Imperial College London

ProfessorGavinDonaldson

Faculty of MedicineNational Heart & Lung Institute

Professor of Respiratory Studies
 
 
 
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Contact

 

+44 (0)20 7594 7859gavin.donaldson

 
 
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Location

 

B141Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

335 results found

Kole TM, Vanden Berghe E, Kraft M, Vonk JM, Nawijn MC, Siddiqui S, Sun K, Fabbri LM, Rabe KF, Chung KF, Nicolini G, Papi A, Brightling C, Singh D, van der Molen T, Dahlén S-E, Agusti A, Faner R, Wedzicha JA, Donaldson GC, Adcock IM, Lahousse L, Kerstjens HAM, van den Berge M, ATLANTIS, U-BIOPRED, CADSET investigatorset al., 2022, Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study., The Lancet Respiratory Medicine, ISSN: 2213-2600

BACKGROUND: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study. METHODS: In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18-65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort. FINDINGS: Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43

Journal article

Allinson JP, Patel PH, Donaldson GC, 2022, Obesity, Insulin Resistance and Asthma., Am J Respir Crit Care Med

Journal article

Silver JS, Chiang C, Elneima O, Haldar K, Mcauley HJ, Singh R, Singh D, Donaldson GC, Wedzicha JA, Brightling CE, Cohen S, Digiandomenico A, Kearley Jet al., 2022, Proteomic Analysis of Sputum from COPD Patients Reveal That Decreased PIGR and IgA Correlate with Exacerbation Frequency and Haemophilus Influenzae Burden, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Martinez FJ, Agusti A, Celli BR, Han MK, Allinson JP, Bhatt SP, Calverley P, Chotirmall SH, Chowdhury B, Darken P, Da Silva CA, Donaldson G, Dorinsky P, Dransfield M, Faner R, Halpin DM, Jones P, Krishnan JA, Locantore N, Martinez FD, Mullerova H, Price D, Rabe KF, Reisner C, Singh D, Vestbo J, Vogelmeier CF, Wise RA, Tal-Singer R, Wedzicha JAet al., 2022, Treatment Trials in Young Patients with Chronic Obstructive Pulmonary Disease and Pre-Chronic Obstructive Pulmonary Disease Patients Time to Move Forward, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: 275-287, ISSN: 1073-449X

Journal article

Paschalaki K, Rossios C, Pericleous C, MacLeod M, Rothery S, Donaldson G, Wedzicha J, Gorgoulis V, Randi A, Barnes Pet al., 2022, Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients, Thorax, Vol: 77, ISSN: 0040-6376

Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonarydisease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC),we have demonstrated accelerated senescence in smokers and COPD patients compared tonon-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence(Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damageresponse (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. Invitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICSon the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protectivemolecular mechanism of action of corticosteroids on endothelium.

Journal article

Martinez FJ, Brochard L, Bush A, Donaldson G, Han MKet al., 2022, Advancing Global Respiratory Health, Sleep, and Critical Care: Editorial from the New American Journal of Respiratory and Critical Care Medicine Team, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: I-II, ISSN: 1073-449X

Journal article

Allinson JP, Afzal S, Çolak Y, Jarvis D, Backman H, van den Berge M, Boezen HM, Breyer M-K, Breyer-Kohansal R, Brusselle G, Burghuber OC, Faner R, Hartl S, Lahousse L, Langhammer A, Lundbäck B, Nwaru BI, Rönmark E, Vikjord SAA, Vonk JM, Wijnant SRA, Lange P, Nordestgaard BG, Olvera N, Agusti A, Donaldson GC, Wedzicha JA, Vestbo J, Vanfleteren LEGW, CADSET Clinical Research Collaborationet al., 2022, Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies., Lancet Respir Med, Vol: 10, Pages: 83-94

BACKGROUND: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. METHODS: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. FINDINGS: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FV

