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1. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study

Author

Manuela Carugati, Stefano Aliberti, Luis Felipe Reyes, Ricardo Franco Sadud, Muhammad Irfan, Cristina Prat, Nilam J. Soni, Paola Faverio, Andrea Gori, Francesco Blasi, Marcos I. Restrepo, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I. Garzón, Victor Hugo Cambursano, Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M. Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Florencio Varela, Sonali Shah, Felix Lötsch, Florian Thalhammer, Kurt Anseeuw, Camille A. Francois, Eva Van Braeckel, Jean Louis Vincent, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-Knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W. Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Katerina Dimakou, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mina Gaga, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A. Koul, P.A. Mahesh, B.S. Jayaraj, Kiran Vishnu Narayan, Hirennappa B. Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M. Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Roberta Petrino, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Fabio Franzetti, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F. Villegas, Milic Medenica, E.M.W. van de Garde, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N.O. Nwankwo, Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N. Ukwaja, Lukasz Minarowski, Skoczyński Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Sofia B Ravara, Victoria Brocovschii, Chesov Ion, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Nada Bogdanović, Branislava Milenkovic, Dragica Pesut, Charles Feldman, Ho Kee Yum, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J. Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Jordi Rello, Silvia Moyano, Francisco Sanz, Oriol Sibila, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job F.M. van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J. Dhasmana, Andrew Feneley, Rhiannon Ions, Julie Skeemer, Gerrit Woltmann, Carole Hancock, Adam T. Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, Karen S. Allen, Veronica Brito, Jessica Dietz, Claire E. Dysart, Susan M. Kellie, Ricardo A. Franco-Sadud, Garnet Meier, Thomas L. Holland, Stephen P. Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B. Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I. Hinojosa, Stephanie M. Levine, Luis F. Angel, Antonio Anzueto, K. Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G. Wunderink, Ray D. Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, and Lucía Labra

Subjects
Medicine
Abstract

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p

Published
2018
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3. Aspiration Risk Factors, Microbiology, and Empiric Antibiotics for Patients Hospitalized With Community-Acquired Pneumonia

