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1. Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Author

Evans, RA, Leavy, OC, Richardson, M, Elneima, O, McCauley, HJC, Shikotra, A, Singapuri, A, Sereno, M, Saunders, RM, Harris, VC, Houchen-Wolloff, L, Aul, R, Beirne, P, Bolton, CE, Brown, JS, Choudhury, G, Diar-Bakerly, N, Easom, N, Echevarria, C, Fuld, J, Hart, N, Hurst, J, Jones, MG, Parekh, D, Pfeffer, P, Rahman, NM, Rowland-Jones, SL, Shah, AM, Wootton, DG, Chalder, T, Davies, MJ, De Soyza, A, Geddes, JR, Greenhalf, W, Greening, NJ, Heaney, LG, Heller, S, Howard, LS, Jacob, J, Jenkins, RG, Lord, JM, Man, WD-C, McCann, GP, Neubauer, S, Openshaw, PJM, Porter, JC, Rowland, MJ, Scott, JT, Semple, MG, Singh, SJ, Thomas, DC, Toshner, M, Lewis, KE, Thwaites, RS, Briggs, A, Docherty, AB, Kerr, S, Lone, NI, Quint, J, Sheikh, A, Thorpe, M, Zheng, B, Chalmers, JD, Ho, LP, Horsley, A, Marks, M, Poinasamy, K, Raman, B, Harrison, EM, Wain, LV, Brightling, CE, Abel, K, Adamali, H, Adeloye, D, Adeyemi, O, Adrego, R, Jimenez, LAA, Ahmad, S, Haider, NA, Ahmed, R, Ahwireng, N, Ainsworth, M, Al-Sheklly, B, Alamoudi, A, Ali, M, Aljaroof, M, All, AM, Allan, L, Allen, RJ, Allerton, L, Allsop, L, Almeida, P, Altmann, D, Corral, MA, Amoils, S, Anderson, D, Antoniades, C, Arbane, G, Arias, A, Armour, C, Armstrong, L, Armstrong, N, Arnold, D, Arnold, H, Ashish, A, Ashworth, A, Ashworth, M, Aslani, S, Assefa-Kebede, H, Atkin, C, Atkin, P, Aung, H, Austin, L, Avram, C, Ayoub, A, Babores, M, Baggott, R, Bagshaw, J, Baguley, D, Bailey, L, Baillie, JK, Bain, S, Bakali, M, Bakau, M, Baldry, E, Baldwin, D, Ballard, C, Banerjee, A, Bang, B, Barker, RE, Barman, L, Barratt, S, Barrett, F, Basire, D, Basu, N, Bates, M, Bates, A, Batterham, R, Baxendale, H, Bayes, H, Beadsworth, M, Beckett, P, Beggs, M, Begum, M, Bell, D, Bell, R, Bennett, K, Beranova, E, Bermperi, A, Berridge, A, Berry, C, Betts, S, Bevan, E, Bhui, K, Bingham, M, Birchall, K, Bishop, L, Bisnauthsing, K, Blaikely, J, Bloss, A, Bolger, A, Bonnington, J, Botkai, A, Bourne, C, Bourne, M, Bramham, K, Brear, L, Breen, G, Breeze, J, Bright, E, Brill, S, Brindle, K, Broad, L, Broadley, A, Brookes, C, Broome, M, Brown, A, Brown, J, Brown, M, Brown, V, Brown, CW, Brugha, T, Brunskill, N, Buch, M, Buckley, P, Bularga, A, Bullmore, E, Burden, L, Burdett, T, Burn, D, Burns, G, Burns, A, Busby, J, Butcher, R, Butt, A, Byrne, S, Cairns, P, Calder, PC, Calvelo, E, Carborn, H, Card, B, Carr, C, Carr, L, Carson, G, Carter, P, Casey, A, Cassar, M, Cavanagh, J, Chablani, M, Chambers, RC, Chan, F, Channon, KM, Chapman, K, Charalambou, A, Chaudhuri, N, Checkley, A, Chen, J, Cheng, Y, Chetham, L, Childs, C, Chilvers, ER, Chinoy, H, Chiribiri, A, Chong-James, K, Choudhury, N, Chowienczyk, P, Christie, C, Chrystal, M, Clark, D, Clark, C, Clarke, J, Clohisey, S, Coakley, G, Coburn, Z, Coetzee, S, Cole, J, Coleman, C, Conneh, F, Connell, D, Connolly, B, Connor, L, Cook, A, Cooper, B, Cooper, J, Cooper, S, Copeland, D, Cosier, T, Coulding, M, Coupland, C, Cox, E, Craig, T, Crisp, P, Cristiano, D, Crooks, MG, Cross, A, Cruz, I, Cullinan, P, Cuthbertson, D, Daines, L, Dalton, M, Daly, P, Daniels, A, Dark, P, Dasgin, J, David, A, David, C, Davies, E, Davies, F, Davies, G, Davies, GA, Davies, K, Dawson, J, Daynes, E, Deakin, B, Deans, A, Deas, C, Deery, J, Defres, S, Dell, A, Dempsey, K, Denneny, E, Dennis, J, Dewar, A, Dharmagunawardena, R, Dickens, C, Dipper, A, Diver, S, Diwanji, SN, Dixon, M, Djukanovic, R, Dobson, H, Dobson, SL, Donaldson, A, Dong, T, Dormand, N, Dougherty, A, Dowling, R, Drain, S, Draxlbauer, K, Drury, K, Dulawan, P, Dunleavy, A, Dunn, S, Earley, J, Edwards, S, Edwardson, C, El-Taweel, H, Elliott, A, Elliott, K, Ellis, Y, Elmer, A, Evans, D, Evans, H, Evans, J, Evans, R, Evans, RI, Evans, T, Evenden, C, Evison, L, Fabbri, L, Fairbairn, S, Fairman, A, Fallon, K, Faluyi, D, Favager, C, Fayzan, T, Featherstone, J, Felton, T, Finch, J, Finney, S, Finnigan, J, Finnigan, L, Fisher, H, Fletcher, S, Flockton, R, Flynn, M, Foot, H, Foote, D, Ford, A, Forton, D, Fraile, E, Francis, C, Francis, R, Francis, S, Frankel, A, Fraser, E, Free, R, French, N, Fu, X, Furniss, J, Garner, L, Gautam, N, George, J, George, P, Gibbons, M, Gill, M, Gilmour, L, Gleeson, F, Glossop, J, Glover, S, Goodman, N, Goodwin, C, Gooptu, B, Gordon, H, Gorsuch, T, Greatorex, M, Greenhaff, PL, Greenhalgh, A, Greenwood, J, Gregory, H, Gregory, R, Grieve, D, Griffin, D, Griffiths, L, Guerdette, A-M, Guio, BG, Gummadi, M, Gupta, A, Gurram, S, Guthrie, E, Guy, Z, Henson, HH, Hadley, K, Haggar, A, Hainey, K, Hairsine, B, Haldar, P, Hall, I, Hall, L, Halling-Brown, M, Hamil, R, Hancock, A, Hancock, K, Hanley, NA, Haq, S, Hardwick, HE, Hardy, E, Hardy, T, Hargadon, B, Harrington, K, Harris, E, Harrison, P, Harvey, A, Harvey, M, Harvie, M, Haslam, L, Havinden-Williams, M, Hawkes, J, Hawkings, N, Haworth, J, Hayday, A, Haynes, M, Hazeldine, J, Hazelton, T, Heeley, C, Heeney, JL, Heightman, M, Henderson, M, Hesselden, L, Hewitt, M, Highett, V, Hillman, T, Hiwot, T, Hoare, A, Hoare, M, Hockridge, J, Hogarth, P, Holbourn, A, Holden, S, Holdsworth, L, Holgate, D, Holland, M, Holloway, L, Holmes, K, Holmes, M, Holroyd-Hind, B, Holt, L, Hormis, A, Hosseini, A, Hotopf, M, Howard, K, Howell, A, Hufton, E, Hughes, AD, Hughes, J, Hughes, R, Humphries, A, Huneke, N, Hurditch, E, Husain, M, Hussell, T, Hutchinson, J, Ibrahim, W, Ilyas, F, Ingham, J, Ingram, L, Ionita, D, Isaacs, K, Ismail, K, Jackson, T, James, WY, Jarman, C, Jarrold, I, Jarvis, H, Jastrub, R, Jayaraman, B, Jezzard, P, Jiwa, K, Johnson, C, Johnson, S, Johnston, D, Jolley, CJ, Jones, D, Jones, G, Jones, H, Jones, I, Jones, L, Jones, S, Jose, S, Kabir, T, Kaltsakas, G, Kamwa, V, Kanellakis, N, Kaprowska, S, Kausar, Z, Keenan, N, Kelly, S, Kemp, G, Kerslake, H, Key, AL, Khan, F, Khunti, K, Kilroy, S, King, B, King, C, Kingham, L, Kirk, J, Kitterick, P, Klenerman, P, Knibbs, L, Knight, S, Knighton, A, Kon, O, Kon, S, Kon, SS, Koprowska, S, Korszun, A, Koychev, I, Kurasz, C, Kurupati, P, Laing, C, Lamlum, H, Landers, G, Langenberg, C, Lasserson, D, Lavelle-Langham, L, Lawrie, A, Lawson, C, Layton, A, Lea, A, Lee, D, Lee, J-H, Lee, E, Leitch, K, Lenagh, R, Lewis, D, Lewis, J, Lewis, V, Lewis-Burke, N, Li, X, Light, T, Lightstone, L, Lilaonitkul, W, Lim, L, Linford, S, Lingford-Hughes, A, Lipman, M, Liyanage, K, Lloyd, A, Logan, S, Lomas, D, Loosley, R, Lota, H, Lovegrove, W, Lucey, A, Lukaschuk, E, Lye, A, Lynch, C, MacDonald, S, MacGowan, G, Macharia, I, Mackie, J, Macliver, L, Madathil, S, Madzamba, G, Magee, N, Magtoto, MM, Mairs, N, Majeed, N, Major, E, Malein, F, Malim, M, Mallison, G, Mandal, S, Mangion, K, Manisty, C, Manley, R, March, K, Marciniak, S, Marino, P, Mariveles, M, Marouzet, E, Marsh, S, Marshall, B, Marshall, M, Martin, J, Martineau, A, Martinez, LM, Maskell, N, Matila, D, Matimba-Mupaya, W, Matthews, L, Mbuyisa, A, McAdoo, S, McCall, JW, McAllister-Williams, H, McArdle, A, McArdle, P, McAulay, D, McCormick, J, McCormick, W, McCourt, P, McGarvey, L, McGee, C, Mcgee, K, McGinness, J, McGlynn, K, McGovern, A, McGuinness, H, McInnes, IB, McIntosh, J, McIvor, E, McIvor, K, McLeavey, L, McMahon, A, McMahon, MJ, McMorrow, L, Mcnally, T, McNarry, M, McNeill, J, McQueen, A, McShane, H, Mears, C, Megson, C, Megson, S, Mehta, P, Meiring, J, Melling, L, Mencias, M, Menzies, D, Morillas, MM, Michael, A, Milligan, L, Miller, C, Mills, C, Mills, NL, Milner, L, Misra, S, Mitchell, J, Mohamed, A, Mohamed, N, Mohammed, S, Molyneaux, PL, Monteiro, W, Moriera, S, Morley, A, Morrison, L, Morriss, R, Morrow, A, Moss, AJ, Moss, P, Motohashi, K, Msimanga, N, Mukaetova-Ladinska, E, Munawar, U, Murira, J, Nanda, U, Nassa, H, Nasseri, M, Neal, A, Needham, R, Neill, P, Newell, H, Newman, T, Newton-Cox, A, Nicholson, T, Nicoll, D, Nolan, CM, Noonan, MJ, Norman, C, Novotny, P, Nunag, J, Nwafor, L, Nwanguma, U, Nyaboko, J, O'Donnell, K, O'Brien, C, O'Brien, L, O'Regan, D, Odell, N, Ogg, G, Olaosebikan, O, Oliver, C, Omar, Z, Orriss-Dib, L, Osborne, L, Osbourne, R, Ostermann, M, Overton, C, Owen, J, Oxton, J, Pack, J, Pacpaco, E, Paddick, S, Painter, S, Pakzad, A, Palmer, S, Papineni, P, Paques, K, Paradowski, K, Pareek, M, Parfrey, H, Pariante, C, Parker, S, Parkes, M, Parmar, J, Patale, S, Patel, B, Patel, M, Patel, S, Pattenadk, D, Pavlides, M, Payne, S, Pearce, L, Pearl, JE, Peckham, D, Pendlebury, J, Peng, Y, Pennington, C, Peralta, I, Perkins, E, Peterkin, Z, Peto, T, Petousi, N, Petrie, J, Phipps, J, Pimm, J, Hanley, KP, Pius, R, Plant, H, Plein, S, Plekhanova, T, Plowright, M, Polgar, O, Poll, L, Porter, J, Portukhay, S, Powell, N, Prabhu, A, Pratt, J, Price, A, Price, C, Price, D, Price, L, Prickett, A, Propescu, J, Pugmire, S, Quaid, S, Quigley, J, Qureshi, H, Qureshi, IN, Radhakrishnan, K, Ralser, M, Ramos, A, Ramos, H, Rangeley, J, Rangelov, B, Ratcliffe, L, Ravencroft, P, Reddington, A, Reddy, R, Redfearn, H, Redwood, D, Reed, A, Rees, M, Rees, T, Regan, K, Reynolds, W, Ribeiro, C, Richards, A, Richardson, E, Rivera-Ortega, P, Roberts, K, Robertson, E, Robinson, E, Robinson, L, Roche, L, Roddis, C, Rodger, J, Ross, A, Ross, G, Rossdale, J, Rostron, A, Rowe, A, Rowland, A, Rowland, J, Roy, K, Roy, M, Rudan, I, Russell, R, Russell, E, Saalmink, G, Sabit, R, Sage, EK, Samakomva, T, Samani, N, Sampson, C, Samuel, K, Samuel, R, Sanderson, A, Sapey, E, Saralaya, D, Sargant, J, Sarginson, C, Sass, T, Sattar, N, Saunders, K, Saunders, P, Saunders, LC, Savill, H, Saxon, W, Sayer, A, Schronce, J, Schwaeble, W, Scott, K, Selby, N, Sewell, TA, Shah, K, Shah, P, Shankar-Hari, M, Sharma, M, Sharpe, C, Sharpe, M, Shashaa, S, Shaw, A, Shaw, K, Shaw, V, Shelton, S, Shenton, L, Shevket, K, Short, J, Siddique, S, Siddiqui, S, Sidebottom, J, Sigfrid, L, Simons, G, Simpson, J, Simpson, N, Singh, C, Singh, S, Sissons, D, Skeemer, J, Slack, K, Smith, A, Smith, D, Smith, S, Smith, J, Smith, L, Soares, M, Solano, TS, Solly, R, Solstice, AR, Soulsby, T, Southern, D, Sowter, D, Spears, M, Spencer, LG, Speranza, F, Stadon, L, Stanel, S, Steele, N, Steiner, M, Stensel, D, Stephens, G, Stephenson, L, Stern, M, Stewart, I, Stimpson, R, Stockdale, S, Stockley, J, Stoker, W, Stone, R, Storrar, W, Storrie, A, Storton, K, Stringer, E, Strong-Sheldrake, S, Stroud, N, Subbe, C, Sudlow, CL, Suleiman, Z, Summers, C, Summersgill, C, Sutherland, D, Sykes, DL, Sykes, R, Talbot, N, Tan, AL, Tarusan, L, Tavoukjian, V, Taylor, A, Taylor, C, Taylor, J, Te, A, Tedd, H, Tee, CJ, Teixeira, J, Tench, H, Terry, S, Thackray-Nocera, S, Thaivalappil, F, Thamu, B, Thickett, D, Thomas, C, Thomas, S, Thomas, AK, Thomas-Woods, T, Thompson, T, Thompson, AAR, Thornton, T, Tilley, J, Tinker, N, Tiongson, GF, Tobin, M, Tomlinson, J, Tong, C, Touyz, R, Tripp, KA, Tunnicliffe, E, Turnbull, A, Turner, E, Turner, S, Turner, V, Turner, K, Turney, S, Turtle, L, Turton, H, Ugoji, J, Ugwuoke, R, Upthegrove, R, Valabhji, J, Ventura, M, Vere, J, Vickers, C, Vinson, B, Wade, E, Wade, P, Wainwright, T, Wajero, LO, Walder, S, Walker, S, Wall, E, Wallis, T, Walmsley, S, Walsh, JA, Walsh, S, Warburton, L, Ward, TJC, Warwick, K, Wassall, H, Waterson, S, Watson, E, Watson, L, Watson, J, Welch, C, Welch, H, Welsh, B, Wessely, S, West, S, Weston, H, Wheeler, H, White, S, Whitehead, V, Whitney, J, Whittaker, S, Whittam, B, Whitworth, V, Wight, A, Wild, J, Wilkins, M, Wilkinson, D, Williams, N, Williams, J, Williams-Howard, SA, Willicombe, M, Willis, G, Willoughby, J, Wilson, A, Wilson, D, Wilson, I, Window, N, Witham, M, Wolf-Roberts, R, Wood, C, Woodhead, F, Woods, J, Wormleighton, J, Worsley, J, Wraith, D, Wright, C, Wright, L, Wright, S, Wyles, J, Wynter, I, Xu, M, Yasmin, N, Yasmin, S, Yates, T, Yip, KP, Young, B, Young, S, Young, A, Yousuf, AJ, Zawia, A, Zeidan, L, Zhao, B, Zongo, O, Group, The PHOSP-COVID Collaborative, National Institute for Health Research, and UKRI MRC COVID-19 Rapid Response Call

