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Andrew N Menzies-Gow,1,2 Trung N Tran,3 Brooklyn Stanley,4 Victoria Ann Carter,4 Josef S Smolen,5 Arnaud Bourdin,6 J Mark Fitzgerald7 ,† Tim Raine,8 Jatin Chapaneri,2 Benjamin Emmanuel,3 David J Jackson,9,10 David B Price4,11 1Royal Brompton and Harefield Hospitals, Guys & St Thomas’ NHS Foundation Trust, London, UK; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA; 4Observational and Pragmatic Research Institute, Singapore; 5Medical University of Vienna, Vienna, Austria; 6Université de Montpellier, CHU Montpellier, PhyMedExp, INSERM, CNRS, Montpellier, France; 7The University of British Columbia, Vancouver, British Columbia, Canada; 8Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK; 9Guy’s Severe Asthma Centre, Guy’s & St Thomas’ NHS Trust, London, UK; 10School of Immunology & Microbial Sciences, King’s College London, London, UK; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK†J. Mark Fitzgerald passed away on January 18, 2022Correspondence: David B Price, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building-Foresterhill, Aberdeen, AB25 2ZD, UK, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Associations between systemic glucocorticoid (SGC) exposure and risk for adverse outcomes have spurred a move toward steroid-sparing treatment strategies. Real-world changes in SGC exposure over time, after the introduction of steroid-sparing treatment strategies, reveal areas of successful risk mitigation as well as unmet needs.Patients and Methods: A population-based ecological study was performed from the Optimum Patient Care Research Database to describe SGC prescribing trends of steroid-sparing treatment strategies in primary care practices before and after licensure of biologics in the United Kingdom from 1990 to 2019. Each analysis year included patients aged ≥ 5 years who were registered for ≥ 1 year with a participating primary care practice. The primary analysis was SGC exposure, defined as total cumulative SGC dose per patient per year, for asthma, severe asthma, chronic obstructive pulmonary disease (COPD), nasal polyps, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, and systemic lupus erythematosus. Secondary outcomes were percentages of patients prescribed SGCs and number of SGC prescriptions per patient per year.Results: The number of patients who met study inclusion criteria ranged from 219,862 (1990) to 1,261,550 (2019). At the population level, patients with asthma or COPD accounted for 67.7% to 73.2% of patients per year with an SGC prescription. Over three decades, decreases in SGC total yearly dose ≥ 1000 mg have been achieved in multiple conditions. Patients with COPD prescribed SGCs increased from 5.8% (1990) to 34.8% (2017). SGC prescribing trends for severe asthma, Crohn’s disease, and ulcerative colitis show decreased prescribing trends after the introduction of biologics.Conclusion: Decreases in total yearly SGC doses have been shown in multiple conditions; however, for conditions such as severe asthma and COPD, an unmet need remains for increased awareness of SGC burden and the adoption or development of SGC-sparing alternatives to reduce overuse.Keywords: glucocorticoids, practice patterns, drug prescriptions, biological products, drug utilization

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Andrew N Menzies-Gow,1 Claire McBrien,2 Bindhu Unni,3 Celeste M Porsbjerg,4 Mona Al-Ahmad,5 Christopher S Ambrose,6 Karin Dahl Assing,7 Anna von Bülow,4 John Busby,8 Borja G Cosio,9 J Mark FitzGerald,10 Esther Garcia Gil,11 Susanne Hansen,12 Liam G aHeaney,8 Mark Hew,13,14 David J Jackson,15,16 Maria Kallieri,17 Stelios Loukides,17 Njira L Lugogo,18 Andriana I Papaioannou,17 Désirée Larenas-Linnemann,19 Wendy C Moore,20 Luis A Perez-de-Llano,21 Linda M Rasmussen,22 Johannes M Schmid,23 Salman Siddiqui,24 Marianna Alacqua,25 Trung N Tran,6 Charlotte Suppli Ulrik,26 John W Upham,27 Eileen Wang,28,29 Lakmini Bulathsinhala,3,30 Victoria A Carter,3,30 Isha Chaudhry,3,30 Neva Eleangovan,3,30 Ruth B Murray,3,30 Chris A Price,3,30 David B Price3,30,31 1UK Severe Asthma Network and National Registry, Royal Brompton & Harefield Hospitals, London, UK; 2Kingston Hospital, London, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 5Al-Rashed Allergy Center, Ministry of Health, Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait, Kuwait; 6AstraZeneca, Gaithersburg, MD, USA; 7Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 8UK Severe Asthma Network and National Registry, Queen’s University Belfast, Belfast, Northern Ireland; 9Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 10The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada; 11AstraZeneca, Barcelona, Spain; 12Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 13Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 14Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 15UK Severe Asthma Network andNational Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 16School of Immunology & Microbial Sciences, King’s College London, London, UK; 17 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 18Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 19Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 20Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 21Department of Respiratory Medicine, Hospital Universitario Lucus Augusti, Lugo, Spain; 22Allergy Clinic, Department of Dermato-Allergology, Gentofte Hospital, Copenhagen, Denmark; 23University Hospital of Aarhus, Aarhus, Denmark; 24University of Leicester, Department of Respiratory Sciences & NIHR Leicester Biomedical Research Centre (Respiratory Theme), Leicester, UK; 25AstraZeneca, Cambridge, UK; 26Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 27Diamantina Institute & PA-Southside Clinical Unit, The University of Queensland, Brisbane, Australia; 28Division of Allergy & Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA; 29Division of Allergy & Clinical Immunology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 30Optimum Patient Care, Cambridge, UK; 31Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceObservational and Pragmatic Research Institute, 22 Sin Ming Lane, #06 Midview City, Singapore, 573969 Tel +65 3105 1489Email dprice@opri.sgIntroduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors.Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015– 2020) or the CHRONICLE Study (2018– 2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups.Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti–IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti–IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization.Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.Keywords: severe asthma, biologics, prescribing, cohort study, management, international

