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2. Medication Adherence in Patients With Severe Asthma Prescribed Oral Corticosteroids in the U-BIOPRED Cohort

Author

P. J. Sterk, John H. Riley, Thomas Sandström, Anna Selby, Laurie Pahus, C. Auffray, Ioannis Pandis, Julie Corfield, R. Djukanovic, K. Sun, Massimo Caruso, Jørgen Vestbo, Matthew J. Loza, Andrew J. Simpson, Dominic Burg, I.M. Adcock, S. Bates, Scott Wagers, Ana R. Sousa, J. Corfield, Ariane H. Wagener, René Lutter, Barbro Dahlén, Ratko Djukanovic, G. Praticò, I. Pandis, N. Mores, G. Hedlin, Navin Rao, I. Horváth, Alexander Mazein, B. De Meulder, Richard G. Knowles, John-Olof Thörngren, Wolfgang Seibold, P H Howarth, Victoria M. Goss, Cristina Gómez, Clare S. Murray, Paul Brinkman, Ildiko Horvath, Anthony D. Postle, M. Caruso, Martina Gahlemann, M. Puig Valls, F.K. Chung, P. Montuschi, Dominick E. Shaw, Kai Sun, Aruna T. Bansal, Fahad Alahmadi, Amphun Chaiboonchoe, Graham Roberts, Kian Fan Chung, Yike Guo, H. Ahmed, Thomas Geiser, Klaus Bønnelykke, M. Miralpeix, Simone Hashimoto, Diane Lefaudeux, S.S. Wagers, D. Erzen, B. Thornton, Florian Singer, Louise Fleming, Stephen J. Fowler, Neil Fitch, P. Bakke, Craig E. Wheelock, Nadja Hawwa Vissing, Tim Higenbottam, Jamie Matthews, F. Singer, S.E. Dahlén, Sarah Masefield, Roelinde Middelveld, Jens M. Hohlfeld, Anthony V. D'Amico, Paul Skipp, W.M.C. van Aalderen, Alan J. Knox, Sven-Erik Dahlén, Andrew Bush, A.T. Bansal, Pieter-Paul Hekking, Joost Brandsma, Stewart Bates, L.J. Fleming, Norbert Krug, N. Krug, Magnus Ericsson, J. Riley, P. Powel, Jacek Musiał, Amanda Roberts, Peter J. Sterk, Ian M. Adcock, Pascal Chanez, Cecile T.J. Holweg, F. Baribaud, Stelios Pavlidis, Veit J. Erpenbeck, Z. Weiszhart, C.E. Wheelock, Ralf Sigmund, James P.R. Schofield, Alexander Manta, Andrea Meiser, Susan J. Wilson, Jeanette Bigler, G. Roberts, M. van Geest, Hans Bisgaard, Urs Frey, Michael Boedigheimer, Per Bakke, Chris Compton, Enrica Bucchioni, Paolo Montuschi, David Myles, E.H.D. Bel, Anna James, Elena Formaggio, Anthony Rowe, Dominic E. Shaw, J. Haughney, P. Chanez, A.R. Sousa, S.J. Fowler, K. Fichtner, B. Dahlèn, Publica, Commission of the European Communities, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pulmonology, AII - Inflammatory diseases, and Paediatric Pulmonology

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, urinary corticosteroids, Prescription Drugs, Settore BIO/14 - FARMACOLOGIA, medicine.drug_class, [SDV]Life Sciences [q-bio], Urinary system, Respiratory System, Administration, Oral, 610 Medicine & health, Critical Care and Intensive Care Medicine, Hospital Anxiety and Depression Scale, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Interquartile range, Internal medicine, Surveys and Questionnaires, Administration, Inhalation, Medicine, Humans, 030212 general & internal medicine, adherence, Glucocorticoids, ComputingMilieux_MISCELLANEOUS, U-BIOPRED Study Group, Asthma, Dose-Response Relationship, Drug, business.industry, 1103 Clinical Sciences, Middle Aged, asthma, medicine.disease, 030228 respiratory system, Cohort, Prednisolone, Quality of Life, Corticosteroid, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Published
2021
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6. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Zala Jevnikar, Jörgen Östling, Elisabeth Ax, Jenny Calvén, Kristofer Thörn, Elisabeth Israelsson, Lisa Öberg, Akul Singhania, Laurie C.K. Lau, Susan J. Wilson, Jonathan A. Ward, Anoop Chauhan, Ana R. Sousa, Bertrand De Meulder, Matthew J. Loza, Frédéric Baribaud, Peter J. Sterk, Kian Fan Chung, Kai Sun, Yike Guo, Ian M. Adcock, Debbie Payne, Barbro Dahlen, Pascal Chanez, Dominick E. Shaw, Norbert Krug, Jens M. Hohlfeld, Thomas Sandström, Ratko Djukanovic, Anna James, Timothy S.C. Hinks, Peter H. Howarth, Outi Vaarala, Marleen van Geest, Henric Olsson, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F.K. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, V. Goss, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, A.J. James, R. Knowles, A.J. Knox, N. Krug, D. Lefaudeux, M.J. Loza, A. Manta, J.G. Matthews, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, A. Postle, P. Powel, G. Praticò, N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, J.P.R. Schofield, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Publica, HUS Children and Adolescents, Commission of the European Communities, Pulmonology, AII - Inflammatory diseases, and Paediatric Pulmonology

