EClinicalMedicine (Feb 2024)
Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional studyResearch in context
- Hazim Abozid,
- Jaymini Patel,
- Peter Burney,
- Sylvia Hartl,
- Robab Breyer-Kohansal,
- Kevin Mortimer,
- Asaad A. Nafees,
- Mohammed Al Ghobain,
- Tobias Welte,
- Imed Harrabi,
- Meriam Denguezli,
- Li Cher Loh,
- Abdul Rashid,
- Thorarinn Gislason,
- Cristina Barbara,
- Joao Cardoso,
- Fatima Rodrigues,
- Terence Seemungal,
- Daniel Obaseki,
- Sanjay Juvekar,
- Stefanni Nonna Paraguas,
- Wan C. Tan,
- Frits M.E. Franssen,
- Filip Mejza,
- David Mannino,
- Christer Janson,
- Hamid Hacene Cherkaski,
- Mahesh Padukudru Anand,
- Hasan Hafizi,
- Sonia Buist,
- Parvaiz A. Koul,
- Asma El Sony,
- Marie-Kathrin Breyer,
- Otto C. Burghuber,
- Emiel F.M. Wouters,
- Andre F.S. Amaral,
- Hasan Hafizi,
- Anila Aliko,
- Donika Bardhi,
- Holta Tafa,
- Natasha Thanasi,
- Arian Mezini,
- Alma Teferici,
- Dafina Todri,
- Jolanda Nikolla,
- Rezarta Kazasi,
- Hamid Hacene Cherkaski,
- Amira Bengrait,
- Tabarek Haddad,
- Ibtissem Zgaoula,
- Maamar Ghit,
- Abdelhamid Roubhia,
- Soumaya Boudra,
- Feryal Atoui,
- Randa Yakoubi,
- Rachid Benali,
- Abdelghani Bencheikh,
- Nadia Ait-Khaled,
- Christine Jenkins,
- Guy Marks,
- Tessa Bird,
- Paola Espinel,
- Kate Hardaker,
- Brett Toelle,
- Michael Studnicka,
- Torkil Dawes,
- Bernd Lamprecht,
- Lea Schirhofer,
- Akramul Islam,
- Syed Masud Ahmed,
- Shayla Islam,
- Qazi Shafayetul Islam,
- Mesbah-Ul-Haque,
- Tridib Roy Chowdhury,
- Sukantha Kumar Chatterjee,
- Dulal Mia,
- Shyamal Chandra Das,
- Mizanur Rahman,
- Nazrul Islam,
- Shahaz Uddin,
- Nurul Islam,
- Luiza Khatun,
- Monira Parvin,
- Abdul Awal Khan,
- Maidul Islam,
- Herve Lawin,
- Arsene Kpangon,
- Karl Kpossou,
- Gildas Agodokpessi,
- Paul Ayelo,
- Benjamin Fayomi,
- Bertrand Mbatchou,
- Atongno Humphrey Ashu,
- Wan C. Tan,
- Wen Wang,
- NanShan Zhong,
- Shengming Liu,
- Jiachun Lu,
- Pixin Ran,
- Dali Wang,
- Jin-ping Zheng,
- Yumin Zhou,
- Rain Jogi,
- Hendrik Laja,
- Katrin Ulst,
- Vappu Zobel,
- Toomas-Julius Lill,
- Ayola Akim Adegnika,
- Tobias Welte,
- Isabelle Bodemann,
- Henning Geldmacher,
- Alexandra SchwedaLinow,
- Thorarinn Gislason,
- Bryndis Benedikdtsdottir,
- Kristin Jorundsdottir,
- Lovisa Gudmundsdottir,
- Sigrun Gudmundsdottir,
- Gunnar Gudmundsson,
- Mahesh Rao,
- Parvaiz A. Koul,
- Sajjad Malik,
- Nissar A. Hakim,
- Umar Hafiz Khan,
- Rohini Chowgule,
- Vasant Shetye,
- Jonelle Raphael,
- Rosel Almeda,
- Mahesh Tawde,
- Rafiq Tadvi,
- Sunil Katkar,
- Milind Kadam,
- Rupesh Dhanawade,
- Umesh Ghurup,
- Sanjay Juvekar,
- Siddhi Hirve,
- Somnath Sambhudas,
- Bharat Chaidhary,
- Meera Tambe,
- Savita Pingale,
- Arati Umap,
- Archana Umap,
- Nitin Shelar,
- Sampada Devchakke,
- Sharda Chaudhary,
- Suvarna Bondre,
- Savita Walke,
- Ashleshsa Gawhane,
- Anil Sapkal,
- Rupali Argade,
- Vijay Gaikwad,
- Sundeep Salvi,
- Bill Brashier,
- Jyoti Londhe,
- Sapna Madas,
- Althea Aquart-Stewart,
- Akosua Francia Aikman,
- Talant M. Sooronbaev,
- Bermet M. Estebesova,
- Meerim Akmatalieva,
- Saadat Usenbaeva,
- Jypara Kydyrova,
- Eliza Bostonova,
- Ulan Sheraliev,
- Nuridin Marajapov,
- Nurgul Toktogulova,
- Berik Emilov,
- Toktogul Azilova,
- Gulnara Beishekeeva,
- Nasyikat Dononbaeva,
- Aijamal Tabyshova,
- Kevin Mortimer,
- Wezzie Nyapigoti,
- Ernest Mwangoka,
- Mayamiko Kambwili,
- Martha Chipeta,
- Gloria Banda,
- Suzgo Mkandawire,