John Busby,1 David Price,2– 4 Riyad Al-Lehebi,5 Sinthia Bosnic-Anticevich,6– 8 Job FM van Boven,9 Benjamin Emmanuel,10 J Mark FitzGerald,11 Mina Gaga,12 Susanne Hansen,13,14 Mark Hew,15,16 Takashi Iwanaga,17 Désirée Larenas Linnemann,18 Bassam Mahboub,19,20 Patrick Mitchell,21 Daniela Morrone,22 Jonathan Pham,15,23 Celeste Porsbjerg,14 Nicolas Roche,24,25 Eileen Wang,26,27 Neva Eleangovan,2,3 Liam G Heaney28 1Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 2Optimum Patient Care, Cambridge, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 6Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; 7Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia; 8Central Sydney Local Area Health District, Sydney, Australia; 9Department of Clinical Pharmacy & Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 10BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 11Department of Medicine, The University of British Columbia, Vancouver, Canada; 12 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital, Athens, Greece; 13Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 14Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 15Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 16Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 17Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 18Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 19College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 20Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 21Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 22Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy; 23Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Melbourne, Australia; 24Respiratory Medicine, Cochin Hospital, APHP.Centre, Paris, France; 25University of Paris, Cochin Institute (UMR1016), Paris, France; 26Division of Allergy & Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA; 27Division of Allergy & Clinical Immunology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 28Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern IrelandCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 6962 3627Email dprice@opri.sgIntroduction: Asthma morbidity and health-care utilization are known to exhibit a steep socioeconomic gradient. Further investigation into the modulators of this effect is required to identify potentially modifiable factors.Methods: We identified a cohort of patients with asthma from the Optimum Patient Care Research Database (OPCRD). We compared demographics, clinical variables, and health-care utilization by quintile of the UK 2011 Indices of Multiple Deprivation based on the location of the patients’ general practice. Multivariable analyses were conducted using generalized linear models adjusting for year, age, and sex. We conducted subgroup analyses and interaction tests to investigate the impact of deprivation by age, sex, ethnicity, and treatment step.Results: Our analysis included 127,040 patients with asthma. Patients from the most deprived socio-economic status (SES) quintile were more likely to report uncontrolled disease (OR: 1.54, 95% CI: 1.16, 2.05) and to have an exacerbation during follow-up (OR: 1.27, 95% CI: 1.13, 1.42) than the least deprived quintile. They had higher blood eosinophils (ratio: 1.03; 95% CI: 1.00, 1.06) and decreased peak flow (ratio: 0.95, 95% CI: 0.94, 0.97) when compared to those in the least deprived quintile. The effect of deprivation on asthma control was greater among those aged over 75 years (OR = 1.81, 95% CI: 1.20, 2.73) compared to those aged less than 35 years (OR: 1.22, 95% CI: 0.85, 1.74; pinteraction=0.019). Similarly, socioeconomic disparities in exacerbations were larger among those from ethnic minority groups (OR: 1.94, 95% CI: 1.40, 2.68) than white patients (OR: 1.24, 95% CI: 1.10, 1.39; pinteraction=0.012).Conclusion: We found worse disease control and increased exacerbation rates among patients with asthma from more deprived areas. There was evidence that the magnitude of socioeconomic disparities was elevated among older patients and those from ethnic minority groups. The drivers of these differences require further exploration.Keywords: asthma, socioeconomic status, disparities

Malcolm Begg,1 J Nicole Hamblin,1 Emily Jarvis,2 Glyn Bradley,3 Stephen Mark,4 David Michalovich,5 Mark Lennon,6 Hannah E Wajdner,5 Augustin Amour,5 Robert Wilson,1 Ken Saunders,5 Rikako Tanaka,7 Saki Arai,7 Teresa Tang,8 Cedric Van Holsbeke,9 Jan De Backer,9 Wim Vos,9 Ingrid L Titlestad,10 J Mark FitzGerald,11 Kieran Killian,12 Jean Bourbeau,13 Claude Poirier,14 François Maltais,15 Anthony Cahn,1 Edith M Hessel1 1Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK; 2Biostatistics, GlaxoSmithKline R&D, Stevenage, UK; 3Computational Biology, Medicinal Science and Technology, GlaxoSmithKline, Stevenage, UK; 4Study Management, Clinical Development, GlaxoSmithKline, Mississauga, ON, Canada; 5Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK; 6Nonclinical and Translational Statistics, GlaxoSmithKline, Stevenage, UK; 7Data Management & Strategy, Clinical Development, GlaxoSmithKline, Tokyo, Japan; 8Pharma Safety, Clinical Development, GlaxoSmithKline, Brentford, Middlesex, UK; 9FLUIDDA nv, Kontich, 2550, Belgium; 10Department of Respiratory Medicine, Odense University Hospital and University of Southern Denmark, Odense, Denmark; 11Centre for Heart and Lung Health, University of British Columbia, Vancouver, BC, Canada; 12Cardiorespiratory Research Laboratory, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 13Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada; 14Department of Medicine, Respiratory Medicine Division, University of Montreal, Montreal, QC, Canada; 15Institut Universitaire de Cardiologie et de Pneumologie de Québe, Université Laval, Quebec City, QC, CanadaCorrespondence: Malcolm BeggRefractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, Herts, UKEmail malcolm.5.begg@gsk.comBackground: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals − 46, 315mL) with a probability that the true treatment ratio was > 0% (Pr(θ> 0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged.Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.Keywords: nemiralisib, sputum, transcriptomics, COPD exacerbations, PI3Kdelta