Subjects
Male, 0301 basic medicine, MMP3, Allergy, MATRIX METALLOPROTEINASES, Respiratory Medicine and Allergy, Eepithelial integrity, airway inflammation, Systemic inflammation, DISEASE, Cohort Studies, transcriptomics, 0302 clinical medicine, Receptors, Immunology and Allergy, Lung, Macrophage inflammatory protein, Cells, Cultured, Lungmedicin och allergi, remodeling, Toll-like receptor, Cultured, CHITINASE-LIKE PROTEIN, 3. Good health, Phenotype, TARGET, medicine.anatomical_structure, 1107 Immunology, Airway Remodeling, eosinophils, medicine.symptom, Life Sciences & Biomedicine, hierarchical clustering, Signal Transduction, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, lung epithelium, 03 medical and health sciences, HYPERRESPONSIVENESS, Respiratory Hypersensitivity, medicine, Humans, Hierarchical Clustering, Inflammation, Science & Technology, Innate immune system, exacerbation frequency, Interleukin-6, business.industry, Sputum, Epithelial Cells, Gene signature, Receptors, Interleukin-6, DYSFUNCTION, Asthma, respiratory tract diseases, Eosinophils, Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes study group, Cross-Sectional Studies, SEVERITY, 030104 developmental biology, Gene Expression Regulation, 030228 respiratory system, INTERLEUKIN-6 RECEPTOR, BARRIER FUNCTION, 3121 General medicine, internal medicine and other clinical medicine, CELLS, epithelial integrity, IL-6 signaling, Exacerbation frequency, Transcriptome, business, Biomarkers
Abstract

BackgroundAlthough several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear.ObjectiveWe sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.MethodsAn IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS–specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens.ResultsActivation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS–high asthma with increased epithelial expression of IL-6TS–inducible genes in the absence of systemic inflammation. The IL-6TS–high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β.ConclusionsLocal lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.

Published
2019
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7. IL-17-high asthma with features of a psoriasis immunophenotype

Author

Jörgen Östling, Marleen van Geest, James P.R. Schofield, Zala Jevnikar, Susan Wilson, Jonathan Ward, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Sven-Erik Dahlen, Stephen J. Fowler, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Ana R. Sousa, Yike Guo, Ian M. Adcock, Peter Howarth, Kian Fan Chung, Jeanette Bigler, Peter J. Sterk, Paul J. Skipp, Ratko Djukanović, Outi Vaarala, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, K.F. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, A.J. Knox, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powell, G. Praticò, M. Puig N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Antonios Aliprantis, David Allen, Kjell Alving, P. Badorrek, David Balgoma, S. Ballereau, Clair Barber, Manohara Kanangana Batuwitage, A. Bautmans, A. Bedding, A.F. Behndig, Jorge Beleta, A. Berglind, A. Berton, Grazyna Bochenek, Armin Braun, D. Campagna, Leon Carayannopoulos, C. Casaulta, Romanas Chaleckis, B. Dahlén, imothy Davison, Jorge De Alba, Inge De Lepeleire, Tamara Dekker, Ingrid Delin, P. Dennison, Annemiek Dijkhuis, Paul Dodson, Aleksandra Draper, K. Dyson, Jessica Edwards, L. El Hadjam, Rosalia Emma, Magnus Ericsson, C. Faulenbach, Breda Flood, G. Galffy, Hector Gallart, D. Garissi, J. Gent, M. Gerhardsson de Verdier, D. Gibeon, Cristina Gomez, Kerry Gove, Neil Gozzard, E. Guillmant-Farry, E. Henriksson, Lorraine Hewitt, U. Hoda, Richard Hu, Sile Hu, X. Hu, E. Jeyasingham, K. Johnson, N. Jullian, Juliette Kamphuis, Erika J. Kennington, Dyson Kerry, G. Kerry, M. Klüglich, Hugo Knobel, Johan Kolmert, J.R. Konradsen, Maxim Kots, Kosmas Kretsos, L. Krueger, Scott Kuo, Maciej Kupczyk, Bart Lambrecht, A.-S. Lantz, Christopher Larminie, L.X. Larsson, P. Latzin, N. Lazarinis, N. Lemonnier, Saeeda Lone-Latif, L.A. Lowe, Alexander Manta, Lisa Marouzet, Jane Martin, Caroline Mathon, L. McEvoy, Sally Meah, A. Menzies-Gow, Leanne Metcalf, Maria Mikus, Philip Monk, Shama Naz, K. Nething, Ben Nicholas, U. Nihlén, Peter Nilsson, R. Niven, B. Nordlund, S. Nsubuga, Antonio Pacino, Susanna Palkonen, J. Pellet, Giorgio Pennazza, Anne Petrén, Sandy Pink, C. Pison, Anthony Postle, Malayka Rahman-Amin, Lara Ravanetti, Emma Ray, Stacey Reinke, Leanne Reynolds, K. Riemann, Martine Robberechts, J.P. Rocha, C. Rossios, Kirsty Russell, Michael Rutgers, G. Santini, Marco Santoninco, M. Saqi, Corinna Schoelch, S. Scott, N. Sehgal, Marcus Sjödin, Barbara Smids, Caroline Smith, Jessica Smith, Katherine M. Smith, P. Söderman, A. Sogbessan, F. Spycher, Doroteya Staykova, S. Stephan, J. Stokholm, K. Strandberg, M. Sunther, M. Szentkereszty, L. Tamasi, K. Tariq, John-Olof Thörngren, Jonathan Thorsen, S. Valente, Marianne van de Pol, C.M. van Drunen, Jonathan Van Eyll, Jenny Versnel, Anton Vink, C. von Garnier, A. Vyas, Frans Wald, Samantha Walker, Kristiane Wetzel, Coen Wiegman, Siân Williams, Xian Yang, Elizabeth Yeyasingham, W. Yu Amgen, W. Zetterquist, Z. Zolkipli, A.H. Zwinderman, Publica, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Pulmonology, AII - Inflammatory diseases, Experimental Immunology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, and Commission of the European Communities