Author

Judith Marin-Corral, Sergi Pascual-Guardia, Francesco Amati, Stefano Aliberti, Joan R Masclans, Nilam Soni, Alejandro Rodriguez, Oriol Sibila, Francisco Sanz, Giovanni Sotgiu, Antonio Anzueto, Katerina Dimakou, Roberta Petrino, Ewoudt van de Garde, Marcos I Restrepo, GLIMP investigators, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I Garzón, Victor Hugo Cambursano, V H Dr Cazaux A Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Sonali Shah, Felix Lötsch, Florian Thalhammer, Kurt Anseeuw, Camille A Francois, Eva Van Braeckel, Jean Louis Vincent, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-Fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-Knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A Koul, P A Mahesh, B S Jayaraj, Kiran Vishnu Narayan, Hirennappa B Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Paola Faverio, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Ospedale San Luca, Fabio Franzetti, Manuela Carugati, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F Villegas, Milic Medenica, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N O Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N Ukwaja, Muhammad Irfan, Lukasz Minarowski, Skoczyński Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Cláudia Ferrão, João Neves, Abel Salazar, Sofia B Ravara, Victoria Brocovschii, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Serbia Nada Bogdanović, Branislava Milenkovic, Dragica Pesut, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Medicina Interna, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González Del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Alicia Lacoma de la Torre, Ignasi García-Olivé, Jordi Rello, Silvia Moyano, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job Fm van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Charles Feldman, Ho Kee Yum, Inje Univ Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Izmir Dr Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J Dhasmana, Andrew Feneley, Adam T Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, C Hancock, David Villafuerte, Karen S Allen, Veronica Brito, Jessica Dietz, Claire E Dysart, Susan M Kellie, Clement J Ricardo A Franco-Sadud, Garnet Meier, Mina Gaga, Thomas L Holland, Stephen P Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I Hinojosa, Stephanie M Levine, Luis F Reyes, Luis F Angel, K Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G Wunderink, Ray D Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, Lucía Labra, Marin-Corral J., Pascual-Guardia S., Amati F., Aliberti S., Masclans J.R., Soni N., Rodriguez A., Sibila O., Sanz F., Sotgiu G., Anzueto A., Dimakou K., Petrino R., van de Garde E., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Adrian Ceccato V.H.D.C.A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Pefura Yone E.W., Mbatchou Ngahane B.H., Shen N., Xu J.-F., Bustamante Rico C.A., Buitrago R., Pereira Paternina F.J., Kayembe Ntumba J.-M., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M.-L., Christensen A.B., Heitmann Bodtger U.C., Meyer C.N., Jensen A.V., Baunbaek-knudsen G., Petersen P.T., Andersen S., El-Said Abd El-Wahhab I., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Faverio P., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A.D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., San Luca O., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Adefuye Bolanle Olufunlola O.N.O., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Abel Salazar, Ravara S.B., Brocovschii V., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z.A., Edathodu J., Fathy A., Abdulaziz Enani A.M., Mohamed N.E., Memon J.U., Bella A., Bogdanovic S.N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N.M., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Interna M., Gallego M., Gaspar-GarcIa I., Gonzalez del Castillo J., Victoria P.J., Martinez E.L., Malo de Molina R., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Arnauld Attannon Fiogbe I.U., Yangui F., Bilaceroglu S., Levent Dalar I.D., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Hancock C., Villafuerte D., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Ricardo A. Franco-Sadud C.J., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Reyes L.F., Angel L.F., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., Labra L., Marin-Corral, Judith, Pascual-Guardia, Sergi, Amati, Francesco, Aliberti, Stefano, R Masclans, Joan, Soni, Nilam, Rodriguez, Alejandro, Sibila, Oriol, Sanz, Francisco, Sotgiu, Giovanni, Anzueto, Antonio, Dimakou, Katerina, Petrino, Roberta, van de Garde, Ewoudt, I Restrepo, Marco, Investigators, Glimp, Karina Aruj, Patricia, Attorri, Silvia, Barimboim, Enrique, Pablo Caeiro, Juan, I Garzón, María, Hugo Cambursano, Victor, A Adrian Ceccato, V H Dr Cazaux, Chertcoff, Julio, Lascar, Florencia, Di Tulio, Fernando, Cordon Díaz, Ariel, de Vedia, Lautaro, Cristina Ganaha, Maria, Lambert, Sandra, Lopardo, Gustavo, M Luna, Carlo, Gerardo Malberti, Alessio, Morcillo, Nora, Tartara, Silvina, Pensotti, Claudia, Pereyra, Betiana, Gustavo Scapellato, Pablo, Pablo Stagnaro, Juan, Shah, Sonali, Lötsch, Felix, Thalhammer, Florian, Anseeuw, Kurt, A Francois, Camille, Van Braeckel, Eva, Louis Vincent, Jean, Zannou Djimon, Marcel, Bashi, Jule, Dodo, Roger, Aranha Nouér, Simone, Chipev, Peter, Encheva, Milena, Miteva, Darina, Petkova, Diana, Dodo Balkissou, Adamou, Walter Pefura Yone, Eric, Hugo Mbatchou Ngahane, Bertrand, Shen, Ning, Xu, Jin-Fu, Andres Bustamante Rico, Carlo, Buitrago, Ricardo, Jose Pereira Paternina, Fernando, Kayembe Ntumba, Jean-Marie, Vladic Carevic, Vesna, Jakopovic, Marko, Jankovic, Mateja, Matkovic, Zinka, Mitrecic, Ivan, Bouchy Jacobsson, Marie-Laure, Bro Christensen, Anette, Christian Heitmann Bødtger, Uffe, Niels Meyer, Christian, Vestergaard Jensen, Andrea, Baunbæk-Knudsen, Gertrud, Trier Petersen, Pelle, Andersen, Stine, El-Said Abd El-Wahhab, Ibrahim, Elsayed Morsy, Nesreen, Shafiek, Hanaa, Sobh, Eman, Abdella Abdulsemed, Kedir, Bertrand, Fabrice, Brun-Buisson, Christian, de Montmollin, Etienne, Fartoukh, Muriel, Messika, Jonathan, Tattevin, Pierre, Khoury, Abdo, Ebruke, Bernard, Dreher, Michael, Kolditz, Martin, Meisinger, Matthia, W Pletz, Mathia, Hagel, Stefan, Rupp, Jan, Schaberg, Tom, Spielmanns, Marc, Creutz, Petra, Suttorp, Norton, Siaw-Lartey, Beatrice, Papapetrou, Dimostheni, Tsigou, Evdoxia, Ampazis, Dimitrio, Kaimakamis, Evangelo, Bhatia, Mohit, Dhar, Raja, D'Souza, George, Garg, Rajiv, A Koul, Parvaiz, A Mahesh, P, S Jayaraj, B, Vishnu Narayan, Kiran, B Udnur, Hirennappa, Bhaskara Krishnamurthy, Shashi, Kant, Surya, Swarnakar, Rajesh, Limaye, Sneha, Salvi, Sundeep, Golshani, Keihan, M Keatings, Vera, Martin-Loeches, Ignacio, Maor, Yasmin, Strahilevitz, Jacob, Faverio, Paola, Battaglia, Salvatore, Carrabba, Maria, Ceriana, Piero, Confalonieri, Marco, d'Arminio Monforte, Antonella, Del Prato, Bruno, De Rosa, Marino, Fantini, Riccardo, Fiorentino, Giuseppe, Antonia Gammino, Maria, Menzella, Francesco, Milani, Giuseppe, Nava, Stefano, Palmiero, Gerardo, Gabrielli, Barbra, Rossi, Paolo, Sorino, Claudio, Steinhilber, Gundi, Zanforlin, Alessandro, San Luca, Ospedale, Franzetti, Fabio, Carugati, Manuela, Morosi, Manuela, Monge, Elisa, Carone, Mauro, Patella, Vincenzo, Scarlata, Simone, Comel, Andrea, Kurahashi, Kiyoyasu, Aoun Bacha, Zeina, Barajas Ugalde, Daniel, Ceballos Zuñiga, Omar, F Villegas, José, Medenica, Milic, Raj Mihsra, Deebya, Shrestha, Poojan, Ridgeon, Elliott, Ishola Awokola, Babatunde, O Adefuye Bolanle Olufunlola, Ogonna N, Olumide, Segaolu, N Ukwaja, Kingsley, Irfan, Muhammad, Minarowski, Lukasz, Szymon, Skoczyński, Froes, Felipe, Leuschner, Pedro, Meireles, Mariana, Ferrão, Cláudia, Neves, João, Salazar, Abel, B Ravara, Sofia, Brocovschii, Victoria, Rusu, Doina, Toma, Cristina, Chirita, Daniela, Mihaela Dorobat, Carmen, Birkun, Alexei, Kaluzhenina, Anna, Almotairi, Abdullah, Abdulbaqi Ali Bukhary, Zakeya, Edathodu, Jameela, Fathy, Amal, Mushira Abdulaziz Enani, Abdullah, Eltayeb Mohamed, Nazik, Ulhadi Memon, Jawed, Bella, Abdelhaleem, Nada Bogdanović, Serbia, Milenkovic, Branislava, Pesut, Dragica, Borderìas, Lui, Manuel Bordon Garcia, Noel, Cabello Alarcón, Hugo, Cilloniz, Catia, Torres, Antoni, Diaz-Brito, Vicen, Casas, Xavier, Encabo González, Alicia, Luisa Fernández-Almira, Maria, Interna, Medicina, Gallego, Miguel, Gaspar-GarcÍa, Inmaculada, González Del Castillo, Juan, Javaloyes Victoria, Patricia, Laserna Martínez, Elena, Malo de Molina, Rosa, J Marcos, Pedro, Menéndez, Rosario, Pando-Sandoval, Ana, Prat Aymerich, Cristina, Lacoma de la Torre, Alicia, García-Olivé, Ignasi, Rello, Jordi, Moyano, Silvia, Rodrigo-Troyano, Ana, Solé-Violán, Jordi, Uranga, Ane, Fm van Boven, Job, Vendrell Torra, Ester, Almirall Pujol, Jordi, Feldman, Charle, Kee Yum, Ho, Univ Arnauld Attannon Fiogbe, Inje, Yangui, Ferdaou, Bilaceroglu, Semra, Dr Levent Dalar, Izmir, Yilmaz, Ufuk, Bogomolov, Artemii, Elahi, Naheed, J Dhasmana, Devesh, Feneley, Andrew, T Hill, Adam, Rudran, Banu, Ruiz-Buitrago, Silvia, Campbell, Marion, Whitaker, Paul, Youzguin, Alexander, Singanayagam, Anika, Hancock, C, Villafuerte, David, S Allen, Karen, Brito, Veronica, Dietz, Jessica, E Dysart, Claire, M Kellie, Susan, A Franco-Sadud, Clement J Ricardo, Meier, Garnet, Gaga, Mina, L Holland, Thoma, P Bergin, Stephen, Kheir, Fayez, Landmeier, Mark, Lois, Manuel, B Nair, Girish, Patel, Hemali, Reyes, Katherine, Rodriguez-Cintron, William, Saito, Shigeki, Noda, Julio, I Hinojosa, Cecilia, M Levine, Stephanie, F Reyes, Lui, F Angel, Lui, Scott Whitlow, K, Hipskind, John, Sukhija, Kunal, Totten, Vicken, G Wunderink, Richard, D Shah, Ray, John Mateyo, Kondwelani, Noriega, Lorena, Alvarado, Ezequiel, Aman, Mohamed, Labra, Lucía, Marin-Corral, J, Pascual-Guardia, S, Amati, F, Aliberti, S, Masclans, J, Soni, N, Rodriguez, A, Sibila, O, Sanz, F, Sotgiu, G, Anzueto, A, Dimakou, K, Petrino, R, van de Garde, E, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Adrian Ceccato, V, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Bashi, J, Dodo, R, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Pefura Yone, E, Mbatchou Ngahane, B, Shen, N, Xu, J, Bustamante Rico, C, Buitrago, R, Pereira Paternina, F, Kayembe Ntumba, J, Carevic, V, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Bouchy Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, Baunbaek-knudsen, G, Petersen, P, Andersen, S, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Faverio, P, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Menzella, F, Milani, G, Nava, S, Palmiero, G, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, San Luca, O, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Adefuye Bolanle Olufunlola, O, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Neves, J, Abel, S, Ravara, S, Brocovschii, V, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Ali Bukhary, Z, Edathodu, J, Fathy, A, Abdulaziz Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, S, Milenkovic, B, Pesut, D, Borderias, L, Bordon Garcia, N, Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Interna, M, Gallego, M, Gaspar-GarcIa, I, Gonzalez del Castillo, J, Victoria, P, Martinez, E, Malo de Molina, R, Marcos, P, Menendez, R, Pando-Sandoval, A, Aymerich, C, Lacoma de la Torre, A, Garcia-Olive, I, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Arnauld Attannon Fiogbe, I, Yangui, F, Bilaceroglu, S, Levent Dalar, I, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Villafuerte, D, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Ricardo, A, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Reyes, L, Angel, L, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Wunderink, R, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, and Labra, L