Clarus Leung,1 Jean Bourbeau,2 Don D Sin,1 Shawn D Aaron,3 J Mark FitzGerald,4 François Maltais,5 Darcy D Marciniuk,6 Denis O’Donnell,7 Paul Hernandez,8 Kenneth R Chapman,9 Brandie Walker,10 Jeremy D Road,4 Liyun Zheng,1 Carl Zou,1 James C Hogg,1 Wan C Tan1 On behalf of the CanCOLD Collaborative Research Group1Centre for Heart Lung Innovation, St Pauls Hospital, The University of British Columbia, Vancouver, BC, Canada; 2Research Institute McGill University Health Centre, McGill University, Montreal, Quebec, Canada; 3The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; 4Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada; 5Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada; 6Respiratory Research Centre, University of Saskatchewan, Saskatoon, Canada; 7Department of Medicine, Queen’s University, Kingston, Canada; 8Department of Medicine, Dalhousie University, Halifax, Canada; 9Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada; 10Department of Medicine, University of Calgary (BW), Alberta, CanadaCorrespondence: Wan C TanCentre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Rm 166, 1081 Burrard Street, Vancouver, B.C, V6Z 1Y6, CanadaTel +1-604-682-2344 ext 62749Fax +1-604-806-9274Email wan.tan@hli.ubc.caPurpose: To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors.Patients and Methods: In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥ 40 years were generated by random digit dialling. Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 (fixed ratio, FR) and as FEV1/FVC < 5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I2 and Tau2 analyses were used to evaluate heterogeneity.Results: Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0– 57.2)) had spirometry that satisfied ATS criteria. The population prevalence of COPD was 16.2% (95% CI, 14.5– 17.8) by FR and 11.2% (95% CI, 9.7– 12.6) by LLN. Male predominance in prevalence was shown by FR but not by LLN criteria. Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33– 1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42– 4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17– 2.80). In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55– 4.80). Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau2 analyses. Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease.Conclusion: This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD.Keywords: prevalence, heterogeneity, COPD

Iraj Poureslami, 1, 2 Jessica Shum, 1, 2 Jacek Kopec, 3 Richard Sawatzky, 4 Samir Gupta, 5 Smita Pakhale, 6 Saron Kassay, 1, 2 Kassie Starnes, 1, 2 Alizeh Akhtar, 2 J Mark FitzGerald 1, 2 On behalf of the Canadian Airways Health Literacy Study Group 1Division of Respiratory Medicine, Department of Medicine, Institute for Heart and Lung Health, The University of British Columbia, Gordon and Leslie Diamond Health Care Centre, Vancouver, BC V5Z 1M9, Canada; 2Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, The University of British Columbia, Vancouver, BC V5Z 1M9, Canada; 3Division of Epidemiology, Biostatistics, and Public Health Practice, School of Population and Public Health, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada; 4School of Nursing, Trinity Western University, Langley, BC V2Y 1Y1, Canada; 5Division of Respirology, Department of Medicine, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; 6Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, CanadaCorrespondence: J Mark FitzGeraldDivision of Respiratory Medicine, Department of Medicine, Institute for Heart and Lung Health, The University of British Columbia, Gordon and Leslie Diamond Healthcare Centre, The Lung Centre, 7th Floor, 2775 Laurel Street, Vancouver, BC V5Z 1M9, CanadaTel +1 604 875 4122Email mark.fitzgerald@vch.caBackground: Health literacy (HL) is a person’s ability to practically apply a wide range of cognitive and non-cognitive skills in health-related decisions. HL includes five domains: navigate/access, understand, communicate, evaluate, and use of health information and services. Currently, no tool accurately captures and measures HL in adult patients with asthma and COPD, while utilizing all 5-HL domains.Objective: Develop a comprehensive functional-based measurement tool for adult asthma and/or COPD patients, while assessing HL on routine actions required to manage their chronic respiratory condition(s).Methods: We developed our HL tool based on a conceptualization of the link between HL and asthma and COPD management, during needs assessment stage including; a systematic review, which was followed by patient-oriented focus groups, and key-informant and respirologist interviews. Preliminary face and content validation were obtained by patients’ and health professionals’ input prior to the pretesting stage. The needs assessment information enabled us to develop passages in scenario-format and corresponding items to assess HL core domains, in addition to numeracy skills, across nine self-management topics: peak flow meters, prednisone use, pulmonary rehabilitation, action plans, flu shots, inhaler technique, lifestyle (nutrition and exercise), trigger control, and map navigation. The tool was pretested with asthma and COPD patients to assess its relevance, clarity, and difficulty.Results: Our systematic review identified the deficiencies of existing HL tools that assessed the HL skills of asthma and COPD patients. The patient-oriented focus groups (n=93) enabled us to identify self-management topics and develop items for our proposed HL tool, which were enriched by input from 45 key informants (eg, policy makers, clinicians, etc.) and 17 respiratory physicians. Preliminary pretesting with a new cohort of participants (36 asthma and COPD patients and 39 key informants) aided in the refinement and finalized our tool. The modified tool included passages and corresponding items related to asthma and COPD management was pretested with 75 asthma/COPD patients who completed the questionnaire and provided their feedback on the clarity, relevance, and difficulty of the tool. The main barrier to self-management pertained to “communication” skills. The flu shot was the most relevant topic (91.2%), while map navigation was the least relevant (63.9%). Action plans were the most difficult topic, where only 55% knew when to utilize their action plans. Numeracy items challenged COPD patients the most.Conclusion: We summarized findings from the development and preliminary testing stages of a new asthma/COPD HL tool. This tool will now be validated with a new cohort of patients.Practice Implications: Knowledge gained in this study has been applied to the final version of the tool, which is currently being validated.Keywords: COPD and asthma management, health literacy, measurement tool, functional skills