Journal article

Wedzicha JA, Brochard L, Donaldson GC, Martinez FD, Martinez FJet al., 2021, Ending on a Crescendo: Reflections on Seven Years of a Successful Journal, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 1351-1352, ISSN: 1073-449X

Journal article

Wang G, Hallberg J, Charalampopoulos D, Sanahuja MC, Breyer-Kohansal R, Langhammer A, Granell R, Vonk JM, Mian A, Olvera N, Laustsen LM, Ronmark E, Abellan A, Agusti A, Arshad SH, Bergstrom A, Boezen HM, Breyer M-K, Burghuber O, Bolund AC, Custovic A, Devereux G, Donaldson GC, Duijts L, Esplugues A, Faner R, Ballester F, Garcia-Aymerich J, Gehring U, Haider S, Hartl S, Backman H, Holloway JW, Koppelman GH, Lertxundi A, Holmen TL, Lowe L, Mensink-Bout SM, Murray CS, Roberts G, Hedman L, Schlunssen V, Sigsgaard T, Simpson A, Sunyer J, Torrent M, Turner S, Van den Berge M, Vermeulen RCH, Vikjord SAA, Wedzicha JA, van der Zee AHM, Melen Eet al., 2021, Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study, ERJ OPEN RESEARCH, Vol: 7

Journal article

Donaldson GC, Ritchie AI, Calverley PMA, Vestbo J, Fageras M, de la Hoz A, Bucchioni E, Compton CH, Mezzi K, Wedzicha JAet al., 2021, Impact of the UK lockdown on people at risk of COPD., ERJ Open Research, Vol: 7, Pages: 1-4, ISSN: 2312-0541

Journal article

Kamal F, Kumar S, Edwards MR, Veselkov K, Belluomo I, Kebadze T, Romano A, Trujillo-Torralbo M-B, Shahridan Faiez T, Walton R, Ritchie AI, Wiseman DJ, Laponogov I, Donaldson G, Wedzicha JA, Johnston SL, Singanayagam A, Hanna GBet al., 2021, Virus-induced volatile organic compounds are detectable in exhaled breath during pulmonary infection., American Journal of Respiratory and Critical Care Medicine, Vol: 204, Pages: 1075-1085, ISSN: 1073-449X

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation trigger is important to guide appropriate therapy but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection aetiology. METHODS: We used serial sampling within in vitro and in vivo studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas-chromatography mass spectrometry (GC-MS) techniques were used to measure VOC production from infected airway epithelial cell cultures and in exhaled breath samples of healthy subjects experimentally challenged with rhinovirus A16 and COPD subjects with naturally-occurring exacerbations. RESULTS: We identified a novel VOC signature comprising of decane and other related long chain alkane compounds that is induced during rhinovirus infection of cultured airway epithelial cells and is also increased in the exhaled breath of healthy subjects experimentally challenged with rhinovirus and of COPD patients during naturally-occurring viral exacerbations. These compounds correlated with magnitude of anti-viral immune responses, virus burden and exacerbation severity but were not induced by bacterial infection, suggesting they represent a specific virus-inducible signature. CONCLUSION: Our study highlights the potential for measurement of exhaled breath VOCs as rapid, non-invasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.

Journal article

Hoffmann C, Liebers U, Humbsch P, Drozdek M, Bölke G, Hoffmann P, Holzgreve A, Donaldson GC, Witt Cet al., 2021, Erratum to: “An adaptation strategy to urban heat: Hospital rooms with radiant cooling accelerate patient recovery” (ERJ Open Res), ERJ Open Research, Vol: 7

This article was originally published with an error in the key to figure 3. “Radiant cooled room” and “Conventional room” were presented with the incorrect colour codes. The corrected figure is shown below and has been corrected in the published article.

