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8. Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis

Author

Subramaniam, Ashwin, Anstey, Christopher, Curtis, J. Randall, Ashwin, Sushma, Ponnapa Reddy, Mallikarjuna, Aliberti, Márlon Juliano Romero, Avelino-Silva, Thiago Junqueira, Welch, Carly, Koduri, Gouri, Prowle, John R., Wan, Yize I., Laurent, Michaël R., Marengoni, Alessandra, Lim, Jun Pei, Pilcher, David, and Shekar, Kiran

Published
2022
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9. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina

Subjects
616.238, WD Disorders of systemic, metabolic or environmental origin
Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified a potentially important pathway in which to focus the development of effective asthma therapies. Future directions will include functional analysis of replicated variants and tests of interactions between the multiple genetic and environmental factors likely to be involved in disease.

Published
2011

14. Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Author

Pearse, Rupert, Ranieri, Marco, Abbott, Tom, Pakats, Mari-Lii, Piervincenzi, Edoardo, Patel, Akshaykumar, Kahan, Brennan, Rhodes, Andrew, Dias, Priyanthi, Hewson, Russell, Jammer, Ib, Chew, Michelle, Aldecoa, Cesar, Rodseth, Reitze, Biccard, Bruce, Stephens, Tim, Payne, Sara, Hepworth, David, Pischke, Soeren, Asvall, Joerund, Hausken, John, Jhanji, Shaman, Rooms, Martin, Flint, Neil, Hales, Dawn, Szakmany, Tama, Leitch, Andrew, Spadaro, Savino, Chiumello, Davide, Johnston, Paul, Yeung, Joyce, Tellan, Guglielmo, Veenith, Tonny, Macmillan, Josep, Terragni, Pierpaolo, Sander, Caroline, Kasipandian, Vidya, Ahmad, Tahania, Lee, Aaron, Tammaro, Marcello, Mcauley, Danny, Skene, Simon, Vohra, Ravinder, Wilson, Matt, Edwards, Mark, Griffiths, Ewen, Pritchard, Naomi, Filippini, Claudia, Aasmundstad, Tor, Aksnes, Einar, Alpers, Lise-Merete, Barratt-Due, Andrea, Dahl, Anita, Feldt, Linda, Figari, Elisa, Flåten, Eva, Granheim, Karen, Hagring, Minna, Haugaa, Håkon, Kjoesen, Gisle, Klaevahaugen, Inge, Lenz, Harald, Myhre, Marianne, Orrem, Hilde, Stitt, Emily, Inge Toennessen, Tor, Al-Kadhimi, Samuel, Anker, Robert, Balint, Mihaela, Barraclough, Lauren, Black, Ethel, Clayton, Matt, Conneely, Leonora, Edwards, Zara, Eeles, Alex, Evans, Matthew, Gerstman, Michelle, Greenshields, Nicole, Harvey, Eleanor, Hegarty, Aoife, Hester, Natalie, Hutchinson, Jenna, Kasivisvanathan, Ramanathan, Lawrence, Helen, Marsh, Veronica, Matthews, Laura, Mazzola, Francesca, Mccanny, Jamie, Morrison, Ben, O'Mahony, Michelle, Ling Pang, Ching, Parkinson, David, Pirie, Katrina, Rao Baikady, Ravishankar, Shovel, Louisa, Smith, Lorna, Tatham, Kate, Thomas, Peter, Uren, Sophie, Walker, Susanna, Wills, Alasdair, Andreou, Prematie, Howson, Alex, Kaur, Jasmin, Lewszuk, Adam, Molina, Esther, Ramsamy, Nirmalabaye, Roberts, Emma, Amaral, Vanessa, Begum, Salma, Bekele, Soliana, Cashmore, Richard, Correia, Carmen, Dunkley, Steven, Fernandez, Maria, Fowler, Alexander, Garcia, Amaia, Della Giovampaola, Maria, Greaves, Kathryn, Griffiths, Bethan, Haines, Ryan, Haslop, Richard, Hu, Ying, Hui, Sarah, Januszewska, Marta, Manon, Vasi, Martin, Tim, May, Shaun, Minicozzi, Annamaria, Niebrzegowska, Edyta, Oliveira, Monica, Pates, Katherine, Santos, Filipa, Shahid, Tasnin, Simili, Paolo, Somerville, Alastair, Subhedar, Emily, Uddin, Ruzena, Walker, Sophie, Wan, Yize, Whalley, Jan, Zolfaghari, Parjam, Gunter, Una, Hodkinson, Gemma, Howe, Gwenllian, Baratozzi, Valentina, Casotto, Giulia, Darai, Giulia, Ferrari, Erica, Mistraletti, Giovanni, Palmaverdi, Valentina, Furlani, Stefano, Priani, Paolo, Ragazzi, Riccardo, Salmaso, Marco, Verri, Marco, Volta, Carlo, Nutt, Chri, Mckay, Emma, O'Neill, Orla, Patel, Jaimin, Atterbury, Katie, Ballinger, Sarah, Carling, Natalie, Ellis, Kaytie, Gresty, Jo, Melody, Teresa, Monk, Jade, Norman, Chloe, Reeves, Eleanor, Sampson, Julia, Sutton, Peter, Thomas, Marie, Bamford, Amy, Bergin, Colin, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Fellows, Emma, Goundry, Stephanie, Harkett, Samantha, Ip, Peter, Mason, Tracy, Mcghee, Christopher, Mclaughlin, Aisling, Neal, Aoife, Pope, Martin, Porter, Stephanie, Smith, Hazel, Snelson, Catherine, Spruce, Elaine, Vigo, Ylenia, Whitehouse, Arlo, Whitehouse, Tony, Donatiello, Maria, Gazzanelli, Sergio, Mezzapesa, Mario, Savino, Martina, Settesoldi, Giacomo, Kunst, Gudrun, Birch, Sian, Greig, Louise, Noble, Harriet, Pappa, Evita, Penhaligon, Bethany, Cossu, Andrea, Floris, Leda, Piredda, Davide, Racca, Alberto, Brattstrom, Olof, Heggelund, Bente, Flodberg, Magnu, Månsson, Sandra, Ahmed, Mamoona, Allen, Jonathan, Bell, Paula, Genetu, Roman, Glennon, Julia, Hanley, Janice, Jenner, Katy, Jogi, Summayyah, Mahjoob, Parisa, Mcgovern, Clare, Murphy, Anthony, Nazari, Roonak, Routledge, Jacki, Uttamlal, Trishna, Ward, Sinead, Iotti, Giorgio, Picchioni, Raffaella, Poma, Silvia, Navalesi, Paolo, Bruni, Andrea, De Leonardis, Brunella, Garofalo, Eugenio, Patel, Panna, Mcarthur, Carol, Burns, Karen, Peters, Steven, Foti, Giuseppe, Calcinati, Serena, Grassi, Alice, Villa, Silvia, Berridge, John, Kanakaraj, Muthuraj, Cahill, Hazel, Forshaw, Greg, Gibson, Andy, Grainger, Lia, Howard, Kate, James, Katherine, Murphy, Zoe, Sweeting, Helen, Tait, Rebecca, Wilcock, Danielle, Yates, David, Cope, Sean, Allan, Ashley, Betts, Rebecca, Cornell, Sarah, Sheriff, Julie, Woods, Lindsey, Grasselli, Giacomo, Brioni, Matteo, Castagna, Luigi, von Rahden, Richard, Farina, Zane, Green, Samantha, Gumede, Simphiwe, Rajah, Chantal, Ramkillawan, Arisha, Moug, Susan, Alcorn, David, Dalton, Carol, Dickinson, Natalie, Edwards, Jennifer, Henderson, Steven, Mcilveen, Erin, Ramsaran, Richard, Bell, Joanne, Fleming, Lorna, Monks, Kathleen, Parker, Jane, Stamper, Sean, Stokes-Denson, Jo, Elías, Elisa, Guerra, Yessica, Rico-Feijoo, Jesu, Kidel, Carlo, Filipe, Helder, Asis, Gretchelle, Gleeson, Yvonne, Harvey, Alice, Jackson, Christine, Mcneil, Margaret, Mingo, Sara, Pakou, Glykeria, Pinto, Manuel, Wright, Stephen, Babio-Galan, Maite, Buckley, David, Calder, Verity, Chishti, Ahmad, Cosgrove, Joseph, Cullen, Katherine, Dunn, Leigh, Faulds, Matthew, Fortune, Jonathan, Gardner, Matthew, Harrison, Abigail, Hays, Carole, Jones, Gerry, Macfie, Caroline, Mccullagh, Iain, Nesbitt, Ian, O'Neil, Suzanne, Phoenix, Catherine, Rangaswamy, Girish, Samson, Craig, Scott, Carmen, Shrestha, Tara, Singh, Rita, Soulsby, Graham, Walton, Jon, Zwiggelaar, Kimberley, Lynch, Ceri, Clarke, Heidi, Deacon, Bethan, Ivatt, Helen, Jones, Leanne, Latif, Ahmed, Oram, Shaun, Perman, Chri, Roche, Lisa, Duys, Rowan, Flint, Margot, Bhagwan, Kamal, Coetzee, Ettienne, Joubert, Ivan, Montoya-Pelaez, Felipe, Navsaria, Pradeep, Picken, Guy, Porrill, Owen, Strathie, Grant, Zungu, Thembinkosi, Aluri, Sireesha, Chau, Simon, Cooper, Deborah, Cunningham, Mishell, Daniels, Allison, Hope, Susan, Nicholson, Alice, Walker, Laura, Giarratano, Antonino, Accurso, Giuseppe, Raineri, Santi, Tricoli, Giuseppe, Innes, Richard, Doble, Patricia, Hutter, Joanne, Pawley, Corinne, Tait, Moira, Hamilton, Mark, Andrade, Edward, Barnes, Veronica, Dalton, Claire, Delgado, Carlo, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Howlett, Luisa, Joseph, Gipsy, Krupa, Monika, Leaver, Susannah, Macedo, Joao, Maher, Karen, Mellinghoff, Johanne, Oguntimehin, Rachel, Pereira, Joel, Robinson, France, Ryan, Christine, Shah, Nirav, Shirley, Paula, Torborg, Alexandra, Biyase, Thuli, Drummond, Leanne, Kusel, Belinda, Mbuyisa, Mbalenhle, Solala, Sivuyisiwe, Taylor, Jenna, Ezihe-Ejiofor, Adanma, Aduse-Poku, Maame, Colville, Gary, Davies, Louise, Kang, Soo, Phillips, Alex, Kirk-Bayley, Justin, Kelliher, Leigh, Carvelli, Paula, Daysal, Gokce, Dickinson, Matthew, Doyle, Nancileigh, Hughes, Christina, Montague, Laura, Potter, Elizabeth, Salberg, Armorel, Sibug, Sheena, Sivarajan, Sinduja, Thomson, Milo, Wakeford, Nichola, Rocco, Monica, Alampi, Daniela, Conway, Daniel, Clark, Richard, Maria, Jashmin, Pomeroy, Fiona, Quraishi, Tanviha, Williams, Abigail, Chukkambotla, Srikanth, Aherne, Caroline, Harrison-Briggs, Donna, Fitchett, Jill, Duberley, Stephen, Zanoni, Andrea, Cardinale, Daniela, Righi, Claudia, Blunt, Mark, Fuller, Tracy, Hodgson, Ruth, Rosbergen, Melissa, Brennan, Andrew, Akeroyd, Louise, Boardman, Victoria, Bull, Christopher, Carrick, Mike, Chadderton, Ian, Cooper, Sarah, Goellner, Sarah, Graham, Laura, Ilyas, Carl, King, Jame, Laklouk, Muhammad, Lawton, Tom, Macrow, Christopher, Munro, Michael, Neep, Adam, Northey, Martin, Peacock, Victoria, Pye, Kate, Radley, Lydia, Sira, Jame, Smithson, Beth, Syddall, Stuart, Tooth, David, White, Thoma, Hoel, Sindre, Aakre, Elin, Bakke, Monica, Hoivik, Tone, Makowski, Arystarch, Alcock, Harry, Cardoso, Sean, Coetzee, Samantha, Everett, Mary, Ibrahim, Mohamed, Kouridaki, Christina, Ogbeide, Vongayi, Bertellini, Elisabetta, Bertolotti, Valentina, Buono, Antonio, Fanigliulo, Maria, Kumar, Ram, Richards, Nicole, Allana, Alisha, Bacciarelli, Samantha, Barker, Helen, De Bois, Jessica, Bradley, Isabel, Crooks, Jennifer, Daum, Peter, Feben, Alex, Gannon, Lizzie, Kipling, Sarah, Peetamsingh, Andrew, Quamina, Charlotte, Sethi, Sahiba, Sivadhas, Harry, Sollesta, Kathryn, Swain, Andrew, Tan, Evalyn, Willis, Joan, Zou, Maggie, Cranshaw, Juliu, Barratt, Nina, Bowman, Katie, Branney, Debbie, Letts, Maria, Pitts, Sally, Day, Christopher, Benyon, Sarah, Eddy, Sara, Green, Adam, Grice, Anna, Kelly, Sinéad, Mackle, Daisy, Mariano, Victor, Park, Linda, Sibley, Pauline, Spencer, William, Bignami, Elena, Bellini, Valentina, Forfori, Francesco, Curci, Maria, Leo, Alessandra, Jackson, Matthew, Awolesi, Jennifer, Hodgkinson, Sheila, Kent, Alissa, Leonard, Dee, Stapleton, Claire, Tibke, Clare, Alexander-Sefre, Farhad, Campey, Lorraine, Hall, Kathryn, Spimpolo, Jennifer, Nilsson, Malin, Didriksson, Helen, Hamilton, Emma, Carnahan, Mandy, Mowatt, Chri, Stickley, Jo, Corcione, Antonio, Rossi, Giuseppe, Fladby, Hege, Andersen, Nina, Bjoernå, Gunhild, Reite, Mad, Roertveit, Linda, Seidel, Philipp, Arnold, Glenn, Benavente, Melissa, Chattersingh, Anjalee, Chironga, Nyasha, Hornzee, Gillian, Kibaru, Joyce, Malik, Ihtisham, Mcleavy, Laura, Pathmanathan, Byiravey, Prior, Florence, Strudwick, Rhea, Vezyrgiannis, Mario, Sinha, Aneeta, Babu, Sheeba, Batuwitage, Bisanth, Daly, Zoe, Ellinor, Katharine, Hawes, Elizabeth, Holmes, Ann, Hudson, Karen, Nightingale, Jeremy, Le Poidevin, Alison, Roberts, Lindsey, Kubisz-Pudelko, Agnieszka, Allison, Joanna, Pippard, Lucy, Hamlyn, Vincent, Organ, Angie, Prabhahar, Thaventhran, Bridger, Hayley, Dvorkin, Lee, Manhas, Vitul, Vincent, Rachel, Laha, Shondipon, Cromie, Terri-Louise, Doyle, Donna, Howarth, Rachel, Verlander, Mark, Watt, Ailsa, Williams, Alexandra, Antonelli, Massimo, Cutuli, Salvatore, Montini, Luca, Graterol, Juan, Adams, Benita, Bean, Sarah, Burt, Karen, Hammonds, Fiona, Jigajinni, Suyogi, Fulton, Laura, Kinghorn, Stephen, Mullenheim, Jost, Baillie, Kirsty, Cain, Martyn, Colling, Kerry, Hannaway, Carol, Corso, Ruggero, Calli, Morena, Ferrando, Carlo, Romero, Esther, Jorge-Monjas, Pablo, Soria-García, María, Gómez-Herreras, José, Rodríguez-Jiménez, Rita, De Prada-Martín, Blanca, Massimo Antonelli (ORCID:0000-0003-3007-1670), Luca Montini (ORCID:0000-0003-4602-5134), Pearse, Rupert, Ranieri, Marco, Abbott, Tom, Pakats, Mari-Lii, Piervincenzi, Edoardo, Patel, Akshaykumar, Kahan, Brennan, Rhodes, Andrew, Dias, Priyanthi, Hewson, Russell, Jammer, Ib, Chew, Michelle, Aldecoa, Cesar, Rodseth, Reitze, Biccard, Bruce, Stephens, Tim, Payne, Sara, Hepworth, David, Pischke, Soeren, Asvall, Joerund, Hausken, John, Jhanji, Shaman, Rooms, Martin, Flint, Neil, Hales, Dawn, Szakmany, Tama, Leitch, Andrew, Spadaro, Savino, Chiumello, Davide, Johnston, Paul, Yeung, Joyce, Tellan, Guglielmo, Veenith, Tonny, Macmillan, Josep, Terragni, Pierpaolo, Sander, Caroline, Kasipandian, Vidya, Ahmad, Tahania, Lee, Aaron, Tammaro, Marcello, Mcauley, Danny, Skene, Simon, Vohra, Ravinder, Wilson, Matt, Edwards, Mark, Griffiths, Ewen, Pritchard, Naomi, Filippini, Claudia, Aasmundstad, Tor, Aksnes, Einar, Alpers, Lise-Merete, Barratt-Due, Andrea, Dahl, Anita, Feldt, Linda, Figari, Elisa, Flåten, Eva, Granheim, Karen, Hagring, Minna, Haugaa, Håkon, Kjoesen, Gisle, Klaevahaugen, Inge, Lenz, Harald, Myhre, Marianne, Orrem, Hilde, Stitt, Emily, Inge Toennessen, Tor, Al-Kadhimi, Samuel, Anker, Robert, Balint, Mihaela, Barraclough, Lauren, Black, Ethel, Clayton, Matt, Conneely, Leonora, Edwards, Zara, Eeles, Alex, Evans, Matthew, Gerstman, Michelle, Greenshields, Nicole, Harvey, Eleanor, Hegarty, Aoife, Hester, Natalie, Hutchinson, Jenna, Kasivisvanathan, Ramanathan, Lawrence, Helen, Marsh, Veronica, Matthews, Laura, Mazzola, Francesca, Mccanny, Jamie, Morrison, Ben, O'Mahony, Michelle, Ling Pang, Ching, Parkinson, David, Pirie, Katrina, Rao Baikady, Ravishankar, Shovel, Louisa, Smith, Lorna, Tatham, Kate, Thomas, Peter, Uren, Sophie, Walker, Susanna, Wills, Alasdair, Andreou, Prematie, Howson, Alex, Kaur, Jasmin, Lewszuk, Adam, Molina, Esther, Ramsamy, Nirmalabaye, Roberts, Emma, Amaral, Vanessa, Begum, Salma, Bekele, Soliana, Cashmore, Richard, Correia, Carmen, Dunkley, Steven, Fernandez, Maria, Fowler, Alexander, Garcia, Amaia, Della Giovampaola, Maria, Greaves, Kathryn, Griffiths, Bethan, Haines, Ryan, Haslop, Richard, Hu, Ying, Hui, Sarah, Januszewska, Marta, Manon, Vasi, Martin, Tim, May, Shaun, Minicozzi, Annamaria, Niebrzegowska, Edyta, Oliveira, Monica, Pates, Katherine, Santos, Filipa, Shahid, Tasnin, Simili, Paolo, Somerville, Alastair, Subhedar, Emily, Uddin, Ruzena, Walker, Sophie, Wan, Yize, Whalley, Jan, Zolfaghari, Parjam, Gunter, Una, Hodkinson, Gemma, Howe, Gwenllian, Baratozzi, Valentina, Casotto, Giulia, Darai, Giulia, Ferrari, Erica, Mistraletti, Giovanni, Palmaverdi, Valentina, Furlani, Stefano, Priani, Paolo, Ragazzi, Riccardo, Salmaso, Marco, Verri, Marco, Volta, Carlo, Nutt, Chri, Mckay, Emma, O'Neill, Orla, Patel, Jaimin, Atterbury, Katie, Ballinger, Sarah, Carling, Natalie, Ellis, Kaytie, Gresty, Jo, Melody, Teresa, Monk, Jade, Norman, Chloe, Reeves, Eleanor, Sampson, Julia, Sutton, Peter, Thomas, Marie, Bamford, Amy, Bergin, Colin, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Fellows, Emma, Goundry, Stephanie, Harkett, Samantha, Ip, Peter, Mason, Tracy, Mcghee, Christopher, Mclaughlin, Aisling, Neal, Aoife, Pope, Martin, Porter, Stephanie, Smith, Hazel, Snelson, Catherine, Spruce, Elaine, Vigo, Ylenia, Whitehouse, Arlo, Whitehouse, Tony, Donatiello, Maria, Gazzanelli, Sergio, Mezzapesa, Mario, Savino, Martina, Settesoldi, Giacomo, Kunst, Gudrun, Birch, Sian, Greig, Louise, Noble, Harriet, Pappa, Evita, Penhaligon, Bethany, Cossu, Andrea, Floris, Leda, Piredda, Davide, Racca, Alberto, Brattstrom, Olof, Heggelund, Bente, Flodberg, Magnu, Månsson, Sandra, Ahmed, Mamoona, Allen, Jonathan, Bell, Paula, Genetu, Roman, Glennon, Julia, Hanley, Janice, Jenner, Katy, Jogi, Summayyah, Mahjoob, Parisa, Mcgovern, Clare, Murphy, Anthony, Nazari, Roonak, Routledge, Jacki, Uttamlal, Trishna, Ward, Sinead, Iotti, Giorgio, Picchioni, Raffaella, Poma, Silvia, Navalesi, Paolo, Bruni, Andrea, De