Asthma Clinical Research Articles

Editorial introductions

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Susan M. TarloSusan M. TarloDr Susan M. Tarlo, MBBS, FRCP(C) is a Professor in the Department of Medicine and in the Dalla Lana School of Public Health at the University of Toronto, Canada. She is a respiratory physician at the University Health Network, Toronto Western Hospital, Canada and at the Gage Occupational and Environmental Health Unit and Centre of Research Excellence in Occupational Diseases of St Michael's Hospital in Toronto, Canada. Her main areas of clinical practice and research are in occupational and environmental lung diseases and allergic responses, especially occupational asthma. She initially graduated from medical school at London University, England, and underwent postgraduate training in England for four years before coming to Queen's University, Kingston, Ontario, Canada for a year as a fellow in allergy and clinical immunology, followed by a respiratory medicine residency for two years at McMaster University, Hamilton, Canada. She has been in Toronto as a staff physician at the Toronto General Hospital and then at Toronto Western Hospital as well as at the Gage Occupational and Environmental Health Unit since 1976 as well as holding academic positions at the University of Toronto since that time. Piero MaestrelliPiero MaestrelliDr Maestrelli, MD, completed his medical degree at University of Padova, Italy, and then specialised in occupational medicine and in pulmonology. He completed a two year post doctoral fellowship at the Institute of Occupational Medicine, University of Padova, and then a two year research fellowship at the Department of Allergy and Clinical Immunology of Cardiothoracic Institute, London, UK. Dr Maestrelli has written over 150 scientific papers and book chapters, and has lectured nationally and internationally. He has been Chairman of the Interest Group on Occupational Allergy of European Academy of Allergology and Clinical Immunology for three years. He is currently Professor of Occupational Medicine at University of Padova, Department of Cardiologic, Thoracic and Vascular Sciences, Italy, and Head of the Laboratory of Lung Pathophysiology of the Unit of Occupational Medicine at the University Hospital of Padova. Leonard B. BacharierLeonard B. BacharierDr Bacharier is Professor of Pediatrics and Medicine at Washington University School of Medicine, USA and Clinical Director of the Division of Pediatric Allergy, Immunology and Pulmonary Medicine, and Unit co-Leader for the Pediatric Patient Orientated Research Unit. He received his undergraduate degree in biophysics from The Johns Hopkins University, USA and his medical degree from Washington University School of Medicine. Dr Bacharier was an intern and resident in pediatrics at St. Louis Children's Hospital and a fellow in pediatric allergy and immunology at Children's Hospital, Boston and Harvard Medical School, USA. He was a recipient of the 2005 Samuel R. Goldstein Leadership Award in Medical Student Education from Washington University School of Medicine and is a member of several organizations including the American Academy of Allergy, Asthma and Immunology and the American Thoracic Society. Dr Bacharier's research focuses on childhood asthma. Specifically, he is a principal investigator in the NHLBI-funded AsthmaNet, a multi-centered network examining therapeutic approaches to childhood asthma. He is an Investigator in the NHLBI's Severe Asthma Research Program (SARP) and the Inner City Asthma Consortium's URECA study examining the influence of urban environments on the development of asthma and allergic disorders. He is also an investigator in the American Lung Association's Asthma Clinical Research Center Network. Dr Bacharier is also currently investigating the role of early infection with Respiratory Syncytial Virus upon the subsequent development of asthma. These research projects have been published in numerous journals, including the New England Journal of Medicine, The Journal of Allergy and Clinical Immunology, Pediatrics, and The American Journal of Respiratory and Critical Care Medicine. Dr Bacharier serves on the Editorial Boards of The Journal of Allergy and Clinical Immunology and The Journal of Allergy and Clinical Immunology: In Practice, and has been a guest editor for Immunology and Allergy Clinics of North America.

Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper.

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥ 8 days/month) asthma-like symptoms or recurrent (≥ 2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified.

Editorial introductions

Editorial introductions

205 Does an Emergency Department Asthma Pathway and Clinical Asthma Score Significantly Increase the Emergency Department Length of Stay?