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Adolescent, PHOSP-COVID Collaborative Group, 1117 Public Health and Health Services, Post-Acute COVID-19 Syndrome, SDG 3 - Good Health and Well-being, Humans, Longitudinal Studies, Obesity, Prospective Studies, long COVID, Retrospective Studies, Inflammation, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, Middle Aged, prospective observational study, United Kingdom, Hospitalization, Quality of Life, Female, 1199 Other Medical and Health Sciences
Abstract

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research.

Published
2022
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2. Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19

Author

Daines, L, Zheng, B, Elneima, O, Harrison, E, Lone, NI, Hurst, JR, Brown, JS, Sapey, E, Chalmers, JD, Quint, JK, Pfeffer, P, Siddiqui, S, Walker, S, Poinasamy, K, McAuley, H, Sereno, M, Shikotra, A, Singapuri, A, Docherty, AB, Marks, M, Toshner, M, Howard, LS, Horsley, A, Jenkins, G, Porter, JC, Ho, L-P, Raman, B, Wain, LV, Brightling, CE, Evans, RA, Heaney, LG, De Soyza, A, Sheikh, A, Daines, Luke [0000-0003-0564-4000], Lone, Nazir I [0000-0003-2707-2779], Hurst, John R [0000-0002-7246-6040], Sapey, Elizabeth [0000-0003-3454-5482], Quint, Jennifer K [0000-0003-0149-4869], McAuley, Hamish [0000-0001-8997-0764], Marks, Michael [0000-0002-7585-4743], Toshner, Mark [0000-0002-3969-6143], Howard, Luke S [0000-0003-2822-210X], Horsley, Alex [0000-0003-1828-0058], Porter, Joanna C [0000-0002-7307-169X], Raman, Betty [0000-0002-1239-9608], Wain, Louise V [0000-0003-4951-1867], Evans, Rachael A [0000-0002-1667-868X], De Soyza, Anthony [0000-0002-8566-0344], and Apollo - University of Cambridge Repository

Subjects
Pulmonary and Respiratory Medicine, Mental Health, Clinical Research, Behavioral and Social Science, Respiratory, 32 Biomedical and Clinical Sciences, 3 Good Health and Well Being, 3202 Clinical Sciences, Respiratory infections and tuberculosis, Brain Disorders
Abstract

Funder: UK Health Data Research BREATHE Hub, BACKGROUND: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. METHODS: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. RESULTS: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). CONCLUSIONS: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

Published
2023
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3. Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Author

Zheng, B, Vivaldi, G, Daines, L, Leavy, OC, Richardson, M, Elneima, O, McAuley, HJC, Shikotra, A, Singapuri, A, Sereno, M, Saunders, RM, Harris, VC, Houchen-Wolloff, L, Greening, NJ, Pfeffer, PE, Hurst, JR, Brown, JS, Shankar-Hari, M, Echevarria, C, De Soyza, A, Harrison, EM, Docherty, AB, Lone, N, Quint, JK, Chalmers, JD, Ho, LP, Horsley, A, Marks, M, Poinasamy, K, Raman, B, Heaney, LG, Wain, LV, Evans, RA, Brightling, CE, Martineau, A, Sheikh, A, and Group, The PHOSP-COVID Study Collaborative

Subjects
Model organisms, Chemical Biology & High Throughput, Human Biology & Physiology, Metabolism, Ecology,Evolution & Ethology, FOS: Clinical medicine, Immunology, Synthetic Biology, Computational & Systems Biology
Abstract

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders.

Published
2023
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4. S43 Results from the STAR-COVID19 trial, a double-blind RCT of stabilised, synthetic sulforaphane in hospitalised patients with suspected COVID19

Author

Long, MB, primary, Abo-Leyah, H, additional, Giam, YH, additional, Vadiveloo, T, additional, Hull, RC, additional, Keir, HR, additional, Pembridge, T, additional, Alferes de Lima, D, additional, New, BJM, additional, Inglis, S, additional, Gilmour, A, additional, Hughes, C, additional, Delgado, L, additional, MacLennan, G, additional, Dinkova-Kostova, AT, additional, and Chalmers, JD, additional

Published
2022
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5. T3 Altered neutrophil proteomes in COVID19 patients 29-days post hospital admission are associated with delayed recovery: results from the PREDICT-COVID19 study

Author

Long, MB, primary, Brenes, AJ, additional, Howden, AJM, additional, Keir, HR, additional, Rollings, C, additional, Giam, YH, additional, Pembridge, T, additional, Delgado, L, additional, Abo-Leyah, H, additional, Lloyd, A, additional, Sollberger, G, additional, Hull, RC, additional, Gilmour, A, additional, Hughes, C, additional, Gallant, S, additional, Cassidy, DM, additional, New, BJM, additional, Connell, D, additional, Richardson, H, additional, Shoemark, A, additional, Lamond, AI, additional, Cantrell, DA, additional, and Chalmers, JD, additional

Published
2022
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7. Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study