Leonardis, Brunella, Garofalo, Eugenio, Patel, Panna, Mcarthur, Carol, Burns, Karen, Peters, Steven, Foti, Giuseppe, Calcinati, Serena, Grassi, Alice, Villa, Silvia, Berridge, John, Kanakaraj, Muthuraj, Cahill, Hazel, Forshaw, Greg, Gibson, Andy, Grainger, Lia, Howard, Kate, James, Katherine, Murphy, Zoe, Sweeting, Helen, Tait, Rebecca, Wilcock, Danielle, Yates, David, Cope, Sean, Allan, Ashley, Betts, Rebecca, Cornell, Sarah, Sheriff, Julie, Woods, Lindsey, Grasselli, Giacomo, Brioni, Matteo, Castagna, Luigi, von Rahden, Richard, Farina, Zane, Green, Samantha, Gumede, Simphiwe, Rajah, Chantal, Ramkillawan, Arisha, Moug, Susan, Alcorn, David, Dalton, Carol, Dickinson, Natalie, Edwards, Jennifer, Henderson, Steven, Mcilveen, Erin, Ramsaran, Richard, Bell, Joanne, Fleming, Lorna, Monks, Kathleen, Parker, Jane, Stamper, Sean, Stokes-Denson, Jo, Elías, Elisa, Guerra, Yessica, Rico-Feijoo, Jesu, Kidel, Carlo, Filipe, Helder, Asis, Gretchelle, Gleeson, Yvonne, Harvey, Alice, Jackson, Christine, Mcneil, Margaret, Mingo, Sara, Pakou, Glykeria, Pinto, Manuel, Wright, Stephen, Babio-Galan, Maite, Buckley, David, Calder, Verity, Chishti, Ahmad, Cosgrove, Joseph, Cullen, Katherine, Dunn, Leigh, Faulds, Matthew, Fortune, Jonathan, Gardner, Matthew, Harrison, Abigail, Hays, Carole, Jones, Gerry, Macfie, Caroline, Mccullagh, Iain, Nesbitt, Ian, O'Neil, Suzanne, Phoenix, Catherine, Rangaswamy, Girish, Samson, Craig, Scott, Carmen, Shrestha, Tara, Singh, Rita, Soulsby, Graham, Walton, Jon, Zwiggelaar, Kimberley, Lynch, Ceri, Clarke, Heidi, Deacon, Bethan, Ivatt, Helen, Jones, Leanne, Latif, Ahmed, Oram, Shaun, Perman, Chri, Roche, Lisa, Duys, Rowan, Flint, Margot, Bhagwan, Kamal, Coetzee, Ettienne, Joubert, Ivan, Montoya-Pelaez, Felipe, Navsaria, Pradeep, Picken, Guy, Porrill, Owen, Strathie, Grant, Zungu, Thembinkosi, Aluri, Sireesha, Chau, Simon, Cooper, Deborah, Cunningham, Mishell, Daniels, Allison, Hope, Susan, Nicholson, Alice, Walker, Laura, Giarratano, Antonino, Accurso, Giuseppe, Raineri, Santi, Tricoli, Giuseppe, Innes, Richard, Doble, Patricia, Hutter, Joanne, Pawley, Corinne, Tait, Moira, Hamilton, Mark, Andrade, Edward, Barnes, Veronica, Dalton, Claire, Delgado, Carlo, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Howlett, Luisa, Joseph, Gipsy, Krupa, Monika, Leaver, Susannah, Macedo, Joao, Maher, Karen, Mellinghoff, Johanne, Oguntimehin, Rachel, Pereira, Joel, Robinson, France, Ryan, Christine, Shah, Nirav, Shirley, Paula, Torborg, Alexandra, Biyase, Thuli, Drummond, Leanne, Kusel, Belinda, Mbuyisa, Mbalenhle, Solala, Sivuyisiwe, Taylor, Jenna, Ezihe-Ejiofor, Adanma, Aduse-Poku, Maame, Colville, Gary, Davies, Louise, Kang, Soo, Phillips, Alex, Kirk-Bayley, Justin, Kelliher, Leigh, Carvelli, Paula, Daysal, Gokce, Dickinson, Matthew, Doyle, Nancileigh, Hughes, Christina, Montague, Laura, Potter, Elizabeth, Salberg, Armorel, Sibug, Sheena, Sivarajan, Sinduja, Thomson, Milo, Wakeford, Nichola, Rocco, Monica, Alampi, Daniela, Conway, Daniel, Clark, Richard, Maria, Jashmin, Pomeroy, Fiona, Quraishi, Tanviha, Williams, Abigail, Chukkambotla, Srikanth, Aherne, Caroline, Harrison-Briggs, Donna, Fitchett, Jill, Duberley, Stephen, Zanoni, Andrea, Cardinale, Daniela, Righi, Claudia, Blunt, Mark, Fuller, Tracy, Hodgson, Ruth, Rosbergen, Melissa, Brennan, Andrew, Akeroyd, Louise, Boardman, Victoria, Bull, Christopher, Carrick, Mike, Chadderton, Ian, Cooper, Sarah, Goellner, Sarah, Graham, Laura, Ilyas, Carl, King, Jame, Laklouk, Muhammad, Lawton, Tom, Macrow, Christopher, Munro, Michael, Neep, Adam, Northey, Martin, Peacock, Victoria, Pye, Kate, Radley, Lydia, Sira, Jame, Smithson, Beth, Syddall, Stuart, Tooth, David, White, Thoma, Hoel, Sindre, Aakre, Elin, Bakke, Monica, Hoivik, Tone, Makowski, Arystarch, Alcock, Harry, Cardoso, Sean, Coetzee, Samantha, Everett, Mary, Ibrahim, Mohamed, Kouridaki, Christina, Ogbeide, Vongayi, Bertellini, Elisabetta, Bertolotti, Valentina, Buono, Antonio, Fanigliulo, Maria, Kumar, Ram, Richards, Nicole, Allana, Alisha, Bacciarelli, Samantha, Barker, Helen, De Bois, Jessica, Bradley, Isabel, Crooks, Jennifer, Daum, Peter, Feben, Alex, Gannon, Lizzie, Kipling, Sarah, Peetamsingh, Andrew, Quamina, Charlotte, Sethi, Sahiba, Sivadhas, Harry, Sollesta, Kathryn, Swain, Andrew, Tan, Evalyn, Willis, Joan, Zou, Maggie, Cranshaw, Juliu, Barratt, Nina, Bowman, Katie, Branney, Debbie, Letts, Maria, Pitts, Sally, Day, Christopher, Benyon, Sarah, Eddy, Sara, Green, Adam, Grice, Anna, Kelly, Sinéad, Mackle, Daisy, Mariano, Victor, Park, Linda, Sibley, Pauline, Spencer, William, Bignami, Elena, Bellini, Valentina, Forfori, Francesco, Curci, Maria, Leo, Alessandra, Jackson, Matthew, Awolesi, Jennifer, Hodgkinson, Sheila, Kent, Alissa, Leonard, Dee, Stapleton, Claire, Tibke, Clare, Alexander-Sefre, Farhad, Campey, Lorraine, Hall, Kathryn, Spimpolo, Jennifer, Nilsson, Malin, Didriksson, Helen, Hamilton, Emma, Carnahan, Mandy, Mowatt, Chri, Stickley, Jo, Corcione, Antonio, Rossi, Giuseppe, Fladby, Hege, Andersen, Nina, Bjoernå, Gunhild, Reite, Mad, Roertveit, Linda, Seidel, Philipp, Arnold, Glenn, Benavente, Melissa, Chattersingh, Anjalee, Chironga, Nyasha, Hornzee, Gillian, Kibaru, Joyce, Malik, Ihtisham, Mcleavy, Laura, Pathmanathan, Byiravey, Prior, Florence, Strudwick, Rhea, Vezyrgiannis, Mario, Sinha, Aneeta, Babu, Sheeba, Batuwitage, Bisanth, Daly, Zoe, Ellinor, Katharine, Hawes, Elizabeth, Holmes, Ann, Hudson, Karen, Nightingale, Jeremy, Le Poidevin, Alison, Roberts, Lindsey, Kubisz-Pudelko, Agnieszka, Allison, Joanna, Pippard, Lucy, Hamlyn, Vincent, Organ, Angie, Prabhahar, Thaventhran, Bridger, Hayley, Dvorkin, Lee, Manhas, Vitul, Vincent, Rachel, Laha, Shondipon, Cromie, Terri-Louise, Doyle, Donna, Howarth, Rachel, Verlander, Mark, Watt, Ailsa, Williams, Alexandra, Antonelli, Massimo, Cutuli, Salvatore, Montini, Luca, Graterol, Juan, Adams, Benita, Bean, Sarah, Burt, Karen, Hammonds, Fiona, Jigajinni, Suyogi, Fulton, Laura, Kinghorn, Stephen, Mullenheim, Jost, Baillie, Kirsty, Cain, Martyn, Colling, Kerry, Hannaway, Carol, Corso, Ruggero, Calli, Morena, Ferrando, Carlo, Romero, Esther, Jorge-Monjas, Pablo, Soria-García, María, Gómez-Herreras, José, Rodríguez-Jiménez, Rita, De Prada-Martín, Blanca, Massimo Antonelli (ORCID:0000-0003-3007-1670), and Luca Montini (ORCID:0000-0003-4602-5134)

Abstract

Background Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity.Methods PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-totreat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545.Findings Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8.1%) of 2396 patients in the CPAP group and 197 (8.2%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1.01 [95% CI 0.81-1.24]; p=0.95). 200 (8.9%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3.5%] of 2241 patients), oronasal dryness (43 [1.9%]), excessive air leak (36 [1.6%]), vomiting (26 [1.2%]), and pain (24 [1.1%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability.Interpretation In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or

Published
2021

18. A Large-Scale, Consortium-Based Genomewide Association Study of Asthma

Author

Moffatt, Miriam F. Gut, Ivo G. Demenais, Florence Strachan, David P. Bouzigon, Emmanuelle Heath, Simon von Mutius, Erika and Farrall, Martin Lathrop, Mark Cookson, William O. C. M. and Kumar, Ashish Burney, Peter Jarvis, Debbie Wjst, Matthias and Kogevinas, Manolis Jogi, Rain Janson, Christer Franklin, Karl A. Omenaas, Ernst Leynaert, Benedicte Pin, Isabelle and Heinrich, Joachim Probst-Hensch, Nicole M. Anto, Josep M. and Sunyer, Jordi Maldonado, Jose-Antonio Martinez-Moratalla, Jesus and Urrutia, Isabel Payo, Felix Kauffmann, Francine Dizier, Marie-Helene Siroux, Valerie Boznanski, Andrzej and Braun-Fahrlaender, Charlotte Genuneit, Jon Glas, Juergen and Horak, Elisabeth Kabesch, Michael Pillai, Sreekumar G. and Helms, Peter J. Carlsen, Karin Carlsen, Kai-Hakon Gerritsen, Jorrit Silverman, Michael Sly, Peter Tsanakas, John Von Berg, Andrea Whyte, Moira Blumenthal, Malcolm Imboden, Medea and Rochat, Thierry Thun, Gian Andri Gerbase, Margaret W. and Curjuric, Ivan Gaspoz, Jean-Michel Liu, Lee-Jane S. Wouters, Inge M. Sigsgaard, Torben Heederik, Dick Basinas, Ioannis and Schlunssen, Vivi Omland, Oyvind Cullinan, Paul and Vermeulen, Roel Henderson, John Granell, Raquel McArdle, Wendy L. Smith, George Davey James, Alan L. Hui, Jennie and Palmer, Lyle J. Beilby, John Musk, A. William Laprise, Catherine Hudson, Thomas J. Lemire, Mathieu Daley, Denise and Becker, Allan Chan-Yeung, Moira Sandford, Andrew and Kozyrskyj, Anita L. Pare, Peter Ferguson, Alexander and Dimich-Ward, Helen Watson, Wade T. Freidin, Maxim B. and Bragina, Elena Iu. Deev, Ivan A. Deeva, Eugenia V. and Kobyakova, Olga S. Puzyrev, Valery P. Ogorodova, Ludmila M. and Khusnutdinova, Elza K. Karunas, Alexandra S. Fedorova, Yuliya Y. and Hall, Ian P. Sayers, Ian Tobin, Martin D. Wan, Yize I. and Heaney, Liam G. Al-Momani, Basima A. H. Mansur, Adel H. and Manney, Sarah Thomson, Neil C. Chaudhuri, Rekha Brightling, Christopher E. Bafadhel, Mona Singapuri, Amisha Niven, Robert Simpson, Angela Holloway, John W. Howarth, Peter H. and Polonikov, Alexey V. Ivanov, Vladimir P. Solodilova, Maria A. Melen, Erik Pershagen, Goeran Bergstroem, Anna Kull, Inger Nyberg, Fredrik Wickman, Magnus Soderhall, Cilla and Kere, Juha Postma, Dirkje S. Kerkhof, Marjan Brunekreef, Bert Smit, Henriette A. de Jongste, Johan C. Wijga, Alet and Aalberse, R. C. Hoekstra, Maarten O. Koppelman, Gerard H. and Binia, Aristea Chung, Kian Fan Bhavsar, Pankaj Chow, Florence Macedo, Patricia Menzies-Gow, Andrew van Stiphout, Nicole Bush, Andrew Lee, Young-Ae Esparza-Gordillo, Jorge and Nickel, Renate Wahn, Ulrich Lau, Susanne Marenholz, Ingo and Haahtela, Tari von Hertzen, Leena Jousilahti, Pekka and Laatikainen, Tiina Makela, Mika J. Vartiainen, Erkki and Laitinen, Tarja Balding, David J. Peden, John F. Corda, Eve and Lechner, Doris Besse, Celine Zelenika, Diana Boland, Anne Bacq, Delphine Demonchy, Stephanie Blanche, Helene and Kamatani, Yoichiro von Mutius, Erika Farrall, Martin and Lathrop, Mark Cookson, William O. C. M. GABRIEL Consortium

Abstract

BACKGROUND Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease. METHODS We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma. RESULTS We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P = 3x10(-9)); rs9273349 on chromosome 6, implicating HLA-DQ (P = 7x10(-14)); rs1342326 on chromosome 9, flanking IL33 (P = 9x10(-10)); rs744910 on chromosome 15 in SMAD3 (P = 4x10(-9)); and rs2284033 on chromosome 22 in IL2RB (P = 1.1x10(-8)). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease (rs2305480, P = 6x10(-23)). Only HLA-DR showed a significant genomewide association with the total serum IgE concentration, and loci strongly associated with IgE levels were not associated with asthma. CONCLUSIONS Asthma is genetically heterogeneous. A few common alleles are associated with disease risk at all ages. Implicated genes suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation. Variants at the ORMDL3/GSDMB locus are associated only with childhood-onset disease. Elevation of total serum IgE levels has a minor role in the development of asthma.

Published
2010

19. Genome-wide association study to identify genetic determinants of severe asthma

Author

Wan, Yize, Shrine, Nick, Soler Artigas, Maria, Wain, Louise, Blakey, John, Moffatt, Miriam, Bush, A., Chung, Kian Fan, Cookson, William, Brown, Matthew, other, and, Wan, Yize, Shrine, Nick, Soler Artigas, Maria, Wain, Louise, Blakey, John, Moffatt, Miriam, Bush, A., Chung, Kian Fan, Cookson, William, Brown, Matthew, and other, and

Abstract

Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(-8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(-8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Published
2012

