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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. 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

4. 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

5. 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

6. POSA59 Using Disease Registries for Cost of Illness Studies: The European Bronchiectasis Registry Case

Author: Jommi, C, primary, Cavallo, MC, additional, Blasi, F, additional, Burgel, PR, additional, Ringshausen, FC, additional, Cardosi, L, additional, Sibila, O, additional, and Chalmers, JD, additional
Published: 2022
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7. 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

8. 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

9. 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

10. Sputum neutrophil elastase in bronchiectasis: a Southern European cohort study

Author: Gramegna, A, Aliberti, S, Sibila, O, Di Francesco, C, Sotgiu, G, Perea, L, Terranova, L, Oriano, M, Pilocane, T, Saderi, L, Chalmers, JD, Marchisio, P, and Blasi, F
Published: 2020

11. 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

12. 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

13. Severity assessment in community-acquired pneumonia: a review

Author: Singanayagam, A, Chalmers, JD, and Hill, AT
Published: 2009

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. Antibiotic prophylaxis is ineffective in preventing pneumonia post-stroke

Author: Rae, N, primary and Chalmers, JD, additional
Published: 2015
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26. Early outcomes in CAP: Clinical stability, clinical failure and nonresolving pneumonia

Author: Chalmers, JD, Pletz, MW, Aliberti, S, Welte, T, Faverio, P, Aliberti S., Faverio P., Chalmers, JD, Pletz, MW, Aliberti, S, Welte, T, Faverio, P, Aliberti S., and Faverio P.
Abstract: Clinical stability is the first step of clinical improvement in patients with pneumonia. Clinical stability has been proven to be useful in guiding the switch of antibiotic therapy from intravenous to oral formulations. Given its importance in patient management, several sets of criteria have been created to standardise its definition. However, a single set of criteria cannot fit everybody; therefore, a personalised approach based on the resolution of the patient's most prominent clinical features should be considered. Moreover, it is important to choose the set of criteria that best fits the standard of care at each site of practice. Clinical failure is considered a predictive factor of adverse clinical outcomes. The identification of the aetiology of clinical failure is important to determine the subsequent patient management. The term 'nonresolving pneumonia' is used to indicate a failure to improve without clinical deterioration. Few epidemiological data have been published on this condition. Therefore, future studies should specifically address this topic. © 2014.
Published: 2014

27. Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

Author: James D. Chalmers, Dave Singh, Alberto de la Hoz, Gary T. Ferguson, Jadwiga A. Wedzicha, Ioanna Tsiligianni, Janwillem W. H. Kocks, Wenqiong Xue, Marc Miravitlles, Klaus F. Rabe, Groningen Research Institute for Asthma and COPD (GRIAC), Institut Català de la Salut, [Rabe KF] LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research (DZL), Grosshansdorf, Germany. Christian Albrechts University Kiel, Airway Research Center North, German Center for Lung Research (DZL), Kiel, Germany. [Chalmers JD] Tayside Respiratory Research Group, University of Dundee, Dundee, UK. [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. [Kocks JWH] General Practitioners Research Institute, Groningen, The Netherlands. Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Observational and Pragmatic Research Institute, Singapore, Singapore. [Tsiligianni I] Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece. [de la Hoz A] Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 030213 general clinical medicine, Exacerbation, IMPACT, INITIAL MAINTENANCE TREATMENT, Pulmons - Malalties obstructives - Tractament, Other subheadings::Other subheadings::/drug therapy [Other subheadings], chemistry.chemical_compound, 0302 clinical medicine, Bronchodilator, Pharmacology (medical), INDEX, OUTCOMES, COPD, Broncodilatadors - Ús terapèutic, Chronic obstructive pulmonary disease, Olodaterol, Hazard ratio, LAMA, General Medicine, Obstructive lung disease, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES], 030220 oncology & carcinogenesis, Cardiology, LAMA/LABA COMBINATION THERAPY, medicine.medical_specialty, Combination therapy, medicine.drug_class, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Health status, LABA/LAMA COMBINATION, Exacerbations, POOLED ANALYSIS, Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Autonomic Agents::Bronchodilator Agents [CHEMICALS AND DRUGS], 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::fármacos del sistema nervioso periférico::fármacos del sistema nervioso autónomo::broncodilatadores [COMPUESTOS QUÍMICOS Y DROGAS], DUAL BRONCHODILATION, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], business.industry, Tiotropium, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, PREVENTION, Lung function, respiratory tract diseases, chemistry, Avaluació de resultats (Assistència sanitària), business
Abstract: Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naive patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID. Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George’s Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID. Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P
Published: 2020
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28. Automated method of bronchus and artery dimension measurement in an adult bronchiectasis population.

Author: Pieters ALP, Lv Q, Meerburg JJ, van der Veer T, Andrinopoulou ER, Ciet P, Chalmers JD, Loebinger MR, Haworth CS, Elborn JS, and Tiddens HAWM
Abstract: Aim: Bronchiectasis (BE) is a disease defined by irreversible dilatation of the airway. Computed tomography (CT) plays an important role in the detection and quantification of BE. The aim of this study was three-fold: 1) to assess bronchus-artery (BA) dimensions using fully automated software in a cohort of BE disease patients; 2) to compare BA dimensions with semi-quantitative BEST-CT (Bronchiectasis Scoring Technique for CT) scores for BE and bronchial wall thickening; and 3) to explore the structure-function relationship between BA-method lumen dimensions and spirometry outcomes., Methods: Baseline CTs of BE patients who participated in a clinical trial were collected retrospectively. CTs were analysed manually with the BEST-CT scoring system and automatically using LungQ (v.2.1.0.1, Thirona, The Netherlands), which measures the following BA dimensions: diameters of bronchial outer wall (B out ), bronchial inner wall (B in ) and artery (A), and bronchial wall thickness (B wt ) and computes BA ratios (B out /A and B in /A) to assess bronchial widening. To assess bronchial wall thickness, we used the B wt /A ratio and the ratio between the bronchus wall area (B wa ) and the area defined by the outer airway (B oa ) (B wa /B oa )., Results: In total, 65 patients and 16 900 BA pairs were analysed by the automated BA method. The median (range) percentage of BA pairs defined as widened was 69 (55-84)% per CT using a cut-off value of 1.5 for B out /A, and 53 (42-65)% of bronchial wall were thickened using a cut-off value of 0.14 for B wt /A. BA dimensions were correlated with comparable outcomes for the BEST-CT scoring method with a correlation coefficient varying between 0.21 to 0.51. The major CT BA determinants of airflow obstruction were bronchial wall thickness (p=0.001) and a narrower bronchial inner diameter (p=0.003)., Conclusion: The automated BA method, which is an accurate and sensitive tool, demonstrates a stronger correlation between visual and automated assessment and lung function when using a higher cut-off value to define bronchiectasis., Competing Interests: Author contributions: A.L.P. Pieters contributed to the design of the work, data collection and drafted the manuscript up to the final version. Q. Lv contributed to the data collection, analyses and gave final approval for the manuscript. J.J. Meerburg contributed to the data collection for her previous studies. E-R. Andrinopoulou contributed to the analyses and gave final approval for the manuscript. H.A.W.M. Tiddens contributed to the design and analyses of the work and gave final approval for the manuscript. T. van der Veer, P. Ciet, J.D. Chalmers, M.R. Loebinger, C.S. Haworth and J.S. Elborn contributed to the design of the work and gave final approval for the manuscript. Conflict of interest: A.L.P. Pieters, Q. Lv, T. van der Veer, J.J. Meerburg, J.S. Elborn and E-R. Andrinopoulou declare no conflict of interest. Conflict of interest: P. Ciet has received grants or contract fees from NOW-Dutch Research Council and Horizon Pathfinder; and has received payment or honoraria for lectures, presentations etc. from Chiesi and Vertex, and travel support from the European Respiratory Society. He holds a leadership role as Chair of the Thoracic Group of the Cardiothoracic Taskforce of the European Society of Pediatric Radiology. Conflict of interest: J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell; has received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon; and is an associate editor of this journal. Conflict of interest: M.R. Loebinger has received consulting fees from Armata, 30T, AstraZeneca, Parion, Ismed, Chiesi, Zambon, Electromed, Recode and Boehringer Ingelheim; and has received payment or honoraria for lectures, presentations etc. from Chiesi, Insmed, Mylan and Zambon. Conflict of interest: C.S. Haworth has received consulting fees from 30 Technology, CSL Behring, Chiesi, Ismed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex and Zambon; and has received payment or honoraria for lectures, presentations etc. from Chiesi, Ismed, Mylan and Zambon. Conflict of interest: H.A.W.M. Tiddens is professor emeritus at Erasmus MC and the CMO of Thirona; he has received consulting fees for Insmed, Chiesi and Boehringer, a provides paid courses for Vertex., (Copyright ©The authors 2024.)
Published: 2024
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29. A worldwide look into long COVID-19 management: an END-COVID survey.

