K D Fitch

Hebrew University of Jerusalem, Yerushalayim, Jerusalem District, Israel

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Publications (40)130.82 Total impact

  • Simon Godfrey, Kenneth D Fitch
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    ABSTRACT: This article examines in detail the history of more than half a century of investigations into elucidating the causation of exercise-induced bronchoconstriction. Despite earnest attempts by many researchers from many countries, answers to some pivotal questions await the next generation of investigators into exercise-induced bronchoconstriction.
    Immunology and allergy clinics of North America 08/2013; 33(3):283-97. · 3.18 Impact Factor
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    ABSTRACT: Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established.
    British journal of sports medicine 04/2012; 46(7):471-6. · 3.67 Impact Factor
  • Kenneth D Fitch
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    ABSTRACT: Data from the past five Olympic Games obtained from athletes seeking to inhale β2 adrenoceptor agonists (IBA) have identified those athletes with documented asthma and airway hyper-responsiveness (AHR). With a prevalence of about 8%, asthma/AHR is the commonest chronic medical condition experienced by Olympic athletes. In Summer and Winter athletes, there is a marked preponderance of asthma/AHR in endurance-trained athletes. The relatively late onset of asthma/AHR in many older athletes is suggestive that years of endurance training may be a contributory cause. Inspiring polluted or cold air is considered a significant aetiological factor in some but not all sports. During the last five Olympic Games, there has been improved management of athletes with asthma/AHR with a much higher proportion of athletes combining inhaled corticosteroids (ICS) with IBA and few using long-acting IBA as monotherapy. Athletes with asthma/AHR have consistently outperformed their peers, which research suggests is not due to their treatment enhancing sports performance. Research is necessary to determine how many athletes will continue to experience asthma/AHR in the years after they cease intensive endurance training.
    British journal of sports medicine 01/2012; 46(6):413-6. · 3.67 Impact Factor
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    Alan R Morton, Kenneth D Fitch
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    ABSTRACT: Asthma, a chronic inflammatory disorder of the airways is associated with variable obstruction to the airways and is provoked by many triggers including exercise. The management of asthma is primarily pharmacological, but exercise, despite causing bronchoconstriction in almost all asthmatics, is an important adjunct to treatment. With adequate control of the hyperresponsive airways obtained with inhaled corticosteroids (ICS) and inhaled beta 2 agonists (IBA), used as both a pre-exercise preventive agent and a reliever if necessary, all asthmatics should benefit from an exercise program. Some have realised this benefit with such success as to become Olympic and world champions in many sports. Exercise programs should be individually tailored, follow established guidelines and result in similar benefits to those obtained by non-asthmatics. However asthmatics must try to avoid or minimise triggers whenever possible. A specific benefit of a physical training program is that it allows asthmatics to exercise with less bronchoconstriction at the same exercise stress, although it does not abolish or reduce airway hyperresponsiveness (AHR).
    Journal of science and medicine in sport / Sports Medicine Australia. 03/2011; 14(4):312-6.
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    ABSTRACT: The biochemical actions and side effects of recombinant erythropoietins (rhEPOs), their analogs and mimetics, their misuse as doping agents, and the principal analytical strategies developed to identify them in athletes' biologic fluids are reviewed. Patients who experience a range of pathologies have benefited from the administration of rhEPOs to correct severe anemia. Currently, monitoring the biologic effect of rhEPO in patients under treatment is by measuring the hemoglobin concentration. However, it may be valuable to directly monitor the actual levels of the administered drug and determine a dose-dependent correlation with any clinical adverse effect observed. This may permit the adoption of a patient-specific administration regime. Currently, the method of detecting EPO approved for doping control is an isoelectric-focusing, double-blotting, chemiluminescence assay based on charge differences between isoforms of rhEPOs and endogenous EPO in urine. The advantages and limitations of this method are presented. A new approach using sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a complementary tool to the established method is discussed. The application of matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography combined with tandem mass spectrometry for the direct detection of the rhEPO molecules may prove to be promising. Indirect evidence of rhEPO abuse by athletes is based on the analysis of blood parameters (hemoglobin hematocrit, reticulocytes, macrocytes, etc) and serum markers (concentration of EPO and serum transferrin receptors, etc). Enrichment of the screened parameters with gene or biochemical markers revealing altered erythropoiesis and adoption of longitudinal monitoring of athletes' hematologic and biochemical parameters could also be a complementary approach in the fight against doping.