Asthma is the most common chronic disease of childhood, affecting more than 7 million children in the United States (US). Many hospitals have developed emergency department (ED) clinical pathways for the assessment and treatment of asthma to improve the quality of care for these patients. These ED asthma pathways (EDAP) typically use standardized clinical asthma scoring systems (CAS) which physicians and nurses use to guide consistent ED treatment and to help determine further observation or need for hospital admission. Previous studies have evaluated these EDAP for rate of hospitalization as well as the effect on return visits. There are concerns that the additional evaluation required by the CAS could lead to extended ED length of stay (EDLOS) which leads to ED crowding. A few studies in other countries have analyzed the effect of such pathways on the EDLOS, but there is limited similar data for the US. The goal of this study was to determine if the EDAP and CAS would significantly increase the EDLOS for asthma patients while also evaluating the effect on hospitalization rate and return visits at a children’s hospital in the US. This was a retrospective before-and-after study performed at an academic children’s hospital ED during two five-month periods, a year before and immediately after the initiation of an EDAP. All patients seen at the children’s emergency department from September 2012 through January 2013 were compared to those from September 2013 through January 2014. Using the hospital’s electronic medical record, EDLOS, disposition, and return visits within 72 hours were evaluated for each period. The total number of ED visits during the study periods increased from 9,724 prior to the pathway to 10,398 after the pathway (6.5% increase). The number of visits for asthma related issues increased from 327 to 382 during the two study periods (16.8% increase, P=.23). The average age and fraction of males were similar for both groups (6.7 years, 59% male). Prior to use of the EDAP, 70 asthma patients (21.4%) were admitted to the hospital. Following initiation of the EDAP, 111 (29.1%) patients were admitted (7.7% increase, P=.02). The EDLOS for all asthma patients increased from 147 minutes to 160 minutes (8.8% increase, P=.02). Although the pathway detected more patients that required admission, the EDLOS of discharged asthma patients increased only 6 minutes from 129 minutes to 135 minutes (4.7% increase, P=.17). The fraction of discharged patients that returned within 72 hours remained similar for both groups (4.0% and 2.6%, P=.31). This is a novel study on the effect of an EDAP on a children’s hospital EDLOS in the US. The EDAP detected more asthma patients that required admission, which increased the total EDLOS for these patients. However, the EDAP did not significantly affect the EDLOS for discharged patients. This suggests that acquiring a CAS and using an EDAP will provide more consistent care and decisionmaking amongst a variety of providers while having little effect the EDLOS for the majority of asthma patients. This study is limited by the single site and short study periods. Additional studies are needed to evaluate if further use and familiarity with the EDAP and CAS will lead to decreased EDLOS for all patients in multiple emergency departments and a more consistent approach to a common childhood disease.

The American Lung Association: Asthma Clinical Research Centers network: addressing real life questions in asthma management

Clinical trials are designed to answer specific questions regarding the safety, efficacy and effectiveness of biomedical or behavioral interventions in human subjects. Results from clinical trials have led to many breakthroughs in disease prevention and treatment, and provided evidence to support optimal standards of care into clinical or public health practice. Clinical trials form the evidence base for clinical treatment guidelines. The American Lung Association Asthma Clinical Research Centers network is a multicenter clinical trials’ network based in the USA that has significantly contributed to the evidence base for asthma management in both adults and pediatric patients. The purpose of this paper is to provide an overview of how selected Asthma Clinical Research Center studies have affected the treatment and the management of asthma over the past 13 years.