Author: Nigro M, Valenzuela C, Arancibia F, Cohen M, Lam DCL, Maves RC, Rath B, Simpson SQ, Song Y, Tsiodras S, Chalmers JD, and Aliberti S
Abstract: Background: Long COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide., Methods: A survey-based study investigating long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID and PATS). A global analysis of the results is provided here, alongside sub-population analysis based on continents, national income levels, type of involved healthcare professional and inclusion or exclusion of paediatric patients., Findings: 1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre., Interpretation: Long COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included., Competing Interests: Conflict of interest: M. Nigro has nothing to disclose. Conflict of interest: C. Valenzuela reports consulting fees from Boehringer Ingelheim, Hoffman-La Roche Ltd and BMS, and payment of honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events and support for attending meetings and/or travel from Boehringer Ingelheim, in the past 36 months. Conflict of interest: F. Arancibia has nothing to disclose. Conflict of interest: M. Cohen is past president of ALAT. Conflict of interest: D.C.L. Lam is president of the APSR and FIRS. Conflict of interest: R.C. Maves reports clinical trial funding to his institution from AiCuris, Sound Pharmaceuticals and GeoVax; travel funding provided for committee work as a member of the American College of Chest Physicians (CHEST) Scientific Program Committee from CHEST, the Society of Critical Care Medicine (SCCM) Scientific Program Committee from the SCCM and the American Board of Internal Medicine (ABIM) Critical Care Medicine Approval Committee from the ABIM; honoraria paid to himself for clinical trial support as a medical monitor and data safety monitoring board member from LumaBridge, and for scientific advisory panel membership from Shionogi, all in the past 36 months; and a US patent on the candidate dengue vaccine unrelated to this study; and is chair of the CHEST Disaster Response and Global Health Section, and the CHEST Rapid Response Task Force, and a member of the CHEST Scientific Program Committee (all unpaid except for official travel funding as above); chair of the SCCM FCCS Crisis Management Committee, a member of the SCCM Congress Program Committee, Co-Vice Chair of the SCCM 2025 Critical Care Congress and Designated Co-Chair of the SCCM 2026 Critical Care Congress (all unpaid except for official travel funding as above); and a member of the ABIM Critical Care Medicine Approval Committee (travel funded plus honorarium for Board service). Conflict of interest: B. Rath reports European Union funding only; support for attending meetings and/or travel for MedScape and scientific societies only; patents not pertinent to this article; participation on a data safety monitoring or advisory board for GSK COVID-19 and influenza infant clinical trials, all in the past 36 months; and is on ISIRV, ESGREV, AAP and IPA vaccination-related steering committees. Conflict of interest: S.Q. Simpson is a board member of the American College of Chest Physicians and Chair of the Board of Directors of the Sepsis Alliance. Conflict of interest: Y. Song is a board member of the American College of Chest Physicians and Chair of the Board of Directors of the Sepsis Alliance. Conflict of interest: S. Tsiodras reports grants or contracts for the European Union (EU) projects EU-RESPONSE (funded by EU Horizon 2020), EU Prevent and EU Reverse, paid to his institution in the past 36 months. Conflict of interest: J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Chiesi, Gilead Sciences, Grifols, Genentech, GlaxoSmithKline, Insmed and Novartis; and consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Gilead Sciences, Grifols, Genentech, GlaxoSmithKline, Insmed, Novartis, Roche, Trudell, Zambon, Janssen and Pfizer, all in the past 36 months; and is an associate editor of this journal. Conflict of interest: S. Aliberti reports grants or contracts from Insmed Inc., Chiesi, Fisher and Paykel and GSK, paid to his institution; royalties or licences from McGraw Hill, paid to himself; consulting fees from Insmed Inc., Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline Spa, paid to himself; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline Spa, ThermoFisher Scientific, Insmed Italy, Insmed Ireland Ltd, Zambon and Fondazione Internazionale Menarini; and participation on a data safety monitoring or advisory board from Insmed Inc., Insmed Italy, AstraZeneca UK Ltd and MSD Italia S.r.l., all in the past 36 months., (Copyright ©The authors 2024.)
Published: 2024
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30. Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.

Author: Harrington NE, Kottara A, Cagney K, Shepherd MJ, Grimsey EM, Fu T, Hull RC, Chong CE, Baker KS, Childs DZ, Fothergill JL, Chalmers JD, Brockhurst MA, and Paterson S
Subjects: Humans, Genome, Bacterial, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Male, Female, Mutation, Drug Resistance, Multiple, Bacterial genetics, Bronchiectasis microbiology, Bronchiectasis genetics, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa isolation & purification, Genetic Variation, Pseudomonas Infections microbiology, Phylogeny, Whole Genome Sequencing
Abstract: Objectives: Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies. We aimed to determine strain diversity, adaptation mechanisms, and AMR features to better inform treatment., Methods: P. aeruginosa from 180 bronchiectasis patients in 15 countries, obtained prior to a phase 3, randomised clinical trial (ORBIT-3), were analysed by whole-genome sequencing. Phylogenetic groups and sequence types were determined, and between versus within patient genetic diversity compared using Analysis of Molecular Variance (AMOVA). The frequency of AMR-associated genes and mutations was also determined., Results: A total of 2854 P. aeruginosa isolates were analysed, predominantly belonging to phylogenetic group 1 (83%, n = 2359). Genetic diversity was far greater between than within patients, responsible for >99.9% of total diversity (AMOVA: phylogroup 1: df = 145, P < 0.01). Numerous pathways were under selection, some shared with CF (e.g., motility, iron acquisition), some unique to bronchiectasis (e.g., novel efflux pump PA1874). Multidrug resistance features were also frequent., Conclusions: We present a 10-fold increase in the availability of genomic data for P. aeruginosa in bronchiectasis, highlighting key distinctions with cystic fibrosis and potential targets for future treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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31. Aggregatibacter is inversely associated with inflammatory mediators in sputa of patients with chronic airway diseases and reduces inflammation in vitro.

Author: Goeteyn E, Taylor SL, Dicker A, Bollé L, Wauters M, Joossens M, Van Braeckel E, Simpson JL, Burr L, Chalmers JD, Rogers GB, and Crabbé A
Subjects: Humans, Female, Male, Middle Aged, Aged, Adult, Cohort Studies, Asthma metabolism, Asthma microbiology, Inflammation metabolism, Inflammation microbiology, Chronic Disease, Bronchiectasis metabolism, Bronchiectasis microbiology, Bronchiectasis immunology, Sputum metabolism, Sputum microbiology, Inflammation Mediators metabolism
Abstract: Background: Chronic airway disease (CAD) is characterized by chronic airway inflammation and colonization of the lungs by pro-inflammatory pathogens. However, while various other bacterial species are present in the lower airways, it is not fully understood how they influence inflammation. We aimed to identify novel anti-inflammatory species present in lower airway samples of patients with CAD., Methods: Paired sputum microbiome and inflammatory marker data of adults with CAD across three separate cohorts (Australian asthma and bronchiectasis, Scottish bronchiectasis) was analyzed using Linear discriminant analysis Effect Size (LEfSE) and Spearman correlation analysis to identify species associated with a low inflammatory profile in patients., Results: We identified the genus Aggregatibacter as more abundant in patients with lower levels of airway inflammatory markers in two CAD cohorts (Australian asthma and bronchiectasis). In addition, the relative abundance of Aggregatibacter was inversely correlated with sputum IL-8 (Australian bronchiectasis) and IL-1β levels (Australian asthma and bronchiectasis). Subsequent in vitro testing, using a physiologically relevant three-dimensional lung epithelial cell model, revealed that Aggregatibacter spp. (i.e. A. actinomycetemcomitans, A. aphrophilus) and their cell-free supernatant exerted anti-inflammatory activity without influencing host cell viability., Conclusions: These findings suggest that Aggregatibacter spp. might act to reduce airway inflammation in CAD patients., (© 2024. The Author(s).)
Published: 2024
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32. Digital technologies in bronchiectasis physiotherapy services: a survey of patients and physiotherapists in a UK centre.

