Imperial College London

DrPhilipMolyneaux

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Interstitial Lung Disease
 
 
 
//

Contact

 

p.molyneaux

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Publication Type
Year
to

67 results found

Allden SJ, Ogger PP, Ghai P, McErlean P, Hewitt R, Toshner R, Walker SA, Saunders P, Kingston S, Molyneaux PL, Maher TM, Lloyd CM, Byrne AJet al., 2019, The Transferrin Receptor CD71 Delineates Functionally Distinct Airway Macrophage Subsets during Idiopathic Pulmonary Fibrosis., Am J Respir Crit Care Med

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease with limited therapeutic options. Airway macrophages (AMs) are key components of the defence of the airways and are implicated in the pathogenesis of IPF. Alterations in iron metabolism have been described during fibrotic lung disease and in murine models of lung fibrosis. However, the role of transferrin receptor-1 (CD71)-expressing AMs in IPF is not known. OBJECTIVES: To assess the role of CD71 expressing AMs in the IPF-lung. METHODS: We utilized multi-parameter flow cytometry, gene expression analysis and phagocytosis/transferrin uptake assays to delineate the role of AMs expressing, or lacking, CD71 in the BAL of patients with IPF or healthy controls. MEASUREMENTS AND MAIN RESULTS: There was a distinct increase in proportions of AMs lacking CD71 in IPF patients in comparison to healthy controls. Levels of BAL transferrin were enhanced in IPF-BAL and furthermore, CD71- AMs had an impaired ability to sequester transferrin. CD71+ and CD71- AMs were phenotypically, functionally and transcriptionally distinct, with CD71- AMs characterised by reduced expression of markers of macrophage maturity, impaired phagocytosis and enhanced expression of pro-fibrotic genes. Importantly, proportions of AMs lacking CD71 were independently associated with worse survival, underlining the importance of this population in IPF and as a potential therapeutic target. CONCLUSIONS: Taken together these data highlight how CD71 delineates AM subsets which play distinct roles in IPF and furthermore, CD71- AMs may be an important pathogenic component of fibrotic lung disease.

JOURNAL ARTICLE

Segal LN, Molyneaux PL, 2019, The Challenging Road of Moving from Association to Causation for Microbiome Research in Idiopathic Pulmonary Fibrosis., Am J Respir Crit Care Med, Vol: 199, Pages: 1054-1056

JOURNAL ARTICLE

Moore C, Blumhagen RZ, Yang IV, Walts A, Powers J, Walker T, Bishop M, Russell P, Vestal B, Cardwell J, Markin CR, Mathai SK, Schwarz MI, Steele MP, Lee J, Brown KK, Loyd JE, Crapo JD, Silverman EK, Cho MH, James JA, Guthridge JM, Cogan JD, Kropski JA, Swigris JJ, Bair C, Soon Kim D, Ji W, Kim H, Song JW, Maier LA, Pacheco KA, Hirani N, Poon AS, Li F, Jenkins RG, Braybrooke R, Saini G, Maher TM, Molyneaux PL, Saunders P, Zhang Y, Gibson KF, Kass DJ, Rojas M, Sembrat J, Wolters PJ, Collard HR, Sundy JS, O'Riordan T, Strek ME, Noth I, Ma S-F, Porteous MK, Kreider ME, Patel NB, Inoue Y, Hirose M, Arai T, Akagawa S, Eickelberg O, Fernandez IE, Behr J, Mogulkoc N, Corte TJ, Glaspole I, Tomassetti S, Ravaglia C, Poletti V, Crestani B, Borie R, Kannengiesser C, Parfrey H, Fiddler C, Rassl D, Molina-Molina M, Machahua C, Montes Worboys A, Gudmundsson G, Isaksson HJ, Lederer DJ, Podolanczuk AJ, Montesi SB, Bendstrup E, Danchel V, Selman M, Pardo A, Henry MT, Keane MP, Doran P, Vašáková M, Sterclova M, Ryerson CJ, Wilcox PG, Okamoto T, Furusawa H, Miyazaki Y, Laurent G, Baltic S, Prele C, Moodley Y, Shea BS, Ohta K, Suzukawa M, Narumoto O, Nathan SD, Venuto DC, Woldehanna ML, Kokturk N, de Andrade JA, Luckhardt T, Kulkarni T, Bonella F, Donnelly SC, McElroy A, Armstrong ME, Aranda A, Carbone RG, Puppo F, Beckman KB, Nickerson DA, Fingerlin TE, Schwartz DAet al., 2019, Resequencing study confirms host defense and cell senescence gene variants contribute to the risk of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X