Author

Plekhanova, T, Rowlands, A, Evans, RA, Edwardson, CL, Bishop, NC, Bolton, CE, Chalmers, JD, Davies, MJ, Daynes, E, Dempsey, PC, Docherty, AB, Elneima, O, Greening, NJ, Greenwood, SA, Hall, AP, Harris, VC, Harrison, EM, Henson, J, Ho, L-P, Horsley, A, Houchen-Wolloff, L, Khunti, K, Leavy, OC, Lone, N, Marks, M, Maylor, B, McAuley, HJC, Nolan, CM, Poinasamy, K, Quint, JK, Raman, B, Richardson, M, Sargeant, JA, Saunders, RM, Sereno, M, Shikotra, A, Singapuri, A, Steiner, M, Stensel, DJ, Wain, L, Whitney, J, Wootton, DG, Brightling, CE, Man, WD-C, Singh, SJ, Yates, T, Plekhanova, T, Rowlands, A, Evans, RA, Edwardson, CL, Bishop, NC, Bolton, CE, Chalmers, JD, Davies, MJ, Daynes, E, Dempsey, PC, Docherty, AB, Elneima, O, Greening, NJ, Greenwood, SA, Hall, AP, Harris, VC, Harrison, EM, Henson, J, Ho, L-P, Horsley, A, Houchen-Wolloff, L, Khunti, K, Leavy, OC, Lone, N, Marks, M, Maylor, B, McAuley, HJC, Nolan, CM, Poinasamy, K, Quint, JK, Raman, B, Richardson, M, Sargeant, JA, Saunders, RM, Sereno, M, Shikotra, A, Singapuri, A, Steiner, M, Stensel, DJ, Wain, L, Whitney, J, Wootton, DG, Brightling, CE, Man, WD-C, Singh, SJ, and Yates, T

Abstract

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of p

Published
2022

8. Neisseria species as pathobionts in bronchiectasis.

Author

Li, L, Mac Aogáin, M, Xu, T, Jaggi, TK, Chan, LLY, Qu, J, Wei, L, Liao, S, Cheng, HS, Keir, HR, Dicker, AJ, Tan, KS, De Yun, W, Koh, MS, Ong, TH, Lim, AYH, Abisheganaden, JA, Low, TB, Hassan, TM, Long, X, Wark, PAB, Oliver, B, Drautz-Moses, DI, Schuster, SC, Tan, NS, Fang, M, Chalmers, JD, Chotirmall, SH, Li, L, Mac Aogáin, M, Xu, T, Jaggi, TK, Chan, LLY, Qu, J, Wei, L, Liao, S, Cheng, HS, Keir, HR, Dicker, AJ, Tan, KS, De Yun, W, Koh, MS, Ong, TH, Lim, AYH, Abisheganaden, JA, Low, TB, Hassan, TM, Long, X, Wark, PAB, Oliver, B, Drautz-Moses, DI, Schuster, SC, Tan, NS, Fang, M, Chalmers, JD, and Chotirmall, SH

Abstract

Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.

Published
2022

9. Therapeutic Targeting of the Respiratory Microbiome.

Author

Chotirmall, SH, Bogaert, D, Chalmers, JD, Cox, MJ, Hansbro, PM, Huang, YJ, Molyneaux, PL, O'Dwyer, DN, Pragman, AA, Rogers, GB, Segal, LN, Dickson, RP, Chotirmall, SH, Bogaert, D, Chalmers, JD, Cox, MJ, Hansbro, PM, Huang, YJ, Molyneaux, PL, O'Dwyer, DN, Pragman, AA, Rogers, GB, Segal, LN, and Dickson, RP

Published
2022

12. P93 Comparison of inflammatory profiles between COVID-19 and other acute lower respiratory tract infections: Results from the PREDICT-COVID19 study

Author

Keir, HR, primary, Long, MB, additional, Giam, YH, additional, Leyah, HA, additional, Pembridge, T, additional, Delgado, L, additional, Hull, R, additional, Hughes, C, additional, Gilmour, A, additional, Hocking, C, additional, New, BJM, additional, Connell, D, additional, Richardson, H, additional, Cassidy, D, additional, Shoemark, A, additional, and Chalmers, JD, additional

Published
2021
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13. S69 Inflammatory biomarkers predict clinical outcomes in patients with COVID-19 infection: results from the PREDICT-COVID19 study

Author

Long, MB, primary, Keir, HR, additional, Giam, YH, additional, Abo Leyah, H, additional, Pembridge, T, additional, Delgado, L, additional, Hull, R, additional, Gilmour, A, additional, Hughes, C, additional, Hocking, C, additional, New, BJM, additional, Connell, D, additional, Richardson, H, additional, Cassidy, DM, additional, Shoemark, A, additional, and Chalmers, JD, additional

Published
2021
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14. S55 Persistent changes to the nasal ciliated epithelium following SARS-CoV2 infection: a longitudinal cohort analysis from FOLLOW-COVID

Author

Shoemark, A, primary, Bottier, M, additional, Pinto, A, additional, Delgado, L, additional, Abo-Leyah, H, additional, Rai, R, additional, Parcell, B, additional, Hocking, C, additional, Hogg, C, additional, Dicker, A, additional, Khan, F, additional, Gallant, S, additional, Cassidy, DM, additional, Connell, D, additional, and Chalmers, JD, additional

Published
2021
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16. ROSE: radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Author

Traversi L, Miravitlles M, Martinez-Garcia MA, Shteinberg M, Bossios A, Dimakou K, Jacob J, Hurst JR, Paggiaro PL, Ferri S, Hillas G, Vogel-Claussen J, Dettmer S, Aliberti S, Chalmers JD, and Polverino E

Subjects
RISK-FACTOR, MORTALITY, FREQUENT EXACERBATOR PHENOTYPE, CYSTIC FIBROSIS BRONCHIECTASIS, COHORT, ADULT PATIENTS
Abstract