Author: O'Neill K, O'Neill B, McLeese RH, Chalmers JD, Boyd J, De Soyza A, McCallion P, and Bradley JM
Abstract: Introduction: We aimed to explore how digital technology is currently used, could be used and how services could be improved in order to optimise bronchiectasis physiotherapy care., Methods: Online surveys were designed and distributed amongst people with bronchiectasis and physiotherapists in Northern Ireland. Responses to closed and open question formats were collected and analysed., Results: The survey was completed by 48 out of 100 physiotherapists (48%) between January 2020 and January 2021 and by 205 out of 398 people with bronchiectasis (52%) between October 2020 and October 2021. 56% of physiotherapists (27 out of 48) reporting using some type of digital technology to facilitate services, whereas 44% (21 out of 48) reported that they had never used a digital technology in this patient group. When physiotherapists were asked whether they would be likely to use certain remote and/or digital options to deliver follow-up care for airway clearance techniques, most (31-38 out of 48; 65-79%) indicated that they would. Regarding patient responses, most reported that they would use telephone consultation (145 out of 199, 73%) and a smaller proportion were likely to use video consultation (64 out of 199, 32%). The most commonly mentioned theme for improvement amongst patients was follow-ups, while improved access, quality of services and treatments were the most commonly mentioned amongst physiotherapists., Conclusion: Despite a large proportion of physiotherapists in this survey reporting no current use of digital technology in bronchiectasis physiotherapy care, there was significant interest and willingness to do so, amongst both physiotherapists and patients. This survey highlighted a range of care areas, specifically follow-up visits, where digital methods could be further explored., Competing Interests: Conflict of interest: K. O'Neill has nothing to disclose. Conflict of interest: B. O'Neil has nothing to disclose. Conflict of interest: R.H. McLeese has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Novartis and Insmed; and received consultancy or speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis and Zambon, in the past 36 months; and is an associate editor of this journal. Conflict of interest: J. Boyd is an employee of the European Lung Foundation. Conflict of interest: A. De Soyza reports grants or contracts from GlaxoSmithKline, AstraZeneca, Bayer, Gilead and Insmed, for work outside that presented in this article, with payment made to his institution; and a leadership or fiduciary role on the National Institute for Health Research HTA programme, in the past 36 months. Conflict of interest: P. McCallion has nothing to disclose. Conflict of interest: J.M. Bradley reports grants or contracts from Health and Social Care (Northern Ireland) and iABC (Polyphor and Alaxia), and using data analytics to design innovative clinical trials in respiratory disease, CLEAR, RECOVERY (RECOVERY-RS Respiratory Support), DIBS (Dual Bronchodilators in Bronchiectasis Study), ECFS-CTN, NI Clinical Research Facility, CLEAR 2, MARCH, Rejuvenating Rehab and PREPARE (Prehabilitation for Patients Awaiting Liver Transplantation), with all funding to her institution; and equipment for the Clear Trail study provided by Pari, in the past 36 months., (Copyright ©The authors 2024.)
Published: 2024
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33. Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review.

Author: Upadhyay H, Aliberti S, Husband A, Chalmers JD, Hester K, and De Soyza A
Abstract: Non-cystic fibrosis bronchiectasis is a long-term lung disease characterised by abnormal dilatation of the bronchi, with patients experiencing chronic productive cough and recurrent exacerbations. Currently, there are no licensed drugs for use in bronchiectasis while clinical trials have been conducted to either test new drugs or repurpose existing ones. These drugs target the underlying pathophysiology of bronchiectasis which is known to include infection, inflammation, mucus hypersecretion and retention. Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab)., (© The Author(s), 2024.)
Published: 2024
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34. Priorities and barriers for research related to primary ciliary dyskinesia.

Author: Goutaki M, Lam YT, Rubbo B, Chalmers JD, Kouis P, Marsh G, Papon JF, Raidt J, Robinson P, Behan L, and Lucas JS
Abstract: Background: Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease-specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research., Methods: To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with PCD specialists selected using purposive sampling. We transcribed, coded and analysed interview data using thematic analysis. Based on interview themes that we identified, we developed an anonymous survey and circulated it widely through the BEAT-PCD network., Results: We interviewed 28 participants from 15 countries across different disciplines and expertise levels. The main themes identified as priorities for PCD research were improving diagnosis; understanding prevalence and disease course; phenotypic variability; disease monitoring; treatment strategies; clinical trial end-points; and poorly researched areas. In total, 136 participants (49% paediatric pulmonologists) from 36 countries completed the survey. Most commonly reported barriers for research were low awareness about PCD and difficulties securing funding - in more than one-third of cases, participants reported undertaking predominantly unfunded research. Research questions ranked highest included priorities related to further improving diagnosis, treating PCD, managing upper and lower airway problems, and studying clinical variability and disease prognosis., Conclusion: We need to overcome barriers of limited funding and low awareness and promote collaborations between centres, disciplines, experts and patients to address identified PCD priorities effectively. Our results contribute to the ongoing efforts of guiding the use of existing limited research resources and setting up a roadmap for future research activities., Competing Interests: Conflict of interest: M. Goutaki reports grants from the Johanna Dürmüller-Bol Foundation outside the submitted work and is Co-Chair of the BEAT-PCD clinical research collaboration. Conflict of interest: Y.T. Lam is Work Package Co-Lead in clinical research collaboration BEAT-PCD funded by the European Respiratory Society. Conflict of interest: J.D. Chalmers reports grants from AstraZeneca, GlaxoSmithKline, Grifols, Gilead Sciences, Boehringer Ingelheim, Trudell, Insmed and Genentech; and consulting fees from AstraZeneca, GlaxoSmithKline, Grifols, Boehringer Ingelheim, Trudell, Insmed, Genentech, Pfizer, Antabio and Zambon, all outside the submitted work; and is an associate editor of this journal. Conflict of interest: J-F. Papon reports grants and consulting fees from Sanofi, GSK, Medtronic, AstraZeneca and ALK; lecture honoraria from Sanofi, GSK and Medtronic; and travel support from Sanofi and GSK, all outside the submitted work. Conflict of interest: J.S. Lucas reports grants from the Medical Research Council, Life Arc, NHS England, NIHR Southampton Biomedical Research Centre, AAIR charity, NIHR Research for Patient Benefit and Wessex Medical Research, outside the submitted work. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)
Published: 2024
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35. 1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