RATIONALE: Several common and rare genetic variants have been associated with Idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. OBJECTIVE: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. METHODS: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (N=3,624) and controls (N=4,442) across genes and regions previously associated with disease. We tested for association between disease and a) individual common variants via logistic regression and b) groups of rare variants via a sequence kernel association test. MEASUREMENTS AND MAIN RESULTS: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant, rs35705950, with an OR of 5.45 (95% CI: 4.91-6.06) for one copy of the risk allele and 18.68 (95% CI: 13.34-26.17) for two copies of the risk allele (p=9.60 x 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in risk of IPF in the TERT and RTEL1 gene regions, and found that the FAM13A and TERT regions have independent common and rare variant signals. CONCLUSIONS: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions; these genetic variants focus on biological mechanisms of host defense and cell senescence.

JOURNAL ARTICLE

Garner JL, Garner SD, Hardie RJ, Molyneaux PL, Singh S, Kemp SV, Shah PLet al., 2019, Evaluation of a re-useable bronchoscopy biosimulator with ventilated lungs, ERJ Open Research, Vol: 5, ISSN: 2312-0541

Background: Restrictions on respiratory trainee time and access to procedures reduce the opportunities toacquire necessary skills in bronchoscopy. Simulation, not subject to such impediments, is a usefulsupplementary aid to teaching bronchoscopic techniques in a safe environment but there is a limitedchoice of simulators that are sufficiently realistic and not prohibitively expensive. This study evaluated alow-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 thecomputerised CAE AccuTouch.Results: Participants were largely positive about their experience (mean score of 4.76). The bronchoscopybiosimulator was found to be realistic (mean score 4.64), easy to use (mean score 4.88), and helpful inlearning to perform a variety of diagnostic and therapeutic procedures (mean score 4.85). Importantly, thebronchoscopy biosimulator compared favourably to the computer simulator (mean score 4.84).Conclusions: These data support the concept of the bronchoscopy biosimulator as an acceptable modelwith which to supplement the experience of bronchoscopic procedures.

JOURNAL ARTICLE

Mackintosh JA, Desai SR, Adamali H, Patel K, Chua F, Devaraj A, Kouranos V, Kokosi M, Margaritopoulos G, Renzoni EA, Wells AU, Molyneaux PL, Kumar S, Maher TM, George PMet al., 2019, In Patients with Idiopathic Pulmonary Fibrosis the Presence of Hiatus Hernia is Associated with Disease Progression and Mortality., Eur Respir J

JOURNAL ARTICLE

Lukey PT, Harrison SA, Yang S, Man Y, Holman BF, Rashidnasab A, Azzopardi G, Grayer M, Simpson JK, Bareille P, Paul L, Woodcock HV, Toshner R, Saunders P, Molyneaux PL, Thielemans K, Wilson FJ, Mercer PF, Chambers RC, Groves AM, Fahy WA, Marshall RP, Maher TMet al., 2019, A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis., Eur Respir J, Vol: 53

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2 mg twice daily).17 subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose-related increases in insulin and glucose were observed. Pharmacokinetic analysis demonstrated that exposure in the blood predicts lung exposure. Exposure-dependent inhibition of phosphatidylinositol 3,4,5 trisphosphate and pAKT confirmed target engagement in blood and lungs. 18F-2-fluoro-2-deoxy-d-glucose(FDG)-positron emission tomography/computed tomography scans revealed an exposure-dependent reduction in 18F-FDG uptake in fibrotic areas of the lung, as measured by target-to-background, ratio thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.