    Therapeutic drug monitoring 02/2011; 33(1):3-13. · 2.43 Impact Factor
  • Donald C McKenzie, Kenneth D Fitch
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    ABSTRACT: The asthmatic athlete has a long history in competitive sport in terms of success in performance and issues related to doping. Well documented are detailed objective tests used to evaluate the athlete with symptoms of asthma or airway hyperresponsiveness and the medical management. Initiated at the 2002 Salt Lake City Games, the International Olympic Committee's Independent Asthma Panel required testing to justify the use of inhaled beta-2 agonists (IBAs) in Olympic athletes and has provided valuable guidelines to the practicing physician. This program was educational and documented the variability in prevalence of asthma and/or airway hyperresponsiveness and IBA use between different sports and different countries. It provided a standard of care for the athlete with respiratory symptoms and led to the discovery that asthmatic Olympic athletes outperformed their peers at both Summer and Winter Olympic Games from 2002 to 2010. Changes to the World Anti-Doping Agency's Prohibited List in 2010 permitted the use of 2 IBA produced by the same pharmaceutical company. All others remain prohibited. However, there is no pharmacological difference between the permitted and prohibited IBAs. As a result of these changes, asthmatic athletes are being managed differently based on a World Anti-Doping Agency directive that has no foundation in pharmacological science or in clinical practice.
    Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 01/2011; 21(1):46-50. · 1.50 Impact Factor
  • Kenneth D Fitch
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    ABSTRACT: Exercise-induced bronchoconstriction (EIB) is experienced by the majority of an estimated 300 million individuals who have asthma, a condition that affects all ages and is increasing globally. Respiratory water loss with dehydration of the airways causing mediator release and airway narrowing is considered the cause of EIB, the severity of which will be increased if the inhaled air is cold or polluted. Adequate control of asthma is essential to minimize or prevent EIB and permit normal levels of physical activity and sport. This is important because exercise is a necessary component of daily living, assists in obtaining and maintaining a healthy body and has been demonstrated to benefit asthmatics. Inhaled glucocorticosteroids and inhaled β(2)-adrenoceptor agonists (IβA) are the pharmacological agents of choice to manage asthma and minimize EIB, assisted when necessary, by other drugs including leukotriene receptor antagonists and chromones. Tolerance from daily use of IβA is of concern and more flexible drug therapy needs to be considered. Optimal use of inhalers to deliver drugs effectively requires closer attention. Pharmacogenetics may hold the key to future drug therapy.
    Expert Review of Clinical Pharmacology 01/2010; 3(1):139-52.
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    ABSTRACT: To examine the use of food supplements and pharmaceutical preparations by elite Paralympic athletes. Survey study. Athens 2004 Paralympic Games. Data obtained from two sources: (i) athletes' declaration of intake of drugs/supplements recorded on the Doping Control Official Record during sample collection for doping control; (ii) athletes' application forms for granting of a therapeutic use exemption. Classification of declared food supplements according to the active ingredient and medications according to therapeutic actions and active compounds. 64.2% of the athletes tested for doping control declared use of medications or food supplements, and 81.3% of these athletes declared intake of fewer than four preparations. Non-invasive routes of administration dominated. Food supplements (42.1%) were popular, and drugs used to treat several pathological conditions noted. Non-steroidal anti-inflammatory agents and analgesics were commonly used (9.8% and 5.6%, respectively). The prevalence of inhaled beta2-agonist use (4.8%) was higher than expected and exceeded that at the Athens Olympic Games. This review, the first to examine elite Paralympic athletes, shows a more rational approach to the use of medication and food supplements, but a similar consumption pattern to that of athletes at the Athens Olympic Games. Because of the dearth of such studies, consumption trends among Paralympic athletes remain unclear. The need to counsel athletes with disabilities on their nutritional needs is confirmed, and close monitoring by healthcare professionals is recommended.