Author: Leavy OC, Russell RJ, Harrison EM, Lone NI, Kerr S, Docherty AB, Sheikh A, Richardson M, Elneima O, Greening NJ, Harris VC, Houchen-Wolloff L, McAuley HJC, Saunders RM, Sereno M, Shikotra A, Singapuri A, Aul R, Beirne P, Bolton CE, Brown JS, Choudhury G, Diar Bakerly N, Easom N, Echevarria C, Fuld J, Hart N, Hurst JR, Jones M, Parekh D, Pfeffer P, Rahman NM, Rowland-Jones S, Shah AM, Wootton DG, Jolley C, Thompson AAR, Chalder T, Davies MJ, De Soyza A, Geddes JR, Greenhalf W, Heller S, Howard L, Jacob J, Jenkins RG, Lord JM, Man WD, McCann GP, Neubauer S, Openshaw PJM, Porter J, Rowland MJ, Scott JT, Semple MG, Singh SJ, Thomas D, Toshner M, Lewis K, Heaney LG, Briggs A, Zheng B, Thorpe M, Quint JK, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Raman B, Wain LV, Brightling CE, and Evans RA
Abstract: Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge., Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias., Findings: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups., Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed., Competing Interests: Conflict of interest: O.C. Leavy declares that their institute received joint funding from UKRI and NIHR (MR/V027859/1 and COV0319) to complete this work. A.B. Docherty declares that they were awarded funding from a Wellcome Clinical Research Career Development Fellowship (216606/Z/19/Z) to complete this work. A Sheikh declares that their institute was awarded grant funding from NIHR and UKRI to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca's Thrombotic Thrombocytopenic Taskforce; and leadership or fiduciary roles for UK and Scottish Government COVID-19 advisory groups. C.E. Bolton declares that their institute received grant funding from NIHR/UKRI and NIHR to complete this work; and their institute received grant funding from Nottingham Hospitals Charity and University of Nottingham. G. Choudhury declares funding from GlaxoSmithKline and AstraZeneca; received honoraria for delivering talks from GSK, AZ, Chiesi and BI; participation on a Data Safety Monitoring Board or Advisory Board as Chair on the Act on COPD Programme for AZ in Scotland; and a leadership or fiduciary role as Chair for the Lothian Respiratory Managed Clinical Network. N.D. Bakerly declares they have received nonrestrictive educational grants from Chiesi, AZ and Teva for attending conferences; honoraria from Teva, AZ and GSK; support for attending meetings and/or travel from Chiesi and AZ; participation on a Data Safety Monitoring Board or Advisory Board for Teva; and receipt of equipment from Global Access Diagnostics (previously Mologic Inc). A. Shikotra declares that their institute was awarded joint funding from UKRI and the NIHR (MR/V027859/1 and COV0319) to complete this work. R. Aul declares lecture fees and support for attending a meeting from Boehringer Ingelheim. C. Echevarria declares a grant from GSK. J.R. Hurst declares funding from AstraZeneca; consulting fees from AstraZeneca and GSK; payment for lectures and presentations from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi and Takeda; support for attending meetings and/or travel from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca; and receipt of equipment from Nonin. M. Jones declares funding from the MRC to complete this work; funding from the MRC, British Lung Foundation and Boehringer Ingelheim; consulting fees from Skyhawk Therapeutics; and a leadership or fiduciary role in the AAIR Charity Scientific Committee. P. Pfeffer declares funding from NIHR. S. Rowland-Jones declares that their institute received funding from UKRI to complete this work; and their institute received funding from NIHR Sheffield Biomedical Research centre, Bill and Melinda Gates Foundation, UKRI (MRC) and EDCTP. D. Parekh declares funding from NIHR and MRC; and a leadership or fiduciary role for the Faculty of Intensive Care Medicine Board. A.A.R. Thompson declares that their institute was awarded a fellowship from the British Heart Foundation, and grant funding from Heart Research UK and the National Institute for Health and Care Research; payment for lectures and presentations from Janssen-Cilag Ltd; and support for attending meetings from Janssen-Cilag Ltd. M.J. Davies declares grant funding from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen; consulting fees from Eli Lilly, Boehringer Ingelheim, Novo Nordisk and Sanofi; payment for speaking for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, AstraZeneca, Amgen, Napp Pharmaceuticals and Novartis; and is an advisory board member for Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc., and Zealand Pharma. A. De Soyza declares that their institute was awarded grant funding from AstraZeneca, Bayer, GSK, Chiesi, Novartis and Pfizer, outside the submitted manuscript; consulting fees from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed and Gilead; payment for lectures and presentations from AstraZeneca, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T; participation on a Data Safety Monitoring Board or Advisory Board for Bayer; and receipt of drugs from GSK outside the submitted manuscript. S. Heller declares consulting fees from NovoNordisk; and participation on a Data Safety Monitoring Board or Advisory Board for Eli Lilly with payments made to their institution. J. Jacob declares funding from Gilead, Microsoft Research and GlaxoSmithKline; consulting fees from Boehringer Ingelheim, Roche, GlaxoSmithKline and NHSX; payment for lectures and presentations received from Boehringer Ingelheim, Roche, GlaxoSmithKline and Takeda; support for attending meetings and/or travel from Boehringer Ingelheim; patents planned, issued or pending (UK patent application number 2113765.8 and UK patent application number GB2211487.0); and participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim and Roche. R.G. Jenkins declares that their institute received funding from AstraZeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX and Pliant; consulting fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics and Pliant; payment for lectures and presentations received from Boehringer Ingelheim, Chiesi, Roche, PatientMPower and AstraZeneca; payment for expert testimony from Pinsent Masons LLP; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, Galapagos and Vicore; and a leadership or fiduciary role for NuMedii and is president for Action for Pulmonary Fibrosis. W.D-C. Man declares that their institute received funding from National Institute for Health Research and NHS Accelerated Access Collaborative; and is Honorary President of the Association for Respiratory Technology and Physiology, and an associate editor of ERJ Open Research. G.P. McCann declares funding from NIHR (RP-2017-ST2-007) to complete this work; funding from the British Heart Foundation, Wellcome Trust and NIHR; and research support from Resonance Health, Circle CVi and Perspectum. S. Neubauer declares grant funding from Oxford NIHR Biomedical Research centre. P.J.M. Openshaw declares funding from UKRI-MRC/DHSC NIHR and UKRI-BEIS. M.J. Rowland declares support for attending meetings and/or travel from Novartis Pharmaceuticals; stock or stock options from Novartis Pharmaceuticals and Roche Pharmaceuticals; and is employed full time as a Senior Clinical Development Medical Director at Novartis Pharmaceuticals. J. Porter declares funding from Breathing Matters and UCL/H BRC (NIHR), and consulting fees from The Limbic. L.G. Heaney declares that their institute received funding from GSK, AstraZeneca and Roche/Genentech; payment for lectures received from AstraZeneca, Novartis, Roche/Genentech, Sanofi, Circassia, GlaxoSmithKline, Chiesi and Teva; support to travel to meetings from AstraZeneca and GSK; participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Roche/Genentech, GSK, Teva and Celltrion; and funding from the NIHR (RfPB grant PB-PG-0317-20032). J.T. Scott declares funding from UKRI. M.G. Semple declares grant funding from National Institute of Health Research UK, Medical Research Council UK and Health Protection Research Unit in Emerging and Zoonotic Infections, and University of Liverpool to complete this work; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer; leadership or fiduciary roles as Chair of Infectious Disease Scientific Advisory Board Integrum Scientific LLC and Director of MedEx Solutions Ltd; stock or stock options as minority owner of Integrum Scientific LLC and majority owner of MedEx Solutions Ltd; receipt of equipment, materials, drugs, medical writing, gifts or other services from Chiesi Farmaceutici SpA; and is a nonremunerated independent member of HMG UK Scientific Advisory Group for Emergencies (SAGE), COVID-19 Response (March 2020 to March 2022) and a nonremunerated independent member of HMG UK New Emerging Respiratory Virus Threats Advisory Group (NERVTAG) (2014 to July 2023). S.J. Singh declares grants or contracts from NIHR (programme grant (NIHR 202020), Wellcome Doctoral Training Programme, HTA Project Grant (NIHR 131015), NIHR DHSC/UKRI COVID-19 Rapid Response Initiative, NIHR Global Research Group (NIHR 17/63/20)), Actegy Limited and NIHR Senior Investigator; payment for presentations for GSK, Ministry of Justice, CIPLA, Sherbourne Gibbs; participation on NICE Expert Adviser Panel (long COVID), Wales Long COVID Advisory Board and NHS-E Long Covid Your Covid Recovery working group; and leadership or fiduciary roles as ATS Pulmonary Rehabilitation Assembly Chair, Clinical Lead RCP Pulmonary Rehabilitation Accreditation Scheme and Clinical Lead NACAP Audit for Pulmonary Rehabilitation. M. Toshner declares grant funding from the NIHR Cambridge BRC and NIHR HTA to complete this work; consulting fees from Janssen; support for attending meetings and/or travel from GSK and Janssen; and participation on a Data Safety Monitoring Board or Advisory Board for ComCov and FluCov. A. Horsley declares that their institute was awarded funding from UK Research and Innovation (MR/V027859/1), the National Institute of Health Research (NIHR) (COV0319) and NIHR Manchester BRC; and is Chair for the NIHR Translational Research Collaboration. M. Marks declares that their institute received joint funding from UKRI and NIHR to complete this work. K. Poinasamy declares funding from UKRI and NIHR to complete this work. A. Briggs declares consulting fees from Roche, Merck, Sanofi and GSK. J.K. Quint declares that their institute received funding from the Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GSK, BI, Asthma+Lung UK and AZ; and consulting fees from GlaxoSmithKline, Evidera, Chiesi, AstraZeneca and Insmed. J.D. Chalmers declares funding from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead Sciences, Insmed, Genentech and GlaxoSmithKline; consulting fees from AstraZeneca, Boehringer Ingelheim, Grifols, Gilead Sciences, Insmed, Genentech, Glaxosmithkline, Antabio, Zambon and Trudell; and leadership or fiduciary roles as Chief Editor of the European Respiratory Journal and associate editor of ERJ Open Research, Chair of the British Thoracic Society Science and Research Committee, and Trustee of the British Thoracic Society. L.V. Wain declares funding from UK Research and Innovation (MR/V027859/1), GSK/Asthma+Lung UK (Professorship (C17-1)) and National Institute of Health Research (COV0319) to complete this work; funding from Orion Pharma, GSK, Genentech, AstraZeneca, Nordic Bioscience and Sysmex (OGT); consulting fees Galapagos, Boehringer Ingelheim and GSK; support for attending meetings and/or travel Genentech; participation on Advisory Board for Galapagos; leadership or fiduciary roles as an associate editor for the European Respiratory Journal, and Medical Research Council Board member and Deputy Chair. C.E. Brightling declares that their institute received grant funding from MRC/NIHR and NIHR to complete this work; their institute received grant funding from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma and Mologic; and consulting fees from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Novartis, Chiesi, 4Dpharma, Mologic and Areteia. R.A. Evans declares funding from UKRI/MRC/NIHR to complete this work; funding from Wolfson Foundation and Genentech/Roche; consulting fees from AstraZeneca/Evidera; speaking fees from Boehringer and Moderna; support for attending meetings from Chiesi; and leadership or fiduciary roles as ERS Group 01.02 Pulmonary Rehabilitation and Chronic Care Secretary, and ATS Pulmonary Rehabilitation Assembly Chair. All other authors declare no conflicts of interest., (Copyright ©The authors 2024.)
Published: 2024
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36. Bronchiectasis in Asia: a review of current status and challenges.