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.drug_class, Aspiration risk, Antibiotics, Nursing home resident, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Critical Care and Intensive Care Medicine, Microbiology, anaerobic, aspiration, bacteria, pneumonia, risk factors, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Community-acquired pneumonia, Taverne, Anti-Bacterial Agent, medicine, Humans, Community-Acquired Infection, 030212 general & internal medicine, Stroke, Aged, Aged, 80 and over, business.industry, Respiratory Aspiration, Middle Aged, medicine.disease, Antibiotic coverage, Anti-Bacterial Agents, Community-Acquired Infections, Hospitalization, Pneumonia, 030228 respiratory system, Risk factors, risk factor, Female, Underweight, medicine.symptom, business, Cardiology and Cardiovascular Medicine
Abstract

Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research Question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study Design and Methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P =.021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P 50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage.

Published
2021

4. Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study

Author

Stefano Aliberti, Luis F Reyes, Paola Faverio, Giovanni Sotgiu, Simone Dore, Alejandro H Rodriguez, Nilam J Soni, Marcos I Restrepo, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I Garzón, Victor Hugo Cambursano, Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Sonali Shah, Felix Lötsch, Florian Thalhammer, Jean Louis Vincent, Kurt Anseeuw, Camille A Francois, Eva Van Braeckel, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Katerina Dimakou, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A Koul, P A Mahesh, B S Jayaraj, Kiran Vishnu Narayan, Hirennappa B Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Roberta Petrino, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Fabio Franzetti, Manuela Carugati, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F Villegas, Milic Medenica, E M W van de Garde, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N O Nwankwo, Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N Ukwaja, Muhammad Irfan, Lukasz Minarowski, Skoczynski Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Cláudia Ferrão, João Neves, Sofia B Ravara, Victoria Brocovschii, Chesov Ion, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Nada Bogdanovic, Branislava Milenkovic, Dragica Pesut, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Alicia Lacoma de la Torre, Ignasi García-Olivé, Jordi Rello, Silvia Moyano, Francisco Sanz, Oriol Sibila, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job FM van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Charles Feldman, Ho Kee Yum, Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J Dhasmana, Andrew Feneley, Rhiannon Ions, Julie Skeemer, Gerrit Woltmann, Carole Hancock, Adam T Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, Karen S Allen, Veronica Brito, Jessica Dietz, Claire E Dysart, Susan M Kellie, Ricardo A Franco-Sadud, Garnet Meier, Mina Gaga, Thomas L Holland, Stephen P Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I Hinojosa, Stephanie M Levine, Luis F Angel, Antonio Anzueto, K Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G Wunderink, Ray D Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, Lucía Labra, Aliberti, S., Reyes, L. F., Faverio, P., Sotgiu, G., Dore, S., Rodriguez, A. H., Soni, N. J., Restrepo, M. I., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, Vh., Ceccato, A., Chertcoff, J., Lascar, F., Di Tulio, F., Cordon Diaz, A., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Vincent, J. L., Anseeuw, K., Francois, C. A., Van Braeckel, E., Djimon, M. Z., Bashi, J., Dodo, R., Aranha Nouer, S., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A. D., Pefura Yone, E. W., Mbatchou Ngahane, B. H., Shen, N., Xu, J. F., Bustamante Rico, C. A., Buitrago, R., Pereira Paternina, F. J., Kayembe Ntumba, J. M., Vladic Carevic, V., Jakopovic, M., Jankovic, M., Matkovic, Z., Mitrecic, I., Bouchy Jacobsson, M. L., Bro Christensen, A., Heitmann Bodtger, U. C., Meyer, C. N., Vestergaard Jensen, A., Baunbaek-Knudsen, G., Trier Petersen, P., Andersen, S., El-Said Abd El-Wahhab, I., Elsayed Morsy, N., Shafiek, H., Sobh, E., Abdulsemed, K. A., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Kaimakamis, E., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Swarnakar, R., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., d'Arminio Monforte, A., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M. A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Franzetti, F., Carugati, M., Morosi, M., Monge, E., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Aoun Bacha, Z., Barajas Ugalde, D., Ceballos Zuniga, O., Villegas, J. F., Medenica, M., van de Garde, Emw., Raj Mihsra, D., Shrestha, P., Ridgeon, E., Ishola Awokola, B., Nwankwo, Ono., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrao, C., Neves, J., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Zaa., Edathodu, J., Fathy, A., Mushira Abdulaziz Enani, A., Eltayeb Mohamed, N., Ulhadi Memon, J., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderias, L., Bordon Garcia, N. M., Cabello Alarcon, H., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Encabo Gonzalez, A., Fernandez-Almira, M. L., Gallego, M., Gaspar-GarcIa, I., Gonzalez Del Castillo, J., Javaloyes Victoria, P., Laserna Martinez, E., Malo de Molina, R., Marcos, P. J., Menendez, R., Pando-Sandoval, A., Prat Aymerich, C., Lacoma de la Torre, A., Garcia-Olive, I., Rello, J., Moyano, S., Sanz, F., Sibila, O., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F., Vendrell Torra, E., Pujol, J. A., Feldman, C., Kee Yum, H., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Feneley, A., Ions, R., Skeemer, J., Woltmann, G., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Reyes, K., Rodriguez-Cintron, W., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Anzueto, A., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Wunderink, R. G., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., Labra, L., Aliberti S., Reyes L.F., Faverio P., Sotgiu G., Dore S., Rodriguez A.H., Soni N.J., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano VH., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Cordon Diaz A., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Vincent J.L., Anseeuw K., Francois C.A., Van Braeckel E., Djimon M.Z., Bashi J., Dodo R., Aranha Nouer S., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Pefura Yone E.W., Mbatchou Ngahane B.H., Shen N., Xu J.F., Bustamante Rico C.A., Buitrago R., Pereira Paternina F.J., Kayembe Ntumba J.M., Vladic Carevic V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M.L., Bro Christensen A., Heitmann Bodtger U.C., Meyer C.N., Vestergaard Jensen A., Baunbaek-Knudsen G., Trier Petersen P., Andersen S., El-Said Abd El-Wahhab I., Elsayed Morsy N., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio Monforte A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Aoun Bacha Z., Barajas Ugalde D., Ceballos Zuniga O., Villegas J.F., Medenica M., van de Garde EMW., Raj Mihsra D., Shrestha P., Ridgeon E., Ishola Awokola B., Nwankwo ONO., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary ZAA., Edathodu J., Fathy A., Mushira Abdulaziz Enani A., Eltayeb Mohamed N., Ulhadi Memon J., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N.M., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Encabo Gonzalez A., Fernandez-Almira M.L., Gallego M., Gaspar-GarcIa I., Gonzalez Del Castillo J., Javaloyes Victoria P., Laserna Martinez E., Malo de Molina R., Marcos P.J., Menendez R., Pando-Sandoval A., Prat Aymerich C., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F., Vendrell Torra E., Pujol J.A., Feldman C., Kee Yum H., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., Labra L., Aliberti, S, Reyes, L, Faverio, P, Sotgiu, G, Dore, S, Rodriguez, A, Soni, N, and Restrepo, M