JOURNAL ARTICLE

Macaluso C, Furcada JM, Alzaher O, Chaube R, Chua F, Wells AU, Maher TM, George PM, Renzoni EA, Molyneaux PLet al., 2019, The potential impact of azithromycin in idiopathic pulmonary fibrosis, EUROPEAN RESPIRATORY JOURNAL, Vol: 53, ISSN: 0903-1936

JOURNAL ARTICLE

Visca D, Mori L, Tsipouri V, Fleming S, Firouzi A, Bonini M, Pavitt MJ, Alfieri V, Canu S, Bonifazi M, Boccabella C, De Lauretis A, Stock CJW, Saunders P, Montgomery A, Hogben C, Stockford A, Pittet M, Brown J, Chua F, George PM, Molyneaux PL, Margaritopoidos GA, Kokosi M, Kouranos V, Russell AM, Birring SS, Chetta A, Maher TM, Cullinan P, Hopkinson NS, Banya W, Whitty JA, Adamali H, Spencer LG, Farquhar M, Sestini P, Wells AU, Renzoni EAet al., 2018, Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label mixed-method, crossover randomised controlled trial, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: 759-770, ISSN: 2213-2600

JOURNAL ARTICLE

Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles RS, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WPet al., 2018, PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production., Sci Transl Med, Vol: 10

Pulmonary fibrosis is a progressive inflammatory disease with high mortality and limited therapeutic options. Previous genetic and immunologic investigations suggest common intersections between idiopathic pulmonary fibrosis (IPF), sarcoidosis, and murine models of pulmonary fibrosis. To identify immune responses that precede collagen deposition, we conducted molecular, immunohistochemical, and flow cytometric analysis of human and murine specimens. Immunohistochemistry revealed programmed cell death-1 (PD-1) up-regulation on IPF lymphocytes. PD-1+CD4+ T cells with reduced proliferative capacity and increased transforming growth factor-β (TGF-β)/interleukin-17A (IL-17A) expression were detected in IPF, sarcoidosis, and bleomycin CD4+ T cells. PD-1+ T helper 17 cells are the predominant CD4+ T cell subset expressing TGF-β. Coculture of PD-1+CD4+ T cells with human lung fibroblasts induced collagen-1 production. Strikingly, ex vivo PD-1 pathway blockade resulted in reductions in TGF-β and IL-17A expression from CD4+ T cells, with concomitant declines in collagen-1 production from fibroblasts. Molecular analysis demonstrated PD-1 regulation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Chemical blockade of STAT3, using the inhibitor STATTIC, inhibited collagen-1 production. Both bleomycin administration to PD-1 null mice or use of antibody against programmed cell death ligand 1 (PD-L1) demonstrated significantly reduced fibrosis compared to controls. This work identifies a critical, previously unrecognized role for PD-1+CD4+ T cells in pulmonary fibrosis, supporting the use of readily available therapeutics that directly address interstitial lung disease pathophysiology.