Author: Choi H, Xu JF, Chotirmall SH, Chalmers JD, Morgan LC, and Dhar R
Subjects: Humans, Risk Factors, Asia epidemiology, Comorbidity, Female, Male, Lung physiopathology, Prognosis, Disease Progression, Asian People, Health Status Disparities, Prevalence, Bronchiectasis epidemiology, Bronchiectasis therapy, Bronchiectasis diagnosis
Abstract: Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China. Asian patients with bronchiectasis are less likely to show female predominance and experience exacerbations, are more likely to be younger, have milder disease, and have fewer options for guideline-recommended treatment than those living in other global regions. Furthermore, Asian bronchiectasis patients demonstrate different comorbidities, microbiological profiles and unique endophenotypes, including post-tuberculosis and dry bronchiectasis. Notably, each Asian region reveals further geographic variations and inter-patient differences. Future studies are warranted to better characterise Asian patients with bronchiectasis., Competing Interests: Conflict of interest: H. Choi reports grant from the Basic Science Research Program of the Korean Ministry of Education (grant no. 2021R1I1A3052416); and consulting and lecture fees from Boryung Pharmaceutical Co., Ltd. and Kolon Pharma. J-F. Xu reports leadership or fiduciary roles in other boards, societies, committees, or advocacy groups (unpaid) with the Shanghai Medical Association, Chinese Thoracic Society, and Chinese Association of Chest Physicians. S.H. Chotirmall has served on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, on data monitoring boards for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University, and has received personal fees from AstraZeneca and Chiesi Farmaceutici, all unrelated to this work J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. L.C. Morgan reports payment or honoraria for speakers’ bureau from Boehringer Ingelheim, AstraZeneca and Insmed, and educational events from GSK Pharmaceutical and AstraZeneca, all unrelated to this work. In addition, L.C. Morgan reports a leadership or fiduciary role in other boards, societies, committees, or advocacy groups (unpaid) as Chair of the Lung Foundation Australia. R. Dhar reports grants from GSK Pharmaceutical and Glenmark and Thorasis; and lecture fees from Cipla Ltd., Lupin Respira, Glenmark, Abbott, Sanofi and AstraZeneca., (Copyright ©The authors 2024.)
Published: 2024
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37. Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.

Author: Mall MA, Davies JC, Donaldson SH, Jain R, Chalmers JD, and Shteinberg M
Subjects: Humans, Animals, Serine Proteinase Inhibitors therapeutic use, Serine Proteases metabolism, Anti-Inflammatory Agents therapeutic use, Signal Transduction, Bronchiectasis drug therapy, Bronchiectasis enzymology, Cystic Fibrosis drug therapy, Cystic Fibrosis enzymology, Neutrophils enzymology, Neutrophils metabolism, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Molecular Targeted Therapy, Inflammation Mediators metabolism, Lung drug effects, Lung enzymology
Abstract: Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease., Competing Interests: Conflict of interest: M.A. Mall has received research grants paid to their institution from the German Research Foundation (DFG), German Ministry for Education and Research (BMBF), German Innovation Fund and Vertex Pharmaceuticals; consultancy fees from Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Santhera, Splisense and Vertex Pharmaceuticals; speaker fees from Vertex Pharmaceuticals; and travel grants for participation in advisory boards for Boehringer Ingelheim and Vertex Pharmaceuticals. M.A. Mall is listed as inventor on an issued patent filed by the University of North Carolina at Chapel Hill, describing the Scnn1b-transgenic mouse. M.A. Mall also reports advisory board participation for Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari and Vertex Pharmaceuticals, and is a fellow of ERS. J.C. Davies has received research grants from the UK Cystic Fibrosis Trust, Cystic Fibrosis Foundation, Cystic Fibrosis Ireland, EPSRC and NIHR, has received fees for clinical trial leadership and/or advisory board participation and speaking roles from Abbvie, Algipharma, Arcturus, Boehringer Ingelheim, Eloxx, Enterprise Therapeutics, Genentech, LifeArc, Recode, Tavanta and Vertex Pharmaceuticals, and is the Deputy Editor for the Journal of Cystic Fibrosis. J.C. Davies acknowledges funding from the National Institute of Health and Care Research through the Imperial Biomedical Research Centre and a Senior Investigator Award and grant funding from the Cystic Fibrosis Trust. S.H. Donaldson reports grants from the Cystic Fibrosis Foundation and the NIH; clinical trial contracts from AstraZeneca, Calithera and Vertex Pharmaceuticals; consulting fees from Chiesi USA, Inc., Polarean and 501 Ventures; and travel grants from Enterprise Therapeutics and Gilead Sciences. S.H. Donaldson also reported advisory board participation for Boehringer Ingelheim and data and safety monitoring board participation for Abbvie. R. Jain reports research grants from the CF Foundation, consulting fees from Boehringer Ingelheim, Insmed and Recode, and payment of honoraria for participation in the Vertex Innovation Awards review committee from Vertex Pharmaceuticals. R. Jain also reports advisory/data and safety monitoring board participation for Armata. J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Zambon, and has received consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Insmed, Pfizer and Zambon. M. Shteinberg reports having received research grants paid to their institution from GlaxoSmithKline, Novartis and Trudell; travel grants from Actelion, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Rafa; speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Kamada, Novartis, Sanofi and Teva; and consultancy fees from Boehringer Ingelheim, GlaxoSmithKline, Kamada and Zambon. M. Shteinberg also reports data and safety monitoring board participation for Bonus Therapeutics, Israel and has unpaid roles in EMBARC, the Israel Pulmonology Society board and the Israel Society for TB and Mycobacterial Diseases., (Copyright ©The authors 2024.)
Published: 2024
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38. A systematic literature review of the clinical and socioeconomic burden of bronchiectasis.

Author: Chalmers JD, Mall MA, McShane PJ, Nielsen KG, Shteinberg M, Sullivan SD, and Chotirmall SH
Subjects: Humans, Health Care Costs, Socioeconomic Factors, Female, Male, Bronchiectasis economics, Bronchiectasis epidemiology, Bronchiectasis therapy, Bronchiectasis mortality, Bronchiectasis diagnosis, Cost of Illness, Quality of Life
Abstract: Background: The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162)., Methods: Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017-December 2022). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included. Editorials, narrative reviews and systematic literature reviews were included to identify primary studies. PRISMA guidelines were followed., Results: 1585 unique publications were identified, of which 587 full texts were screened and 149 were included. A further 189 citations were included from reference lists of editorials and reviews, resulting in 338 total publications. Commonly reported symptoms and complications included dyspnoea, cough, wheezing, sputum production, haemoptysis and exacerbations. Disease severity across several indices and increased mortality compared with the general population was reported. Bronchiectasis impacted quality of life across several patient-reported outcomes, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation was considerable and substantial medical costs related to hospitalisations, treatments and emergency department and outpatient visits were accrued. Indirect costs included sick pay and lost income., Conclusions: Bronchiectasis causes significant clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce both healthcare resource utilisation and overall costs are needed. Further systematic analyses of specific aetiologies and paediatric disease may provide more insight into unmet therapeutic needs., Competing Interests: Conflict of interest: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell, and received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon. M.A. Mall reports research grants paid to their institution from the German Research Foundation (DFG), German Ministry for Education and Research (BMBF), German Innovation Fund, Vertex Pharmaceuticals and Boehringer Ingelheim; consultancy fees from AbbVie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Santhera, Splisense and Vertex Pharmaceuticals; speaker fees from Vertex Pharmaceuticals; and travel support from Boehringer Ingelheim and Vertex Pharmaceuticals. M.A. Mall also reports advisory board participation for AbbVie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari and Vertex Pharmaceuticals and is a fellow of ERS (unpaid). P.J. McShane is an advisory board member for Boehringer Ingelheim's Airleaf trial and Insmed's Aspen trial. P.J. McShane is also a principal investigator for clinical trials with the following pharmaceutical companies: Insmed: Aspen, 416; Boehringer Ingelheim: Airleaf; Paratek: oral omadacycline; AN2 Therapeutics: epetraborole; Renovian: ARINA-1; Redhill; Spero; and Armata. K.G. Nielsen reports advisory board membership for Boehringer Ingelheim. M. Shteinberg reports having received research grants from Novartis, Trudell Pharma and GlaxoSmithKline; travel grants from Novartis, Actelion, Boehringer Ingelheim, GlaxoSmithKline and Rafa; speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Insmed, Teva, Novartis, Kamada and Sanofi; and advisory fees (including steering committee membership) from GlaxoSmithKline, Boehringer Ingelheim, Kamada, Syncrony Medical, Zambon and Vertex Pharmaceuticals. M. Shteinberg also reports data and safety monitoring board participation for Bonus Therapeutics, Israel and is an ERS Task Force member on bronchiectasis guideline development. S.D. Sullivan has participated in advisory boards for Boehringer Ingelheim and has research grants from Pfizer, Bayer and GlaxoSmithKline. S.H. Chotirmall is on advisory boards for CSL Behring, Boehringer Ingelheim and Pneumagen Ltd, served on a data and safety monitoring board for Inovio Pharmaceuticals Inc., and has received personal fees from AstraZeneca and Chiesi Farmaceutici., (Copyright ©The authors 2024.)
Published: 2024
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39. Disease severity and activity in bronchiectasis: A paradigm shift in bronchiectasis management.