J Mark FitzGerald,1 Eugene R Bleecker,2 Arnaud Bourdin,3 William W Busse,4 Gary T Ferguson,5 Laura Brooks,6 Peter Barker,6 Ubaldo J Martin6 1Centre for Heart and Lung Health, The Lung Centre Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, Canada; 2Divisions of Pharmacogenomics and Genetics, Genomics and Precision Medicine, University of Arizona College of Medicine, Tucson, AZ, United States; 3Department of Respiratory Diseases, Hôpital Arnaud De Villeneuve, Montpellier, France; 4Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; 5Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, United States; 6AstraZeneca, Gaithersburg, MD, United StatesCorrespondence: J Mark FitzGeraldThe Lung Centre, Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre, 2775 Laurel Street, Vancouver BC V5Z 1M9, CanadaTel +1604-875-4122Email mark.fitzgerald@vch.caBackground: Benralizumab is an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody. Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year for patients with severe, uncontrolled eosinophilic asthma.Objective: We explored whether benralizumab efficacy was sustained after an additional year of treatment while maintaining an acceptable safety profile.Methods: Data from the pivotal 48-week SIROCCO and 56-week CALIMA studies were integrated with data from the predefined 56-week adult phase of the BORA extension study to provide a 2-year integrated efficacy and safety analysis of benralizumab. BORA enrolled patients who had completed SIROCCO or CALIMA. Patients receiving benralizumab 30 mg subcutaneously, either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W), were assessed. Efficacy was evaluated based on baseline blood eosinophil counts from the pivotal studies (≥300 and Results: Mean treatment exposures were 24.3 (Q4W, n=518) and 24.6 (Q8W, n=512) months. Exacerbation frequency reductions observed in SIROCCO/CALIMA were maintained; 50% of the patients had no exacerbations during the 2-year study period (crude exacerbation rate, Q8W: 0.56 exacerbations/year for patients with blood eosinophil counts ≥300 cells/μL). Lung function improvements with benralizumab were maintained for 2 years, as represented by increases in mean prebronchodilator forced expiratory volume in 1 second from baseline of 0.343 L and 0.364 L with 1 and 2 years of benralizumab Q8W treatment, respectively, for patients with blood eosinophil counts ≥300 cells/μL. Health-related quality of life improvements with benralizumab observed in the pivotal studies were also sustained. Adverse events and serious adverse event rates were similar between the BORA extension and SIROCCO/CALIMA periods, with no new or unexpected occurrence of adverse events.Conclusion: This benralizumab 2-year integrated analysis further supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.Keywords: asthma, benralizumab, clinical features, eosinophilic inflammation, interleukin-5 receptor, safety

Hamid Tavakoli1, Kate M Johnson1, J Mark FitzGerald2, Don D Sin3, Andrea S Gershon4, Tetyana Kendzerska5, Mohsen Sadatsafavi1,2 On behalf of the Canadian Respiratory Research Network1Respiratory Evaluation Sciences Program, Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada; 2Institute for Heart and Lung Health, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; 3Centre for Heart Lung Innovation (the James Hogg Research Centre), St. Paul’s Hospital, Vancouver, British Columbia, Canada; 4Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; 5Department of Medicine, Division of Respirology, The Ottawa Hospital Research Institute/University of Ottawa, Ottawa, Ontario, CanadaCorrespondence: Hamid TavakoliFaculty of Pharmaceutical Sciences, University of British, Columbia, Vancouver Campus, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, CanadaTel +1 604 723 4923Fax +1 604 875 5179Email Hamid.tavakoli@ubc.caBackground: The patterns of medication use in chronic obstructive pulmonary disease (COPD) may change over time due to the availability of new medications, updates in guideline-based recommendations, and changes in patient and care provider preferences.Objectives: To document population-level trends of filled prescriptions and costs for major classes of inhaled COPD therapies.Method: We used administrative health databases of the province of British Columbia, Canada, from 1997 to 2015, to create a retrospective cohort of COPD patients. We documented the percentage of patients receiving major inhaled COPD-related medications, including short-acting beta-2 adrenoreceptor agonists (SABA), long-acting beta-2 adrenoreceptor agonists (LABA), inhaled corticosteroids (ICS), short-acting muscarinic receptor antagonists (SAMA), and long-acting muscarinic receptor antagonists (LAMA). We quantified the average, and relative annual change in, dispensed quantities and costs (in 2015 Canadian dollars [$]) of medications. Combination therapy was assessed as the proportion of time covered by two or more long-acting medications of different classes.Results: A total of 176,338 patients were included in the final cohort (mean age at entry 68.7, 48.5% female). In 2015, the most common medication was ICS (45.7% of the patients), followed by LABA (36.5%). LAMA was the least used medication (18.9%). The number of filled prescriptions per patient per year for LAMA (+7.8% per year) and LABA (+4.9%) increased, while they decreased for SAMA (−6.3%) and SABA (−3.8%), and remained relatively constant for ICS. The average annual per-patient costs of inhaled medications were $570.8 in 2015, which was double the costs from 1997. Single-inhaler ICS/LABA had the highest rate of increase (11.6% per year), and comprised 53.7% of the total costs of inhalers in 2015. In 2015, 28.5% of the patient time was on combination therapies, with 7.1% on triple ICS/LABA/LAMA therapy.Conclusion: Utilization of inhaled therapies for COPD has changed significantly over time. The low utilization of LAMA and high utilization of combination therapies (particularly those containing ICS) do not seem to be aligned with COPD treatment guidelines.Keywords: COPD, medication, cost, trend, SABA, ICS, LABA, LAMA, SAMA