Subjects
Male, antibiotic resistance, Prevalence, MRSA, medicine.disease_cause, pneumonia, staphylococcus aureus, Global Health, Cohort Studies, 0302 clinical medicine, Community-acquired pneumonia, Risk Factors, Retrospective Studie, Community-Acquired Infection, 030212 general & internal medicine, education.field_of_study, Cross Infection, Respiratory tract infections, Methicillin-Resistant Staphylococcus aureu, Staphylococcal Infections, Hospitals, Community-Acquired Infections, Infectious Diseases, Infectious diseases, Female, Human, Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Population, Admission, staphylococcus aureu, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, Hospital, Internal medicine, medicine, Humans, Risk factor, education, Intensive care medicine, Staphylococcal Infection, Retrospective Studies, Aged, business.industry, Risk Factor, Odds ratio, Pneumonia, medicine.disease, Methicillin-resistant Staphylococcus aureus, 030228 respiratory system, Methicillin Resistance, Cohort Studie, business
Abstract

BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia.METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis.FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68).INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.FUNDING: None.

Published
2016
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5. Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease

Author

Seamas C. Donnelly, J. Stolk, R. Rabinovich, M. O’connor, Noor Kalsheker, Leslie Daly, Pieter S. Hiemstra, Vera M. Keatings, Josep Roca, Ann B. Millar, Sally Chappell, Kevin Morgan, T. Guetta Baranes, Massimo Miniati, Simonetta Monti, and William MacNee

Subjects
Pulmonary and Respiratory Medicine, business.industry, Immunology, Haplotype, Hum, Pulmonary disease, Medicine, business
Published
2006
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6. Glucocorticoid treatment reduces exhaled nitric oxide in cystic fibrosis patients

Author

S.J. Linnane, Vera M. Keatings, Muiris X. Fitzgerald, John B Moynihan, A. G. Thin, and Paul McLoughlin

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Cystic Fibrosis, Prednisolone, Nitric Oxide, Cystic fibrosis, Nitric oxide, chemistry.chemical_compound, Double-Blind Method, Internal medicine, medicine, Humans, Cross-Over Studies, biology, medicine.diagnostic_test, business.industry, medicine.disease, Nitric oxide synthase, Endocrinology, Breath Tests, chemistry, Exhaled nitric oxide, biology.protein, Female, Lung Volume Measurements, business, Peroxynitrite, Glucocorticoid, medicine.drug
Abstract

In cystic fibrosis (CF), low concentrations of exhaled nitric oxide (NO) and reduced expression of inducible nitric oxide synthase (iNOS) in airway epithelium have been reported. However, abundant iNOS expression has been found in the subepithelial tissues and elevated concentrations of NO metabolites in breath condensate and sputum. These conflicting results may be explained by increased scavenging of NO by superoxide radicals, resulting in rapid conversion to peroxynitrite, so that only a small proportion of the NO produced in the lung tissue reaches the airway lumen. If iNOS were active in the CF lung, exhaled NO would be further reduced by glucocorticoid treatment.CF patients (n=13) were recruited to a double-blind, placebo-controlled study with crossover. Treatment comprised prednisolone or placebo for 5 days with a 9 day washout. After each treatment, exhaled NO was measured, spirometry performed and blood collected for measurement of serum nitrogen dioxide/nitrous oxide (NO2/NO3).Ten patients (8 male) completed the study. Following prednisolone treatment (mean±sd) exhaled NO concentration (3.1±1.6 parts per billion (ppb)) was significantly reducedversusplacebo treatment (4.9±4.2 ppb; p2/NO3concentration were unchanged.These findings support the hypothesis that glucocorticoids suppress nitric oxide production in cystic fibrosis airways by reducing inducible nitric oxide synthase expression or by inhibiting recruitment of neutrophils, cells which express inducible nitric oxide synthase.