Editorial introductions

Editorial introductions

Severe Cutaneous Adverse Reaction

Min Suk Yang, Jae Woo Jung, and Hye-Ryun Kang Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center; Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center; Drug Allergy Workgroup of the Korean Academy of Asthma Allergy and Clinical Immunology; Department of Internal Medicine, Chung-Ang University College of Medicine; Department of Internal Medicine, Seoul National University College of Medicine; Seoul National University Hospital Regional Pharmacovigilance Center, Seoul, Korea

Editorial introductions

Editorial introductions

Sex differences in asthma symptom profiles and control in the American Lung Association Asthma Clinical Research Centers

Important differences between men and women with asthma have been demonstrated, with women describing more symptoms and worse asthma-related quality of life (QOL) despite having similar or better pulmonary function. While current guidelines focus heavily on assessing asthma control, they lack information about whether sex-specific approaches to asthma assessment should be considered. We sought to determine if sex differences in asthma control or symptom profiles exist in the well-characterized population of participants in the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials. We reviewed baseline data from four trials published by the ALA-ACRC to evaluate individual item responses to three standardized asthma questionnaires: the Juniper Asthma Control Questionnaire (ACQ), the multi-attribute Asthma Symptom Utility Index (ASUI), and Juniper Mini Asthma Quality of Life Questionnaire (mini-AQLQ). In the poorly-controlled population, women reported similar overall asthma control (mean ACQ 1.9 vs. 1.8; p=0.54), but were more likely to report specific symptoms such as nocturnal awakenings, activity limitations, and shortness of breath on individual item responses. Women reported worse asthma-related QOL on the mini-AQLQ (mean 4.5 vs. 4.9; p<0.001) and more asthma-related symptoms with a lower mean score on the ASUI (0.73 vs. 0.77; p≤0.0001) and were more likely to report feeling bothered by particular symptoms such as coughing, or environmental triggers. In participants with poorly-controlled asthma, women had outwardly similar asthma control, but had unique symptom profiles on detailed item analyses which were evident on evaluation of three standardized asthma questionnaires.

Daily Diaries vs Retrospective Questionnaires to Assess Asthma Control and Therapeutic Responses in Asthma Clinical Trials: Is Participant Burden Worth the Effort?

Background Presently, there is insufficient information to compare the value of daily diaries vs retrospective questionnaires for assessing symptoms in relationship to asthma control in clinical trials. Daily symptom diaries are often burdensome to gather, incomplete, susceptible to fabrication, and of questionable reliability. There is also concern that retrospective symptom questionnaires may be subject to poor recall and may be insensitive. Methods To compare these two methods of assessing symptoms reporting, we analyzed data collected during the Best Add-on Therapy Giving Effective Responses (BADGER) trial. During the trial, asthma control in 182 children aged 6 to 17 years was assessed in two ways: (1) by asthma control days (ACDs) determined by manually recorded daily diary symptom and rescue medication use scores and (2) by monthly retrospective report of symptoms embedded within the age-appropriate version of the Asthma Control Test (ACT). Correlations between ACDs and ACT scores were analyzed, and the sensitivity of each method for measuring asthma control and determining the differential response among the three BADGER treatments was evaluated. Results Although validated using a 4-week recall period, ACT correlated better with daily diary information from the last 2 weeks of the 4-week recall (r = 0.46) than from the first 2 weeks (r = 0.34). In addition, clinically significant differential treatment responses were detected using ACDs but not ACT scores. Conclusions The results of this study indicate that daily diaries used to determine ACDs can be a more sensitive tool than ACT for assessing differential treatment responses with respect to asthma control. Presently, there is insufficient information to compare the value of daily diaries vs retrospective questionnaires for assessing symptoms in relationship to asthma control in clinical trials. Daily symptom diaries are often burdensome to gather, incomplete, susceptible to fabrication, and of questionable reliability. There is also concern that retrospective symptom questionnaires may be subject to poor recall and may be insensitive. To compare these two methods of assessing symptoms reporting, we analyzed data collected during the Best Add-on Therapy Giving Effective Responses (BADGER) trial. During the trial, asthma control in 182 children aged 6 to 17 years was assessed in two ways: (1) by asthma control days (ACDs) determined by manually recorded daily diary symptom and rescue medication use scores and (2) by monthly retrospective report of symptoms embedded within the age-appropriate version of the Asthma Control Test (ACT). Correlations between ACDs and ACT scores were analyzed, and the sensitivity of each method for measuring asthma control and determining the differential response among the three BADGER treatments was evaluated. Although validated using a 4-week recall period, ACT correlated better with daily diary information from the last 2 weeks of the 4-week recall (r = 0.46) than from the first 2 weeks (r = 0.34). In addition, clinically significant differential treatment responses were detected using ACDs but not ACT scores. The results of this study indicate that daily diaries used to determine ACDs can be a more sensitive tool than ACT for assessing differential treatment responses with respect to asthma control.