Journal article

Ritchie AI, Baker JR, Parekh TM, Allinson JP, Bhatt SP, Donnelly LE, Donaldson GCet al., 2021, Update in Chronic Obstructive Pulmonary Disease 2020, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 14-22, ISSN: 1073-449X

Journal article

Hoffmann C, Liebers U, Humbsch P, Drozdek M, Bolke G, Hoffmann P, Holzgreve A, Donaldson GC, Witt Cet al., 2021, An adaptation strategy to urban heat: hospital rooms with radiant cooling accelerate patient recovery, ERJ OPEN RESEARCH, Vol: 7

Journal article

Donaldson GC, Ritchie AI, McLean F, King B, Yip K, Beech AS, Bikov A, Jenkins AR, Deans A, Bolton CE, Calverley PM, Choudhury G, McGarvey L, Sapey E, Vestbo J, Wedzicha JAet al., 2021, Impact of the UK lockdown on early COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, Pages: 1-2, ISSN: 1073-449X

INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changesin life-style, including loss or risk to employment and social isolation. We wished to assess how these measuredeffected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: Atenrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history,FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. Duringlock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits.The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, HospitalAnxiety and Depression questionnaire were completed in writing by the participant and returned by post orphotographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLIpredicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increasedfrom 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233; p=0.010) during lock-down; depression scores increased from 4.30(3.9) to 5.14 (SD 4.1; n=233; p<0.001). Anxiety increased in 78/233 and depression in 89/233 participants by 2or more units, 2 units is considered the minimally important (MCID) in bronchiectasis, COPD and ILD (Wynne,2020) Figure 1 shows that during lock-down, the proportion of participants not smoking increased from 31/259(12.0%) to 62/259 (23.9%; p<0.001). In those who continued to smoke, cigarettes per day (p=0.59) and rollingtobacco consumption (g/week) (p=0.92) were unchanged. Participants reported less chronic bronchitis definedas “do you bring up phlegm like this on most da

Conference paper

Singh R, Belchamber K, Fenwick P, Chana K, Donaldson G, Wedzicha J, Barnes P, Donnelly Let al., 2021, Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD, Respiratory Research, Vol: 22, Pages: 1-11, ISSN: 1465-9921

BackgroundLower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.MethodsMonocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.ResultsPhagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.ConclusionImpaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.

Journal article

Gregson FKA, Watson NA, Orton CM, Haddrell AE, McCarthy LP, Finnie TJR, Gent N, Donaldson GC, Shah PL, Calder JD, Bzdek BR, Costello D, Reid JPet al., 2021, Comparing aerosol concentrations and particle size distributions generated by singing, speaking and breathing, Aerosol Science and Technology, Vol: 55, Pages: 681-691, ISSN: 0278-6826

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented shutdown in social and economic activity, with the cultural sector particularly severely affected. Restrictions on musical performances have arisen from a perception that there is a significantly higher risk of aerosol production from singing than speaking, based upon high-profile examples of clusters of COVID-19 following choral rehearsals. However, comparing aerosol generation from different types of vocalization, including singing, across a range of volumes is a rapidly evolving area of research. Here, we measured aerosols from singing, speaking and breathing from a large cohort of 25 professional singers in a range of musical genres in a zero-background environment, allowing unequivocal attribution of aerosol production to specific vocalizations. We do not assess the relative volumes at which people speak and sing. However, both showed steep increases in mass concentration with increase in loudness (spanning a factor of 20–30 across the dynamic range measured, p < 0.001). At the quietest volume (50 to 60 dBA), neither singing (p = 0.19) nor speaking (p = 0.20) were significantly different to breathing. At the loudest volume (90 to 100 dBA), a statistically significant difference (p < 0.001) was observed between singing and speaking, but with singing only generating a factor of between 1.5 and 3.4 more aerosol mass. Guidelines for musical performances should be based on the loudness and duration of the vocalization, the number of participants and the environment in which the activity occurs, rather than the type of vocalization. Mitigations such as the use of amplification and increased attention to ventilation should be employed where practicable.