20. A Large-Scale, Consortium-Based Genomewide Association Study of Asthma

Author

Moffatt, Miriam F. Gut, Ivo G. Demenais, Florence Strachan, David P. Bouzigon, Emmanuelle Heath, Simon von Mutius, Erika and Farrall, Martin Lathrop, Mark Cookson, William O. C. M. and Kumar, Ashish Burney, Peter Jarvis, Debbie Wjst, Matthias and Kogevinas, Manolis Jogi, Rain Janson, Christer Franklin, Karl A. Omenaas, Ernst Leynaert, Benedicte Pin, Isabelle and Heinrich, Joachim Probst-Hensch, Nicole M. Anto, Josep M. and Sunyer, Jordi Maldonado, Jose-Antonio Martinez-Moratalla, Jesus and Urrutia, Isabel Payo, Felix Kauffmann, Francine Dizier, Marie-Helene Siroux, Valerie Boznanski, Andrzej and Braun-Fahrlaender, Charlotte Genuneit, Jon Glas, Juergen and Horak, Elisabeth Kabesch, Michael Pillai, Sreekumar G. and Helms, Peter J. Carlsen, Karin Carlsen, Kai-Hakon Gerritsen, Jorrit Silverman, Michael Sly, Peter Tsanakas, John Von Berg, Andrea Whyte, Moira Blumenthal, Malcolm Imboden, Medea and Rochat, Thierry Thun, Gian Andri Gerbase, Margaret W. and Curjuric, Ivan Gaspoz, Jean-Michel Liu, Lee-Jane S. Wouters, Inge M. Sigsgaard, Torben Heederik, Dick Basinas, Ioannis and Schlunssen, Vivi Omland, Oyvind Cullinan, Paul and Vermeulen, Roel Henderson, John Granell, Raquel McArdle, Wendy L. Smith, George Davey James, Alan L. Hui, Jennie and Palmer, Lyle J. Beilby, John Musk, A. William Laprise, Catherine Hudson, Thomas J. Lemire, Mathieu Daley, Denise and Becker, Allan Chan-Yeung, Moira Sandford, Andrew and Kozyrskyj, Anita L. Pare, Peter Ferguson, Alexander and Dimich-Ward, Helen Watson, Wade T. Freidin, Maxim B. and Bragina, Elena Iu. Deev, Ivan A. Deeva, Eugenia V. and Kobyakova, Olga S. Puzyrev, Valery P. Ogorodova, Ludmila M. and Khusnutdinova, Elza K. Karunas, Alexandra S. Fedorova, Yuliya Y. and Hall, Ian P. Sayers, Ian Tobin, Martin D. Wan, Yize I. and Heaney, Liam G. Al-Momani, Basima A. H. Mansur, Adel H. and Manney, Sarah Thomson, Neil C. Chaudhuri, Rekha Brightling, Christopher E. Bafadhel, Mona Singapuri, Amisha Niven, Robert Simpson, Angela Holloway, John W. and Moffatt, Miriam F. Gut, Ivo G. Demenais, Florence Strachan, David P. Bouzigon, Emmanuelle Heath, Simon von Mutius, Erika and Farrall, Martin Lathrop, Mark Cookson, William O. C. M. and Kumar, Ashish Burney, Peter Jarvis, Debbie Wjst, Matthias and Kogevinas, Manolis Jogi, Rain Janson, Christer Franklin, Karl A. Omenaas, Ernst Leynaert, Benedicte Pin, Isabelle and Heinrich, Joachim Probst-Hensch, Nicole M. Anto, Josep M. and Sunyer, Jordi Maldonado, Jose-Antonio Martinez-Moratalla, Jesus and Urrutia, Isabel Payo, Felix Kauffmann, Francine Dizier, Marie-Helene Siroux, Valerie Boznanski, Andrzej and Braun-Fahrlaender, Charlotte Genuneit, Jon Glas, Juergen and Horak, Elisabeth Kabesch, Michael Pillai, Sreekumar G. and Helms, Peter J. Carlsen, Karin Carlsen, Kai-Hakon Gerritsen, Jorrit Silverman, Michael Sly, Peter Tsanakas, John Von Berg, Andrea Whyte, Moira Blumenthal, Malcolm Imboden, Medea and Rochat, Thierry Thun, Gian Andri Gerbase, Margaret W. and Curjuric, Ivan Gaspoz, Jean-Michel Liu, Lee-Jane S. Wouters, Inge M. Sigsgaard, Torben Heederik, Dick Basinas, Ioannis and Schlunssen, Vivi Omland, Oyvind Cullinan, Paul and Vermeulen, Roel Henderson, John Granell, Raquel McArdle, Wendy L. Smith, George Davey James, Alan L. Hui, Jennie and Palmer, Lyle J. Beilby, John Musk, A. William Laprise, Catherine Hudson, Thomas J. Lemire, Mathieu Daley, Denise and Becker, Allan Chan-Yeung, Moira Sandford, Andrew and Kozyrskyj, Anita L. Pare, Peter Ferguson, Alexander and Dimich-Ward, Helen Watson, Wade T. Freidin, Maxim B. and Bragina, Elena Iu. Deev, Ivan A. Deeva, Eugenia V. and Kobyakova, Olga S. Puzyrev, Valery P. Ogorodova, Ludmila M. and Khusnutdinova, Elza K. Karunas, Alexandra S. Fedorova, Yuliya Y. and Hall, Ian P. Sayers, Ian Tobin, Martin D. Wan, Yize I. and Heaney, Liam G. Al-Momani, Basima A. H. Mansur, Adel H. and Manney, Sarah Thomson, Neil C. Chaudhuri, Rekha Brightling, Christopher E. Bafadhel, Mona Singapuri, Amisha Niven, Robert Simpson, Angela Holloway, John W.

Abstract

BACKGROUND Susceptibility to asthma is influenced by genes and environment; implicated genes may indicate pathways for therapeutic intervention. Genetic risk factors may be useful in identifying subtypes of asthma and determining whether intermediate phenotypes, such as elevation of the total serum IgE level, are causally linked to disease. METHODS We carried out a genomewide association study by genotyping 10,365 persons with physician-diagnosed asthma and 16,110 unaffected persons, all of whom were matched for ancestry. We used random-effects pooled analysis to test for association in the overall study population and in subgroups of subjects with childhood-onset asthma (defined as asthma developing before 16 years of age), later-onset asthma, severe asthma, and occupational asthma. RESULTS We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P = 3x10(-9)); rs9273349 on chromosome 6, implicating HLA-DQ (P = 7x10(-14)); rs1342326 on chromosome 9, flanking IL33 (P = 9x10(-10)); rs744910 on chromosome 15 in SMAD3 (P = 4x10(-9)); and rs2284033 on chromosome 22 in IL2RB (P = 1.1x10(-8)). Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease (rs2305480, P = 6x10(-23)). Only HLA-DR showed a significant genomewide association with the total serum IgE concentration, and loci strongly associated with IgE levels were not associated with asthma. CONCLUSIONS Asthma is genetically heterogeneous. A few common alleles are associated with disease risk at all ages. Implicated genes suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation. Variants at the ORMDL3/GSDMB locus are associated only with childhood-onset disease. Elevation of total serum IgE levels has a minor role in the development of asthma.

Published
2010

22. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified a potentially important pathway in which to focus the development of effective asthma therapies. Future directions will include functional analysis of replicated variants and tests of interactions between the multiple genetic and environmental factors likely to be involved in disease.

23. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina and Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified

24. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina and Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified

25. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina and Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified

26. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina and Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified

27. Genetic epidemiology of atopy and asthma

Author

Wan, Yize Isalina and Wan, Yize Isalina

Abstract

The evidence for genetic contributions to the development of asthma and atopy has been well established. Refining the major genetic factors underlying these contributions will lead to a greater understanding of the pathophysiology of these conditions and potentially identify novel therapeutic targets. This thesis describes a series of studies designed primarily using genome-wide association (GWA) approaches to examine common single nucleotide polymorphisms (SNPs) contributing to these phenotypes in the Caucasian population. Susceptibility to atopy was assessed using both non-parametric association tests of SNPs across the genome and focused analysis of two regions on chromosomes 3p22.1-q22.1 and 17p12-q24.3 previously identified through a meta-analysis of genome-wide linkage studies (GSMA). The discovery cohort consisted of 1,083 cases and 2,770 controls, replication analyses were undertaken in four independent population cohorts. A GWA study of severe asthma was carried out in 933 cases and 3,346 controls with replication in a further 231 cases and 1,345 controls. The contribution of SNPs within all previously reported asthma susceptibility loci identified using a comprehensive literature search was also evaluated. Overall, there is evidence for a large number of loci influencing both atopy and severe asthma, each harbouring modest effects. A number of potentially novel loci meeting nominal significance in both GWA studies have been identified requiring further work. Strong evidence was found to support the IL1RL1-IL33 signalling pathway in asthma pathogenesis. Molecular characterisation of the 5’ untranslated regions of IL1RL1 and IL33 suggest a complex regulatory role of identified common variants involving multiple promoters for IL1RL1. A number of asthma specific variants within the chromosome 2q12 and 9p24.1 regions were detected using next generation re-sequencing in homogenised pools of cases and controls warranting further analyses. This work has identified

28. Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Author

Rupert Pearse, Marco Ranieri, Tom Abbott, Mari-Liis Pakats, Edoardo Piervincenzi, Akshaykumar Patel, Brennan Kahan, Andrew Rhodes, Priyanthi Dias, Russell Hewson, Ib Jammer, Michelle Chew, Cesar Aldecoa, Reitze Rodseth, Bruce Biccard, Tim Stephens, Sara Payne, David Hepworth, Soeren Pischke, Joerund Asvall, John Hausken, Shaman Jhanji, Martin Rooms, Neil Flint, Dawn Hales, Tamas Szakmany, Andrew Leitch, Savino Spadaro, Davide Chiumello, Paul Johnston, Joyce Yeung, Guglielmo Tellan, Tonny Veenith, Josep Macmillan, Pierpaolo Terragni, Caroline Sander, Vidya Kasipandian, Tahania Ahmad, Aaron Lee, Marcello Tammaro, Danny McAuley, Simon Skene, Ravinder Vohra, Matt Wilson, Mark Edwards, Ewen Griffiths, Naomi Pritchard, Claudia Filippini, Tor Aasmundstad, Einar Aksnes, Lise-Merete Alpers, Andreas Barratt-Due, Anita Dahl, Linda Feldt, Elisa Figari, Eva Flåten, Karen Granheim, Minna Hagring, Håkon Haugaa, Gisle Kjoesen, Inge Klaevahaugen, Harald Lenz, Marianne Myhre, Hilde Orrem, Emily Stitt, Tor Inge Toennessen, Samuel Al-Kadhimi, Robert Anker, Mihaela Balint, Lauren Barraclough, Ethel Black, Matt Clayton, Leonora Conneely, Zara Edwards, Alex Eeles, Matthew Evans, Michelle Gerstman, Nicole Greenshields, Eleanor Harvey, Aoife Hegarty, Natalie Hester, Jenna Hutchinson, Ramanathan Kasivisvanathan, Helen Lawrence, Veronica Marsh, Laura Matthews, Francesca Mazzola, Jamie McCanny, Ben Morrison, Michelle O'Mahony, Ching Ling Pang, David Parkinson, Katrina Pirie, Ravishankar Rao Baikady, Louisa Shovel, Lorna Smith, Kate Tatham, Peter Thomas, Sophie Uren, Susanna Walker, Alasdair Wills, Prematie Andreou, Alex Howson, Jasmin Kaur, Adam Lewszuk, Esther Molina, Nirmalabaye Ramsamy, Emma Roberts, Vanessa Amaral, Salma Begum, Soliana Bekele, Richard Cashmore, Carmen Correia, Steven Dunkley, Maria Fernandez, Alexander Fowler, Amaia Garcia, Maria Della Giovampaola, Kathryn Greaves, Bethan Griffiths, Ryan Haines, Richard Haslop, Ying Hu, Sarah Hui, Marta Januszewska, Vasi Manon, Tim Martin, Shaun May, Annamaria Minicozzi, Edyta Niebrzegowska, Monica Oliveira, Katherine Pates, Filipa Santos, Tasnin Shahid, Paolo Simili, Alastair Somerville, Emily Subhedar, Ruzena Uddin, Sophie Walker, Yize Wan, Jan Whalley, Parjam Zolfaghari, Una Gunter, Gemma Hodkinson, Gwenllian Howe, Valentina Baratozzi, Giulia Casotto, Giulia Darai, Erica Ferrari, Giovanni Mistraletti, Valentina Palmaverdi, Stefano Furlani, Paolo Priani, Riccardo Ragazzi, Marco Salmaso, Marco Verri, Carlo Volta, Chris Nutt, Emma McKay, Orla O'Neill, Jaimin Patel, Katie Atterbury, Sarah Ballinger, Natalie Carling, Kaytie Ellis, Jo Gresty, Teresa Melody, Jade Monk, Chloe Norman, Eleanor Reeves, Julia Sampson, Peter Sutton, Marie Thomas, Amy Bamford, Colin Bergin, Ronald Carrera, Lauren Cooper, Liesl Despy, Karen Ellis, Emma Fellows, Stephanie Goundry, Samantha Harkett, Peter Ip, Tracy Mason, Christopher McGhee, Aisling McLaughlin, Aoife Neal, Martin Pope, Stephanie Porter, Hazel Smith, Catherine Snelson, Elaine Spruce, Ylenia Vigo, Arlo Whitehouse, Tony Whitehouse, Maria Donatiello, Sergio Gazzanelli, Mario Mezzapesa, Martina Savino, Giacomo Settesoldi, Gudrun Kunst, Sian Birch, Louise Greig, Harriet Noble, Evita Pappa, Bethany Penhaligon, Andrea Cossu, Leda Floris, Davide Piredda, Alberto Racca, Olof Brattstrom, Bente Heggelund, Magnus Flodberg, Sandra Månsson, Mamoona Ahmed, Jonathan Allen, Paula Bell, Roman Genetu, Julia Glennon, Janice Hanley, Katy Jenner, Summayyah Jogi, Parisa Mahjoob, Clare McGovern, Anthony Murphy, Roonak Nazari, Jacki Routledge, Trishna Uttamlal, Sinead Ward, Giorgio Iotti, Raffaella Picchioni, Silvia Poma, Paolo Navalesi, Andrea Bruni, Brunella De Leonardis, Eugenio Garofalo, Panna Patel, Carol McArthur, Karen Burns, Steven Peters, Giuseppe Foti, Serena Calcinati, Alice Grassi, Silvia Villa, John Berridge, Muthuraj Kanakaraj, Hazel Cahill, Greg Forshaw, Andy Gibson, Lia Grainger, Kate Howard, Katherine James, Zoe Murphy, Helen Sweeting, Rebecca Tait, Danielle Wilcock, David Yates, Sean Cope, Ashley Allan, Rebecca Betts, Sarah Cornell, Julie Sheriff, Lindsey Woods, Giacomo Grasselli, Matteo Brioni, Luigi Castagna, Richard von Rahden, Zane Farina, Samantha Green, Simphiwe Gumede, Chantal Rajah, Arisha Ramkillawan, Susan Moug, David Alcorn, Carol Dalton, Natalie Dickinson, Jennifer Edwards, Steven Henderson, Erin McIlveen, Richard Ramsaran, Joanne Bell, Lorna Fleming, Kathleen Monks, Jane Parker, Sean Stamper, Jo Stokes-Denson, Elisa Elías, Yessica Guerra, Jesus Rico-Feijoo, Carlos Kidel, Helder Filipe, Gretchelle Asis, Yvonne Gleeson, Alice Harvey, Christine Jackson, Margaret McNeil, Sara Mingo, Glykeria Pakou, Manuel Pinto, Stephen Wright, Maite Babio-Galan, David Buckley, Verity Calder, Ahmad Chishti, Joseph Cosgrove, Katherine Cullen, Leigh Dunn, Matthew Faulds, Jonathan Fortune, Matthew Gardner, Abigail Harrison, Carole Hays, Gerry Jones, Caroline Macfie, Iain Mccullagh, Ian Nesbitt, Suzanne O'Neil, Catherine Phoenix, Girish Rangaswamy, Craig Samson, Carmen Scott, Tara Shrestha, Rita Singh, Graham Soulsby, Jon Walton, Kimberley Zwiggelaar, Ceri Lynch, Heidi Clarke, Bethan Deacon, Helen Ivatt, Leanne Jones, Ahmed Latif, Shaun Oram, Chris Perman, Lisa Roche, Rowan Duys, Margot Flint, Kamal Bhagwan, Ettienne Coetzee, Ivan Joubert, Felipe Montoya-Pelaez, Pradeep Navsaria, Guy Picken, Owen Porrill, Grant Strathie, Thembinkosi Zungu, Sireesha Aluri, Simon Chau, Deborah Cooper, Mishell Cunningham, Allison Daniels, Susan Hope, Alice Nicholson, Laura Walker, Antonino Giarratano, Giuseppe Accurso, Santi Raineri, Giuseppe Tricoli, Richard Innes, Patricia Doble, Joanne Hutter, Corinne Pawley, Moira Tait, Mark Hamilton, Edward Andrade, Veronica Barnes, Claire Dalton, Carlos Delgado, Sarah Farnell-Ward, Helen Farrah, Geraldine Gray, Luisa Howlett, Gipsy Joseph, Monika Krupa, Susannah Leaver, Joao Macedo, Karen Maher, Johannes Mellinghoff, Rachel Oguntimehin, Joel Pereira, Frances Robinson, Christine Ryan, Nirav Shah, Paula Shirley, Alexandra Torborg, Thuli Biyase, Leanne Drummond, Belinda Kusel, Mbalenhle Mbuyisa, Sivuyisiwe Solala, Jenna Taylor, Adanma Ezihe-Ejiofor, Maame Aduse-Poku, Gary Colville, Louise Davies, Soo Kang, Alex Phillips, Justin Kirk-Bayley, Leigh Kelliher, Paula Carvelli, Gokce Daysal, Matthew Dickinson, Nancileigh Doyle, Christina Hughes, Laura Montague, Elizabeth Potter, Armorel Salberg, Sheena Sibug, Sinduja Sivarajan, Milo Thomson, Nichola Wakeford, Monica Rocco, Daniela Alampi, Daniel Conway, Richard Clark, Jashmin Maria, Fiona Pomeroy, Tanviha Quraishi, Abigail Williams, Srikanth Chukkambotla, Caroline Aherne, Donna Harrison-Briggs, Jill Fitchett, Stephen Duberley, Andrea Zanoni, Daniela Cardinale, Claudia Righi, Mark Blunt, Tracy Fuller, Ruth Hodgson, Melissa Rosbergen, Andrew Brennan, Louise Akeroyd, Victoria Boardman, Christopher Bull, Mike Carrick, Ian Chadderton, Sarah Cooper, Sarah Goellner, Laura Graham, Carl Ilyas, James King, Muhammad Laklouk, Tom Lawton, Christopher Macrow, Michael Munro, Adam Neep, Martin Northey, Victoria Peacock, Kate Pye, Lydia Radley, James Sira, Beth Smithson, Stuart Syddall, David Tooth, Thomas White, Sindre Hoel, Elin Aakre, Monica Bakke, Tone Hoivik, Arystarch Makowski, Harry Alcock, Sean Cardoso, Samantha Coetzee, Mary Everett, Mohamed Ibrahim, Christina Kouridaki, Vongayi Ogbeide, Elisabetta Bertellini, Valentina Bertolotti, Antonio Buono, Maria Fanigliulo, Ram Kumar, Nicole Richards, Alisha Allana, Samantha Bacciarelli, Helen Barker, Jessica De Bois, Isabel Bradley, Jennifer Crooks, Peter Daum, Alex Feben, Lizzie Gannon, Sarah Kipling, Andrew Peetamsingh, Charlotte Quamina, Sahiba Sethi, Harry Sivadhas, Kathryn Sollesta, Andrew Swain, Evalyn Tan, Joan Willis, Maggie Zou, Julius Cranshaw, Nina Barratt, Katie Bowman, Debbie Branney, Maria Letts, Sally Pitts, Christopher Day, Sarah Benyon, Sara Eddy, Adam Green, Anna Grice, Sinéad Kelly, Daisy Mackle, Victor Mariano, Linda Park, Pauline Sibley, William Spencer, Elena Bignami, Valentina Bellini, Francesco Forfori, Maria Curci, Alessandra Leo, Matthew Jackson, Jennifer Awolesi, Sheila Hodgkinson, Alissa Kent, Dee Leonard, Claire Stapleton, Clare Tibke, Farhad Alexander-Sefre, Lorraine Campey, Kathryn Hall, Jennifer Spimpolo, Malin Nilsson, Helen Didriksson, Emma Hamilton, Mandy Carnahan, Chris Mowatt, Jo Stickley, Antonio Corcione, Giuseppe Rossi, Hege Fladby, Nina Andersen, Gunhild Bjoernå, Mads Reite, Linda Roertveit, Philipp Seidel, Glenn Arnold, Melissa Benavente, Anjalee Chattersingh, Nyasha Chironga, Gillian Hornzee, Joyce Kibaru, Ihtisham Malik, Laura McLeavy, Byiravey Pathmanathan, Florence Prior, Rhea Strudwick, Marios Vezyrgiannis, Aneeta Sinha, Sheeba Babu, Bisanth Batuwitage, Zoe Daly, Katharine Ellinor, Elizabeth Hawes, Ann Holmes, Karen Hudson, Jeremy Nightingale, Alison Le Poidevin, Lindsey Roberts, Agnieszka Kubisz-Pudelko, Joanna Allison, Lucy Pippard, Vincent Hamlyn, Angie Organ, Thaventhran Prabhahar, Hayley Bridger, Lee Dvorkin, Vitul Manhas, Rachel Vincent, Shondipon Laha, Terri-Louise Cromie, Donna Doyle, Rachel Howarth, Mark Verlander, Ailsa Watt, Alexandra Williams, Massimo Antonelli, Salvatore Cutuli, Luca Montini, Juan Graterol, Benita Adams, Sarah Bean, Karen Burt, Fiona Hammonds, Suyogi Jigajinni, Laura Fulton, Stephen Kinghorn, Jost Mullenheim, Kirsty Baillie, Martyn Cain, Kerry Colling, Carol Hannaway, Ruggero Corso, Morena Calli, Carlos Ferrando, Esther Romero, Pablo Jorge-Monjas, María Soria-García, José Gómez-Herreras, Rita Rodríguez-Jiménez, Blanca De