Published
2001
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7. A Polymorphism in the Tumor Necrosis Factor-α Gene Promoter Region May Predispose to a Poor Prognosis in COPD

Author

Muiris X. Fitzgerald, Vera M. Keatings, Michael J. Henry, Kevin Morgan, Clare O'Connor, Samantha J. Cave, and Noor Kalsheker

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Genotype, Critical Care and Intensive Care Medicine, Polymerase Chain Reaction, Gastroenterology, Gene Frequency, Internal medicine, Humans, Medicine, Outpatient clinic, Genetic Predisposition to Disease, Lung Diseases, Obstructive, Prospective Studies, Risk factor, Promoter Regions, Genetic, Prospective cohort study, Survival rate, Allele frequency, Alleles, Aged, COPD, Polymorphism, Genetic, Tumor Necrosis Factor-alpha, business.industry, Respiratory disease, DNA, Neoplasm, Middle Aged, Prognosis, medicine.disease, Survival Rate, Cross-Sectional Studies, Immunology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Study objectives: To determine whether the adenine (A)-guanine (G) substitution polymorphism at position - 308 on the tumor necrosis factor-a gene confers susceptibility to COPD or to the development of a more severe form of disease. Design: A cross-sectional study was undertaken to compare the frequency of the A allele in a group of 106 patients with COPD with that in a control population (n 5 99). Patients were followed up prospectively for a period of 2 years. Participants and setting: Participants included 106 COPD patients recruited from a respiratory outpatient clinic and 99 control subjects recruited from patients admitted for cardiac catheterization. Measurements and results: DNA was extracted from venous blood, and each subject was genotyped for the polymorphism by polymerase chain reaction amplification and restriction digestion using Nco1. There was no increased frequency of the A allele in patients compared to control subjects. AA homozygous patients had less reversible airflow obstruction (p < 0.05) and a significantly greater mortality (both all-cause and respiratory deaths) on follow-up (p < 0.001), despite a shorter cigarette smoking history. Conclusions: This study suggests that homozygosity for this A allele predisposes to more severe airflow obstruction and a worse prognosis in COPD. (CHEST 2000; 118:971‐975)

Published
2000
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8. Variation in the tumour necrosis factor gene is not associated with susceptibility to COPD

Author

Vera M. Keatings, Tamar Guetta Baranes, Leslie Daly, J. Stolk, Ann B. Millar, Clare O'Connor, Pieter S. Hiemstra, R. Rabinovich, Josep Roca, Sally Chappell, Noor Kalsheker, Massimo Miniati, Simonetta Monti, Seamas C. Donnelly, William MacNee, and Kevin Morgan

Subjects
Pulmonary and Respiratory Medicine, Lymphotoxin alpha, COPD, business.industry, Haplotype, Case-control study, medicine.disease, Lymphotoxin, Genotype, Immunology, medicine, media_common.cataloged_instance, Tumor necrosis factor alpha, European union, business, media_common
Abstract

To the Editors: In a recent issue of the European Respiratory Journal , Tanaka et al. 1 studied polymorphisms in the tumour necrosis factor (TNF) and lymphotoxin A genes with respect to their effect on lung function of smokers, and failed to find any association with chronic obstructive pulmonary disease (COPD) phenotypes. Tanaka et al. 1 acknowledge that their work is not a true case–control study, but that it would be better described as an investigation of genetic contribution to disease severity. There have been several studies of variation in TNF with respect to susceptibility to COPD, although many of these have used relatively small sample sizes and are therefore underpowered, and so are likely to lead to results that cannot be replicated. As part of a European Union collaborative project, we have …

Published
2007
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9. The SERPINE2 Gene and Chronic Obstructive Pulmonary Disease

Author

Simonetta Monti, Kevin Morgan, Jan Stolk, Tamar Guetta Baranes, Clare O'Connor, William MacNee, Ann B. Millar, Pieter S. Hiemstra, Josep Roca, Noor Kalsheker, Sally Chappell, Seamas C. Donnelly, Massimo Miniati, Roberto A Rabinovich, Leslie Daly, and Vera M. Keatings

Subjects
Genetics, 0303 health sciences, Candidate gene, Linkage disequilibrium, Single-nucleotide polymorphism, Biology, Population stratification, 3. Good health, Genotype frequency, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Population study, Genetics(clinical), International HapMap Project, Allele frequency, Genetics (clinical), 030304 developmental biology
Abstract

To the Editor: In the February 2006 issue of the Journal, DeMeo et al.1 identified SERPINE2 as a positional candidate gene for susceptibility to chronic obstructive pulmonary disease (COPD [MIM 606963]) and reported on the association of polymorphic variants of this gene with early-onset disease in a family-based study and with severe disease in a case-control study. With early prior information provided by the authors, we have independently tested for an association of the SERPINE2 gene with COPD in the largest case-control study reported to date. Our study consists of 1,018 COPD cases and 911 controls prospectively recruited from six European centers. We have provided details about the patients elsewhere.2 The study population was screened for genotypes at the Medical Research Council (United Kingdom) Gene Services Unit for five SNPs (table 1) in the SERPINE2 gene. All the SNPs evaluated were reported in the study by DeMeo et al. as associated with disease, with three of the five associated with disease in both the family and case-control study cohorts they assessed. Table 1. LD between SERPINE2 SNPs Expressed as r2[Note] We examined linkage disequilibrium (LD) between the SNPs (table 1) and evaluated SNP and haplotype associations as described elsewhere.2 DeMeo et al. did not report specific LD values between SNPs or noncontiguous SNPs contributing to haplotypes. SNPs and genotype frequencies in the study population are shown in table 2. We found no significant deviation from Hardy-Weinberg equilibrium in frequencies for any of the SNPs. Table 2. SERPINE2 Genotype and Allele Frequencies in Controls and COPD Cases We found no association between any of the SERPINE2 SNPs and disease, in examining both the allelic and genotype distributions, although our study was well powered to detect associations of the magnitude observed by DeMeo et al., and we would have expected to see these frequency differences with the SNPs that we studied. We also failed to find a relationship between any haplotypes of these SNPs and disease (data not shown). It was of interest that the allele and genotype frequencies observed in our control and patient groups were virtually identical to those observed in control subjects by DeMeo et al., indicating a common distribution of SERPINE2 variants in the European and North American populations studied. Our previous study has also shown that there is no evidence of population stratification in our sample. Patients evaluated in both the family-based and case-control studies reported by DeMeo et al. represent a severe subset of the disease spectrum. To determine whether the association with SERPINE2 noted by DeMeo et al. was related to disease severity, we also analyzed SNP allele and genotype frequencies in the subgroup of our patients with forced expiratory volume at 1 s ⩽45% (n=388), a group that represents severe disease, but we failed to observe any association. Our inability to replicate the observations of DeMeo et al. in a more highly powered case-control study may be related to differences in the disease phenotype of the patients studied, because our patients included those with and without emphysema. The possibility, however, that the associations reported by DeMeo et al. represent false-positive results must also be considered. In this respect, it is of note that, in the study by DeMeo et al., different associations were reported for SNPs that are in linkage disequilibrium with one another. For example, rs3795879 and rs3795877 have an r2 value of 1 in HapMap, yet different associations with quantitative spirometric phenotypes were reported for the family study. Similarly, rs1438831 and rs920251 are in complete LD, with an r2 value of 1 in HapMap and 0.95 in our study; however, in DeMeo et al.’s case-control study, the allele and genotype frequencies of rs920251 were found to be significantly associated with disease (P values of 0.015 and 0.011, respectively), whereas no similar association was observed for rs1438831. In both instances, the almost complete linkage between these pairs of SNPs would be expected to result in similar associations. These results underline the importance of replication in other large independent studies before SERPINE2 can be unequivocally assigned as a candidate gene for COPD. It is becoming apparent that, to detect modest genetic effects for complex diseases, several independent studies may be required and the data may need to be subjected to meta-analysis. For example, this approach has been used to study Alzheimer disease (see Alzheimer's Association Web site). Similar approaches need to be adopted for COPD. It would also be helpful to have similar criteria adapted for phenotypic selection and to plan prospective studies on this basis.