INTRODUCTION: The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. METHODS: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the "COPD- [bronchiectasis] BE association".A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of =6 points (scale 0 to 9) in =70% of answers across two scoring rounds. RESULTS: 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of "COPD-BE association" was: "The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in =1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV(1)/[forced vital capacity] FVC

Published
2021

17. Integrative microbiomics in bronchiectasis exacerbations

Author

Mac Aogáin, M, Narayana, JK, Tiew, PY, Ali, NABM, Yong, VFL, Jaggi, TK, Lim, AYH, Keir, HR, Dicker, AJ, Thng, KX, Tsang, A, Ivan, FX, Poh, ME, Oriano, M, Aliberti, S, Blasi, F, Low, TB, Ong, TH, Oliver, B, Giam, YH, Tee, A, Koh, MS, Abisheganaden, JA, Tsaneva-Atanasova, K, Chalmers, JD, Chotirmall, SH, Mac Aogáin, M, Narayana, JK, Tiew, PY, Ali, NABM, Yong, VFL, Jaggi, TK, Lim, AYH, Keir, HR, Dicker, AJ, Thng, KX, Tsang, A, Ivan, FX, Poh, ME, Oriano, M, Aliberti, S, Blasi, F, Low, TB, Ong, TH, Oliver, B, Giam, YH, Tee, A, Koh, MS, Abisheganaden, JA, Tsaneva-Atanasova, K, Chalmers, JD, and Chotirmall, SH

Abstract

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.

Published
2021

18. Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: IBEST study

Author

Loebinger, MR, Polverino, E, Chalmers, JD, Tiddens, H.A.W.M., Goossens, H, Tunney, M, Ringshausen, FC, Hill, AT, Pathan, R, Angyalosi, G, Blasi, F, Elborn, SJ, Haworth, CS, Loebinger, MR, Polverino, E, Chalmers, JD, Tiddens, H.A.W.M., Goossens, H, Tunney, M, Ringshausen, FC, Hill, AT, Pathan, R, Angyalosi, G, Blasi, F, Elborn, SJ, and Haworth, CS

Abstract

The study aimed to determine the efficacy of a safe and well-Tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis. This is a phase II, double-blind, randomised study in bronchiectasis patients aged 18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: Three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively and were followed up for 8 weeks. Overall, 107 patients were randomised to cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the P. aeruginosa sputum density from baseline to day 29 versus placebo in a dosedependent manner (p 0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous TIP and 42.9% on cyclical TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of bronchiectasis was the most frequent (37.4%) adverse event. Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to adverse events. Continuous-and cyclical-TIP regimens with all three doses were safe and effective in reducing the P. aeruginosa sputum density in patients with bronchiectasis and chronic P. aeruginosa infection.

Published
2021

20. Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals

Author

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, DM, 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, and Maslove, DM

Abstract

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.

Published
2020

21. Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues

Author

Davies, KA, Fitzgibbon, C, Young, SN, Garnish, SE, Yeung, W, Coursier, D, Birkinshaw, RW, Sandow, JJ, Lehmann, WIL, Liang, L-Y, Lucet, IS, Chalmers, JD, Patrick, WM, Kannan, N, Petrie, EJ, Czabotar, PE, Murphy, JM, Davies, KA, Fitzgibbon, C, Young, SN, Garnish, SE, Yeung, W, Coursier, D, Birkinshaw, RW, Sandow, JJ, Lehmann, WIL, Liang, L-Y, Lucet, IS, Chalmers, JD, Patrick, WM, Kannan, N, Petrie, EJ, Czabotar, PE, and Murphy, JM

Abstract

The MLKL pseudokinase is the terminal effector in the necroptosis cell death pathway. Phosphorylation by its upstream regulator, RIPK3, triggers MLKL's conversion from a dormant cytoplasmic protein into oligomers that translocate to, and permeabilize, the plasma membrane to kill cells. The precise mechanisms underlying these processes are incompletely understood, and were proposed to differ between mouse and human cells. Here, we examine the divergence of activation mechanisms among nine vertebrate MLKL orthologues, revealing remarkable specificity of mouse and human RIPK3 for MLKL orthologues. Pig MLKL can restore necroptotic signaling in human cells; while horse and pig, but not rat, MLKL can reconstitute the mouse pathway. This selectivity can be rationalized from the distinct conformations observed in the crystal structures of horse and rat MLKL pseudokinase domains. These studies identify important differences in necroptotic signaling between species, and suggest that, more broadly, divergent regulatory mechanisms may exist among orthologous pseudoenzymes.

Published
2020

22. T6 Sputum proteomics identifies mechanisms of disease severity and treatment response in bronchiectasis

Author

Keir, HR, primary, Shoemark, A, additional, Crichton, ML, additional, Dicker, A, additional, Pollock, J, additional, Giam, A, additional, Cassidy, A, additional, Fong, C, additional, Finch, S, additional, Furrie, E, additional, Suarez-Cuartin, G, additional, Fardon, TC, additional, Einarsson, G, additional, Elborn, JS, additional, Aliberti, S, additional, Sibila, O, additional, Huang, J, additional, and Chalmers, JD, additional

Published
2021
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25. A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

Author

Shoemark, A, Cant, E, Carreto, L, Smith, A, Oriano, M, Keir, HR, Perea, L, Canto, E, Terranova, L, Vidal, S, Moffitt, K, Aliberti, S, Sibila, O, and Chalmers, JD

Abstract

Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik (R)) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk. Methods: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik (R), which scores neutrophil elastase concentration from 0 (6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy. Measurements and main results: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 (p=0.02). A high NEATstik (R) grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p

Published
2019

26. British Thoracic Society guideline for bronchiectasis in adults (BMJ Open)

Author

Hill, AT, Sullivan, AL, Chalmers, JD, De Soyza, A, Elborn, JS, Floto, RA, Grillo, L, Gruffydd-Jones, K, Harvey, A, Haworth, CS, Hiscocks, E, Hurst, JR, Johnson, C, Kelleher, WP, Bedi, P, Payne, K, Saleh, H, Screaton, NJ, Smith, M, Tunney, M, Whitters, D, Wilson, R, and Loebinger, MR

Abstract

Copyright information: © Author(s) (or their employer(s)) 2018. The full British Thoracic Society Guideline for Bronchiectasis in Adults is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline.

