Imperial College London

DrMichaelCox

Faculty of MedicineNational Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 7974michael.cox1 Website

 
 
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Location

 

413Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

56 results found

Ahmed B, Cox MJ, Cuthbertson L, 2019, Growing up with your airway microbiota: a risky business., Thorax, Vol: 74, Pages: 525-526

JOURNAL ARTICLE

Ahmed B, Cox MJ, Cuthbertson L, James P, Cookson WOC, Davies JC, Moffatt MF, Bush Aet al., 2019, Longitudinal development of the airway microbiota in infants with cystic fibrosis, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

JOURNAL ARTICLE

Turek E, Cox M, Hunter M, Hui J, James P, Willis-Owen SAG, Cuthbertson L, James A, Musk W, Moffatt M, Cookson WOCMet al., 2019, Distinctive airway microbial ecology of smokers and asthmatics

The airways of the lung carry microbiota that contribute to respiratory health 1 . The ecology of normal airway microbial communities, their responses to environmental events, and the mechanisms through which they cause or modify disease are poorly understood. Cigarette smoking is the dominant malign environmental influence on lung function, causing 11·5% of deaths globally 2 . Asthma is the most prevalent chronic respiratory disease worldwide 3,4 , but was uncommon 100 years ago 5 . The asthma pandemic is linked to urbanization, leading to considerations of protective microbiota loss (the “hygiene hypothesis”) 6-8 and acquisition of strains that may damage the airway epithelia 9 . We therefore investigated oropharyngeal airway microbial community structures in a general population sample of Australian adults. We show here that airway bacterial communities were strongly organized into distinctive co-abundance networks (“guilds”), just seven of which contained 99% of all oropharyngeal operational taxonomic units (OTUs). Smoking was associated with diversity loss, negative effects on abundant taxa, profound alterations to network structure and marked expansion of Streptococcus spp.. These perturbations may influence chronic obstructive pulmonary disease 10 (COPD) and lung cancer 11 . In contrast to smokers, the loss of diversity in asthmatics selectively affected low abundance but prevalent OTUs from poorly understood genera such as Selenomonas, Megasphaera and Capnocytophaga , without coarse scale network disruption. The results open the possibility that replacement of specific organisms may mitigate asthma susceptibility.

WORKING PAPER

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJM, Habibi MS, Johnston SL, Hansel TT, Levin M, Thwaites RS, Warner JO, Cookson WO, Gazzard BG, Hay A, McCauley J, Aylin P, Ashby D, Barclay WS, Elderfield RA, Nadel S, Herberg JA, Drumright LN, Garcia-Alvarez L, Holmes AH, Kon OM, Aston SJ, Gordon SB, Hussell T, Thompson C, Zambon MC, Baillie KJ, Hume DA, Simmonds P, Hayward A, Smyth RL, McNamara PS, Semple MG, Nguyen-Van-Tam JS, Ho L-P, McMichael AJ, Kellam P, Adamson WE, Carman WF, Griffiths MJet al., 2019, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza (vol 19, pg 625, 2018), NATURE IMMUNOLOGY, Vol: 20, Pages: 373-373, ISSN: 1529-2908

JOURNAL ARTICLE

Wootton DG, Cox MJ, Gloor GB, Litt D, Hoschler K, German E, Court J, Eneje O, Keogan L, Macfarlane L, Wilks S, Diggles PJ, Woodhead M, Moffatt MF, Cookson WOC, Gordon SBet al., 2019, A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

JOURNAL ARTICLE

Brill S, James P, Cuthbertson L, Zhu A, Lawley T, Cookson WOC, Cox M, Wedzicha J, Moffatt Met al., 2018, Haemophilus, antibiotic therapy and the airway microbiome in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a smoking-related illness affecting 64 million people worldwide. Airway infection drives recurrent exacerbations and lung function decline. Prophylactic antibiotics may prevent exacerbations but their use is a significant cause of population antimicrobial resistance. We characterised the sputum microbiome by 16S rRNA gene analysis using 138 samples collected during a randomised controlled trial of prophylactic antibiotics in 71 patients with stable COPD. On comparing the profile of the microbiome obtained by sequencing to the isolates grown from samples using standard culture, there were similarities overall, although with a much narrower spectrum of genera on culture with under-representation of certain genera including Veillonella and Prevotella. There was concordance in the most abundant genera within samples and the number of isolates cultured reflected the measured bacterial diversity. We found that at baseline the microbiota of 17 (24%) patients were dominated by Haemophilus influenzae, accompanied by narrowed microbial diversity and higher levels of sputum inflammatory cytokines. Different H. influenzae strains co-existed within individuals. Opportunistic whole genome sequencing of six H. influenzae isolates obtained during the study revealed that all were non-typeable H. influenzae (NTHI), with a range of different antibiotic resistance gene profiles, but an identical complement of virulence genes. Administration of 13 weeks prophylaxis with moxifloxacin, azithromycin or doxycycline revealed distinctive changes in microbial communities for each group. Haemophilus numbers reduced by 90% compared to placebo only after moxifloxacin, and significant reduction in sputum cytokines occurred in patients dominated by Haemophilus at baseline. Haemophilus influenzae dominance defines COPD patients with active disease who may particularly benefit from antibiotics or vaccination.

WORKING PAPER

Ahmed B, Cox MJ, Cuthbertson L, James PL, Cookson WOC, Davies JC, Moffatt MF, Bush Aet al., 2018, Comparison of the upper and lower airway microbiota in children with chronic lung diseases, PLOS ONE, Vol: 13, ISSN: 1932-6203

JOURNAL ARTICLE

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, NATURE IMMUNOLOGY, Vol: 19, Pages: 625-+, ISSN: 1529-2908

JOURNAL ARTICLE

Groves HT, Cuthbertson L, James P, Moffatt MF, Cox MJ, Tregoning JSet al., 2018, Respiratory Disease following Viral Lung Infection Alters the Murine Gut Microbiota, FRONTIERS IN IMMUNOLOGY, Vol: 9, ISSN: 1664-3224

JOURNAL ARTICLE

Cookson WOCM, Cox MJ, Moffatt MF, 2018, New opportunities for managing acute and chronic lung infections, NATURE REVIEWS MICROBIOLOGY, Vol: 16, Pages: 111-120, ISSN: 1740-1526

JOURNAL ARTICLE

Cox MJ, 2017, Ventilator-associated pneumonia: when is a pathogen not a pathogen?, THORAX, Vol: 72, Pages: 774-775, ISSN: 0040-6376

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

Depner M, Ege MJ, Cox MJ, Dwyer S, Walker AW, Birzele LT, Genuneit J, Horak E, Braun-Fahrlaender C, Danielewicz H, Maier RM, Moffatt MF, Cookson WO, Heederik D, von Mutius E, Legatzki Aet al., 2017, Bacterial microbiota of the upper respiratory tract and childhood asthma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 139, Pages: 826-+, ISSN: 0091-6749

JOURNAL ARTICLE

Cox MJ, Turek EM, Hennessy C, Mirza GK, James PL, Coleman M, Jones A, Wilson R, Bilton D, Cookson WOC, Moffatt MF, Loebinger MRet al., 2017, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients, PLOS ONE, Vol: 12, ISSN: 1932-6203

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

Dickson RP, Cox MJ, 2017, Gut microbiota and protection from pneumococcal pneumonia, GUT, Vol: 66, ISSN: 0017-5749

JOURNAL ARTICLE

Molyneaux PL, James P, Cuthbertson L, Cox MJ, Kim D, Maher TM, Cookson W, Moffatt Met al., 2017, The Role Of The Fungal Mycobiome In Ipf, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Ahmed B, Cox MJ, Cuthbertson L, James P, Cookson WO, Davies JC, Moffatt MF, Bush Aet al., 2016, EARLY DEVELOPMENT OF THE AIRWAY MICROBIOTA IN INFANTS WITH CF, PEDIATRIC PULMONOLOGY, Vol: 51, Pages: 328-328, ISSN: 8755-6863