Prada-Martín, Pearse, Rupert, Ranieri, Marco, Abbott, Tom, Pakats, Mari-Lii, Piervincenzi, Edoardo, Patel, Akshaykumar, Kahan, Brennan, Rhodes, Andrew, Dias, Priyanthi, Hewson, Russell, Jammer, Ib, Chew, Michelle, Aldecoa, Cesar, Rodseth, Reitze, Biccard, Bruce, Stephens, Tim, Payne, Sara, Hepworth, David, Pischke, Soeren, Asvall, Joerund, Hausken, John, Jhanji, Shaman, Rooms, Martin, Flint, Neil, Hales, Dawn, Szakmany, Tama, Leitch, Andrew, Spadaro, Savino, Chiumello, Davide, Johnston, Paul, Yeung, Joyce, Tellan, Guglielmo, Veenith, Tonny, Macmillan, Josep, Terragni, Pierpaolo, Sander, Caroline, Kasipandian, Vidya, Ahmad, Tahania, Lee, Aaron, Tammaro, Marcello, McAuley, Danny, Skene, Simon, Vohra, Ravinder, Wilson, Matt, Edwards, Mark, Griffiths, Ewen, Pritchard, Naomi, Filippini, Claudia, Aasmundstad, Tor, Aksnes, Einar, Alpers, Lise-Merete, Barratt-Due, Andrea, Dahl, Anita, Feldt, Linda, Figari, Elisa, Flåten, Eva, Granheim, Karen, Hagring, Minna, Haugaa, Håkon, Kjoesen, Gisle, Klaevahaugen, Inge, Lenz, Harald, Myhre, Marianne, Orrem, Hilde, Stitt, Emily, Toennessen, Tor Inge, Al-Kadhimi, Samuel, Anker, Robert, Balint, Mihaela, Barraclough, Lauren, Black, Ethel, Clayton, Matt, Conneely, Leonora, Edwards, Zara, Eeles, Alex, Evans, Matthew, Gerstman, Michelle, Greenshields, Nicole, Harvey, Eleanor, Hegarty, Aoife, Hester, Natalie, Hutchinson, Jenna, Kasivisvanathan, Ramanathan, Lawrence, Helen, Marsh, Veronica, Matthews, Laura, Mazzola, Francesca, McCanny, Jamie, Morrison, Ben, O'Mahony, Michelle, Pang, Ching Ling, Parkinson, David, Pirie, Katrina, Rao Baikady, Ravishankar, Shovel, Louisa, Smith, Lorna, Tatham, Kate, Thomas, Peter, Uren, Sophie, Walker, Susanna, Wills, Alasdair, Andreou, Prematie, Howson, Alex, Kaur, Jasmin, Lewszuk, Adam, Molina, Esther, Ramsamy, Nirmalabaye, Roberts, Emma, Amaral, Vanessa, Begum, Salma, Bekele, Soliana, Cashmore, Richard, Correia, Carmen, Dunkley, Steven, Fernandez, Maria, Fowler, Alexander, Garcia, Amaia, Della Giovampaola, Maria, Greaves, Kathryn, Griffiths, Bethan, Haines, Ryan, Haslop, Richard, Hu, Ying, Hui, Sarah, Januszewska, Marta, Manon, Vasi, Martin, Tim, May, Shaun, Minicozzi, Annamaria, Niebrzegowska, Edyta, Oliveira, Monica, Pates, Katherine, Santos, Filipa, Shahid, Tasnin, Simili, Paolo, Somerville, Alastair, Subhedar, Emily, Uddin, Ruzena, Walker, Sophie, Wan, Yize, Whalley, Jan, Zolfaghari, Parjam, Gunter, Una, Hodkinson, Gemma, Howe, Gwenllian, Baratozzi, Valentina, Casotto, Giulia, Darai, Giulia, Ferrari, Erica, Mistraletti, Giovanni, Palmaverdi, Valentina, Furlani, Stefano, Priani, Paolo, Ragazzi, Riccardo, Salmaso, Marco, Verri, Marco, Volta, Carlo, Nutt, Chri, McKay, Emma, O'Neill, Orla, Patel, Jaimin, Atterbury, Katie, Ballinger, Sarah, Carling, Natalie, Ellis, Kaytie, Gresty, Jo, Melody, Teresa, Monk, Jade, Norman, Chloe, Reeves, Eleanor, Sampson, Julia, Sutton, Peter, Thomas, Marie, Bamford, Amy, Bergin, Colin, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Fellows, Emma, Goundry, Stephanie, Harkett, Samantha, Ip, Peter, Mason, Tracy, McGhee, Christopher, McLaughlin, Aisling, Neal, Aoife, Pope, Martin, Porter, Stephanie, Smith, Hazel, Snelson, Catherine, Spruce, Elaine, Vigo, Ylenia, Whitehouse, Arlo, Whitehouse, Tony, Donatiello, Maria, Gazzanelli, Sergio, Mezzapesa, Mario, Savino, Martina, Settesoldi, Giacomo, Kunst, Gudrun, Birch, Sian, Greig, Louise, Noble, Harriet, Pappa, Evita, Penhaligon, Bethany, Cossu, Andrea, Floris, Leda, Piredda, Davide, Racca, Alberto, Brattstrom, Olof, Heggelund, Bente, Flodberg, Magnu, Månsson, Sandra, Ahmed, Mamoona, Allen, Jonathan, Bell, Paula, Genetu, Roman, Glennon, Julia, Hanley, Janice, Jenner, Katy, Jogi, Summayyah, Mahjoob, Parisa, McGovern, Clare, Murphy, Anthony, Nazari, Roonak, Routledge, Jacki, Uttamlal, Trishna, Ward, Sinead, Iotti, Giorgio, Picchioni, Raffaella, Poma, Silvia, Navalesi, Paolo, Bruni, Andrea, De Leonardis, Brunella, Garofalo, Eugenio, Patel, Panna, McArthur, Carol, Burns, Karen, Peters, Steven, Foti, Giuseppe, Calcinati, Serena, Grassi, Alice, Villa, Silvia, Berridge, John, Kanakaraj, Muthuraj, Cahill, Hazel, Forshaw, Greg, Gibson, Andy, Grainger, Lia, Howard, Kate, James, Katherine, Murphy, Zoe, Sweeting, Helen, Tait, Rebecca, Wilcock, Danielle, Yates, David, Cope, Sean, Allan, Ashley, Betts, Rebecca, Cornell, Sarah, Sheriff, Julie, Woods, Lindsey, Grasselli, Giacomo, Brioni, Matteo, Castagna, Luigi, von Rahden, Richard, Farina, Zane, Green, Samantha, Gumede, Simphiwe, Rajah, Chantal, Ramkillawan, Arisha, Moug, Susan, Alcorn, David, Dalton, Carol, Dickinson, Natalie, Edwards, Jennifer, Henderson, Steven, McIlveen, Erin, Ramsaran, Richard, Bell, Joanne, Fleming, Lorna, Monks, Kathleen, Parker, Jane, Stamper, Sean, Stokes-Denson, Jo, Elías, Elisa, Guerra, Yessica, Rico-Feijoo, Jesu, Kidel, Carlo, Filipe, Helder, Asis, Gretchelle, Gleeson, Yvonne, Harvey, Alice, Jackson, Christine, McNeil, Margaret, Mingo, Sara, Pakou, Glykeria, Pinto, Manuel, Wright, Stephen, Babio-Galan, Maite, Buckley, David, Calder, Verity, Chishti, Ahmad, Cosgrove, Joseph, Cullen, Katherine, Dunn, Leigh, Faulds, Matthew, Fortune, Jonathan, Gardner, Matthew, Harrison, Abigail, Hays, Carole, Jones, Gerry, Macfie, Caroline, Mccullagh, Iain, Nesbitt, Ian, O'Neil, Suzanne, Phoenix, Catherine, Rangaswamy, Girish, Samson, Craig, Scott, Carmen, Shrestha, Tara, Singh, Rita, Soulsby, Graham, Walton, Jon, Zwiggelaar, Kimberley, Lynch, Ceri, Clarke, Heidi, Deacon, Bethan, Ivatt, Helen, Jones, Leanne, Latif, Ahmed, Oram, Shaun, Perman, Chri, Roche, Lisa, Duys, Rowan, Flint, Margot, Bhagwan, Kamal, Coetzee, Ettienne, Joubert, Ivan, Montoya-Pelaez, Felipe, Navsaria, Pradeep, Picken, Guy, Porrill, Owen, Strathie, Grant, Zungu, Thembinkosi, Aluri, Sireesha, Chau, Simon, Cooper, Deborah, Cunningham, Mishell, Daniels, Allison, Hope, Susan, Nicholson, Alice, Walker, Laura, Giarratano, Antonino, Accurso, Giuseppe, Raineri, Santi, Tricoli, Giuseppe, Innes, Richard, Doble, Patricia, Hutter, Joanne, Pawley, Corinne, Tait, Moira, Hamilton, Mark, Andrade, Edward, Barnes, Veronica, Dalton, Claire, Delgado, Carlo, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Howlett, Luisa, Joseph, Gipsy, Krupa, Monika, Leaver, Susannah, Macedo, Joao, Maher, Karen, Mellinghoff, Johanne, Oguntimehin, Rachel, Pereira, Joel, Robinson, France, Ryan, Christine, Shah, Nirav, Shirley, Paula, Torborg, Alexandra, Biyase, Thuli, Drummond, Leanne, Kusel, Belinda, Mbuyisa, Mbalenhle, Solala, Sivuyisiwe, Taylor, Jenna, Ezihe-Ejiofor, Adanma, Aduse-Poku, Maame, Colville, Gary, Davies, Louise, Kang, Soo, Phillips, Alex, Kirk-Bayley, Justin, Kelliher, Leigh, Carvelli, Paula, Daysal, Gokce, Dickinson, Matthew, Doyle, Nancileigh, Hughes, Christina, Montague, Laura, Potter, Elizabeth, Salberg, Armorel, Sibug, Sheena, Sivarajan, Sinduja, Thomson, Milo, Wakeford, Nichola, Rocco, Monica, Alampi, Daniela, Conway, Daniel, Clark, Richard, Maria, Jashmin, Pomeroy, Fiona, Quraishi, Tanviha, Williams, Abigail, Chukkambotla, Srikanth, Aherne, Caroline, Harrison-Briggs, Donna, Fitchett, Jill, Duberley, Stephen, Zanoni, Andrea, Cardinale, Daniela, Righi, Claudia, Blunt, Mark, Fuller, Tracy, Hodgson, Ruth, Rosbergen, Melissa, Brennan, Andrew, Akeroyd, Louise, Boardman, Victoria, Bull, Christopher, Carrick, Mike, Chadderton, Ian, Cooper, Sarah, Goellner, Sarah, Graham, Laura, Ilyas, Carl, King, Jame, Laklouk, Muhammad, Lawton, Tom, Macrow, Christopher, Munro, Michael, Neep, Adam, Northey, Martin, Peacock, Victoria, Pye, Kate, Radley, Lydia, Sira, Jame, Smithson, Beth, Syddall, Stuart, Tooth, David, White, Thoma, Hoel, Sindre, Aakre, Elin, Bakke, Monica, Hoivik, Tone, Makowski, Arystarch, Alcock, Harry, Cardoso, Sean, Coetzee, Samantha, Everett, Mary, Ibrahim, Mohamed, Kouridaki, Christina, Ogbeide, Vongayi, Bertellini, Elisabetta, Bertolotti, Valentina, Buono, Antonio, Fanigliulo, Maria, Kumar, Ram, Richards, Nicole, Allana, Alisha, Bacciarelli, Samantha, Barker, Helen, De Bois, Jessica, Bradley, Isabel, Crooks, Jennifer, Daum, Peter, Feben, Alex, Gannon, Lizzie, Kipling, Sarah, Peetamsingh, Andrew, Quamina, Charlotte, Sethi, Sahiba, Sivadhas, Harry, Sollesta, Kathryn, Swain, Andrew, Tan, Evalyn, Willis, Joan, Zou, Maggie, Cranshaw, Juliu, Barratt, Nina, Bowman, Katie, Branney, Debbie, Letts, Maria, Pitts, Sally, Day, Christopher, Benyon, Sarah, Eddy, Sara, Green, Adam, Grice, Anna, Kelly, Sinéad, Mackle, Daisy, Mariano, Victor, Park, Linda, Sibley, Pauline, Spencer, William, Bignami, Elena, Bellini, Valentina, Forfori, Francesco, Curci, Maria, Leo, Alessandra, Jackson, Matthew, Awolesi, Jennifer, Hodgkinson, Sheila, Kent, Alissa, Leonard, Dee, Stapleton, Claire, Tibke, Clare, Alexander-Sefre, Farhad, Campey, Lorraine, Hall, Kathryn, Spimpolo, Jennifer, Nilsson, Malin, Didriksson, Helen, Hamilton, Emma, Carnahan, Mandy, Mowatt, Chri, Stickley, Jo, Corcione, Antonio, Rossi, Giuseppe, Fladby, Hege, Andersen, Nina, Bjoernå, Gunhild, Reite, Mad, Roertveit, Linda, Seidel, Philipp, Arnold, Glenn, Benavente, Melissa, Chattersingh, Anjalee, Chironga, Nyasha, Hornzee, Gillian, Kibaru, Joyce, Malik, Ihtisham, McLeavy, Laura, Pathmanathan, Byiravey, Prior, Florence, Strudwick, Rhea, Vezyrgiannis, Mario, Sinha, Aneeta, Babu, Sheeba, Batuwitage, Bisanth, Daly, Zoe, Ellinor, Katharine, Hawes, Elizabeth, Holmes, Ann, Hudson, Karen, Nightingale, Jeremy, Le Poidevin, Alison, Roberts, Lindsey, Kubisz-Pudelko, Agnieszka, Allison, Joanna, Pippard, Lucy, Hamlyn, Vincent, Organ, Angie, Prabhahar, Thaventhran, Bridger, Hayley, Dvorkin, Lee, Manhas, Vitul, Vincent, Rachel, Laha, Shondipon, Cromie, Terri-Louise, Doyle, Donna, Howarth, Rachel, Verlander, Mark, Watt, Ailsa, Williams, Alexandra, Antonelli, Massimo, Cutuli, Salvatore, Montini, Luca, Graterol, Juan, Adams, Benita, Bean, Sarah, Burt, Karen, Hammonds, Fiona, Jigajinni, Suyogi, Fulton, Laura, Kinghorn, Stephen, Mullenheim, Jost, Baillie, Kirsty, Cain, Martyn, Colling, Kerry, Hannaway, Carol, Corso, Ruggero, Calli, Morena, Ferrando, Carlo, Romero, Esther, Jorge-Monjas, Pablo, Soria-García, María, Gómez-Herreras, José, Rodríguez-Jiménez, Rita, and De Prada-Martín, Blanca