Kevin Gruffydd-Jones,1 Mike Thomas,2 Miguel Roman-Rodríguez,3 Antonio Infantino,4 J Mark FitzGerald,5 Ian Pavord,6 Jennifer M Haddon,7 Ulrich Elsasser,8 Christian Vogelberg91Box Surgery, Box, Wiltshire, UK; 2Primary Care and Population Sciences, University of Southampton, Southampton, UK; 3Son Pisà Primary Health Care Centre, Balearic Health Centre, Palma de Mallorca, Spain; 4Società Italiana Interdisciplinare per le Cure Primarie (SIICP), Bari, Italy; 5Institute for Heart and Lung Health, University of British Columbia, Vancouver, British Columbia, Canada; 6Respiratory Medicine Unit and Oxford Respiratory NIHR Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 7TA Dig Excellence + Healthcare Inno Med, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 8Biostatistics and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany; 9Department of Pediatric Pneumology and Allergology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, GermanyBackground: Asthma affects millions of people worldwide, with many patients experiencing symptoms that affect their daily lives despite receiving long-term controller medication.Purpose: Work is a large part of most people’s lives, hence this study investigated the impact of uncontrolled asthma on work productivity in adults receiving asthma maintenance therapy.Patients and methods: An online survey was completed by employed adults in Brazil, Canada, Germany, Japan, Spain and the UK. Participants were confirmed as symptomatic using questions from the Royal College of Physicians’ 3 Questions for Asthma tool. The survey contained the Work Productivity and Activity Impairment – Specific Health Problem questionnaire and an open-ended question on the effect of asthma at work.Results: Of the 2,055 patients on long-term maintenance therapy screened, 1,598 were symptomatic and completed the survey. The average percentage of work hours missed in a single week due to asthma symptoms was 9.3%, ranging from 3.5% (UK) to 17.4% (Brazil). Nearly three-quarters of patients reported an impact on their productivity at work caused by asthma. Overall work productivity loss (both time off and productivity whilst at work) due to asthma was 36%, ranging from 21% (UK) to 59% (Brazil). When asked how asthma made participants feel at work, many respondents highlighted how their respiratory symptoms affect them. Tiredness, weakness and mental strain were also identified as particular challenges, with respondents describing concerns about the perception of colleagues and feelings of inferiority.Conclusions: This study emphasizes the extent to which work time is adversely affected by asthma in patients despite the use of long-term maintenance medication, and provides unique personal insights. Strategies to improve patients’ lives may include asthma education, optimizing asthma management plans and running workplace well-being programs. Clinicians, employers and occupational health teams should be more aware of the impact of asthma symptoms on employees, and work together to help overcome these challenges.Keywords: work productivity, asthma, burden, costs

Nawaf M Alotaibi,1,2 Virginia Chen,1,3,4 Zsuzsanna Hollander,1,3,4 Jonathon A Leipsic,5 Cameron J Hague,5 Darra T Murphy,5 Mari L DeMarco,1,6 JM FitzGerald,3,7,8 Bruce M McManus,1,3,4,6 Raymond T Ng,4,9 Don D Sin1,3,7 1Centre for Heart Lung Innovation, James Hogg Research Centre, St Paul’s Hospital, Vancouver, BC, Canada; 2Department of Medicine, Division of Pulmonary Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Institute for Heart and Lung Health, Vancouver, BC, Canada; 4PROOF Centre of Excellence, Vancouver, BC, Canada; 5Department of Radiology, St Paul’s Hospital, Vancouver, BC, Canada; 6Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; 7Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 8The Lung Centre, Vancouver General Hospital, Vancouver, BC, Canada; 9Department of Computer Sciences, University of British Columbia, Vancouver, BC, Canada Background: Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes.Methods: We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts.Results: A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups.Conclusion: Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise. Keywords: COPD, molecular pathogen detection, exacerbation phenotypes

Kate M Johnson,1 Abdollah Safari,1,2 Wan C Tan,3 Jean Bourbeau,4 J Mark FitzGerald,2 Mohsen Sadatsafavi1,2,5 On behalf of the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study and the Canadian Respiratory Research Network 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 2Institute for Heart and Lung Health, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada; 3Centre for Heart Lung Innovation (the James Hogg Research Centre), St Paul’s Hospital, Vancouver, BC, Canada; 4Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre, Montreal, QC, Canada; 5Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, Vancouver, BC, Canada Background: The burden of symptoms varies markedly between patients with COPD and is only weakly correlated with lung function impairment. While heterogeneity in lung function decline and exacerbations have been previously studied, the extent of heterogeneity in symptoms and the factors associated with this heterogeneity are not well understood.Methods: A sample of the general Canadian population ≥40 years with persistent airflow limitation was followed for up to 3 years. Participants reported whether they experienced chronic coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed-effect logistic regression models (separately for each symptom) to assess overall heterogeneity in the occurrence of symptoms between individuals, and the proportion of variation in symptom burden explained by lung function vs all other clinical characteristics of participants.Results: Four hundred forty-nine participants (53% male, mean age 67 years) contributed 968 visits in total, and 89% of patients reported at least one symptom during follow-up. There was substantial heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This heterogeneity was highest for wheeze and dyspnea (IQR of probabilities: 0.13–0.78 and 0.19–0.81, respectively). FEV1 explained 28% of the variation between individuals in the occurrence of dyspnea, 8% for phlegm, 3% for cough, and 2% for wheeze. All clinical characteristics of participants (including FEV1) explained between 26% of heterogeneity in the occurrence of cough to 49% for dyspnea.Conclusion: There is marked heterogeneity in the burden of respiratory symptoms between COPD patients. The ability of lung function and other commonly measured clinical characteristics to explain this heterogeneity differs between symptoms. Keywords: population, respiratory symptoms, chronic obstructive pulmonary disease, variability, cough, phlegm, wheeze, dyspnea

Nawaf M Alotaibi,1,2 Virginia Chen,1,3,4 Zsuzsanna Hollander,1,3,4 Cameron J Hague,5 Darra T Murphy,5 Jonathon A Leipsic,5 Mari L DeMarco,1,6 J Mark FitzGerald,7,8 Bruce M McManus,1,3,4,6 Raymond T Ng,4,9 Don D Sin1,3,7 1Centre for Heart Lung Innovation, James Hogg Research Centre, St Paul’s Hospital, Vancouver, BC, Canada; 2Division of Pulmonary Medicine, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Institute for Heart Lung Health, 4PROOF Centre of Excellence, 5Department of Radiology, St Paul’s Hospital, 6Department of Pathology and Laboratory Medicine, 7Division of Respiratory Medicine, Department of Medicine, University of British Columbia, 8The Lung Centre, Vancouver General Hospital, 9Department of Computer Sciences, University of British Columbia, Vancouver, BC, Canada Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers. Materials and methods: Subjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman’s correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters. Results: A total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV1 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, P