Published
2018

27. The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions

Author

Polverino, E, Dimakou, K, Hurst, J, Martinez-Garcia, MA, Miravitlles, M, Paggiaro, P, Shteinberg, M, Aliberti, S, and Chalmers, JD

Subjects
respiratory system, respiratory tract diseases
Abstract

Bronchiectasis is a clinical and radiological diagnosis associated with cough, sputum production and recurrent respiratory infections. The clinical presentation inevitably overlaps with other respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). In addition, 4-72% of patients with severe COPD are found to have radiological bronchiectasis on computed tomography, with similar frequencies (20-30%) now being reported in cohorts with severe or uncontrolled asthma. Co-diagnosis of bronchiectasis with another airway disease is associated with increased lung inflammation, frequent exacerbations, worse lung function and higher mortality. In addition, many patients with all three disorders have chronic rhinosinusitis and upper airway disease, resulting in a complex "mixed airway" phenotype. The management of asthma, bronchiectasis, COPD and upper airway diseases has traditionally been outlined in separate guidelines for each individual disorder. Recognition that the majority of patients have one or more overlapping pathologies requires that we re-evaluate how we treat airway disease. The concept of treatable traits promotes a holistic, pathophysiology-based approach to treatment rather than a syndromic approach and may be more appropriate for patients with overlapping features. Here, we review the current clinical definition, diagnosis, management and future directions for the overlap between bronchiectasis and other airway diseases.

Published
2018

28. The Severe Paediatric Asthma Collaborative in Europe (SPACE) ERS Clinical Research Collaboration: enhancing participation of children with asthma in therapeutic trials of new biologics and receptor blockers

Author

Grigg, J, Rusconi, F, van Aalderen, W, Rutjes, Nwp, Carlsen, Kcl, Coleman, C, Chalmers, Jd, Cunningham, S, Fernandes, Rm, Fleming, Lj, Frankemölle, B, Gappa, M, Karadag, B, Liu, Nm, Midulla, F, Pijnenburg, MARIA WILHELMINA HELENA, Pediatrics, Paediatric Pulmonology, Graduate School, APH - Personalized Medicine, AII - Inflammatory diseases, and AII - Amsterdam institute for Infection and Immunity

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Severe asthma, MEDLINE, macromolecular substances, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Professional-Family Relations, immune system diseases, medicine, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Patient participation, Child, Intensive care medicine, Asthma, Biological Products, business.industry, musculoskeletal, neural, and ocular physiology, medicine.disease, Therapeutic trial, respiratory tract diseases, Europe, Clinical research, Paediatric asthma, nervous system, 030228 respiratory system, Quality of Life, Patient Compliance, Patient Participation, problematic severe asthma, childhood, definition, features, burden, business
Abstract

The Severe Paediatric Asthma Collaborative in Europe (SPACE) ERS Clinical Research Collaboration is devoted to describing phenotypes of children with severe asthma and to enhancing their participation in therapeutic trials of new drugs http://ow.ly/zxgB30m01zR

Published
2018

33. M26 Convergent validity of bronchiectasis quality of life tools in the BRONCH-UK registry

Author

Brown, J, primary, Bradley, J, additional, Copeland, F, additional, Carroll, M, additional, Crichton, M, additional, Duckers, J, additional, Haworth, C, additional, Floto, RA, additional, Hill, AT, additional, Loebinger, M, additional, Wilson, R, additional, Hurst, J, additional, Cookson, W, additional, Winstanley, C, additional, McGuire, A, additional, McNally, R, additional, Mawson, P, additional, Kelleher, P, additional, Denning, D, additional, Navaratnam, V, additional, Hubbard, R, additional, Kelly, M, additional, Steer, J, additional, Sullivan, A, additional, Gatheral, T, additional, Walker, P, additional, Elborn, JS, additional, Chalmers, JD, additional, and De Soyza, A, additional

Published
2019
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36. M27 Bronchiectasis multicentre cohort; baseline demographics from BRONCHUK

Author

Brown, J, primary, Bradley, J, additional, Copeland, F, additional, Carroll, M, additional, Crichton, M, additional, Duckers, J, additional, Haworth, C, additional, Floto, RA, additional, Hill, AT, additional, Loebinger, M, additional, Wilson, R, additional, Hurst, J, additional, Cookson, W, additional, Winstanley, C, additional, McGuire, A, additional, McNally, R, additional, Mawson, P, additional, Kelleher, P, additional, Denning, D, additional, Navaratnam, V, additional, Hubbard, R, additional, Kelly, M, additional, Steer, J, additional, Sullivan, A, additional, Gatheral, T, additional, Walker, P, additional, Elborn, JS, additional, Chalmers, JD, additional, and De Soyza, A, additional

Published
2019
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37. Severe Paediatric Asthma Collaborative in Europe (SPACE): protocol for a European registry

Author

Liu, NM, van Aalderen, W, Carlsen, KCL, Coleman, C, Chalmers, JD, Cunningham, S, Fernandes, RM, Fleming, LJ, Gappa, M, Karadag, B, Midulla, F, Pijnenburg, Marielle, Rutjes, NW, Rusconi, F, Grigg, J, Liu, NM, van Aalderen, W, Carlsen, KCL, Coleman, C, Chalmers, JD, Cunningham, S, Fernandes, RM, Fleming, LJ, Gappa, M, Karadag, B, Midulla, F, Pijnenburg, Marielle, Rutjes, NW, Rusconi, F, and Grigg, J

Published
2018

38. The microbiome in respiratory medicine: current challenges and future perspectives

Author

Faner, R, Sibila, O, Agusti, A, Bernasconi, E, Chalmers, JD, Huffnagle, GB, Manichanh, C, Molyneaux, PL, Paredes, R, Brocal, VP, Ponomarenko, J, Sethi, S, Dorca, J, and Monso, E

Abstract

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.