Journal article

Wang Z, Locantore N, Haldar K, Ramsheh MY, Beech AS, Ma W, Brown JR, Tal-Singer R, Barer MR, Bafadhel M, Donaldson GC, Wedzicha JA, Singh D, Wilkinson TMA, Miller BE, Brightling CEet al., 2020, Inflammatory Endotype Associated Airway Microbiome in COPD Clinical Stability and Exacerbations - A Multi-Cohort Longitudinal Analysis., Am J Respir Crit Care Med

RATIONALE: Understanding the role of airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches. OBJECTIVES: To understand the association of airway microbiome with neutrophilic and eosinophilic COPD at stability and exacerbations. METHODS: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 COPD patients recruited at four UK sites in BEAT-COPD, COPDMAP and AERIS cohorts. The microbiome was analyzed using COPDMAP and AERIS as discovery dataset and BEAT-COPD as validation dataset. RESULTS: The airway microbiome in neutrophilic COPD was heterogeneous with two primary community types differentiated by the predominance of Haemophilus. The Haemophilus-predominant subgroup had elevated sputum IL-1b and TNFa and was relatively stable over time. The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic. Patients in this state at stability were susceptible to greatest microbiome shifts during exacerbations. This subgroup can temporally switch to both neutrophilic-Haemophilus-predominant and eosinophilic states which were otherwise mutually exclusive. Time-series analysis on the microbiome showed the temporal trajectories of Campylobacter and Granulicatella were indicative of intra-patient switches from neutrophilic to eosinophilic inflammation, and in track with patient sputum eosinophilia over time. Network analysis revealed distinct host-microbiome interaction patterns between neutrophilic-Haemophilus-predominant, neutrophilic-balanced-microbiome and eosinophilic subgroups. CONCLUSIONS: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies. Neutrophilic and eosinophilic COPD are inter-changeable in some patients. Monitoring temporal variability of the airway microbiome may track patient inflammatory status ov

Journal article

Beech AS, Lea S, Kolsum U, Wang Z, Miller BE, Donaldson GC, Wedzicha JA, Brightling CE, Singh Det al., 2020, Bacteria and sputum inflammatory cell counts; a COPD cohort analysis, RESPIRATORY RESEARCH, Vol: 21

Journal article

Wiseman DJ, Thwaites RS, Drysdale SB, Janet S, Donaldson GC, Wedzicha JA, Openshaw PJ, RESCEU Investigatorset al., 2020, Immunological and inflammatory biomarkers of susceptibility and severity in adult respiratory syncytial virus infections, Journal of Infectious Diseases, Vol: 222, Pages: S584-S591, ISSN: 0022-1899

BACKGROUND: . Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults. METHODS: A literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946-October 2016. Nine articles were identified plus 9 from other sources. RESULTS: From observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were: (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection. CONCLUSIONS: Factors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed.

Journal article

Nici L, Mammen MJ, Charbek E, Alexander PE, Au DH, Boyd CM, Criner GJ, Donaldson GC, Dreher M, Fan VS, Gershon AS, Han MK, Krishnan JA, Martinez FJ, Meek PM, Morgan M, Polkey M, Puhan MA, Sadatsafavi M, Sin DD, Washko GR, Wedzicha JA, Aaron SDet al., 2020, Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline (vol 201, pg e56, 2020), AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 910-910, ISSN: 1073-449X

Journal article

Ritchie AI, Brill SE, Vlies BH, Finney LJ, Allinson JP, Alves-Moreira L, Wiseman DJ, Walker PP, Baker E, Elkin SL, Mallia P, Law M, Donaldson GC, Calverley PMA, Wedzicha JAet 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.

Journal article

Haldar K, George L, Wang Z, Mistry V, Ramsheh MY, Free RC, John C, Reeve NF, Miller BE, Tal-Singer R, Webb AJ, Brookes AJ, Tobin MD, Singh D, Donaldson GC, Wedzicha JA, Brown JR, Barer MR, Brightling CEet al., 2020, The sputum microbiome is distinct between COPD and health, independent of smoking history, Respiratory Research, Vol: 21, Pages: 1-12, ISSN: 1465-9921

BackgroundAirway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.MethodsWe compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.ResultsIn healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera. Haemophilus formed only 3% of the healthy microbiome. In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively. There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history. Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).ConclusionThe healthy and COPD sputum microbiomes are distinct and independent of smoking history. Our results underline the important role for Gammaproteobacteria in COPD.