    British journal of sports medicine 10/2009; 43(13):1062-6. · 3.67 Impact Factor
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    ABSTRACT: To gather data and examine the use by elite Olympic athletes of food supplements and pharmaceutical preparations in total and per sport, country, and gender. Survey study. Athens 2004 Olympic Games (OG). Data from 2 sources were collected: athletes' declaration of medications/supplements intake recorded on the Doping Control Official Record during sample collection for doping control, and athletes' application forms for granting of a therapeutic use exemption (TUE) and through the abbreviated TUE process (aTUE). Classification of declared food supplements according to the active ingredient and medications according to therapeutic actions and active compounds. 24.3% of the athletes tested for doping control declared no use of medications or food supplements. Food supplements (45.3%) continue to be popular, with vitamins (43.2%) and proteins/aminoacids (13.9%) in power sports being most widely used. Nonsteroidal antiinflammatory agents and analgesics were also commonly used by athletes (11.1% and 3.7%, respectively). The use of the hemoderivative actovegin and several nonprohibited anabolic preparations are discussed. The prevalence of medication use for asthma and the dangers of drug interactions are also presented.Laboratory analysis data reveal that of the aTUEs received for inhaled glucocorticosteroids, only budesonide was detectable in significant percentage (10.0%). Only 6.5% of the 445 athletes approved to inhale beta2-agonists led to an adverse analytical finding. This review demonstrates that overuse of food supplements was slightly reduced compared to previous OGs and a more rational approach to the use of medication is being adopted.
    Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 02/2009; 19(1):33-8. · 1.50 Impact Factor
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    ABSTRACT: Respiratory symptoms cannot be relied on to make a diagnosis of asthma and/or airways hyperresponsiveness (AHR) in elite athletes. For this reason, the diagnosis should be confirmed with bronchial provocation tests. Asthma management in elite athletes should follow established treatment guidelines (eg, Global Initiative for Asthma) and should include education, an individually tailored treatment plan, minimization of aggravating environmental factors, and appropriate drug therapy that must meet the requirements of the World Anti-Doping Agency. Asthma control can usually be achieved with inhaled corticosteroids and inhaled beta(2)-agonists to minimize exercise-induced bronchoconstriction and to treat intermittent symptoms. The rapid development of tachyphylaxis to beta(2)-agonists after regular daily use poses a dilemma for athletes. Long-term intense endurance training, particularly in unfavorable environmental conditions, appears to be associated with an increased risk of developing asthma and AHR in elite athletes. Globally, the prevalence of asthma, exercise-induced bronchoconstriction, and AHR in Olympic athletes reflects the known prevalence of asthma symptoms in each country. The policy of requiring Olympic athletes to demonstrate the presence of asthma, exercise-induced bronchoconstriction, or AHR to be approved to inhale beta(2)-agonists will continue.
    The Journal of allergy and clinical immunology 09/2008; 122(2):254-60, 260.e1-7. · 12.05 Impact Factor
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    D H Catlin, K D Fitch, A Ljungqvist
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    ABSTRACT: The fight against doping in sports commenced as a result of the death of a Danish cyclist during the Rome Olympic Games in 1960. The International Olympic Committee (IOC) established a Medical Commission (IOC-MC) which had the task of designing a strategy to combat the misuse of drugs in Olympic Sport. Some International Sport Federations (IF) and National Sports Federations followed suit, but progress was modest until the world's best male sprinter was found doped with anabolic steroids at the Olympic Games in Seoul in 1988. Further progress was made following the cessation of the cold war in 1989 and in 1999 public authorities around the world joined the Olympic Movement in a unique partnership by creating WADA--the 'World Anti-Doping Agency'. The troubled history of the anti-doping fight from the 1960s until today is reviewed. In particular, the development of detection methods for an ever increasing number of drugs that can be used to dope is described, as are the measures that have been taken to protect the health of the athletes, including those who may need banned substances for medical reasons.
