Louis-Philippe Boulet

An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice

BACKGROUND The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways. PURPOSE The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older. METHODS A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures. RESULTS The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge about the multiple domains of asthma and asthma control, no single outcome measure can adequately assess asthma control. Its assessment in clinical trials and in clinical practice should include components relevant to both of the goals of asthma treatment, namely achievement of best possible clinical control and reduction of future risk of adverse outcomes. Recommendations are provided for the assessment of asthma control in clinical trials and clinical practice, both at baseline and in the assessment of treatment response. CONCLUSIONS The Task Force recommendations provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy. ERS/ATS guidelines revise the definition of severe asthma, discuss phenotypes and provide guidance on patient management http://ow.ly/roufI

Global asthma prevalence in adults: findings from the cross-sectional world health survey

BackgroundAsthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease.MethodsThe World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months.ResultsThe global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma.ConclusionsThis study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.

Reslizumab for Poorly Controlled, Eosinophilic Asthma: A Randomized, Placebo-controlled Study

RATIONALE Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils. OBJECTIVES To evaluate the effect of the antibody to IL-5, reslizumab, in patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid. METHODS Patients were randomly assigned to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The primary efficacy measure was the difference between the reslizumab and placebo groups in the change in ACQ score from baseline to end of therapy (Week 15 or early withdrawal). MEASUREMENTS AND MAIN RESULTS Mean changes from baseline to end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P = 0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0 and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent of patients in the reslizumab group and 19% of patients in the placebo group had an asthma exacerbation (P = 0.083). The most common adverse events with reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain. CONCLUSIONS Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.

Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses

BACKGROUND Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2λ that binds human TSLP and prevents receptor interaction. METHODS In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge. RESULTS AMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events. CONCLUSIONS Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.).

A summary of the new GINA strategy: a roadmap to asthma control

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations. This paper summarises key changes in the GINA global strategy report, a practical new resource for asthma care http://ow.ly/ObvYi

Overdiagnosis of asthma in obese and nonobese adults

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.

The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies

Sedentary lifestyles and increased pollution brought about by industrialization pose major challenges to the prevention of both obesity and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea and obesity hypoventilation syndrome. Obesity has emerged as an important risk factor for these respiratory diseases, and in many instances weight loss is associated with important symptomatic improvement. Moreover, obesity may influence the development and presentation of these diseases. In this article, we review the current understanding of the influence of obesity on chronic respiratory diseases and the clinical management of obesity concurrent with asthma, COPD, obstructive sleep apnea or obesity hypoventilation syndrome.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma.

Background and objectives The determinants of variability in the clinical expression of atopy are still to be documented. The goals of this study were to determine, in subjects with a clinical diagnosis of symptomatic asthma or rhinitis, what is the possible contribution of different types of indoor and outdoor allergens to the development of their disease, by looking at the prevalence and degree of sensitization to these allergens according to age and gender.