol 23, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring. Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are ...

Abstract	Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring. Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF-related cough. Whilst morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of cough in IPF. Methods We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomised (1:1) to either placebo twice daily or morphine sulphate 5 mg twice daily for 14 days. They will then crossover after a 7-day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at day 14 of treatment. Discussion This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients. Trial registration The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516
Keywords	Morphine ; Cough ; Idiopathic pulmonary fibrosis ; Interstitial lung disease ; Quality of life ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of infection in the pathogenesis of idiopathic pulmonary fibrosis

Philip L. Molyneaux / Toby M. Maher

European Respiratory Review, Vol 22, Iss 129, Pp 376-

2013 Volume 381

Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact triggers, which initiate the fibrotic process, remain unknown. Infectious agents, including both viruses and bacteria, have the capacity to cause alveolar-epithelial cell injury and apoptosis. Relatively few studies have examined the role of infection in IPF. Those that have, point to viruses playing a key role as cofactors in the initiation and progression of IPF. There is also some evidence to suggest that viral infection may be responsible for a proportion of acute exacerbations of IPF. The role played by bacteria in the pathogenesis of IPF is less clear cut. Studies from other respiratory diseases suggest that alterations in the lung microbiome are associated with disease and that these changes influence disease behaviour. Emerging molecular microbiological techniques are making the study of microbial communities in the lung easier. It is hoped that by combining such techniques with the careful longitudinal phenotyping of patients with IPF, it will be possible to elucidate the role played by bacteria and viruses in the pathogenesis of the disease. If infection plays a causal role in IPF then it is possible that therapeutic strategies, utilising currently available antiviral or antibiotic drugs, may be effective in modifying the course of this devastating condition.
Keywords	Diseases of the respiratory system ; RC705-779 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2013-09-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of a re-useable bronchoscopy biosimulator with ventilated lungs

Justin L. Garner / Stefan D. Garner / Robin J. Hardie / Philip L. Molyneaux / Suveer Singh / Samuel V. Kemp / Pallav L. Shah

ERJ Open Research, Vol 5, Iss

2019 Volume 2

Abstract: Background Restrictions on respiratory trainee time and access to procedures reduce the opportunities to acquire necessary skills in bronchoscopy. Simulation, not subject to such impediments, is a useful supplementary aid to teaching bronchoscopic ... ...

Abstract	Background Restrictions on respiratory trainee time and access to procedures reduce the opportunities to acquire necessary skills in bronchoscopy. Simulation, not subject to such impediments, is a useful supplementary aid to teaching bronchoscopic techniques in a safe environment but there is a limited choice of simulators that are sufficiently realistic and not prohibitively expensive. This study evaluated a low-cost device that simulates an intubated and ventilated patient, employing re-useable, inflatable, BioFlex-preserved, porcine lungs. Methods 26 bronchoscopists, trainee and experienced, after using the bronchoscopy biosimulator, completed a questionnaire using a five-point Likert scale comparing its performance with that of the computerised CAE AccuTouch. Results Participants were largely positive about their experience (mean score of 4.76). The bronchoscopy biosimulator was found to be realistic (mean score 4.64), easy to use (mean score 4.88), and helpful in learning to perform a variety of diagnostic and therapeutic procedures (mean score 4.85). Importantly, the bronchoscopy biosimulator compared favourably to the computer simulator (mean score 4.84). Conclusions These data support the concept of the bronchoscopy biosimulator as an acceptable model with which to supplement the experience of bronchoscopic procedures.
Keywords	Medicine ; R
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Muscle stimulation in advanced idiopathic pulmonary fibrosis

William D-C Man / Matthew Maddocks / Toby M Maher / Athol U Wells / Elisabetta A Renzoni / Suhani Patel / Jessica A Walsh / Felix Chua / Philip L Molyneaux / Peter M George / Ruth E Barker / Claire M Nolan / Oliver Polgar / Vasilis Kouranos

BMJ Open, Vol 11, Iss

a randomised placebo-controlled feasibility study

2021 Volume 6

Abstract: Objectives To assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible.Design A randomised, parallel, ...

Abstract	Objectives To assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible.Design A randomised, parallel, two-group, participant and assessor-blinded, placebo-controlled feasibility trial with embedded qualitative interviews.Setting Outpatient department, Royal Brompton and Harefield Hospitals.Participants Twenty-two people with IPF: median (25th, 75th centiles) age 76 (74, 82) years, forced vital capacity 62 (50, 75) % predicted, 6 min walk test distance 289 (149, 360) m.Interventions Usual care (home-based exercise, weekly telephone support, breathlessness management leaflet) with either placebo or active NMES for 6 weeks, with follow-up at 6 and 12 weeks.Primary outcome measures Feasibility of recruitment and retention, treatment uptake and adherence, outcome assessments, participant and outcome assessor blinding and adverse events related to interventions.Secondary outcome measures Outcome measures with potential to be primary or secondary outcomes in a definitive clinical trial. In addition, purposively sampled participants were interviewed to capture their experiences and acceptability of the trial.Results Out of 364 people screened, 23 were recruited: 11 were allocated to each group and one was withdrawn prior to randomisation. Compared with the control group, a greater proportion of the intervention group completed the intervention, remained in the trial blinded to group allocation and experienced intervention-related adverse events. Assessor blinding was maintained. The secondary outcome measures were feasible with most missing data associated with the accelerometer. Small participant numbers precluded identification of an outcome measure suitable for a definitive trial. Qualitative findings demonstrated that trial process and active NMES were acceptable but there were concerns about the credibility of placebo NMES.Conclusions Primarily owing to ...
Keywords	Medicine ; R
Subject code	796
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease

The Journal of Clinical Investigation, Vol 132, Iss

2022 Volume 8

Abstract: The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and ... ...

Abstract	The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with viral load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation, as Muc5ac-deficient (Muc5ac–/–) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.
Keywords	Pulmonology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Role of the Lung’s Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis

Paolo Spagnolo / Philip L. Molyneaux / Nicol Bernardinello / Elisabetta Cocconcelli / Davide Biondini / Federico Fracasso / Mariaenrica Tiné / Marina Saetta / Toby M. Maher / Elisabetta Balestro

International Journal of Molecular Sciences, Vol 20, Iss 22, p

2019 Volume 5618

Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.
Keywords	idiopathic pulmonary fibrosis ; interstitial lung disease ; microbiome ; pathogenesis ; acute exacerbation ; infection ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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