    Journal of Internal Medicine 09/2008; 264(2):99-114. · 6.46 Impact Factor
  • Kenneth D Fitch
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    ABSTRACT: Androgenic-anabolic steroids (AAS) have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic (GDR) from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators (SARMs) can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone (T) therapy may be authorized in sport as a therapeutic use exemption (TUE) and these circumstances are discussed.
    Asian Journal of Andrology 06/2008; 10(3):384-90. · 2.14 Impact Factor
  • Kenneth D Fitch
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    ABSTRACT: The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists.
    Clinical Reviews in Allergy & Immunology 01/2006; 31(2-3):259-68. · 5.59 Impact Factor
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    ABSTRACT: There has been an increase in the number and percentage of athletes competing in Olympic Games notifying use of beta2-agonists, from 1.7% at Los Angeles (1984) to 5.5% at Sydney (2000). For Salt Lake City (2002), the International Olympic Committee requested objective evidence to use beta2-agonists for asthma or exercise-induced asthma (EIA). The objective of this study was to evaluate the evidence submitted for approval to use a beta2-agonist. Objective evidence for asthma or EIA included (1) an increase of 12% or more of the predicted FEV1 in response to bronchodilator, (2) a reduction in FEV1 of 10% or greater from baseline in response to exercise or eucapnic voluntary hyperpnea, (3) a PD20 FEV1 to methacholine or histamine at a dose of less than 200 microg (2 mg/mL) or less than 1320 microg (13.2 mg/mL) for those taking inhaled corticosteroids for 3 months. There were 165 applications. Of these, 147 (89%) included evidence of a challenge, bronchodilator response, or both, and 163 test results were submitted. One hundred thirty (5.2%) applications were approved. For those with positive responses, the median value (1) was 16.2% of predicted FEV1 for response to a bronchodilator (n = 13), (2) was a 15.9% decrease in FEV1 for response to a physical challenge (n = 36), and, (3) for PD20 FEV1, was 173 microg for response to a pharmacologic challenge (n = 45). The analysis demonstrated that it is feasible to request objective evidence to justify use of beta2-agonists on the medical grounds of asthma or EIA.
    Journal of Allergy and Clinical Immunology 02/2003; 111(1):45-50. · 12.05 Impact Factor
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    ABSTRACT: Background: There has been an increase in the number and percentage of athletes competing in Olympic Games notifying use of β2-agonists, from 1.7% at Los Angeles (1984) to 5.5% at Sydney (2000). For Salt Lake City (2002), the International Olympic Committee requested objective evidence to use β2-agonists for asthma or exercise-induced asthma (EIA). Objective: The objective of this study was to evaluate the evidence submitted for approval to use a β2-agonist. Methods: Objective evidence for asthma or EIA included (1) an increase of 12% or more of the predicted FEV1 in response to bronchodilator, (2) a reduction in FEV1 of 10% or greater from baseline in response to exercise or eucapnic voluntary hyperpnea, (3) a PD20 FEV1 to methacholine or histamine at a dose of less than 200 μg (2 mg/mL) or less than 1320 μg (13.2 mg/mL) for those taking inhaled corticosteroids for 3 months. Results: There were 165 applications. Of these, 147 (89%) included evidence of a challenge, bronchodilator response, or both, and 163 test results were submitted. One hundred thirty (5.2%) applications were approved. For those with positive responses, the median value (1) was 16.2% of predicted FEV1 for response to a bronchodilator (n = 13), (2) was a 15.9% decrease in FEV1 for response to a physical challenge (n = 36), and, (3) for PD20 FEV1, was 173 μg for response to a pharmacologic challenge (n = 45). Conclusion: The analysis demonstrated that it is feasible to request objective evidence to justify use of β2-agonists on the medical grounds of asthma or EIA. (J Allergy Clin Immunol 2003;111:45-50.)
    Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2003; 111(1):45-50.