JOURNAL ARTICLE

Sun J, Herazo-Maya JD, Molyneaux PL, Maher TM, Kaminski N, Zhao Het al., 2018, Regularized Latent Class Model for Joint Analysis of High-Dimensional Longitudinal Biomarkers and a Time-to-Event Outcome., Biometrics

Although many modeling approaches have been developed to jointly analyze longitudinal biomarkers and a time-to-event outcome, most of these methods can only handle one or a few biomarkers. In this article, we propose a novel joint latent class model to deal with high dimensional longitudinal biomarkers. Our model has three components: a class membership model, a survival submodel, and a longitudinal submodel. In our model, we assume that covariates can potentially affect biomarkers and class membership. We adopt a penalized likelihood approach to infer which covariates have random effects and/or fixed effects on biomarkers, and which covariates are informative for the latent classes. Through extensive simulation studies, we show that our proposed method has improved performance in prediction and assigning subjects to the correct classes over other joint modeling methods and that bootstrap can be used to do inference for our model. We then apply our method to a dataset of patients with idiopathic pulmonary fibrosis, for whom gene expression profiles were measured longitudinally. We are able to identify four interesting latent classes with one class being at much higher risk of death compared to the other classes. We also find that each of the latent classes has unique trajectories in some genes, yielding novel biological insights.

JOURNAL ARTICLE

Molyneaux PL, Maher TM, 2018, Could quality be the key in connective tissue disease-associated interstitial lung disease?, RESPIROLOGY, Vol: 23, Pages: 801-802, ISSN: 1323-7799

JOURNAL ARTICLE

Mallia P, Webber J, Gill SK, Trujillo-Torralbo M-B, Calderazzo MA, Finney L, Bakhsoliani E, Fame H, Singanayagam A, Footitt J, Hewitt R, Kebadze T, Aniscenko J, Padmanaban V, Molyneaux PL, Adcock IM, Barnes PJ, Ito K, Elkin SL, Kon OM, Cookson WO, Moffat MF, Johnston SL, Tregoning JSet al., 2018, Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 815-+, ISSN: 0091-6749

JOURNAL ARTICLE

Singanayagam A, Woodcock HV, Molyneaux PL, Jenkins Get al., 2018, Review of the British Thoracic Society Winter Meeting 2017, 6-8 December 2017, London, UK., Thorax, Vol: 73, Pages: 872-876

This article reviews the British Thoracic Society Winter Meeting 2017 and summarises the new developments in scientific and clinical research across the breadth of respiratory medicine. The article discusses a number of symposia and selected abstract presentations from the meeting.

JOURNAL ARTICLE

Rogers C, Kent-Bramer J, Devaraj A, Nicholson AG, Molyneaux PL, Wells AU, Saikia S, Maher TM, George PMet al., 2018, Rapidly Progressive Cystic Lung Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 198, Pages: 264-264, ISSN: 1073-449X

JOURNAL ARTICLE

Newton CA, Molyneaux PL, Oldham JM, 2018, Clinical Genetics in Interstitial Lung Disease., Front Med (Lausanne), Vol: 5, ISSN: 2296-858X

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

JOURNAL ARTICLE

Maher TM, Oballa E, Simpson JK, Porte J, Habgood A, Fahy WA, Flynn A, Molyneaux PL, Braybrooke R, Divyateja H, Parfrey H, Rassl D, Russell A-M, Saini G, Renzoni EA, Duggan A-M, Hubbard R, Wells AU, Lukey PT, Marshall RP, Jenkins RGet al., 2017, An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study, LANCET RESPIRATORY MEDICINE, Vol: 5, Pages: 946-955, ISSN: 2213-2600

JOURNAL ARTICLE

Herazo-Maya JD, Sun J, Molyneaux PL, Li Q, Villalba JA, Tzouvelekis A, Lynn H, Juan-Guardela BM, Risquez C, Osorio JC, Yan X, Michel G, Aurelien N, Lindell KO, Klesen MJ, Moffatt MF, Cookson WO, Zhang Y, Garcia JGN, Noth I, Prasse A, Bar-Joseph Z, Gibson KF, Zhao H, Herzog EL, Rosas IO, Maher TM, Kaminski Net al., 2017, Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study, LANCET RESPIRATORY MEDICINE, Vol: 5, Pages: 857-868, ISSN: 2213-2600

