Ass. Prof. Pulmonary and Crit.Care Medical School,University of Athens

Transcription

1 Diagnosis i of Exercise Induced Asthma Ch. Gratziou Ass. Prof. Pulmonary and Crit.Care Medical School,University of Athens

2 Other Diagnostic Challenges for Exercise Induced Asthma Do we need other tests for EIA???

3 Why to diagnose EIA in athletes Underdiagnosis of EIA among athletes Undertreatment!! (lower performance!!) Overtreatment??

4 NIH Asthma Related Deaths in Athletes Non-asthma related deaths 200 Athletes who died during or after sporting activity from 1993 until 2000 were identified Twenty-three per cent out of 263 athletic deaths were asthma related Two used cromolyn sodium, One used inhaled steroids The remainder did not use and controller treatment athletes N umber of athletes % Asthma related deaths 23% Asthma related deaths, age distribution Number of Becker JM et al. JAACI 2004; 113: < >31 Age (years)

5 Treatment for EIA Treatment of EIA: Prophylactic treatment (Anti-inflammatory treatment) Inhaled steroids Leukotriene-antagonists Treatment before exercise Inhaled ß 2 -agonists Shortacting Longacting Disodium cromoglycate Ipratropiumbromide The common guidelines of treating asthma should be followed!!!

6 History of Β2-Agonists use in Olympic Games Prevention and treatment of asthma(εια) and bronchoconstriction ( ΕΙΒ) after exercise ( salbutamol, terbutaline, salmeterol, formoterol) Prohibited on Οlympic Games 1972 Restart (after notification) 1976 Free use Only after medical notification

7 Β2-Agonists use and Olympic Games May 2001 Workshop IOC Medical Commission Increased use of b2-agonists Los Angeles % Atlanta % Nagano % Sydney % Endurance sports Cross-country Ski 17.9 % Cyclist 17.3 % Triathlon 20.0 %

8 Β2-Agonists and Olympic Games ΙΟC recommendations after 2002 Not only medical notification But Objective evidence of asthma and/or EIA or EIB using» Medical history» Clinical signs» Use of medication (3months)» Reversibility in FEV1»Special tests

9 Β2-Agonists use in Olympic Games Special tests suggested by IOC Bronchial reversibility (increase 12 % or at least 200 ml in FEV1) Provocation tests» Exercise (in the laboratory)» Exercise (in the field)» Eucapnic Voluntary hyperpnea test (EVH)» Methacholine provocation Test (PD20 < 400mcg /1µmol PC20 < 4mg/ml-cum.dose PD20 < 1600 mcg/8 µmol, PC20 <16mg/ml-on ICSs)» Hypersmolar Aerosols : Hypertonic Saline 4.5%» Mannitol test

10 Provocation test for BHR Direct & indirect stimulus Direct stimuli methacholine histamine prostaglandin D2 Cys-leukotrienes Indirect stimuli exercise hyper- hypotonic saline Mannitol test cold/dry air EVH adenosine tachykinins methabisulphite, SO2.

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12 Rationale for using an Indirect challenge to identify asthma in elite athletes More than one mediator prostaglandins, leukotrienes, histamine are involved in mechanism This test t can predict severity of exercise-induced id dasthma Identifies those who will respond to inhaled corticosteroids and can be used for monitoring of treatment Negative test excludes exercise-induced asthma False positives are unusual

13 Rationale for using an Indirect challenge to monitor asthma treatment in elite athletes Predicts severity of exercise-induced asthma Responses are inhibited or blocked by drugs used to treat asthma and can therefore be used to monitor efficacy of both acute and chronic treatment.