Published
2006
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10. Exhaled Nitric Oxide and Bronchoalveolar Lavage Nitrite/Nitrate in Active Pulmonary Sarcoidosis

Author

Geraldine A. Finlay, Dearbhaile M. O'donnell, Muiris X. Fitzgerald, Vera M. Keatings, John B Moynihan, Clare O'Connor, and Paul McLoughlin

Subjects
Adult, Male, inorganic chemicals, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cell Count, Nitric Oxide, Critical Care and Intensive Care Medicine, Nitric oxide, chemistry.chemical_compound, Sarcoidosis, Pulmonary, Griess test, Internal medicine, medicine, Humans, Nitrite, Nitrites, Nitrates, Lung, medicine.diagnostic_test, business.industry, Respiratory disease, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Endocrinology, Bronchoalveolar lavage, medicine.anatomical_structure, Breath Tests, chemistry, Luminescent Measurements, Exhaled nitric oxide, Immunology, Female, business, Bronchoalveolar Lavage Fluid, Respiratory tract
Abstract

Increased exhaled nitric oxide (NO) may reflect respiratory tract inflammation in untreated asthmatics. We compared exhaled NO and bronchoalveolar lavage (BAL) nitrate/nitrite (NO3-/NO2-) in 10 patients who had untreated, active pulmonary sarcoidosis with those of normal control subjects. Exhaled NO concentrations, determined by chemiluminescence, were similar in patients and control subjects (peak NO concentration of patients [mean +/- SD]: 13.6 +/- 5.9 parts per billion [ppb], peak NO concentration of control subjects: 11.2 +/- 5.7 ppb, p = 0.32; mean alveolar NO concentration of patients: 7.8 +/- 4.4 ppb, mean alveolar NO concentration of control subjects: 7.1 +/- 4.2 ppb, p = 0.70; end-tidal NO concentration of patients: 6.9 +/- 4.5 ppb, end-tidal NO concentration of control subjects: 6.6 +/- 4.0 ppb, p = 0.60). BAL NO2- was assayed using a modified Griess reaction after reduction of NO3- to NO2-. There was no significant difference in mean BAL NO2- concentrations, expressed as nanomoles per milliliter of epithelial lining fluid (patients: 544 nmol/ml, control subjects: 579 nmol/ml, p = 0.81) or as nanomoles per milliliter of BAL fluid (patients: 6.7 nmol/ml, control subjects: 5.7 nmol/ml, p = 0.41). These data suggest that excess NO generation does not accompany the respiratory tract inflammation of pulmonary sarcoidosis.

Published
1997
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11. Late response to allergen is associated with increased concentrations of tumor necrosis factor-α and IL-5 in induced sputum

Author

Vera M. Keatings, David P. Huston, Lyndon G. Wright, Brian J. O'Connor, Peter J. Barnes, and Christopher Corrigan

Subjects
Adult, Hypersensitivity, Immediate, Allergy, Adolescent, Immunology, Bronchial Provocation Tests, Proinflammatory cytokine, Leukocyte Count, Ribonucleases, Lipocalin-2, Proto-Oncogene Proteins, Humans, Immunology and Allergy, Medicine, Eosinophilia, Interleukin 5, Peroxidase, Oncogene Proteins, Eosinophil cationic protein, biology, Tumor Necrosis Factor-alpha, business.industry, Sputum, Granulocyte-Macrophage Colony-Stimulating Factor, Blood Proteins, Allergens, Eosinophil Granule Proteins, respiratory system, medicine.disease, Asthma, Lipocalins, respiratory tract diseases, Eosinophils, biology.protein, Tumor necrosis factor alpha, Interleukin-5, medicine.symptom, Carrier Proteins, business, Eosinophil peroxidase, Acute-Phase Proteins
Abstract

Bronchial antigen challenge of sensitized atopic patients with asthma results in an early fall in FEV1, followed in a proportion of patients by a late (4 to 24 hours) fall. The late response is accompanied by an increase in bronchial reactivity, which is widely believed to reflect local influx and degranulation of inflammatory cells, particularly eosinophils, in association with elevated local secretion of cytokines. We hypothesized that the development of a late-phase bronchoconstrictor response and airway eosinophilia after allergen challenge of sensitized atopic patients with asthma is associated with elevated induced sputum concentrations of the eosinophil-active cytokines IL-5 and granulocyte-macrophage colony-stimulating factor and the proinflammatory cytokine tumor necrosis factor-alpha. We counted inflammatory leukocytes and measured cytokine concentrations in induced sputum at baseline and 24 hours after inhalational allergen challenge of 15 atopic patients with asthma who had previously demonstrated a late response. We observed significant increases in the numbers of eosinophils and the concentrations of their granule products, eosinophil cationic protein and eosinophil peroxidase. In contrast, the numbers of neutrophils and concentrations of two of their products, myeloperoxidase and human neutrophil lipocalin, did not significantly change. The numbers of sputum eosinophils correlated with the maximal late-phase fall in FEV1. Concentrations of IL-5 and tumor necrosis factor-alpha, but not granulocyte-macrophage colony-stimulating factor, were significantly elevated after allergen challenge. We conclude that the relatively noninvasive technique of induced sputum production can be used to monitor the effect of bronchial provocation on cytokine concentrations in asthma.

