Frederick Hargreave

Publications of Frederick Hargreave

• Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study.

  Authors: Mario Castro, Sameer Mathur, Frederick Hargreave, Louis-Philippe Boulet, Fang Xie, James Young, H Jeffrey Wilkins, Timothy Henkel, Parameswaran Nair

  American journal of respiratory and critical care medicine. 08/2011; 184(10):1125-32.

  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. To evaluate the effect ofEosinophilic 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. 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. 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). 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. 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.

• Clinical equivalence testing of inhaled bronchodilators.

  Authors: Parameswaran Nair, John Hanrahan, Frederick Hargreave

  Polskie archiwum medycyny wewnetrznej. 11/2009; 119(11):731-735.

  There are no standardized methods to demonstrate in-vivo bioequivalence of inhaled bronchodilators. The most practical method of showing therapeutic equivalence in vivo is by estimating theirThere are no standardized methods to demonstrate in-vivo bioequivalence of inhaled bronchodilators. The most practical method of showing therapeutic equivalence in vivo is by estimating their relative potencies (RP) in clinical efficacy studies. The RP of bronchodilators may be estimated by comparing either their bronchodilator or bronchoprotective properties. Bronchodilator studies are easier to perform and may better model the physiologic effect of many agents, including inhaled beta-agonists. However, it may be difficult to demonstrate steep dose-response for these outcomes, except in cumulative study designs. Bioequivalence trials may be especially challenging when involving pressurized metered-dose inhalers, as a single actuation - the lowest feasible dose to include in the evaluation, may already produce bronchodilation that is at or near the plateau of the dose-response curve. Protection against bronchoconstriction induced by a direct inhaled stimulus like methacholine or histamine affords a reliable and practical method of comparing inhaled bronchodilators and estimating their RP. Inhalational bronchoprovocation testing allows for easier repeatability and quantitation of the stimulus necessary to produce a predetermined degree of bronchoconstriction, and the degree of protection afforded by the bronchoprotection agent. RP studies using adequate methodology are necessary to compare long-acting bronchodilators and both short- and long-acting bronchodilators in patients who are also on inhaled corticosteroids.

• Adult Asthma Consensus Guidelines Update 2003.

  Authors: Catherine Lemière, Tony Bai, Meyer Balter, Charles Bayliff, Allan Becker, Louis-Philippe Boulet, Dennis Bowie, André Cartier, Andrew Cave, Kenneth Chapman [......] Shelagh Finlayson, J FitzGerald, Frederick Hargreave, Donna Hogg, Alan Kaplan, Harold Kim, Cheryle Kelm, Paul O'Byrne, Malcolm Sears, Andrea Markham

  Canadian respiratory journal : journal of the Canadian Thoracic Society. 02/2004; 11(Suppl A):9A-18A.

  Background: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma ConsensusBackground: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines. Objectives: To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management. Methods: Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed. Results: The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta2-agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education. Conclusion: The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.

• Cost-effectiveness of various diagnostic approaches for occupational asthma.

  Authors: Wendy A Kennedy, Frédéric Girard, Simone Chaboillez, André Cartier, Johanne Côté, Frederick Hargreave, Manon Labrecque, Jean-Luc Malo, Susan M Tarlo, Carrie A Redlich, Catherine Lemière

  Canadian respiratory journal : journal of the Canadian Thoracic Society. 14(5):276-80.

  BACKGROUND: Diagnosis of occupational asthma (OA) by specific inhalation challenge (SIC) can be costly and is not always available. The use of sputum testing to avoid this in some patients may be aBACKGROUND: Diagnosis of occupational asthma (OA) by specific inhalation challenge (SIC) can be costly and is not always available. The use of sputum testing to avoid this in some patients may be a more cost-effective alternative. OBJECTIVES: To compare the cost-effectiveness of SIC with serial measurements of sputum cell counts (sputum testing) and peak expiratory flow (PEF) monitoring. METHODS: Clinical data and testing costs for OA in 49 patients were collected during a previously published trial, modelled and compared using TreeAge Pro. Clinical outcome was the percentage of accurately diagnosed patients, using SIC as the gold standard. The PEF approach used the most accurate assessment of five experts who were blinded to SIC results. Differences in the proportion of eosinophils during periods on and off work were used for the sputum testing approach and in PEF/sputum for the combined approach. Unit costs were estimated from charges in Canadian hospitals. Data were analyzed by one-way and two-way analyses, and by probabilistic sensitivity analysis using a Monte Carlo simulation technique. RESULTS: The PEF approach had an estimated accuracy of 52% and cost $365 per patient tested. Compared with PEF monitoring, sputum testing was more accurate and cost an estimated $255 for each additional OA patient correctly diagnosed. SIC costs per additional correct diagnosis were $11,032 compared with sputum testing and $6,458 compared with PEF monitoring. The combined PEF/sputum testing approach was not cost-effective in the base case analysis, but cannot be excluded according to probabilistic sensitivity analyses. CONCLUSIONS: Although SIC remains the reference test to diagnose OA, when this test is not available, sputum testing is a cost-effective alternative to PEF for diagnosis of OA.