Journal article

Harhay MO, Donaldson GC, 2020, Guidance on statistical reporting to help improve your chances of a favorable statistical review, American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1035-1038, ISSN: 1073-449X

Journal article

Leisman DE, Harhay MO, Lederer DJ, Abramson M, Adjei AA, Bakker J, Ballas ZK, Barreiro E, Bell SC, Bellomo R, Bernstein JA, Branson RD, Brusasco V, Chalmers JD, Chokroverty S, Citerio G, Collop NA, Cooke CR, Crapo JD, Donaldson G, Fitzgerald DA, Grainger E, Hale L, Herth FJ, Kochanek PM, Marks G, Moorman JR, Ost DE, Schatz M, Sheikh A, Smyth AR, Stewart I, Stewart PW, Swenson ER, Szymusiak R, Teboul J-L, Vincent J-L, Wedzicha JA, Maslove DMet al., 2020, Development and reporting of prediction models: guidance for authors from editors of respiratory, sleep, and critical care journals, Critical Care Medicine, Vol: 48, Pages: 623-633, ISSN: 0090-3493

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of “modifiable risk factors”, measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

Journal article

Nici L, Mammen MJ, Charbek E, Alexander PE, Au DH, Boyd CM, Criner GJ, Donaldson GC, Dreher M, Fan VS, Gershon AS, Han MK, Krishnan JA, Martinez FJ, Meek PM, Morgan M, Polkey MI, Puhan MA, Sadatsafavi M, Sin DD, Washko GR, Wedzicha JA, Aaron SD, American Thoracic Society Assembly on Clinical Problemset al., 2020, Pharmacologic management of COPD: an official American Thoracic Society clinical practice guideline., American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1-14, ISSN: 1073-449X

BACKGROUND: This document provides clinical recommendations for the pharmacologic treatment of COPD. It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the ATS. METHODS: Comprehensive evidence syntheses were performed on all relevant studies which addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using GRADE. RESULTS: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made six recommendations, listed in full in the document. CONCLUSIONS: The task force made recommendations on the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are under-represented in clinical trials is needed, including studies in COPD patients 80 years of age and older, those with multiple chronic health conditions, and those with a co-diagnosis of COPD and asthma.

Journal article

Hurst JR, Skolnik N, Hansen GJ, Anzueto A, Donaldson GC, Dransfield MT, Varghese Pet al., 2020, Understanding the impact of chronic obstructive pulmonary disease exacerbations on patient health and quality of life, EUROPEAN JOURNAL OF INTERNAL MEDICINE, Vol: 73, Pages: 1-6, ISSN: 0953-6205

Journal article

Long GH, Southworth T, Kolsum U, Donaldson GC, Wedzicha JA, Brightling CE, Singh Det al., 2020, The stability of blood Eosinophils in chronic obstructive pulmonary disease, Respiratory Research, Vol: 21, ISSN: 1465-9921

Blood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD). We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort. Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year. 85.3% of patients with eosinophils < 100 cells/μL had stable counts. The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds.

Journal article

Vlies B, Allinson J, Brill SE, Law M, Burnside G, Finney L, Alves-Moreira L, Baker E, Calverley PM, Donaldson GC, Walker PP, Wedzicha JAet al., 2020, A Randomised Controlled Trial Assessing the Effect of Daily Doxycycline on Exacerbation Rate in Patients with COPD, Virtual International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Donaldson GC, Wiseman DJ, Ritchie AI, Macleod M, Allinson J, Wedzicha JAet al., 2020, Use of a Sample Tracking Log as a Measure of Chronic Bronchitis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

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