JOURNAL ARTICLE

Allen RJ, Porte J, Braybrooke R, Flores C, Fingerlin TE, Oldham JM, Guillen-Guio B, Ma S-F, Okamoto T, John AE, Obeidat M, Yang IV, Henry A, Hubbard RB, Navaratnam V, Saini G, Thompson N, Booth HL, Hart SP, Hill MR, Hirani N, Maher TM, McAnulty RJ, Millar AB, Molyneaux PL, Parfrey H, Rassl DM, Whyte MKB, Fahy WA, Marshall RP, Oballa E, Bosse Y, Nickle DC, Sin DD, Timens W, Shrine N, Sayers I, Hall IP, Noth I, Schwartz DA, Tobin MD, Wain LV, Jenkins RGet al., 2017, Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study, LANCET RESPIRATORY MEDICINE, Vol: 5, Pages: 869-880, ISSN: 2213-2600

JOURNAL ARTICLE

Molyneaux PL, Maher TM, 2017, Time for an International Consensus on Hypersensitivity Pneumonitis. A Call to Arms., American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 665-666, ISSN: 1073-449X

JOURNAL ARTICLE

Salisbury ML, Han MK, Dickson RP, Molyneaux PLet al., 2017, Microbiome in interstitial lung disease: from pathogenesis to treatment target., Curr Opin Pulm Med, Vol: 23, Pages: 404-410

PURPOSE OF REVIEW: This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target. RECENT FINDINGS: Although historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. In support of this, studies of interstitial lung diseases other than IPF suggest that it may be the host immune response, which shapes the microbiome in these diseases. Some clinical and mouse model data also suggest that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. SUMMARY: Evidence suggests that the lung microbiome may serve as a prognostic biomarker, a therapeutic target, or provide an explanation for disease pathogenesis in IPF.

JOURNAL ARTICLE

Conforti F, Davies ER, Calderwood CJ, Thatcher TH, Jones MG, Smart DE, Mahajan S, Alzetani A, Havelock T, Maher TM, Molyneaux PL, Thorley AJ, Tetley TD, Warner JA, Packham G, Ganesan A, Skipp PJ, Marshall BJ, Richeldi L, Sime PJ, O'Reilly KMA, Davies DEet al., 2017, The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis, ONCOTARGET, Vol: 8, Pages: 48737-48754, ISSN: 1949-2553

JOURNAL ARTICLE

Molyneaux PL, Willis-Owen SAG, Cox MJ, James P, Cowman S, Loebinger M, Blanchard A, Edwards LM, Stock C, Daccord C, Renzoni EA, Wells AU, Moffatt MF, Cookson WOC, Maher TMet al., 2017, Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 195, Pages: 1640-1650, ISSN: 1073-449X

JOURNAL ARTICLE

Hewitt RJ, Molyneaux PL, 2017, The respiratory microbiome in idiopathic pulmonary fibrosis, ANNALS OF TRANSLATIONAL MEDICINE, Vol: 5, ISSN: 2305-5839

JOURNAL ARTICLE

Faner R, Sibila O, Agustí A, Bernasconi E, Chalmers JD, Huffnagle GB, Manichanh C, Molyneaux PL, Paredes R, Pérez Brocal V, Ponomarenko J, Sethi S, Dorca J, Monsó Eet al., 2017, The microbiome in respiratory medicine: current challenges and future perspectives., Eur Respir J, Vol: 49

The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease. In all of these diseases, a loss of diversity, paralleled by an over-representation of Proteobacteria (dysbiosis), has been related to disease severity and exacerbations. However, it is unknown whether dysbiosis is a cause or a consequence of the damage to bronchoalveolar surfaces.Finally, little is known about bacterial functionality and the interactions between viruses, fungi and bacteria. It is expected that future research in bacterial gene expressions, metagenomics longitudinal analysis and host-microbiome animal models will help to move towards targeted microbiome interventions in respiratory diseases.