Published
1997
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12. The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study

Author

Ann B. Millar, Simonetta Monti, Jan Stolk, Noor Kalsheker, J. Lotya, Tamar Guetta-Baranes, Aiman Alsaegh, Massimo Miniati, Sally Chappell, Roberto A. Rabinovich, Pieter S. Hiemstra, Kevin Morgan, Leslie Daly, Josep Roca, Seamas C. Donnelly, William MacNee, Clare O'Connor, and Vera M. Keatings

Subjects
Male, lcsh:Internal medicine, Candidate gene, lcsh:QH426-470, Iron, Single-nucleotide polymorphism, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Transforming Growth Factor beta1, Pulmonary Disease, Chronic Obstructive, Gene Frequency, Genotype, Odds Ratio, Genetics, Humans, SNP, Genetic Predisposition to Disease, Genetics(clinical), Allele, lcsh:RC31-1245, Iron Regulatory Protein 2, Alleles, Genetics (clinical), Aged, Genetic association, Case-control study, Genetic Variation, Middle Aged, Genotype frequency, lcsh:Genetics, Case-Control Studies, Female, Genome-Wide Association Study, Research Article
Abstract

BackgroundGenetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates includingIREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.MethodsWe have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in theIREB2gene, and for four SNPs in theTGFbeta1gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre.ResultsOur data replicate the association ofIREB2SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified forTGFbeta1.ConclusionsThese studies have therefore confirmed that theIREB2locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

Published
2011
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13. Genetic Variants of Matrix Metalloproteinases 1, 9 and 12 in Chronic Obstructive Pulmonary Disease

Author

Sally Chappell, Seamas C. Donnelly, Simonetta Monti, J. Lotya, Ann B. Millar, Massimo Miniati, Noor Kalsheker, Josep Roca, Roberto A Rabinovich, K Morgan, Simon R. Johnson, Pieter S. Hiemstra, Imran Haq, Leslie Daly, Tamar Guetta Baranes, Jan Stolk, William MacNee, Vera M. Keatings, and Clare O'Connor

Subjects
business.industry, Immunology, Genetic variants, Medicine, Pulmonary disease, Matrix metalloproteinase, business
Published
2009
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14. Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD

Author

Kevin Morgan, Vera M. Keatings, Tamar Guetta-Baranes, William MacNee, Noor Kalsheker, Leslie Daly, Sally Chappell, R. Rabinovich, Jan Stolk, Josep Roca, Clare O'Connor, Ann B. Millar, Pieter S. Hiemstra, Massimo Miniati, Seamas C. Donnelly, Simonetta Monti, and J. Lotya

Subjects
Pulmonary and Respiratory Medicine, Male, Candidate gene, Genotype, Glutamate-Cysteine Ligase, Single-nucleotide polymorphism, EPHX1, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Risk Factors, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Epoxide hydrolase, 030304 developmental biology, Genetics, Epoxide Hydrolases, 0303 health sciences, COPD, Haplotype, Smoking, Genetic Variation, medicine.disease, Glutathione, 3. Good health, 030228 respiratory system, Haplotypes, Microsomal epoxide hydrolase, Case-Control Studies, Female
Abstract

The genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are poorly understood. Many candidate genes have been proposed, including enzymes that protect the lung against oxidative stress, such as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To date, most reported findings have been for EPHX1, particularly in relation to functional variants associated with fast and slow metabolism of epoxide intermediates. The present study aimed to identify any association of variation in these genes with COPD susceptibility or severity. In total, 1,017 white COPD patients and 912 nondiseased age and sex matched smoking controls were genotyped for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and slow variants and associated haplotypes), and eight SNPs in the two genes encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a major contributor to anti-oxidant protection in the lung. No association of variation was found in EPHX1 or GCL with susceptibility to COPD or disease severity. This is the largest reported study to date and is well powered to detect associations that have been previously suggested. The current data indicate that these genetic variants are unlikely to be related to susceptibility or disease severity in white chronic obstructive pulmonary disease patients.

Published
2008

15. Cellular profiles in asthmatic airways: a comparison of induced sputum, bronchial washings, and bronchoalveolar lavage fluid

Author

P. J. Barnes, Vera M. Keatings, David J. Evans, and Brian J. O'Connor

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Sputum Cytology, Pathology, medicine.medical_specialty, Neutrophils, Bronchi, Bronchoscopy, medicine, Humans, Asthma, medicine.diagnostic_test, business.industry, Respiratory disease, Sputum, respiratory system, Eosinophil, medicine.disease, respiratory tract diseases, Eosinophils, Bronchoalveolar lavage, medicine.anatomical_structure, Papers, Immunology, Female, medicine.symptom, Airway, business, Bronchoalveolar Lavage Fluid
Abstract

BACKGROUND: Analysis of bronchoalveolar lavage fluid has improved our understanding of the pathogenesis of asthma. Safety issues and access to expert resources limit this techniques as a research tool. Induced sputum is a non-invasive method of collecting airway fluid which is applicable to subjects with a range of severity of airflow obstruction. The method of sputum collection and processing differs between groups. A study was undertaken to compare induced sputum with bronchoscopically collected fluid. METHODS: Sixteen patients with mild stable asthma underwent both sputum induction and bronchoscopic examination with bronchial washings and bronchoalveolar lavage (BAL) in random order, with each procedure being separated by an interval of 12 days. Airway fluid was processed and stained for differential cell counting. RESULTS: Induced sputum was relatively rich in neutrophils and eosinophils compared with bronchial washings and BAL fluid (mean (SE) 1.3 (0.4)%, 5.0 (2.7)%, and 36.4 (3.7)% neutrophils and 0.6 (0.1)%, 1.6 (0.6)%, and 3.3 (1.1)% eosinophils in BAL fluid, bronchial washings, and induced sputum, respectively). The proportions of cells obtained at sputum induction correlated with those in bronchial washings but not BAL fluid (r = 0.6 and 0.7 for neutrophils and eosinophils, respectively, p < 0.05). By contrast, induced sputum had a lower proportion of lymphocytes and macrophages than bronchial washings or BAL fluid, without any correlation. CONCLUSION: Induced sputum is rich in neutrophils and eosinophils and poor in lymphocytes, suggesting an origin in the larger airways. Induced sputum adequately reflects the findings in fluid collected by direct bronchoscopy.

Published
1997
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16. Induced sputum and BAL analysis in COPD

Author

Clare O'Connor and Vera M. Keatings

Subjects
medicine.medical_specialty, Chronic bronchitis, COPD, Lung, medicine.diagnostic_test, business.industry, Inflammation, Lung biopsy, respiratory system, Airway obstruction, medicine.disease, Gastroenterology, respiratory tract diseases, Bronchoalveolar lavage, medicine.anatomical_structure, Internal medicine, medicine, medicine.symptom, Airway, business
Abstract

An essential component of airways in flammation research is the examination of airway luminal fluid. Since its development as a sampling technique over 20 years ago, bronchoalveolar lavage (BAL) has become the most widely used method of evaluation of distal airway and alveolar inflammation. The widespread use of BAL reflects its relative ease and lack of clinical complications, particularly in comparison to airway or lung biopsy. However, while BAL is now a universally used tool in research and diagnosis of interstitial lung diseases (ILDs) its use in evaluating airway inflammation in COPD is less common. The lesser use of BAL in COPD studies reflects a lower level of tolerance of the procedure in patients with moderate to severe airway obstruction and greater difficulty in obtaining adequate samples from these same patient groups [1, 2].