  • Donald C McKenzie, Ian B Stewart, Kenneth D Fitch
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    ABSTRACT: The large increase in the number of athletes who apply to use inhaled beta agonists (IBAs) at the Olympic Games is a concern to the medical community. This review will examine the use of IBAs in the asthmatic athlete, the variability that exists between countries and sport, and outline a plan to justify the use of these medications. Much of this article is a result of an International Olympic Committee (IOC) Medical Commission-sponsored meeting that took place in May 2001. Records of the use of IBAs at previous Olympics were reviewed. MEDLINE Searches (PubMed interface) were performed using key words to locate published work relating to asthma, elite athletes, performance, treatment, and ergogenic aids. Since 1984 there have been significant increases in the use of IBAs at the Olympic Games as well as marked geographical differences in the percentage of athletes requesting the use of IBAs. There are large differences in the incidence of IBA use between sports with a trend towards increased use in endurance sports. There are no ergogenic effects of any IOC-approved IBA given in a therapeutic dose. In many cases, the prescription of IBAs to this population has been made on empirical grounds. Beginning with the 2002 Winter Games, athletes will be required to submit to the IOC Medical Commission clinical and laboratory evidence that justifies the use of this medication. The eucapnic voluntary hyperpnea test will be used to assess individuals who have not satisfied an independent medical panel of the need to use an IBA.
    Clinical Journal of Sport Medicine 08/2002; 12(4):225-8. · 1.60 Impact Factor
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    ABSTRACT: The International Olympic Committee and World AntiDoping Agency restricts the use of beta2-agonists and only the inhaled administration of terbutaline, salbutamol, formoterol and salmeterol is permitted for therapeutic reasons. The aim of this study was to develop a test for the quantitation of terbutaline in urine and evaluate different parameters to distinguish between oral and inhaled administration of the drug. Urine samples were collected from asthmatic and non-asthmatic recreational swimmers who had received repeated doses of oral (3x2.5 mg plus 1x5 mg during 24 h) and inhaled (12x0.5 mg in 24 h with half of it being in the last 4 h) racemic terbutaline, and single oral (5 mg) or single inhaled doses (1 mg). Total terbutaline concentrations (free+conjugated) were determined by enzyme-linked immunosorbent assay. Results showed that after oral administrations urinary terbutaline concentrations were higher than those detected after inhalation. For confirmation purposes, a chiral capillary electrophoretic procedure was established and validated. A solid-phase extraction with Bond-Elut Certify cartridges was undertaken, separation performed using a 50 mM phosphate buffer (pH 2.5) containing 10 mM of (2-hydroxypropyl)-beta-cyclodextrin as running buffer and diode-array UV detection set at 204 nm. The proposed procedure is rapid, selective and sensitive allowing quantitation of free terbutaline enantiomers in urine. No statistical differences were found between total free terbutaline concentrations [S-(+)+R-(-)] in urine collected after oral and inhaled administrations of the drug. After oral doses enantiomeric [S-(+)]/[R-(-)] ratios lower than those obtained after inhalation were observed probably due to an enantioselective metabolism that take place in the intestine, but differences between both routes of administration were not statistically significant. Although different trends were observed after oral and inhaled doses in total terbutaline, total free terbutaline concentrations and in ratios between its enantiomers, differences observed were not sufficiently significant to establish cut-off values to clearly distinguish between both routes of administration.
    Journal of Chromatography B 04/2002; 768(2):315-24. · 2.49 Impact Factor
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    ABSTRACT: As new delivery devices and formulations are being introduced for drugs given by inhalation, there is a need to evaluate their equivalence with old preparations. One way to do this is to investigate their equivalence in protecting from exercise-induced asthma (EIA). We used a protocol for EIA to compare the protective effect of salbutamol delivered by the pressurised metered dose inhaler (pMDI) and the new Diskus dry powder device. Twenty-seven asthmatic subjects with moderately severe EIA completed an exercise test on four separate days at two study centers. Exercise was performed by cycling for 8 min while inhaling dry air (0% RH, 20-24 degrees C). The target workload in W was predicted as (53.76 x predicted FEV1) - 11.07 and 95% of this target was achieved at 4 min of exercise. This target was chosen in order to achieve ventilation between 50 and 60% of predicted maximum in the last 4 min. There was no significant difference in the workload, ventilation, or heart rate achieved on the study days. The severity of EIA was measured as the % fall in FEV1. EIA severity was similar on the placebo and control day and the coefficient of variation was 19.4%. The mean +/- SD % fall on the control, placebo, salbutamol by Diskus, and pMDI were 42.0% +/- 15, 39.4% +/-17.6, 13.4% +/- 13.2, and 8.5% +/- 13.8, respectively. Salbutamol significantly inhibited the % fall in FEV1 after exercise, and there was no difference between the preparations. The protocol described here is suitable for evaluating equivalence of salbutamol preparations in protecting against EIA and could be used to evaluate the protective effect of other medications.