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_treatment, Population, NO, 03 medical and health sciences, 0302 clinical medicine, CPAP, Abdomen, Settore MED/41 - ANESTESIOLOGIA, Intubation, Intratracheal, medicine, Humans, Intubation, 030212 general & internal medicine, Continuous positive airway pressure, Adverse effect, education, education.field_of_study, Continuous Positive Airway Pressure, business.industry, respiratory complications, continuous positive airway pressure, major abdominal surgery, Pneumonia, Middle Aged, medicine.disease, respiratory tract diseases, Intratracheal, Treatment Outcome, 030228 respiratory system, Respiratory failure, Anesthesia, Vomiting, medicine.symptom, Respiratory Insufficiency, business, Abdominal surgery
Abstract

BackgroundRespiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity.MethodsPRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545.FindingsBetween Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8·1%) of 2396 patients in the CPAP group and 197 (8·2%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1·01 [95% CI 0·81-1·24]; p=0·95). 200 (8·9%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3·5%] of 2241 patients), oronasal dryness (43 [1·9%]), excessive air leak (36 [1·6%]), vomiting (26 [1·2%]), and pain (24 [1·1%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability.InterpretationIn this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended.FundingNational Institute for Health Research, Barts Charity, Intersurgical, Association of Anaesthetists, and Sapienza Università di Roma.

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