JOURNAL ARTICLE

Cox M, Turek E, Hennessy C, Mirza G, James P, Coleman M, Jones A, Wilson R, Bilton D, Cookson W, Moffatt M, Loebinger Met al., 2016, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-CF bronchiectasis patients

Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-CF bronchiectasis microbiome in sputum with respect to clinical variables. Eighty-five patients with non-cystic fibrosis (CF) bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data. Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations. The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbations driven by bacterial overgrowth was not supported, suggesting a need for revision of principles for antibiotic therapy. In individual patients, the management of chronic bronchial infection may be improved by therapy specific to their microbiome, taking into account pathogen load, community stability, and acute and chronic community responses to antibiotics.

WORKING PAPER

Zhang Q, Cox M, Liang Z, Brinkmann F, Cardenas PA, Duff R, Bhavsar P, Cookson W, Moffatt M, Chung KFet al., 2016, Airway Microbiota in Severe Asthma and Relationship to Asthma Severity and Phenotypes, PLOS ONE, Vol: 11, ISSN: 1932-6203

JOURNAL ARTICLE

Cox MJ, Moffatt MF, Cookson WOC, 2015, Outside In: Sequencing the Lung Microbiome, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 192, Pages: 403-404, ISSN: 1073-449X

JOURNAL ARTICLE

Shaw AG, Sim K, Randell P, Cox MJ, McClure ZE, Li M-S, Donaldson H, Langford PR, Cookson WOCM, Moffatt MF, Kroll JSet al., 2015, Late-Onset Bloodstream Infection and Perturbed Maturation of the Gastrointestinal Microbiota in Premature Infants, PLOS ONE, Vol: 10, ISSN: 1932-6203

JOURNAL ARTICLE

Molyneaux PL, Cox MJ, Cookson WO, Moffatt MF, Kim DS, Maher TMet al., 2015, Changes In The Respiratory Microbiome During Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Annamalay AA, James P, Cowman S, Abbott S, Zhang G, Sikazwe C, Khoo S-K, Bizzintino J, Chidlow G, Cox MJ, Moffatt M, Green RJ, Cookson WO, LeSouef PNet al., 2015, Nontuberculous Mycobacteria In Young South African Children With Acute Lower Respiratory Infections, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Wootton DG, Cox MJ, Hickey GL, Eneje O, Court J, Macfarlane L, Wilks S, Woodhead M, Cookson WO, Moffatt MF, Diggle PJ, Gordon SBet al., 2015, The Genus Haemophilus Was Dominant In A Cohort With Community Acquired Pneumonia And Low Species Diversity Was Related To Age And Prior Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Cox MJ, Salter SJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AWet al., 2015, Contamination Of Reagents Can Critically Impact Sequence-Based Microbiome Studies, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Cox MJ, Turek EM, Mirza GK, James PL, Hennessey C, Coleman M, Jones A, Wilson R, Bilton D, Cookson WO, Moffatt MF, Loebinger MRet al., 2015, Longitudinal Analysis Of The Non-Cystic Fibrosis Bronchiectasis Microbiome, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

CONFERENCE PAPER

Ahmed B, Cox MJ, Cookson WOC, Davies JC, Moffatt MF, Bush Aet al., 2014, COMPARISON OF THE UPPER AND LOWER AIRWAY MICROBIOTA IN CHILDREN, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A123-A123, ISSN: 0040-6376

CONFERENCE PAPER

CFelton I, Benson I, Nicholson A, Al-Shafi K, James P, Cox MJ, Walley AJ, Moffatt MF, Bilton D, Loebinger MR, Simmonds NJ, Cookson WOet al., 2014, PRELIMINARY EVALUATION OF THE FUNGAL AIRWAY MICROBIOME IN ADULT CYSTIC FIBROSIS BY NEXT-GENERATION SEQUENCING, CULTURE AND STAINING TECHNIQUES, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A164-A164, ISSN: 0040-6376

CONFERENCE PAPER

Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AWet al., 2014, Reagent and laboratory contamination can critically impact sequence-based microbiome analyses, BMC BIOLOGY, Vol: 12, ISSN: 1741-7007

JOURNAL ARTICLE

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