- Justice Banda,
- Li-Cher Loh,
- Abdul Rashid,
- Siti Sholehah,
- Mohamed C. Benjelloun,
- Chakib Nejjari,
- Mohamed Elbiaze,
- Karima El Rhazi,
- E.F.M. Wouters,
- G.J. Wesseling,
- Daniel Obaseki,
- Gregory Erhabor,
- Olayemi Awopeju,
- Olufemi Adewole,
- Amund Gulsvik,
- Tina Endresen,
- Lene Svendsen,
- Asaad A. Nafees,
- Muhammad Irfan,
- Zafar Fatmi,
- Aysha Zahidie,
- Natasha Shaukat,
- Meesha Iqbal,
- Luisito F. Idolor,
- Teresita S. de Guia,
- Norberto A. Francisco,
- Camilo C. Roa,
- Fernando G. Ayuyao,
- Cecil Z. Tady,
- Daniel T. Tan,
- Sylvia Banal-Yang,
- Vincent M. Balanag, Jr.,
- Maria Teresita N. Reyes,
- Renato B. Dantes,
- Renato B. Dantes,
- Lourdes Amarillo,
- Lakan U. Berratio,
- Lenora C. Fernandez,
- Norberto A. Francisco,
- Gerard S. Garcia,
- Teresita S. de Guia,
- Luisito F. Idolor,
- Sullian S. Naval,
- Thessa Reyes,
- Camilo C. Roa, Jr.,
- Flordeliza Sanchez,
- Leander P. Simpao,
- Ewa Nizankowska-Mogilnicka,
- Jakub Frey,
- Rafal Harat,
- Filip Mejza,
- Pawel Nastalek,
- Andrzej Pajak,
- Wojciech Skucha,
- Andrzej Szczeklik,
- Magda Twardowska,
- Cristina Barbara,
- Fatima Rodrigues,
- Herminia Dias,
- Joao Cardoso,
- João Almeida,
- Maria Joao Matos,
- Paula Simão,
- Moutinho Santos,
- Reis Ferreira,
- M. Al Ghobain,
- H. Alorainy,
- E. El-Hamad,
- M. Al Hajjaj,
- A. Hashi,
- R. Dela,
- R. Fanuncio,
- E. Doloriel,
- I. Marciano,
- L. Safia,
- Eric Bateman,
- Anamika Jithoo,
- Desiree Adams,
- Edward Barnes,
- Jasper Freeman,
- Anton Hayes,
- Sipho Hlengwa,
- Christine Johannisen,
- Mariana Koopman,
- Innocentia Louw,
- Ina Ludick,
- Alta Olckers,
- Johanna Ryck,
- Janita Storbeck,
- Kirthi Gunasekera,
- Rajitha Wickremasinghe,
- Asma Elsony,
- Hana A. Elsadig,
- Nada Bakery Osman,
- Bandar Salah Noory,
- Monjda Awad Mohamed,
- Hasab Alrasoul Akasha Ahmed Osman,
- Namarig Moham ed Elhassan,
- Abdel Mu’is El Zain,
- Marwa Mohamed Mohamaden,
- Suhaiba Khalifa,
- Mahmoud Elhadi,
- Mohand Hassan,
- Dalia Abdelmonam,
- Christer Janson,
- Inga Sif Olafsdottir,
- Katarina Nisser,
- Ulrike SpetzNystrom,
- Gunilla Hagg,
- GunMarie Lund,
- Terence Seemungal,
- Fallon Lutchmansingh,
- Liane Conyette,
- Imed Harrabi,
- Myriam Denguezli,
- Zouhair Tabka,
- Hager Daldoul,
- Zaki Boukheroufa,
- Firas Chouikha,
- Wahbi Belhaj Khalifa,
- Ali Kocabas,
- Attila Hancioglu,
- Ismail Hanta,
- Sedat Kuleci,
- Ahmet Sinan Turkyilmaz,
- Sema Umut,
- Turgay Unalan,
- Peter G.J. Burney,
- Anamika Jithoo,
- Louisa Gnatiuc,
- Hadia Azar,
- Jaymini Patel,
- Caron Amor,
- James Potts,
- Michael Tumilty,
- Fiona McLean,
- Risha Dudhaiya,
- A. Sonia Buist,
- Mary Ann McBurnie,
- William M. Vollmer,
- Suzanne Gillespie,
- Sean Sullivan,
- Todd A. Lee,
- Kevin B. Weiss,
- Robert L. Jensen,
- Robert Crapo,
- Paul Enright,
- David M. Mannino,
- John Cain,
- Rebecca Copeland,
- Dana Hazen,
- Jennifer Methvin
Affiliations
- Hazim Abozid
- Department of Respiratory and Pulmonary Diseases, Clinic Penzing, Vienna Healthcare Group, Vienna, Austria; Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; Corresponding author. Ludwig Boltzmann Institute for Lung Health, Sanatoriumstrasse 2, Vienna A-1140, Austria.
- Jaymini Patel
- National Heart and Lung Institute, Imperial College London, London, UK
- Peter Burney
- National Heart and Lung Institute, Imperial College London, London, UK
- Sylvia Hartl
- Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; Sigmund Freud University, Faculty for Medicine, Vienna, Austria
- Robab Breyer-Kohansal
- Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; Department of Respiratory and Pulmonary Diseases, Clinic Hietzing, Vienna Healthcare Group, Vienna, Austria
- Kevin Mortimer
- University of Cambridge, Cambridge, UK; Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Asaad A. Nafees
- Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
- Mohammed Al Ghobain
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia
- Tobias Welte
- Department of Respiratory Medicine/Infectious Disease, Member of the German Centre for Lung Research, Hannover School of Medicine, Germany
- Imed Harrabi
- Ibn El Jazzar Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia
- Meriam Denguezli
- Department of Pneumology, Faculty of Medicine Annaba, University Badji Mokhtar of Annaba, Annaba, Algeria
- Li Cher Loh
- Royal College of Surgeons in Ireland and University College Dublin Malaysia Campus, Penang, Malaysia
- Abdul Rashid
- Royal College of Surgeons in Ireland and University College Dublin Malaysia Campus, Penang, Malaysia
- Thorarinn Gislason
- Faculty of Medicine, University of Iceland, Reykjavík, Iceland; Department of Sleep, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland
- Cristina Barbara
- Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Joao Cardoso
- Pulmonology Department, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal; NOVA Medical School, Nova University Lisbon, Lisboa, Portugal
- Fatima Rodrigues
- Serviço de Pneumologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal; Institute of Environmental Health, Associate Laboratory TERRA, Lisbon Medical School, Lisbon University, Lisbon, Portugal
- Terence Seemungal
- Faculty of Medical Sciences, University of West Indies, St Augustine, Trinidad and Tobago
- Daniel Obaseki
- Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria; Faculty of Medicine, University of British Columbia, Vancouver, Canada
- Sanjay Juvekar
- Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India
- Stefanni Nonna Paraguas
- Philippine College of Chest Physicians, Manila, Philippines
- Wan C. Tan
- University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada
- Frits M.E. Franssen
- Maastricht University Medical Centre, Maastricht, the Netherlands
- Filip Mejza
- Centre for Evidence Based Medicine, 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland
- David Mannino
- University of Kentucky, Lexington, KY, USA; COPD Foundation, Miami, FL, USA
- Christer Janson
- Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
- Hamid Hacene Cherkaski
- Department of Pneumology, Faculty of Medicine Annaba, University Badji Mokhtar of Annaba, Annaba, Algeria
- Mahesh Padukudru Anand
- Department of Respiratory Medicine, JSS Medical College, JSSAHER, Mysuru, India
- Hasan Hafizi
- Faculty of Medicine, Tirana University Hospital “Shefqet Ndroqi”, Tirana, Albania
- Sonia Buist
- Oregon Health & Science University, Portland, USA
- Parvaiz A. Koul
- Department of Pulmonary Medicine, Sheri Kashmir Institute of Medical Sciences, Srinagar, India
- Asma El Sony
- Epi-Lab, Khartoum, Sudan
- Marie-Kathrin Breyer
- Department of Respiratory and Pulmonary Diseases, Clinic Penzing, Vienna Healthcare Group, Vienna, Austria; Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
- Otto C. Burghuber
- Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; Sigmund Freud University, Faculty for Medicine, Vienna, Austria
- Emiel F.M. Wouters
- Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; Maastricht University Medical Centre, Maastricht, the Netherlands
- Andre F.S. Amaral
- National Heart and Lung Institute, Imperial College London, London, UK; NIHR Imperial Biomedical Research Centre, London, UK
- Hasan Hafizi
- Anila Aliko
- Donika Bardhi
- Holta Tafa
- Natasha Thanasi
- Arian Mezini
- Alma Teferici
- Dafina Todri
- Jolanda Nikolla
- Rezarta Kazasi
- Hamid Hacene Cherkaski
- Amira Bengrait
- Tabarek Haddad
- Ibtissem Zgaoula
- Maamar Ghit
- Abdelhamid Roubhia
- Soumaya Boudra
- Feryal Atoui
- Randa Yakoubi
- Rachid Benali
- Abdelghani Bencheikh
- Nadia Ait-Khaled
- Christine Jenkins
- Guy Marks
- Tessa Bird
- Paola Espinel
- Kate Hardaker
- Brett Toelle
- Michael Studnicka
- Torkil Dawes
- Bernd Lamprecht
- Lea Schirhofer
- Akramul Islam
- Syed Masud Ahmed
- Shayla Islam
- Qazi Shafayetul Islam
- Mesbah-Ul-Haque
- Tridib Roy Chowdhury
- Sukantha Kumar Chatterjee
- Dulal Mia
- Shyamal Chandra Das
- Mizanur Rahman
- Nazrul Islam
- Shahaz Uddin
- Nurul Islam
- Luiza Khatun
- Monira Parvin
- Abdul Awal Khan
- Maidul Islam
- Herve Lawin
- Arsene Kpangon
- Karl Kpossou
- Gildas Agodokpessi
- Paul Ayelo
- Benjamin Fayomi
- Bertrand Mbatchou
- Atongno Humphrey Ashu
- Wan C. Tan
- Wen Wang
- NanShan Zhong
- Shengming Liu
- Jiachun Lu
- Pixin Ran
- Dali Wang
- Jin-ping Zheng
- Yumin Zhou
- Rain Jogi
- Hendrik Laja
- Katrin Ulst
- Vappu Zobel
- Toomas-Julius Lill
- Ayola Akim Adegnika
- Tobias Welte
- Isabelle Bodemann
- Henning Geldmacher
- Alexandra SchwedaLinow
- Thorarinn Gislason
- Bryndis Benedikdtsdottir
- Kristin Jorundsdottir
- Lovisa Gudmundsdottir
- Sigrun Gudmundsdottir
- Gunnar Gudmundsson
- Mahesh Rao
- Parvaiz A. Koul
- Sajjad Malik
- Nissar A. Hakim
- Umar Hafiz Khan
- Rohini Chowgule
- Vasant Shetye
- Jonelle Raphael
- Rosel Almeda
- Mahesh Tawde
- Rafiq Tadvi
- Sunil Katkar
- Milind Kadam
- Rupesh Dhanawade
- Umesh Ghurup
- Sanjay Juvekar
- Siddhi Hirve
- Somnath Sambhudas
- Bharat Chaidhary
- Meera Tambe
- Savita Pingale
- Arati Umap
- Archana Umap
- Nitin Shelar
- Sampada Devchakke
- Sharda Chaudhary
- Suvarna Bondre
- Savita Walke
- Ashleshsa Gawhane
- Anil Sapkal
- Rupali Argade
- Vijay Gaikwad
- Sundeep Salvi
- Bill Brashier
- Jyoti Londhe
- Sapna Madas
- Althea Aquart-Stewart
- Akosua Francia Aikman
- Talant M. Sooronbaev
- Bermet M. Estebesova
- Meerim Akmatalieva
- Saadat Usenbaeva
- Jypara Kydyrova
- Eliza Bostonova
- Ulan Sheraliev
- Nuridin Marajapov
- Nurgul Toktogulova
- Berik Emilov
- Toktogul Azilova
- Gulnara Beishekeeva
- Nasyikat Dononbaeva
- Aijamal Tabyshova
- Kevin Mortimer
- Wezzie Nyapigoti
- Ernest Mwangoka
- Mayamiko Kambwili
- Martha Chipeta
- Gloria Banda
- Suzgo Mkandawire
- Justice Banda
- Li-Cher Loh
- Abdul Rashid
- Siti Sholehah
- Mohamed C. Benjelloun
- Chakib Nejjari
- Mohamed Elbiaze
- Karima El Rhazi
- E.F.M. Wouters
- G.J. Wesseling
- Daniel Obaseki
- Gregory Erhabor
- Olayemi Awopeju
- Olufemi Adewole
- Amund Gulsvik
- Tina Endresen
- Lene Svendsen
- Asaad A. Nafees
- Muhammad Irfan
- Zafar Fatmi
- Aysha Zahidie
- Natasha Shaukat
- Meesha Iqbal
- Luisito F. Idolor
- Teresita S. de Guia
- Norberto A. Francisco
- Camilo C. Roa
- Fernando G. Ayuyao
- Cecil Z. Tady
- Daniel T. Tan
- Sylvia Banal-Yang
- Vincent M. Balanag, Jr.