Author: Im Y, Chalmers JD, and Choi H
Abstract: Bronchiectasis has an increasing prevalence and substantial clinical and economic burden. Therefore, physicians should identify patients with bronchiectasis at high risk of disease progression to ensure optimal management in advance. The heterogeneity of bronchiectasis means it is unlikely that any single parameter could identify high-risk patients, therefore disease severity is usually assessed using validated composite tools, such as the Bronchiectasis Severity Index, FACED, and Bronchiectasis Aetiology Comorbidity Index, to predict long-term outcomes in bronchiectasis. Disease severity, however, implies an advanced process with lung destruction. Earlier intervention may prevent disease progression and improve outcomes. To identify patients at risk, rather than patients with established advanced disease, we need to shift our focus from disease severity to disease activity. Disease activity denotes the activation level of underlying pathophysiological processes and can be measured using clinical presentations and biomarkers. This review discusses a paradigm shift in bronchiectasis management, focusing on disease activity rather than severity, to prevent disease progression.
Published: 2024
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40. Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics.

Author: Chalmers JD, Burgel PR, Daley CL, De Soyza A, Haworth CS, Mauger D, Mange K, Teper A, Fernandez C, Conroy D, and Metersky M
Abstract: Introduction: Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369)., Methods: The ASPEN trial is a global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections), diagnosis confirmed radiologically and ≥2 exacerbations in the prior 12 months. It was designed to evaluate the impact of two brensocatib doses (10 mg and 25 mg) on exacerbation rate over a 52-week treatment period versus placebo. Comprehensive clinical data, including demographics, disease severity, lung function, Pseudomonas aeruginosa status and quality of life, were collected at baseline., Results: 1682 adults from 35 countries were randomised from December 2020 to March 2023. Mean age was 61.3 years and 64.7% were female. ∼70% had moderate-to-severe Bronchiectasis Severity Index (BSI) scores, 29.3% had ≥3 exacerbations in the prior 12 months and 35.7% were positive for P. aeruginosa . Mean BSI scores were highest in Australia/New Zealand (8.3) and lowest in Latin America (5.9). Overall, the most common aetiology was idiopathic (58.4%). In P. aeruginosa- positive versus P. aeruginosa- negative patients, lung function was lower, with greater long-term macrolide (21.5% versus 14.0%) and inhaled corticosteroid use (63.5% versus 53.9%). There was wide regional variation in long-term antibiotic use in patients with bronchiectasis and P. aeruginosa ., Discussion: ASPEN baseline characteristics and treatment profiles were representative of a global bronchiectasis population., Competing Interests: Conflict of interest: J.D. Chalmers reports receiving grants and personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Zambon and Insmed Incorporated, a grant from Gilead, and personal fees from Novartis and Chiesi. Conflict of interest: He is an Associate Editor of this journal. P-R. Burgel reports grants from Vertex and GSK, outside the submitted work. P-R. Burgel also reports clinical trials: acting as main investigator and advisory activity for AstraZeneca, Chiesi, GSK, Insmed Incorporated, MSD, Viatris, Vertex and Zambon. P-R. Burgel reports substantial financial contributions to the budget of an institution he is responsible for from GSK, Vertex, Association Vaincre la Mucoviscidose, Société Française de la Mucoviscidose and Filière MUCO-CFTR. Conflict of interest: C.L. Daley reports grant support, advisory board fees and consulting fees from Insmed Incorporated; grant support from AN2 Therapeutics, Bugworks, Paratek Pharmaceuticals and Juvabis; advisory board work with AN2 Therapeutics, AstraZeneca, Cepheid, Hyfe, MannKind, Matinas Biopharma, NobHill, Spero Therapeutics and Zambon; consulting with Genentech and Pfizer; and data monitoring committee work with Otsuka Pharmaceutical, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Conflict of interest: A. De Soyza reports grants and fees from AstraZeneca, Boehringer Ingelheim, Bayer, Chiesi, Gilead Sciences, GSK, Insmed Incorporated and Zambon. Conflict of interest: C.S. Haworth reports receiving consultancy/speaker fees from 30 Technology, CSL Behring, Chiesi, Insmed Incorporated, Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shinogi, Teva, Vertex and Zambon. Conflict of interest: D. Mauger reports grants from NHLBI and drugs for NIH-funded clinical trials from Genentech, GSK, OM Pharma and Sanofi-Regeneron. Conflict of interest: Conflict of interest: K. Mange, A. Teper, C. Fernandez and D. Conroy are employees of and shareholders in Insmed Incorporated. Conflict of interest: M. Metersky reports receiving consulting fees from AN2 Therapeutics, Boehringer Ingelheim, Insmed Incorporated, Renovion, Tactile Inc. and Zambon. Conflict of interest: J.D. Chalmers, P-R. Burgel, C.L. Daley, A. De Soyza, C.S. Haworth, D. Mauger and M. Metersky served as members of the ASPEN trial steering committee. J.D. Chalmers, P-R. Burgel, C.L. Daley, A. De Soyza, C.S. Haworth and M. Metersky were investigators in the ASPEN trial., (Copyright ©The authors 2024.)
Published: 2024
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41. Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

Author: Elneima O, Hurst JR, Echevarria C, Quint JK, Walker S, Siddiqui S, Novotny P, Pfeffer PE, Brown JS, Shankar-Hari M, McAuley HJC, Leavy OC, Shikotra A, Singapuri A, Sereno M, Richardson M, Saunders RM, Harris VC, Houchen-Wolloff L, Greening NJ, Harrison EM, Docherty AB, Lone NI, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Raman B, Evans RA, Wain LV, Sheikh A, Brightling CE, De Soyza A, and Heaney LG
Abstract: Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown., Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease ( i.e. , asthma, COPD or bronchiectasis) were compared to the non-airways group., Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group., Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge., Competing Interests: Conflict of interest: J.R. Hurst has received support to attend meetings, research grants, and personal payment and payment to his employer from pharmaceutical companies that make medicines to treat airways diseases. J.K. Quint reports grants from Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK and AstraZeneca (AZ), and consulting fees from GSK, Evidera, Chiesi, AZ and Insmed outside the submitted work. P.E. Pfeffer reports grants from NIHR and GSK, Honoraria payments for lectures from AZ, GSK, Sanofi and Chiesi and travel fees from AZ, GSK, Sanofi outside the submitted work. N.J. Greening reports grants from GSK and BioAge, and personal fees and travel grants from Genentech, Roche, Chiesi, AZ, GSK, Pulmonx and Chiesi outside the submitted work. J.D. Chalmers is an associate editor of this journal. A. Horsley reports grants from UKRI, NIHR and NIHR Manchester BRC during the conduct of this study and unenumerated role as the chair of NIHR Translational Research Collaboration. A. Sheikh has served on AZ's thrombotic thrombocytopenic taskforce, and on a number of UK and Scottish Government COVID-19 advisory bodies; all these roles were unremunerated. B. Raman reports grant from BHF Oxford CRE and speaker fees from Axcella Therapeutics. R.A. Evans reports grants from UKRI/MRC, DHSC/NIHR, Wolfson Foundation and Genentec/Roche during the conduct of this study, travel and speaker fees from AZ/Evidera, Boehringer Ingelheim (BI), Moderna and Chiesi, and unremunerated leadership roles in ERS/ATS outside the submitted work. C.E. Brightling declares that their institute was awarded a grant from UKRI/NIHR to complete this work; the author reports grants from GSK, AZ, Sanofi, Regeneron, BI, Chiesi, Novartis, Roche, Genentech, Mologic and 4DPharma; and consultancy fees paid to their institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma and Areteia. A. De Soyza declares receiving personal consulting fees and travel grants from AZ, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T outside the submitted work. All other authors declare no competing interests., (Copyright ©The authors 2024.)
Published: 2024
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42. Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations.