14 Eucapnic Voluntary Hyperventillation ( EVH ) test

15 Eucapnic Voluntary Hyperpnea Test (ΕVH) Introduced as an indirect bronchial challenge test in 1985 ( Philips et al.am Rev.Respir.Dis) Mimics the mechanism which causes bronchoconstriction in subjects with exercise induced asthma The mechanism includes mediators such as histamine, prostaglandins, leukotrienes

16 Mechanisms of exercise-induced asthma Physical exercise Warming inspired air Airway y heat loss Increased ventilation Cold air Moistening inspired air Airway water loss Airway cooling Vagal stimulation Vascular engorgement Exercise Induced Asthma Increased osmolarity l Cl -, Ca ++ influx Mediator release

17 Eucapnic Voluntary Hyperpnea Test (ΕVH) Mechanism Hyperventilation Osmotic and thermal changes Dry cough ΕΙΑ Release of Mediators Bronchoconstriction

18 EVH test vs Exercise test Easy to perform test Can induce ventilation rates equivalent to or higher than exercise Can be performed in any laboratory Less expensive equipment, fewer personnel

19 Eucapnic voluntary hyperpnea test (ΕVH) One stage protocol ( IOC) Voluntary hyperpnea with dry air in room temperature The air contains 5 % CO2 The target ventilation is 30 Χ FEV1,which is equal to 85 % of MVV. Test duration = 6 minutes. (hyperventilation for 6 minutes)

20 Equipment for EVH

21 EVH testing during Olympics in Athens 2004

22 EVH testing during Olympics in Athens 2004 Ventilation (MVV) and CO 2 recording

23 EVH testing during Olympics 2004 FEV 1 in 1,3,5,10, and 20 min Spirometry test Target 10 % drop in FEV 1

24 Evaluation of response in ΕVH test Ventilation rate % of MVV that causes 10 % drop in FEV 1 Expressing the results as ventilation rate % of MVV gives a guide to the intensity of exercise that is required to provoke the reduction in lung function Maximal ventilation on exercise Normal subjects 60 % MVV Εlite athletes 90 % ΜVV

25 Evaluation of response in ΕVH test Average Ventilation rate (l/min) as % of MVV ( MVV = actual FEV1 x35 ) 40 Maximal ventilation on exercise 1 % Fall in FEV Severe Moderate Normal subjects 60 % MVV Εlite athletes 90 % ΜVV 10 Severe Moderate Mild 0 Normal Ventilation rate of Subject (%Pred. of MVV) 90

26 Evaluation of response in ΕVH test Mild FEV1 drop is 10-20% Moderate FEV1 drop is % Severe FEV1 drop is >30 % when drops occur at a ventilation rate 60 % of MVV or more BUT Severe FEV1 drop is >10 % when ventilation rate is less 30 MVV

27 Correlation of EVH test with FEV1 reduction in exercise test L/min) ea PVE15 ( Eucapni ic Hyperpn r p = p < % Fall in FEV 1 to exercise Brannan et al, AJRCCM 1998; 158:1120-6

28 EVH Testing in Athens in Olympic Games athletes tested» 27 ΕVH tests»12 exercise tests t»11 methacholine tests»10 reversibility tests

29 EVH Tests 27 EVH tests ( FEV % pred ) 74 % possitive (Drop in FEV % ( %)»8 severe ( FEV1 >30 )»2 moderate ( FEV1 >20)»10 mild ( FEV1 >10)»VE 102 ( L), 68 % MVV

30 Results of EVH Σοβαρή 50 FEV1 40 Εύκαπνικός Άσκηση Σοβαρή Μέτρια Μέτρια 10 Ήπια Κ.Φ VE%MVV

31 Results of Exercise test 12 exercise tests ( FEV % pred)»50 % positive (6 tests)» FEV1 18 %»VE 84 L ( ), 56.3 % MVV

32 Results of EVH and exercise test FEV1 ΣΤΟΝ ΕΥΚΑΠΝΙΚΟ ΥΠΕΡΑΕΡΙΣΜΟ FEV1 ΣΤΗΝ ΑΣΚΗΣΗ

33 Experience from Olympic Games in Athens 2004 Permission for Β2-agonists use in Olympic Games in applications to use medication Approvals were based 22 % reversibility tests 15 % Exercise tests 32 % Methacholine tests 6 % Hypertonic aerosol tests 24 % ΕVH

34 Mannitol challenge test t

35 Mannitol challenge test It is an Indirect provocation test to identify asthma Mannitol is an osmotic diuretic which causes water loss from the surface of the airways This causes smooth muscle contraction in response to the release of a variety of inflammatory mediators from mast cells in the airways (histamine, i prostaglandins, leukotrienes) The mechanism is similar to exercise testing, EVH and hypertonic saline.