- Maria Teresita N. Reyes
- Renato B. Dantes
- Renato B. Dantes
- Lourdes Amarillo
- Lakan U. Berratio
- Lenora C. Fernandez
- Norberto A. Francisco
- Gerard S. Garcia
- Teresita S. de Guia
- Luisito F. Idolor
- Sullian S. Naval
- Thessa Reyes
- Camilo C. Roa, Jr.
- Flordeliza Sanchez
- Leander P. Simpao
- Ewa Nizankowska-Mogilnicka
- Jakub Frey
- Rafal Harat
- Filip Mejza
- Pawel Nastalek
- Andrzej Pajak
- Wojciech Skucha
- Andrzej Szczeklik
- Magda Twardowska
- Cristina Barbara
- Fatima Rodrigues
- Herminia Dias
- Joao Cardoso
- João Almeida
- Maria Joao Matos
- Paula Simão
- Moutinho Santos
- Reis Ferreira
- M. Al Ghobain
- H. Alorainy
- E. El-Hamad
- M. Al Hajjaj
- A. Hashi
- R. Dela
- R. Fanuncio
- E. Doloriel
- I. Marciano
- L. Safia
- Eric Bateman
- Anamika Jithoo
- Desiree Adams
- Edward Barnes
- Jasper Freeman
- Anton Hayes
- Sipho Hlengwa
- Christine Johannisen
- Mariana Koopman
- Innocentia Louw
- Ina Ludick
- Alta Olckers
- Johanna Ryck
- Janita Storbeck
- Kirthi Gunasekera
- Rajitha Wickremasinghe
- Asma Elsony
- Hana A. Elsadig
- Nada Bakery Osman
- Bandar Salah Noory
- Monjda Awad Mohamed
- Hasab Alrasoul Akasha Ahmed Osman
- Namarig Moham ed Elhassan
- Abdel Mu’is El Zain
- Marwa Mohamed Mohamaden
- Suhaiba Khalifa
- Mahmoud Elhadi
- Mohand Hassan
- Dalia Abdelmonam
- Christer Janson
- Inga Sif Olafsdottir
- Katarina Nisser
- Ulrike SpetzNystrom
- Gunilla Hagg
- GunMarie Lund
- Terence Seemungal
- Fallon Lutchmansingh
- Liane Conyette
- Imed Harrabi
- Myriam Denguezli
- Zouhair Tabka
- Hager Daldoul
- Zaki Boukheroufa
- Firas Chouikha
- Wahbi Belhaj Khalifa
- Ali Kocabas
- Attila Hancioglu
- Ismail Hanta
- Sedat Kuleci
- Ahmet Sinan Turkyilmaz
- Sema Umut
- Turgay Unalan
- Peter G.J. Burney
- Anamika Jithoo
- Louisa Gnatiuc
- Hadia Azar
- Jaymini Patel
- Caron Amor
- James Potts
- Michael Tumilty
- Fiona McLean
- Risha Dudhaiya
- A. Sonia Buist
- Mary Ann McBurnie
- William M. Vollmer
- Suzanne Gillespie
- Sean Sullivan
- Todd A. Lee
- Kevin B. Weiss
- Robert L. Jensen
- Robert Crapo
- Paul Enright
- David M. Mannino
- John Cain
- Rebecca Copeland
- Dana Hazen
- Jennifer Methvin
- Journal volume & issue
-
Vol. 68
p. 102423
Abstract
Summary: Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.