Published
2004
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17. Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis

Author

Vera M. Keatings, Clare O'Connor, John B Moynihan, Paul McLoughlin, Muiris X. Fitzgerald, S.J. Linnane, and Christine M. Costello

Subjects
inorganic chemicals, Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Pathology, Cystic Fibrosis, Critical Care and Intensive Care Medicine, Nitric Oxide, Cystic fibrosis, Gastroenterology, Nitric oxide, chemistry.chemical_compound, Internal medicine, medicine, Humans, Nitrites, Asthma, Bronchiectasis, Lung, Nitrates, business.industry, Respiration, Respiratory disease, Sputum, respiratory system, medicine.disease, respiratory tract diseases, Respiratory Function Tests, medicine.anatomical_structure, Upper respiratory tract infection, chemistry, Breath Tests, Acute Disease, Disease Progression, Female, medicine.symptom, business
Abstract

Nitric oxide (NO) can be detected in exhaled gas in human subjects. It is produced by nitric oxide synthase (NOS) and is rapidly metabolized to nitrite and nitrate (NO2/NO3). Exhaled NO is reported to be elevated in patients with asthma, bronchiectasis, or upper respiratory tract infection. Recent reports have shown no increase of exhaled NO in stable cystic fibrosis (CF). We hypothesized that NOS activity is increased in patients with acute pulmonary exacerbation of CF. We therefore measured exhaled NO and sputum NO2/NO3 in three subject categories: patients with acute pulmonary exacerbation of CF, patients with stable CF, and healthy control subjects. Mean +/- SD exhaled NO was significantly higher in control subjects (8.8 +/- 4.9 ppb) than in both acute (3.8 +/- 3.9 ppb) and stable (5.0 +/- 2.5 ppb) patients. Sputum NO2/NO3 was significantly higher in acute patients (774 +/- 307 micromol/L) when compared with both stable patients (387 +/- 203 micromol/L) and control (421 +/- 261 micromol/L) subjects. Sputum NO2/NO3 did not return to normal in a subgroup of patients assessed after 2 wk of intensive antibiotic and glucocorticoid treatment. These results confirm that exhaled NO is not a useful measure of airway inflammation in CF. Elevated levels of sputum NO2/NO3 suggest that NOS is activated during acute pulmonary exacerbations of CF.

Published
1998

18. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects

Author

Vera M. Keatings and Peter J. Barnes

Subjects
Pulmonary and Respiratory Medicine, Adult, Granulocyte activation, Critical Care and Intensive Care Medicine, Leukocyte Count, Ribonucleases, medicine, Humans, Lung Diseases, Obstructive, Asthma, Aged, COPD, Eosinophil cationic protein, biology, business.industry, Eosinophil Granule Proteins, Sputum, Blood Proteins, respiratory system, Eosinophil, Middle Aged, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Myeloperoxidase, Immunology, biology.protein, Inflammation Mediators, business, Eosinophil peroxidase, Granulocytes
Abstract

Airway inflammation is present in asthma and is thought to play a significant part in the development of airflow obstruction. In chronic obstructive pulmonary disease (COPD), neutrophilic inflammation is present in the airway lumen, whereas the submucosa displays a lymphocytic infiltrate. Less is known about the nature and mechanisms of inflammation in COPD than in asthma. Induced sputum allows noninvasive sampling of respiratory tract secretions from patients and control subjects, allowing characterization of cells and measurement of soluble markers. We exploited this technique in order to compare the presence and quantify specific markers of eosinophil and neutrophil activation in subjects with asthma or COPD, and control subjects. Differential cell counts showed significantly higher neutrophil percentages in the patients with COPD compared with other groups, while patients with asthma had higher numbers of eosinophils. The neutrophil markers myeloperoxidase (MPO), from primary granules in neutrophils, and human neutrophil lipocalin (HNL), released from secondary granules, were elevated in patients with asthma and COPD compared with control subjects but markedly more so in COPD. The difference between COPD and asthma was more marked for HNL than for MPO suggesting that HNL may be a better marker for discriminating between these conditions. Concentrations of the eosinophil granule protein, eosinophil cationic protein (ECP), and the eosinophil granule-derived enzyme, eosinophil peroxidase (EPO) were raised in the patients with asthma and those with COPD.

Published
1997

19. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma

Author

Vera M. Keatings, Denise M. Scott, Paul D. Collins, and Peter J. Barnes

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, Sputum Cytology, Neutrophils, Critical Care and Intensive Care Medicine, Leukocyte Count, medicine, Humans, Lung Diseases, Obstructive, Asthma, Aged, Inflammation, Bronchus, COPD, medicine.diagnostic_test, business.industry, Tumor Necrosis Factor-alpha, Respiratory disease, Interleukin-8, Smoking, Sputum, Reproducibility of Results, Middle Aged, medicine.disease, respiratory tract diseases, Eosinophils, Bronchoalveolar lavage, medicine.anatomical_structure, Immunology, Tumor necrosis factor alpha, Female, medicine.symptom, business, Bronchoalveolar Lavage Fluid
Abstract

Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

Published
1996

20. Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population

Author

Kevin Morgan, Jan Stolk, Tamar Guetta-Baranes, Ann B. Millar, Massimo Miniati, Roberto A Rabinovich, Imran Haq, Noor Kalsheker, Pieter S. Hiemstra, Vera M. Keatings, Simonetta Monti, J. Lotya, William MacNee, Sally Chappell, Leslie Daly, Simon R. Johnson, Clare O'Connor, Seamas C. Donnelly, and Josep Roca

Subjects
Male, lcsh:Internal medicine, Candidate gene, lcsh:QH426-470, Genotype, Single-nucleotide polymorphism, Disease, Biology, Bioinformatics, obstructive pulmonary-disease genetic-polymorphism macrophage elastase induced sputum risk-factors emphysema matrix-metalloproteinase-9 susceptibility expression lungs, Polymorphism, Single Nucleotide, Severity of Illness Index, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Matrix Metalloproteinase 12, medicine, Genetics, SNP, Humans, Genetics(clinical), Genetic Predisposition to Disease, lcsh:RC31-1245, Genetics (clinical), Genetic Association Studies, 030304 developmental biology, Aged, 0303 health sciences, COPD, Haplotype, Case-control study, Odds ratio, Middle Aged, medicine.disease, 3. Good health, lcsh:Genetics, 030228 respiratory system, Haplotypes, Matrix Metalloproteinase 9, Case-Control Studies, Immunology, Female, Matrix Metalloproteinase 1, Research Article
Abstract

Background Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. Methods To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Results Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Conclusions Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Published
2010
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