Author: Katsoulis O, Toussaint M, Jackson MM, Mallia P, Footitt J, Mincham KT, Meyer GFM, Kebadze T, Gilmour A, Long M, Aswani AD, Snelgrove RJ, Johnston SL, Chalmers JD, and Singanayagam A
Subjects: Animals, Humans, Mice, Male, Female, Picornaviridae Infections immunology, Picornaviridae Infections virology, Picornaviridae Infections complications, Mice, Inbred C57BL, DNA immunology, Disease Models, Animal, Middle Aged, Inflammation immunology, Inflammation virology, Aged, Extracellular Traps immunology, Pulmonary Disease, Chronic Obstructive immunology, Pulmonary Disease, Chronic Obstructive virology, Pulmonary Disease, Chronic Obstructive pathology, Rhinovirus immunology, Neutrophils immunology
Abstract: Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD., (© 2024. The Author(s).)
Published: 2024
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43. Biomarkers in bronchiectasis.

Author: Johnson E, Long MB, and Chalmers JD
Subjects: Humans, Prognosis, Lung physiopathology, Lung microbiology, Inflammation Mediators metabolism, Precision Medicine, Animals, Phenotype, Bronchiectasis therapy, Bronchiectasis diagnosis, Bronchiectasis physiopathology, Biomarkers, Predictive Value of Tests
Abstract: Bronchiectasis is a heterogeneous disease with multiple aetiologies and diverse clinical features. There is a general consensus that optimal treatment requires precision medicine approaches focused on specific treatable disease characteristics, known as treatable traits. Identifying subtypes of conditions with distinct underlying biology (endotypes) depends on the identification of biomarkers that are associated with disease features, prognosis or treatment response and which can be applied in clinical practice. Bronchiectasis is a disease characterised by inflammation, infection, structural lung damage and impaired mucociliary clearance. Increasingly there are available methods to measure each of these components of the disease, revealing heterogeneous inflammatory profiles, microbiota, radiology and mucus and epithelial biology in patients with bronchiectasis. Using emerging biomarkers and omics technologies to guide treatment in bronchiectasis is a promising field of research. Here we review the most recent data on biomarkers in bronchiectasis., Competing Interests: Conflict of interest: E. Johnson has nothing to disclose. M.B. Long reports travel support from the British Thoracic Society, Asthma+Lung UK and the American Thoracic Society, outside the submitted work. J.D. Chalmers reports grants from AstraZeneca, Genentech, Gilead Sciences, GlaxoSmithKline, Insmed, Grifols, Novartis and Boehringer Ingelheim; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon, all outside the submitted work., (Copyright ©The authors 2024.)
Published: 2024
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44. EMBARCing on a new era for bronchiectasis: a review series for the Seventh World Bronchiectasis Conference.

Author: Chalmers JD, Goeminne PC, and Ringshausen FC
Subjects: Humans, Bronchiectasis therapy, Bronchiectasis diagnosis, Bronchiectasis physiopathology, Bronchiectasis epidemiology
Abstract: Competing Interests: Conflict of interest: J.D. Chalmers reports grants or contracts from from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. P.C. Goeminne reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, GSK and Chiesi; support for attending meetings and/or travel from Chiesi; and participation on a Data Safety Monitoring Board or Advisory Board with Boehringer Ingelheim, GSK and Pfizer. F.C. Ringshausen reports grants or contracts from the German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA) and iABC Consortium (including Alaxia, Basilea, Novartis and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer and InfectoPharm; consulting fees from Parion, Grifols, Zambon, Insmed and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols, Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for attending meetings and/or travel from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group Mukoviszidose e.V.; participation on a Data Safety Monitoring Board or Advisory Board with Insmed, Grifols and Shionogi; leadership or fiduciary roles in another board, society, committee or advocacy group (paid or unpaid) as Coordinator of the ERN-LUNG Bronchiectasis Core Network, Chair of the German Bronchiectasis Registry PROGNOSIS, Member of the Steering Committee of the European Bronchiectasis Registry EMBARC, Member of the Steering Committee of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, Co-Speaker of the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group, Speaker of the Respiratory Infections and TB group of the German Respiratory Society, Speaker of the Cystic Fibrosis group of German Respiratory Society (DGP), PI of the German Center for Lung Research, Member of the Protocol Review Committee of the PCD-CTN, Member of Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and other financial or non-financial interests with AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon.
Published: 2024
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45. Pathophysiology and genomics of bronchiectasis.

Author: Perea L, Faner R, Chalmers JD, and Sibila O
Subjects: Humans, Microbiota, Host-Pathogen Interactions, Phenotype, Proteomics, Epigenesis, Genetic, Immunity, Innate, Animals, Risk Factors, Metabolomics, Prognosis, Epigenomics, Bronchiectasis physiopathology, Bronchiectasis genetics, Bronchiectasis metabolism, Bronchiectasis immunology, Genomics, Genetic Predisposition to Disease, Lung physiopathology, Lung microbiology, Lung metabolism
Abstract: Bronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology. Genomic approaches may help to identify new endotypes, as has been shown in other chronic airway diseases, such as COPD.Different studies have started to work in this direction, and significant contributions to the understanding of the microbiome and proteome diversity have been made in bronchiectasis in recent years. However, the systematic application of omics approaches to identify new molecular insights into the pathophysiology of bronchiectasis (endotypes) is still limited compared with other respiratory diseases.Given the complexity and diversity of these technologies, this review describes the key components of the pathophysiology of bronchiectasis and how genomics can be applied to increase our knowledge, including the study of new techniques such as proteomics, metabolomics and epigenomics. Furthermore, we propose that the novel concept of trained innate immunity, which is driven by microbiome exposures leading to epigenetic modifications, can complement our current understanding of the vicious vortex. Finally, we discuss the challenges, opportunities and implications of genomics application in clinical practice for better patient stratification into new therapies., Competing Interests: Conflict of interest: L. Perea reports no conflicts of interest. R. Faner reports grants or contracts from AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, Instituto de Salud Carlos III, European Research Council and Fondo Europeo de Desarrollo Regional (FEDER); lecture honoraria from AstraZeneca, Zambon and Chiesi; and consulting fees from AstraZeneca. J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. O. Sibila reports no conflicts of interest., (Copyright ©The authors 2024.)
Published: 2024
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46. A serum calprotectin lateral flow test as an inflammatory and prognostic marker in acute lung infection: a prospective observational study.

Author: Gilmour A, Hughes C, Giam YH, Hull RC, Pembridge T, Abo-Leyah H, Thompson AAR, Condliffe AM, Shoemark A, Chalmers JD, and Long MB
Abstract: A rapid, quantitative serum S100A8/A9 (calprotectin) lateral flow test in combination with clinical status predicted outcomes in people hospitalised with COVID-19 and associated with a patient cluster driven by markers of neutrophil activation https://bit.ly/48e1BIv., Competing Interests: Conflict of interest: A.A.R. Thompson reports grants or contracts from British Heart Foundation, Heart Research UK, and National Institute for Health and Care Research, outside the submitted work; honoraria for lectures from Janssen-Cilag Ltd, outside the submitted work; and support received for travel and conference registration from Janssen-Cilag Ltd, outside the submitted work. Conflict of interest: A.M. Condliffe reports grants or contracts from NIHR and MRC, outside the submitted work. Conflict of interest: A. Shoemark reports grants or contracts from AstraZeneca, outside the submitted work; consulting fees from Spirovant and Translate Bio, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Translate Bio, Ethris and Insmed, outside the submitted work; and involvement in European Respiratory Society Clinical Research Collaborations (EMBARC, BEATPCD and AMR), EMBARC3 is supported by project partners Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Grifols, Insmed, Janssen, Lifearc, Novartis, and Zambon, disclosures made outside the submitted work. Conflict of interest: J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell, outside the submitted work; and consulting fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon, outside the submitted work; and is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)
Published: 2024
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47. Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States.