Subjects
0301 basic medicine, Male, URINARY-EXCRETION, Allergy, Neutrophils, Inflammatory bowel disease, Cohort Studies, DOUBLE-BLIND, 0302 clinical medicine, Immunology and Allergy, POPULATION, Interleukin-13, Interleukin-17, psoriasis, BRODALUMAB, Up-Regulation, IL-17, Phenotype, 1107 Immunology, Biomarker (medicine), Female, Interleukin 17, medicine.symptom, Life Sciences & Biomedicine, ENDOTYPES, Signal Transduction, EXPRESSION, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, PHENOTYPES, Bronchi, 03 medical and health sciences, INFLAMMATION, Psoriasis, medicine, Humans, Interleukin 8, Asthma, U-BIOPRED Study Group, Science & Technology, business.industry, Gene Expression Profiling, biomarkers, Epithelial Cells, asthma, bronchial brushings, medicine.disease, bronchial biopsies, Neutrophilia, 030104 developmental biology, 030228 respiratory system, EXACERBATION, CELLS, Sputum, business, Transcriptome, Biomarkers
Abstract

Background The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Published
2019
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8. Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Author

Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene Lutter, Aruna T. Bansal, Ana R. Sousa, Steve A. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter H. Howarth, Elisabeth H. Bel, Ian M. Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J. Sterk, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F.K. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, J.G. Matthews, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powel, G. Praticò, M Puig Valls, N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Publica, Pulmonology, AII - Inflammatory diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, ARD - Amsterdam Reproduction and Development, Medical Research Council (MRC), and Pediatric surgery

Subjects
0301 basic medicine, Male, Allergy, Severe asthma, ILC3, mast cells, Disease, Eosinophil, Severity of Illness Index, transcriptomics, 0302 clinical medicine, Eosinophilic, Immunology and Allergy, Medicine, Age of Onset, Oligonucleotide Array Sequence Analysis, mechanisms, Innate lymphoid cell, Adult-onset asthma, eosinophils, gene set variation analysis, phenotyping, severe asthma, Middle Aged, Phenotype, Asthma Control Questionnaire, 1107 Immunology, Female, medicine.symptom, Adult, Genetic Markers, Immunology, mechanism, macromolecular substances, Lung injury, 03 medical and health sciences, Humans, adult-onset asthma, Asthma, U-BIOPRED Study Group, business.industry, Gene Expression Profiling, medicine.disease, respiratory tract diseases, 030104 developmental biology, Cross-Sectional Studies, 030228 respiratory system, Sputum, business, Transcriptome, mast cell
Abstract

Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (

Published
2018
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9. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials

Author

S.J. Fowler, Joel Ari Symons, Paul S. Myles, and S. Sabato

Subjects
medicine.medical_specialty, Knee Joint, Nausea, Joint replacement, medicine.medical_treatment, law.invention, Lumbar, Randomized controlled trial, law, medicine, Humans, Arthroplasty, Replacement, Knee, Pain Measurement, Randomized Controlled Trials as Topic, Pain, Postoperative, Lumbar plexus, Urinary retention, business.industry, Nerve Block, Jadad scale, Surgery, Analgesia, Epidural, Anesthesiology and Pain Medicine, Anesthesia, Vomiting, Hypotension, medicine.symptom, business
Abstract

The relative analgesic efficacy and side-effect profile of peripheral nerve blockade (PNB) techniques compared with lumbar epidural analgesia for major knee surgery is unclear. We undertook a systematic review and meta-analysis of all randomized trials comparing epidural analgesia with PNB for major knee surgery. Eight studies were identified that had enrolled a total of 510 patients of whom 464 (91%) had undergone total knee joint replacement. All were small trials and none was blinded (Jadad score 1-3). PNB technique was variable: in addition to a femoral catheter (n=5), femoral single shot (n=2), or lumbar plexus catheter (n=1) techniques, sciatic blockade was performed in three trials. There was no significant difference in pain scores between epidural and PNB at 0-12 or 12-24 h, WMD 0.22 (95% CI: -0.36, 0.81), 0.05 (-1.01, 0.91), respectively, and no clinically significant difference at 24-48 h, WMD -0.35 (-0.64, -0.02). There was also no difference in morphine consumption (mg) at 0-24 h, WMD -6.25 (-18.35, 5.86). Hypotension occurred more frequently among patients who received epidurals [OR 0.19 (0.08, 0.45)], but there was no difference in the incidence of nausea and vomiting. Two studies reported a higher incidence of urinary retention in the epidural group. Patient satisfaction was higher with PNB in two of three studies which measured this, although rehabilitation indices were similar. PNB with a femoral nerve block provides postoperative analgesia which is comparable with that obtained with an epidural technique but with an improved side-effect profile and is less likely to cause a severe neuraxial complication.

Published
2008
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10. Reproducibility and validity of the incremental shuttle walking test in patients following coronary artery bypass surgery

Author

S. Revill, Sally J Singh, and S.J. Fowler

Subjects
medicine.medical_specialty, Reproducibility, education.field_of_study, Rehabilitation, business.industry, medicine.medical_treatment, Population, VO2 max, Physical Therapy, Sports Therapy and Rehabilitation, Cardiorespiratory fitness, Confidence interval, Coronary artery bypass surgery, Internal medicine, Cardiology, Medicine, Treadmill, business, education
Abstract

Objective The incremental shuttle walking test (ISWT) is widely used to assess patients with chronic obstructive pulmonary disease. We hypothesised that it would be an appropriate tool to assess patients with coronary heart disease following coronary artery bypass grafts. We therefore explored the reproducibility, validity and sensitivity of the ISWT following rehabilitation. Design Participants completed three ISWTs and an incremental treadmill test over 7 days. Eleven patients repeated the ISWT following rehabilitation. Setting Cardiac rehabilitation department. Participants Thirty-nine patients, 34 of whom were male, with a mean age of 61.2 years (S.D. 8.5), 6–8 weeks after coronary artery bypass graft surgery. Main outcome measures Maximum oxygen uptake ( V ˙ O 2peak , ml/min/kg) and ISWT. Results Mean (S.D.) distances for the three ISWTs were 448m (137.8), 487m (147.6) and 481m (138.2). There was no statistically significant difference between the three ISWTs. The mean difference between Tests 1 and 2 was 42.8m (95% confidence interval 59.1–26.5m) compared with 1.7m (95% confidence interval −1.86–5.29 V ˙ ) between Tests 2 and 3. The mean V ˙ O 2peak was 21.0 (S.D. 4.5) ml/min/kg. There was a significant relationship between the results for the three ISWTs and V ˙ O 2peak ( r =0.79, r =0.86 and r =0.87 for Tests 1–3, respectively). Following rehabilitation, there was a significant increase in the distance walked; the mean difference between the second ISWT and the post-rehabilitation ISWT was 81.8m (95% confidence interval 53.2–110.4, P Conclusions The ISWT correlates well with V ˙ O 2peak and is a reliable measure of cardiorespiratory fitness in this population after one practice walk.

Published
2005
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12. Incidence of severe complications after central neuraxial block

Author

S.J. Fowler, T.M. Cook, D. Counsell, and J.A.W. Wildsmith

Subjects
medicine.medical_specialty, Anesthesiology and Pain Medicine, Central neuraxial block, business.industry, Incidence (epidemiology), Emergency medicine, Medical audit, medicine, MEDLINE, Data interpretation, business
Published
2009
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