Abdulmajeed Alshabanat,1 Michael C Otterstatter,2,3 Don D Sin,4,5 Jeremy Road,5,6 Carmen Rempel,6 Jane Burns,6 Stephan F van Eeden,4,5 JM FitzGerald5–7 On behalf of the COPD Transition Team Program 1Department of Experimental Medicine, University of British Columbia, 2British Columbia Centre for Disease Control, 3School of Population and Public Health, 4Department of Medicine, Centre for Heart Lung Innovation, St Paul’s Hospital, 5Division of Respirology, Department of Medicine, 6Department of Medicine, Faculty of Medicine, Institute for Heart and Lung Health, University of British Columbia, 7Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, Vancouver, BC, Canada Background: COPD accounts for the highest rate of hospital admissions among major chronic diseases. COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing.Aim: The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD.Materials and methodology: We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days. We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation.Results: A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study. The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%. Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P

Iraj Poureslami,1,2 Susan Kwan,3 Stephen Lam,4,5 Nadia A Khan,6,7 John Mark FitzGerald 8,9 1Respiratory Division, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; 2Department of Graduate Studies, Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, Canada; 3Respiratory Department, Burnaby Hospital, University of British Columbia, Burnaby, Canada; 4Respiratory Division, University of British Columbia, Vancouver, Canada; 5Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, Canada; 6Department of Internal Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; 7Department of Internal Medicine, Providence Health Care Authority, Vancouver, Canada; 8VGH Divisions of Respiratory Medicine, University of British Columbia, Vancouver, Canada; 9Respiratory Medicine, Vancouver Coastal Health Authority, Vancouver Coastal Health Research Institute, Institute for Heart and Lung Health, The Lung Centre, Gordon and Leslie Diamond Health Care Centre, Vancouver, Canada Background: Patient education is a key component in the management of chronic obstructive pulmonary disease (COPD). Delivering effective education to ethnic groups with COPD is a challenge. The objective of this study was to develop and assess the effectiveness of culturally and linguistically specific audiovisual educational materials in supporting self-management practices in Mandarin- and Cantonese-speaking patients. Methods: Educational materials were developed using participatory approach (patients involved in the development and pilot test of educational materials), followed by a randomized controlled trial that assigned 91 patients to three intervention groups with audiovisual educational interventions and one control group (pamphlet). The patients were recruited from outpatient clinics. The primary outcomes were improved inhaler technique and perceived self-efficacy to manage COPD. The secondary outcome was improved patient understanding of pulmonary rehabilitation procedures. Results: Subjects in all three intervention groups, compared with control subjects, demonstrated postintervention improvements in inhaler technique (P

Background: The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone.Methods: We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life.Results: At 14 days the mean±SE change in FEV(1) from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08).Conclusions: Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%.Clinical Trials: gov number NCT 00789997. [ABSTRACT FROM AUTHOR]

Objective: The objectives of our study were to compare patient characteristics and severity of disease in obese and normal-weight-confirmed people with asthma and to explore reasons for misdiagnosis of asthma, including potential interactions with obesity.Methods: We randomly selected patients with physician-diagnosed asthma from eight Canadian cities. Asthma diagnosis was confirmed via a sequential lung function testing algorithm. Logistic analysis was conducted to compare obese and normal-weight-confirmed people with asthma and to assess characteristics associated with misdiagnosis of asthma. Interaction with obesity was investigated.Results: Complete assessments were obtained on 496 subjects who reported physician-diagnosed asthma (242 obese and 254 normal-weight subjects); 346 had asthma confirmed with sequential lung testing, and in 150 subjects a diagnosis of asthma was ruled out. Obese subjects with asthma were significantly more likely to be men, have a history of hypertension and gastroesophageal reflux disease, and have a lower FEV(1) compared with normal-weight subjects with asthma. Older subjects, men, and subjects with higher FEV(1) were more likely to have received misdiagnoses of asthma. Obesity was not an independent predictor of misdiagnosis, however there was an interaction between obesity and urgent visits for respiratory symptoms. The odds ratio for receiving a misdiagnosis of asthma for obese individuals as compared with normal-weight individuals was 4.08 (95% CI, 1.23-13.5) for those with urgent visits in the past 12 months.Conclusions: Obese people with asthma have lower lung function and more comorbidities compared with normal-weight people with asthma. Obese individuals who make urgent visits for respiratory symptoms are more likely to receive a misdiagnosis of asthma. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea.Methods: We conducted a longitudinal study involving nonobese (body mass index 20-25) and obese (body mass index >/= 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months.Results: Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%-37.9%) in the obese group and in 28.7% (95% CI 23.5%-34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period.Interpretation: About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed. [ABSTRACT FROM AUTHOR]

Background: Inhaled corticosteroids (ICS) are commonly prescribed medications for the management of asthma and chronic obstructive pulmonary disease. It is well established that long-term use of these drugs may lower bone mineral density. However, whether ICS increase the risk of fractures remains unknown. Recent studies that have attempted to explore this risk have had conflicting results. We sought to explore the risk of ICS and fractures among older adults by conducting a systematic review and meta-analysis of the literature.Methods: We systematically searched several databases, including MEDLINE, EMBASE and the Cochrane Library, to identify pertinent studies. Those studies that potentially met our inclusion criteria were identified by two reviewers. Relative risks (RRs) were pooled using the random effects model. We also explored dose-response by stratifying the analysis on high and low doses of ICS. Heterogeneity was assessed using the Q statistic and publication bias was assessed using the funnel plot.Results: Thirteen studies, including four randomized controlled trials, were included in the review. The pooled RRs for hip fractures and any fractures were 0.91 (95% CI 0.87, 0.96) and 1.02 (95% CI 0.96, 1.08), respectively. When we restricted the analysis to users of high-dose ICS, the pooled RRs for any fractures and hip fractures were 1.30 (95% CI 1.07, 1.58) and 1.32 (95% CI 0.90, 1.92), respectively. The funnel plot did not show evidence of publication bias.Conclusion: We found no association between the use of ICS and fractures in older adults. A slight increase in risk was seen in those using high-dose ICS. The significance of this association should be investigated further. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL). METHODS: Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference. RESULTS: One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy. [ABSTRACT FROM AUTHOR]