    Medicine &amp Science in Sports &amp Exercise 07/2001; 33(6):893-900. · 4.48 Impact Factor
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    ABSTRACT: The administration of salbutamol is permitted only by inhalation by the International Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the (IOC) authorized use (inhaled) and the (IOC) prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation of variables based on the concentration of nonconjugated enantiomers of salbutamol excreted in urine. Urine was collected from asthmatic and nonasthmatic swimmers who had received various preexercise doses of oral (five doses of 4 mg) or inhaled (two doses of 100 microgram) salbutamol. Urine was also obtained from subjects who had received the maximum dosage of inhaled salbutamol advisable for competing athletes to provide protection from exercise-induced asthma and treatment of asthma (1600 microgram in 24 h, 800 microgram being in the last 4 h). All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S: and R: enantiomers. The discriminant function D = -3.776 + 1.46 x 10(-3) ([S:(+)] + [R:(-)]) + 1.012 ([S:(+)]/[R(-)]) can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventional screening procedures in doping control. An 11.8% false-negative (oral classified as inhaled) rate is assumed with the confirmatory criterion proposed, but virtually no false positives (inhaled classified as oral) are obtained (<1 in 33 000). The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racemic salbutamol concentrations >500 microgram/L by gas chromatography-mass spectrometry or free + conjugated racemic salbutamol concentrations >1400 microgram/L by ELISA.
    Clinical Chemistry 10/2000; 46(9):1365-75. · 7.15 Impact Factor
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    ABSTRACT: Salbutamol administration in athletes is permitted only by inhalation, for the management of asthma. The authors discuss different criteria for suspecting oral use of salbutamol, taking into account the data obtained by application of two conventional screening procedures for doping control: gas chromatography/mass spectrometry (GC/MS) and enzyme-linked immunosorbent assay (ELISA). Urine samples obtained after administration of oral and inhaled salbutamol to asthmatic and nonasthmatic swimmers were analyzed using both analytical approaches. As expected, concentrations obtained by the ELISA test (detection of total salbutamol) were higher than those obtained using the GC/MS procedure (detection of nonsulfated salbutamol). After oral administration, the ELISA test detected significantly higher salbutamol concentrations than those detected after inhalation, reflecting the greater doses administered orally. Urine samples with total salbutamol greater than 1400 ng/mL were obtained after oral doses, but no sample reached this value after inhaled doses. Higher concentrations of nonsulfated salbutamol have also been detected after oral intake, although there is an overlap between the distributions of concentrations after oral and inhaled doses. A cut-off concentration of 500 ng/mL can be used for nonsulfated salbutamol to select suspicious samples, giving 11.8% false negative results and 4.3% false positive results. An additional criterion evaluated was the androsterone-salbutamol peak height ratio, which was lower after oral doses because of the higher concentrations of salbutamol in urine. This ratio was lower than 2 for all the samples collected after oral administration, although 6.8% false positive samples resulted because of low concentrations of androsterone in female urine. Several possibilities for detecting suspicious samples from athletes who have taken prohibited oral salbutamol are available with conventional screening procedures in doping control.
    Therapeutic Drug Monitoring 07/2000; 22(3):277-82. · 2.23 Impact Factor

Publication Stats

722 Citations
130.82 Total Impact Points

Institutions

  • 2013
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem District, Israel
  • 1989–2013
    • University of Western Australia
      • School of Sport Science, Exercise and Health
      Perth City, Western Australia, Australia
  • 2002–2011
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 2001
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia