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1 California Allergy and Asthma Medical Group, Los Angeles, California; 2 Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; 3 Pharmaxis Ltd, Frenchs Forest, New South Wales, Australia; 4 CompleWare Corporation, Iowa City, Iowa, 5 University of Iowa, Iowa City, Iowa
Correspondence and requests for reprints should be addressed to Sandra D. Anderson, Ph.D., Department of Respiratory and Sleep Medicine, E 11 Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown, NSW 2050, Australia. E-mail: sandya{at}med.usyd.edu.au
Introduction: Bronchial provocation tests are used to assist the diagnosis of asthma. Mannitol (Aridol/Osmohale) is a new osmotic kit that includes an inhaler, and capsules containing 0, 5, 10, 20, 40 mg of mannitol dry powder. Aim: To study patients without a clear diagnosis of asthma to estimate sensitivity and specificity of mannitol to detect exercise-induced bronchoconstriction (EIB) and to compare sensitivity/specificity of mannitol and methacholine to identify a respiratory physician diagnosis of asthma (Clin+Dx). Subjects: Had symptoms suggesting asthma; were excluded if they had > 95% or < 5% likelihood of asthma or had current seasonal allergy. Three hundred seventy-five adults and children 6 to 50 years of age (median 22 yr) were studied; median FEV1 was 92% predicted; mean NAEPPII asthma score was 1.2 (SD 0.5); 78% were atopic. Methods: Methacholine (dosimeter) and mannitol tests were performed approximately 7 days apart. Mannitol+ test was 15% fall in FEV1 to cumulative dose of 
635 mg or 10% fall in FEV1 between doses. Methacholine+ test was PC20 16 mg/ml. EIB+ was a 
10% fall in FEV1 at either of two tests. Subjects were assigned Clin+Dx based on exercise test, history, examination, skin tests, and bronchodilator response, but not mannitol or methacholine test result. Results: Sensitivity/specificity of mannitol for: Exc+10% was 59%/65%, Exc+15% was 69%/62%, and Clin+Dx was 56%/73%. Sensitivity/specificity of methacholine for Exc+10% was 56%/69%; Ex+15% was 67%/66%; Clin+Dx was 51%/75%. Positive/negative predictive values were 79%/48% for mannitol, 78%/46% for methacholine. Mannitol+ test was 19.9 minutes (SE 0.9); methacholine+ test 44.5 minutes (SE 1.4). Recovery for both tests was 19 minutes (IQR 17–24). Conclusion: Mannitol and methacholine were therapeutically equivalent to identify EIB and a clinical Dx of asthma, but sensitivity/specificity values were lower than those reported in well-defined populations. Mannitol challenge has potential to replace other challenges for BHR; any of these tests can provide specific information and insight regarding mechanisms in a given patient.
FOOTNOTES
Supported by Pharmaxis Ltd, Unit 2, 10 Rodborough Rd, NSW 2086 Australia.
Conflict of Interest Statement: S.S. has been reimbursed for attending conferences and also for participating as a speaker with AstraZeneca, Genetech, Sanofi-Aventis, and Schering-Plough. He has been involved in clinical research with the following companies: Abbott, Accentia, Amgen, Altana, AstraZeneca, Boehringer-Ingelhiem, CTI, Eli-Lilly, 3M Genetech, GlaxoSmithKline, IgPro, Johnson & Johnson, Medpoint Novartis, Ono Pharma, Sanofi-Aventis, Schering-Plough, Skypharma, and Merck. He is also an investigator for the following studies: 0589BL00003, P05122, SPOM828, POM703, and the pay would be based upon the number of subjects enrolled in the study. S.D.A. is the inventor of the mannitol test; however, the intellectual property is owned by her employer, The Sydney South West Area Health Service, which invoices the company for her services. She has not received any money personally for lectures, studies, or consultancies from Pharmaxis Ltd. Her employer licensed the rights to commercialize the mannitol test to Pharmaxis. In the future she may receive royalties. B.C. is an employee of Pharmaxis and receives full-time salary. He owns shares and options in Pharmaxis. J.M.W. is employed by and owns stock in CompleWare Corporation, the contract research organization paid by Pharmaxis to oversee the conduct of the study. S.N. is employed by and owns stock in CompleWare Corporation, the contract research organization paid by Pharmaxis to oversee the conduct of the study. Pharmaxis sponsored the study.
(Received in original form June 25, 2008; accepted in final form November 4, 2008)
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