Published
2017

39. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research

Author

Hill, AT, Haworth, CS, Aliberti, S, Barker, A, Blasi, F, Boersma, W, Chalmers, JD, De Soyza, A, Dimakou, K, Elborn, JS, Feldman, C, Flume, P, Goeminne, PC, Loebinger, MR, Menendez, R, Morgan, L, Murris, M, Polverino, E, Quittner, A, Ringshausen, FC, Tino, G, Torres, A, Vendrell, M, Welte, T, Wilson, R, Wong, C, O'Donnell, A, Aksamit, T, and EMBARC/BRR definitions working group

Abstract

There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research. A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa. The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required. The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.

Published
2017

43. Diagnostic challenges of bronchiectasis

Author

Suarez-Cuartin, G, Chalmers, JD, and Sibila, O

Abstract

Bronchiectasis is a condition of increasing incidence and prevalence around the world. Many different diseases have been associated with bronchiectasis, and their treatment can differ widely. Recent guidelines have helped to approach aetiological diagnosis but it is still a complex process. Identifying the cause of the bronchiectasis may determine a change in the treatment of a large group of subjects. That is one of the main reasons why the aetiological diagnosis is crucial in the proper management of bronchiectasis patients. Postinfectious bronchiectasis is the most frequent entity among different studies, but a high percentage of cases still remain without a clear aetiology. Bronchiectasis related to allergic bronchopulmonary aspergillosis (ABPA), immunodeficiencies with antibody production deficiency, primary ciliary dyskinesia, cystic fibrosis and alpha-1-antitrypsin deficiency, among others, require a specific management that may improve quality of life and prognosis in a large group of individuals. Therefore, the aim of this article is to review the main bronchiectasis related diseases and to simplify the aetiological diagnosis, in order to improve the management of bronchiectasis patients, especially in those where a specific treatment is available. (C) 2016 Elsevier Ltd. All rights reserved.

Published
2016

44. Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration

Author

Aliberti S, Masefield S, Polverino E, De Soyza A, Loebinger MR, Menendez R, Ringshausen FC, Vendrell M, Powell P, Chalmers JD, and EMBARC Study Group

Abstract

Bronchiectasis is a disease of renewed interest in light of an increase in prevalence and increasing burden on international healthcare systems. There are no licensed therapies, and large gaps in knowledge in terms of epidemiology, pathophysiology and therapy. The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration, funded by ERS to promote high-quality research in bronchiectasis. The objective of this consensus statement was to define research priorities in bronchiectasis. From 2014 to 2015, EMBARC used a modified Delphi process among European bronchiectasis experts to reach a consensus on 55 key research priorities in this field. During the same period, the European Lung Foundation collected 711 questionnaires from adult patients with bronchiectasis and their carers from 22 European countries reporting important research priorities from their perspective. This consensus statement reports recommendations for bronchiectasis research after integrating both physicians and patients priorities, as well as those uniquely identified by the two groups. Priorities identified in this consensus statement provide the clearest possible roadmap towards improving our understanding of the disease and the quality of care for patients with bronchiectasis.

Published
2016

45. Pseudomonas aeruginosa resistance patterns and clinical outcomes in hospitalized exacerbations of COPD

Author

Rodrigo-Troyano, A, Suarez-Cuartin, G, Peiro, M, Barril, S, Castillo, D, Sanchez-Reus, F, Plaza, V, Restrepo, MI, Chalmers, JD, and Sibila, O

Subjects
exacerbation, Pseudomonas aeruginosa, COPD
Abstract

Background and objectiveAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance. MethodsThis was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013-2014. PA was defined as resistant (PA-R) when the antibiogram showed 1 resistance. ResultsFour hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P=0.03) and antibiotics (77% vs 31%, P=0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14-69.56, P=0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33-37.89, P=0.02), respectively. ConclusionPseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections. Pseudomonas aeruginosa (PA) plays an important role in AECOPD. However, the impact of PA resistance patterns on clinical outcomes is not clear. Our study demonstrates that the presence of PA-sensitive is associated with higher mortality.

Published
2016

47. Secreted mucins and airway bacterial colonization in non-CF bronchiectasis

Author

Sibila, O, Suarez-Cuartin, G, Rodrigo-Troyano, A, Fardon, TC, Finch, S, Mateus, EF, Garcia-Bellmunt, L, Castillo, D, Vidal, S, Sanchez-Reus, F, Restrepo, MI, and Chalmers, JD

Subjects
bronchial colonization, mucin, bronchiectasis, lung defense mechanism
Abstract

Background and objective: Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Methods: Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results: A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions: Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.

Published
2015

50. Characterization of bronchiectasis in the elderly

Author

Bellelli, G, primary, Chalmers, JD, additional, Sotgiu, G, additional, Dore, S, additional, McDonnell, MJ, additional, Goeminne, PC, additional, Dimakou, K, additional, Skrbic, D, additional, Lombi, A, additional, Pane, F, additional, Obradovic, D, additional, Fardon, TC, additional, Rutherford, RM, additional, Pesci, A, additional, and Aliberti, S, additional

Published
2016
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