Editorial introductions

Editorial introductions

Physician-, biomarker-, and symptom-based adjustment of inhaled corticosteroids for asthma had similar effects

Source Citation Calhoun WJ, Ameredes BT, King TS, et al; Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute. Comparison of physician-, biomarker-, and symptom-based s...

Editorial introductions

Editorial introductions

P5 Introducing Bronchial Thermoplasty Treatment into a Severe Asthma Clinical Service

Introduction and ObjectivesBronchial thermoplasty involves the delivery of radio frequency energy to the airways during flexible bronchoscopy, and possibly exerts its effect by reduction of airway smooth muscle mass (1)....

Asthma clinical trials of American Lung Association/Asthma Clinical Research Centers (ALA-ACRC): what have we learned in 12 years?

The American Lung Association Asthma Clinical Research Centers (ALA-ACRC) is a research network focused on performing clinical trials that directly affect medical care for adults and children with asthma. The group of eighteen clinical research centers and a data-coordinating center perform studies supported by the American Lung Association, the National Institute of Health/National Heart Lung and Blood Institute (NIH/NHLBI), and partnership with industry. The network has completed and published eight clinical trials (seven randomized control trials and one validation study of a diagnostic tool), numerous ancillary studies, and has four ongoing trials at the time of publication of this review. The network’s trials have focused on areas such as the relative merits of different adjunctive treatments for asthma not controlled on inhaled corticosteroids (ICS) alone, the effect of treatment of comorbid diseases on asthma care, and studies evaluating techniques used in the conduct of clinical trials of treatments for asthma. This review will describe the accomplishments of our network to date and the effect of those accomplishments on asthma care.

Lansoprazole of no benefit in children with asthma

Writing Committee for the American Lung Association Asthma Clinical Research C, Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA 2012;307:373-81.

Key observations from the NHLBI Asthma Clinical Research Network

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed,...

Editorial introductions

Editorial introductions

Evaluation of Atorvastatin for the Treatment of Patients With Asthma: A Double-Blind Randomized Clinical Trial

PurposeStatins are known as cholesterol-lowering agents, but have been suggested for the treatment of asthma because of their anti-inflammatory effects. In this study, the potential therapeutic effects of atorvastatin were investigated in asthmatic patients.MethodsA total of 62 patients with persistent mild to moderate asthma who presented at asthma clinics of Arak University of Medical Sciences were recruited in a double-blind randomized clinical trial. The asthma clinical control score was assessed based on the standardized Asthma Control Test. Lung volume, i.e., percentage of forced expiratory volume in one second (FEV1%) and percentage of forced vital capacity (FVC%), and peripheral blood eosinophils were also measured. The intervention group was treated with atorvastatin 40 mg per day for 8 weeks, while the control group received a placebo. Asthma controller treatments were not changed. At the beginning and end of the study, serum cholesterol and triglyceride levels were measured to evaluate adherence of the patients to the treatment.ResultsThe asthma control score did not significantly differ between the intervention and control groups (P=0.06). Difference in FEV1%, FVC%, and blood eosinophil count between the intervention and control groups were not statistically significant (P>0.05). The differences in post-treatment cholesterol and low-density lipoprotein cholesterol levels were significant (P<0.05).ConclusionsOur study shows that atorvastatin is not effective in the treatment of persistent mild to moderate asthma.

Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults.

In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and⁄or gaps in the previous guidelines. Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations. The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified. The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee's new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.