Rationale: Bronchial thermoplasty (BT) reduces the potential for smooth muscle-mediated bronchoconstriction by reducing the mass of smooth muscle in the walls of conducting airways. Objectives: This study was conducted to examine the safety and impact on lung function and airway responsiveness of BT over 2 yr. Methods: The safety of BT was studied in 16 subjects with mild to moderate asthma. Baseline and 12-wk post-treatment measurements included spirometry, methacholine challenge, daily diary recordings of peak flow, symptoms, and medication usage. Subjects completed follow-up evaluations at 12 wk, 1 yr, and 2 yr. Measurements and Main Results: The procedure was well tolerated; side effects were transient and typical of what is commonly observed after bronchoscopy. All subjects demonstrated improvement in airway responsiveness. The mean PC(20) increased by 2.37 +/- 1.72 (p < 0.001), 2.77 +/- 1.53 (p = 0.007), and 2.64 +/- 1.52 doublings (p < 0.001), at 12 wk, 1 yr, and 2 yr post-procedure, respectively. Data from daily diaries collected for 12 wk indicated significant improvements over baseline in symptom-free days (p = 0.015), morning peak flow (p = 0.01), and evening peak flow (p

BACKGROUND: A patient-driven, adjustable maintenance dosing (AMD) approach to asthma therapy, in which the dose is adjusted by patients according to the severity of their symptoms, has recently been compared with fixed-dose therapy in open-label studies. OBJECTIVE: This study used a double-blind, double-dummy design to compare the efficacy of 2 treatment approaches: stable dosing of salmeterol/fluticasone propionate (SAL/FP) and AMD of formoterol/budesonide (FOR/BUD). METHODS: This was a 1-year, multicenter, randomized, double-blind, double-dummy study in adult patients with symptomatic asthma that was not controlled by therapy with 200 to 500 microg/d inhaled corticosteroid (ICS) plus a long-acting beta2 agonist, or with >500 to 1000 microg/d ICS alone. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 microg BID or 2 inhalations of FOR/BUD 6/200 microg BID, both delivered via dry powder inhaler devices. After 4 weeks of stable dosing in both groups, eligible patients continued the study for an additional 48 weeks, receiving either a stable dose of SAL/FP or AMD of FOR/BUD. According to the AMD treatment plan, patients initially halved their dose and subsequently stepped up or down as indicated by the presence or absence of nocturnal awakenings due to asthma, frequency of rescue medication use, and changes in morning peak expiratory flow (PEF). The primary end point was the percentage of symptom-free days. Other parameters included daily asthma symptom scores, morning PEF, percentage of days free of rescue medication use, daily rescue medication use, percentage of nighttime awakenings due to asthma, percentage of weeks with well-controlled asthma, and number of exacerbations requiring oral corticosteroids or emergency department (ED) visits/hospitalizations. Tolerability was assessed in terms of adverse events spontaneously reported or elicited at clinic visits. RESULTS: The intent-to-treat population comprised 688 patients (344 per treatment arm) with a mean age of 45 years and a mean baseline forced expiratory volume in 1 second 81% of the predicted normal value. After 4 weeks' stable dosing, 581 patients (295 SAL/FP, 286 FOR/BUD) continued beyond visit 3 into the remaining 48-week treatment period. Over weeks 1 through 52, patients receiving stable dosing of SAL/FP had a significantly greater percentage of symptom-free days compared with those receiving AMD of FOR/BUD (median, 58.8% vs 52.1%, respectively; P = 0.034). The incidence of asthma exacerbations requiring oral steroids or an ED visit/hospitalization was 47% lower with SAL/FP compared with FOR/BUD (adjusted annual mean rate, 0.18 vs 0.33; P = 0.008). During weeks 5 through 52, patients in the FOR/BUD AMD group used a mean of 1.8 inhalations/d (equivalent to BUD 360 microg/d), and 235 (82.2%) patients stepped down to 1 inhalation/d. Mean (SD) daily ICS exposure over 52 weeks was 463 (81) microg FP and 480 (238) microg BUD in the respective treatment arms. CONCLUSIONS: In this adult population with persistent asthma, stable dosing of SAL/FP 50/250 microg BID resulted in significantly greater increases in symptom-free days, days free of rescue medication, and morning PEE, as well as almost halving the exacerbation rate, compared with AMD of FOR/BUD 6/200 microg. The results suggest that there is a minimum daily amount of maintenance therapy necessary to prevent exacerbations in adults with persistent asthma. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: To assess the association between socioeconomic status (SES) and short-acting (SA) beta-agonist use, controlling for asthma severity. DESIGN: Cross-sectional study. SETTING: Vancouver, BC, Canada. PARTICIPANTS: Two hundred two asthmatics between 19 years and 50 years of age and residing in the greater Vancouver regional district. MEASUREMENTS: The quantity of SA beta-agonist used in the previous year was collected by self-report; pulmonary function and beta-receptor genotype were measured on each participant. SES was measured at both the individual and population levels. Five methods of adjustment for asthma severity were used, as follows: the Canadian Asthma Consensus Guidelines, three previously developed asthma-severity scores, and forward stepwise multiple regression modeling. Polychotomous logistic regression was used to assess all relationships. RESULTS: Independent of the method used to measure SES or adjust for asthma severity, lower SES was consistently and significantly associated with the use of greater amounts of SA beta-agonist. Adjusting for severity using the multivariate model explained the most variance of SA beta-agonist use (R(2) adjusted, 0.35 to 0.37). In this model, social assistance recipients were more likely to use greater amounts of SA beta-agonist (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.7 to 6.5). An inverse relationship between SA beta-agonist use and both annual household income (> $50,000; OR, 0.28; 95% CI, 0.13 to 0.60; and $20,000 to $50,000; OR, 0.44; 95% CI, 0.21 to 0.96; relative to <$20,000) and education (completing a bachelor's degree vs no formal education; OR, 0.25; 95% CI, 0.14 to 0.71). Participants living in a neighborhood with higher median household income (OR, 0.91; 95% CI, 0.84 to 0.98 per $1,000 increase) or a higher prevalence of having attained a bachelor's degree (OR, 0.96; 95% CI, 0.84 to 0.98 per 1% increase) were also less likely use greater amounts of SA beta-agonist. Results were consistent for neighborhood unemployment rate. CONCLUSIONS: The social gradient in asthma-related outcomes may be at least partially attributable to poorer asthma control in lower-SES asthmatics. [ABSTRACT FROM AUTHOR]