Author: Dean SG, Blakney RA, Ricotta EE, Chalmers JD, Kadri SS, Olivier KN, and Prevots DR
Subjects: Humans, United States epidemiology, Anti-Bacterial Agents therapeutic use, Persistent Infection, Staphylococcus aureus, Electronic Health Records, Mycobacterium avium Complex, Pseudomonas aeruginosa, Bronchiectasis epidemiology, Bronchiectasis complications, Pseudomonas Infections drug therapy, Respiratory Tract Infections complications
Abstract: Background: Bronchiectasis is a pulmonary disease characterized by irreversible dilation of the bronchi and recurring respiratory infections. Few studies have described the microbiology and prevalence of infections in large patient populations outside of specialized tertiary care centers., Methods: We used the Cerner HealthFacts Electronic Health Record database to characterize the nature, burden, and frequency of pulmonary infections among persons with bronchiectasis. Chronic infections were defined based on organism-specific guidelines., Results: We identified 7,749 patients who met our incident bronchiectasis case definition. In this study population, the organisms with the highest rates of isolate prevalence were Pseudomonas aeruginosa with 937 (12%) individuals, Staphylococcus aureus with 502 (6%), Mycobacterium avium complex (MAC) with 336 (4%), and Aspergillus sp. with 288 (4%). Among persons with at least one isolate of each respective pathogen, 219 (23%) met criteria for chronic P. aeruginosa colonization, 74 (15%) met criteria for S. aureus chronic colonization, 101 (30%) met criteria for MAC chronic infection, and 50 (17%) met criteria for Aspergillus sp. chronic infection. Of 5,795 persons with at least two years of observation, 1,860 (32%) had a bronchiectasis exacerbation and 3,462 (60%) were hospitalized within two years of bronchiectasis diagnoses. Among patients with chronic respiratory infections, the two-year occurrence of exacerbations was 53% and for hospitalizations was 82%., Conclusions: Patients with bronchiectasis experiencing chronic respiratory infections have high rates of hospitalization., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
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48. The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583.

Author: Chalmers JD, Badorrek P, Diefenbach C, Kögler H, Sauter W, Kreideweiss S, and Hohlfeld JM
Abstract: Preclinical and phase 1 study results indicate that BI 1291583 is a reversible, highly potent and highly selective CatC inhibitor that markedly inhibits active NSP production in a dose-dependent manner, supporting phase 2 trials in bronchiectasis patients https://bit.ly/47PZ8E5., Competing Interests: Conflict of interest: J.D. Chalmers reports grant support from AstraZeneca, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, Novartis and Zambon, and consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Insmed, Pfizer and Zambon; and is an associate editor of this journal. Conflict of interest: P. Badorrek has nothing to disclose. Conflict of interest: C. Diefenbach, H. Kögler, W. Sauter and S. Kreideweiss are employees of Boehringer Ingelheim. Conflict of interest: J.M. Hohlfeld reports grant support paid to his institution from AltamiraPharma GmbH, Astellas Pharma GmbH, AstraZeneca AB, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, CSL Behring GmbH, Desitin Arzneimittel GmbH, EpiEndo, F. Hoffmann-La Roche AG, Genentech, Inc., M&P Pharma AG, Novartis AG, OM Pharma SA and Sanofi-Aventis Deutschland GmbH, personal fees for consultancy from Boehringer Ingelheim Pharma GmbH & Co. KG, Cureteq and Roche, personal fees for lectures from Novartis AG, and personal fees for board service from CSL Behring GmbH and Nocion., (Copyright ©The authors 2024.)
Published: 2024
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49. SFX-01 in hospitalised patients with community-acquired pneumonia during the COVID-19 pandemic: a double-blind, randomised, placebo-controlled trial.

Author: Long MB, Abo-Leyah H, Giam YH, Vadiveloo T, Hull RC, Keir HR, Pembridge T, Alferes De Lima D, Delgado L, Inglis SK, Hughes C, Gilmour A, Gierlinski M, New BJM, MacLennan G, Dinkova-Kostova AT, and Chalmers JD
Abstract: Introduction: Sulforaphane can induce the transcription factor, Nrf2, promoting antioxidant and anti-inflammatory responses. In this study, hospitalised patients with community-acquired pneumonia (CAP) were treated with stabilised synthetic sulforaphane (SFX-01) to evaluate impact on clinical status and inflammation., Methods: Double-blind, randomised, placebo-controlled trial of SFX-01 (300 mg oral capsule, once daily for 14 days) conducted in Dundee, UK, between November 2020 and May 2021. Patients had radiologically confirmed CAP and CURB-65 (confusion, urea >7 mmol·L -1 , respiratory rate ≥30 breaths·min -1 , blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) score ≥1. The primary outcome was the seven-point World Health Organization clinical status scale at day 15. Secondary outcomes included time to clinical improvement, length of stay and mortality. Effects on Nrf2 activity and inflammation were evaluated on days 1, 8 and 15 by measurement of 45 serum cytokines and mRNA sequencing of peripheral blood leukocytes., Results: The trial was terminated prematurely due to futility with 133 patients enrolled. 65 patients were randomised to SFX-01 treatment and 68 patients to placebo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the cause of CAP in 103 (77%) cases. SFX-01 treatment did not improve clinical status at day 15 (adjusted OR 0.87, 95% CI 0.41-1.83; p=0.71), time to clinical improvement (adjusted hazard ratio (aHR) 1.02, 95% CI 0.70-1.49), length of stay (aHR 0.84, 95% CI 0.56-1.26) or 28-day mortality (aHR 1.45, 95% CI 0.67-3.16). The expression of Nrf2 targets and pro-inflammatory genes, including interleukin (IL)-6, IL-1β and tumour necrosis factor-α, was not significantly changed by SFX-01 treatment. At days 8 and 15, respectively, 310 and 42 significant differentially expressed genes were identified between groups (false discovery rate adjusted p<0.05, log 2 FC >1)., Conclusion: SFX-01 treatment did not improve clinical status or modulate key Nrf2 targets in patients with CAP primarily due to SARS-CoV-2 infection., Competing Interests: Conflict of interest: H.R. Keir reports receiving personal fees for educational lecture from Insmed Inc., outside the submitted work. Conflict of interest: A.T. Dinkova-Kostova participates on the Evgen Pharma Scientific Advisory Board, outside the submitted work. Conflict of interest: J.D. Chalmers reports support for the present manuscript from Lifearc; grants or contracts from AstraZeneca, Genentech, Gilead Sciences, GlaxoSmithKline, Insmed, Grifols, Novartis and Boehringer Ingelheim, outside the submitted work; consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon, outside the submitted work; and is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)
Published: 2024
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50. Sputum metagenomics of people with bronchiectasis.

Author: Rosenboom I, Thavarasa A, Richardson H, Long MB, Wiehlmann L, Davenport CF, Shoemark A, Chalmers JD, and Tümmler B
Abstract: Background: The microbiota in the sputum of people with bronchiectasis has repeatedly been investigated in cohorts of different geographic origin, but so far has not been studied to the species level in comparison to control populations including healthy adults and smokers without lung disease., Methods: The microbial metagenome from sputa of 101 European Bronchiectasis Registry (EMBARC) study participants was examined by using whole-genome shotgun sequencing., Results: Our analysis of the metagenome of people with bronchiectasis revealed four clusters characterised by a predominance of Haemophilus influenzae , Pseudomonas aeruginosa or polymicrobial communities with varying compositions of nonpathogenic commensals and opportunistic pathogens. The metagenomes of the severely affected patients showed individual profiles characterised by low alpha diversity. Importantly, nearly 50% of patients with severe disease were grouped in a cluster characterised by commensals. Comparisons with the sputum metagenomes of healthy smokers and healthy nonsmokers revealed a gradient of depletion of taxa in bronchiectasis, most often Neisseria subflava , Fusobacterium periodonticum and Eubacterium sulci ., Conclusion: The gradient of depletion of commensal taxa found in healthy airways is a key feature of bronchiectasis associated with disease severity., Competing Interests: Conflict of interest: A. Shoemark reports consulting fees from Spirovant and Translate Bio. Conflict of interest: J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Novartis, Genentech, GlaxoSmithKline and Trudell; fees from AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Novartis, Genentech, GlaxoSmithKline, Trudell, Zambon, CSL Behring, Janssen and Antabio; and is an associate editor of this journal. Conflict of interest: B. Tümmler reports grants from Vertex Pharmaceuticals. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)
Published: 2024
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