JOURNAL ARTICLE

Molyneaux PL, Cox MJ, Wells AU, Kim HC, Ji W, Cookson WOC, Moffatt MF, Kim DS, Maher TMet al., 2017, Changes in the respiratory microbiome during acute exacerbations of idiopathic pulmonary fibrosis, RESPIRATORY RESEARCH, Vol: 18, ISSN: 1465-993X

JOURNAL ARTICLE

Russell A-M, Adamali H, Molyneaux PL, Lukey PT, Marshall RP, Renzoni EA, Wells AU, Maher TMet al., 2016, Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 194, Pages: 989-997, ISSN: 1073-449X

JOURNAL ARTICLE

Fingerlin TE, Zhang W, Yang IV, Ainsworth HC, Russell PH, Blumhagen RZ, Schwarz MI, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch DA, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Murphy E, Smith K, McKean D, Pedersen BS, Talbert J, Powers J, Markin CR, Beckman KB, Lathrop M, Freed B, Langefeld CD, Schwartz DAet al., 2016, Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia, BMC GENETICS, Vol: 17, ISSN: 1471-2156

JOURNAL ARTICLE

Chakrabarti AM, Jacobs J, Molyneaux PL, Devaraj A, Chua Fet al., 2016, Smoking-related interstitial lung disease, Clinical Pulmonary Medicine, Vol: 23, Pages: 151-156, ISSN: 1068-0640

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Chronic or heavy smoking can lead to different forms of pathologic remodeling in the airways and distal lung. There is an 8% to 19% prevalence of interstitial lung disease (ILD) in chronic smokers who were unaware that they had a lung disorder. Descriptive pathologic and radiologic analyses have enabled a number of clinical diseases to be identified and grouped within a range of smoking-related ILDs. We review the radiology, pathology, and clinical management of pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-associated ILD, and desquamative interstitial pneumonia. We discuss the difficulties of classification and also where the new entity of airspace enlargement with fibrosis fits into the current grouping. The prognosis for these conditions is variable depending on the intrinsic behavior of each condition. Smoking cessation is the first-line therapy of choice for any smoking-related ILD, whereas treatment with corticosteroids and other agents forms an important, but occasionally futile, intervention.

JOURNAL ARTICLE

Molyneaux PL, Jacob J, Chakrabarti A, Devaraj A, Chua Fet al., 2016, Hypersensitivity Pneumonitis, Clinical Pulmonary Medicine, Vol: 23, Pages: 136-141, ISSN: 1068-0640

© 2016 Wolters Kluwer Health, Inc. Hypersensitivity pneumonitis (HP) is a syndrome caused by an exaggerated immune response to the inhalation and subsequent sensitization to a variety of environmental antigenic particles. The pathogenesis remains unclear; however, a "two-hit hypothesis" implicating a pathologic interaction between an environmental antigen and the immune system of a susceptible host seems likely as only a minority of the exposed individuals develop HP. The presentation may be acute, as in bird fancier's lung, the classical form of HP, or more insidiously as the subacute form of chronic HP caused by repeated lowlevel antigenic exposure. Despite these categorizations, there is frequently an overlap between the clinical entities and no guaranteed linear progression through the different pathologic stages. Prompt diagnosis is crucial, and is based on an exposure history, precipitating antibodies to the offending antigen, and a combination of clinical, radiologic, and physiological findings. The mainstay of treatment is allergen avoidance, but systemic steroids are of value for both the subacute and the chronic forms, although they do not alter the longterm outcome. This review summarizes the current knowledge of the pathophysiology of HP and the main entities in the differential diagnosis.

JOURNAL ARTICLE

Hashim HH, Molyneaux PL, Regan S, Hull JH, Menzies-Gow Aet al., 2015, BONE PROTECTION IN ORAL CORTICOSTEROID DEPENDANT ASTHMATICS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A157-A158, ISSN: 0040-6376

CONFERENCE PAPER

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.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00627916&limit=30&person=true