Asthma guidelines support adjustable maintenance dosing and the use of guided self-management for long-term asthma management and advocate the use of inhaled corticosteroids and long-acting 2-agonists to control symptoms. In this context, budesonide/formoterol in a single inhaler may be used with either a fixed-dosing or adjustable maintenance dosing treatment regimen. Eight randomised studies compared the efficacy and tolerability of budesonide/formoterol adjustable maintenance dosing (one to two inhalations bid with a temporary step-up to four inhalations bid maximum) with fixed-dosing (two inhalations bid). In three studies (>/=6 months in duration), a reduced incidence of exacerbations was reported with adjustable maintenance dosing compared with fixed-dosing. In all studies, adjustable maintenance dosing reduced the mean number of inhalations of budesonide/formoterol per patient per day compared with fixed-dosing while maintaining or improving asthma control. Adjustable maintenance dosing with budesonide/formoterol is well tolerated and has proven to be a more effective treatment strategy for asthma management, despite using less amount of drug compared with fixed-dosing. [ABSTRACT FROM AUTHOR]

This article reports on a study of autobiographical memory in two older adults, wife and husband, over a retention interval of 20 years. The female participant kept a 20-year log of daily events. A sampling of events that varied in distinctiveness, from unique, one-of-a-kind events to routine, almost daily events, was used to examine cued recall using an incremental scoring system. Each event recalled was also rated on phenomenological scales of remembering versus knowing, rehearsal, and importance. The strongest effect on recall was the order of the cues, with an initial what cue, containing the content of the event, proving superior to cues containing who or where elements. When was the most effective second cue. The results demonstrate regularity in retention over time and highlighted the utility of this approach for understanding the factors that influence autobiographical memory performance. [ABSTRACT FROM AUTHOR]

Incidental renal or adrenal masses are sometimes found during imaging for problems unrelated to the kidneys and adrenal glands. Knowledgeable family physicians can reliably diagnose these masses, thereby avoiding unnecessary worry and procedures for their patients. A practical and cost-efficient means of evaluating renal lesions combines ultrasonography and computed tomographic scanning, with close communication between the family physician and the radiologist. Asymptomatic patients with simple renal cysts require no further evaluation. Patients with minimally complicated renal cysts can be followed radiographically. Magnetic resonance imaging is indicated in patients with indeterminate renal masses, and referral is required in patients with symptoms or solid masses. The need for referral of patients with adrenal masses is determined by careful assessment of clinical signs and symptoms, as well as the results of screening laboratory studies and appropriate radiologic studies. Referral is indicated for patients with incidental adrenal masses more than 6 cm in greatest diameter. Appropriate laboratory screening tests include the following: a 24-hour urinary free cortisol measurement for patients with evidence of Cushing's syndrome; a 24-hour urinary metanephrine, vanillylmandelic acid or catecholamine measurement for patients with evidence of pheochromocytoma; and a serum potassium level for patients with evidence of hyperaldosteronism. [ABSTRACT FROM AUTHOR]

Background: The risk for and determinants of transmission of tuberculosis in hospitals caring for moderate numbers of patients with tuberculosis remain uncertain.Objective: To study the association of tuberculin conversion among health care workers with ventilation of patient care areas.Design: Cross-sectional observational survey.Setting: 17 acute-care community or university hospitals.Participants: All personnel who worked at least 2 days per week in the respiratory and physiotherapy departments or in selected nursing units.Measurements: Participating workers underwent tuberculin skin testing and completed self-administered questionnaires. Previous tuberculin tests and bacille Calmette-Guérin vaccinations were verified. Records of patients with tuberculosis who were hospitalized in the 3 years preceding the study were reviewed. Air exchanges per hour in patient care areas were measured by using a tracer gas technique. Multivariate proportional hazards regression was used to estimate the effect of occupational factors on documented tuberculin conversion, after adjustment for nonoccupational factors, among participants with at least one previous negative result on tuberculin skin testing.Results: Tuberculin conversion was associated with ventilation of general or nonisolation patient rooms of less than 2 air exchanges per hour (adjusted hazard ratio, 3.4 [95% CI, 2.1 to 5.8]); with work in moderate- to high-risk hospitals (adjusted hazard ratio, 2.2 [CI, 1.3 to 3.5]); and with work in the nursing (adjusted hazard ratio, 4.3 [CI, 2.7 to 6.9]), respiratory therapy (adjusted hazard ratio, 6.1 [CI, 3.1 to 12.0]), and physiotherapy (adjusted hazard ratio, 3.3 [CI, 1.5 to 7.2]) departments or housekeeping (adjusted hazard ratio, 4.2 [CI, 2.3 to 7.6]). Conversion was not associated with inadequate ventilation of respiratory isolation rooms (adjusted hazard ratio, 1.0 [CI, 0.8 to 1.3]).Conclusion: Tuberculin conversion among health care workers was strongly associated with inadequate ventilation in general patient rooms and with type and duration of work, but not with ventilation of respiratory isolation rooms. [ABSTRACT FROM AUTHOR]