36 Procedure for Mannitol Challenge Testing Available in a Standarised test kit including prefilled Dry powder capsules in specific doses with a single inhaler device Approved in Europe and Australia

37 Procedure for Mannitol Challenge Testing Subjects are seated comfortably,they wear a nose clip and are directed to mouth breath at tidal volume Mannitol dose : Start from step 1( 1 caps) 5mg to step 9 (635 mg) Perform an FEV1 1 min after inhalation Calculate 15 % drop of baseline FEV1.

38 Procedure for Mannitol Challenge Testing

39 Provocation dose for Mannitol Challenge test Dose Dose mg Cumulative dose Capsules per dose x40mg x40mg x40mg x40mg

40 Medications restrictions before test Time to withhold Short acting b2-agonists 8 hours Inhaled Steroids 12 hours Ipratropium Bromide 12 hours Long acting b2-agonists 24 hours Theophylline 24 hours Tiotropium bromide 72 hours Antihistamines 72 hours Leukotriene receptor antagonists 4 days Inhale non-steroidal anti-inflammatory agents

41 Cautions before Mannitol Challenge Testing Foods: coffee,tea,, cola drinks and chocolate should be withheld on the day of the test Exercise: vigorous exercise should not be performed prior to testing in the day of the test Smoking: should refrain from smoking for at least 6 hours prior to testing

42 Evaluation for Mannitol Challenge Testing The provoking dose of mannitol to induce a 15% fall in FEV1 (PD20). or 10% incremental fall in FEV1 between doses The mean time to a positive response is 17 minutes (+/-7) and to a negative response is 26 minutes (+/-6) Inhalation of short acting b2-agonist follows a positive test and the bronchodilator response is measured after 20 minutes.

43 Mannitol vs metacholine test 25 adult asthmatics, Anderson et al. AmJ.Respir.Crit C.Med 1997,156:758 Subbarao et al. Pediatr. Pulmonol. 2000;29:291

44 Mannitol vs Exercise test 23 adult asthmatics,positive to exe test 22 positive to mannitol Brannan et al. AmJ.Respir.Crit C.Med 1998,158:1120

45 Mannitol vs EVH test 50 elite athletes with asthma 24,positive to EVH test 26 positive to mannitol Holzer et al. AmJ.Respir.Crit C.Med 2003,167:534 Brannan et al. AmJ.Respir.Crit C.Med 1998 ; 158:1120

46 Reccomendations for EIA Diagnostic Tests An eucapnic voluntary hyperpnea (EVH) test t with dry air is a good test to identify EIB and widely used in elite athletes A mannitol test has a good sensitivity to identify both EIB / EIA +ve and EVH +ve subjects & provides the opportunity for a standard operating procedure. (Mannitol may be negative in good control of asthma ) A test with methacholine test can have a low sensitivity to identify a EIB +ve subjects so that a negative test does not exclude EIB +ve subject. Not recommended to identify EIB Anderson et al JACI 2006

47 Our Experience with athletes for Olympics 2008 (Gallen Study ) Preliminary Results 83 athletes were screened by specific questionnaire 31 had a positive Q, (37 %) 37 had positive skin tests ( 44,5%)

48 Our Experience with athletes for Olympics 2008 (Gallen Study ) Preliminary Results 19 athletes were tested with provocation tests 19 EVH tests (11 positive) 58 % 16 exercise tests ( 1 positive) 18 methacholine tests (13 positive) 72 % 10 mannitol tests ( 0 positive) A number of athletes were diagnosed for the first time Some of the athletes were well controlled with inhaled steroids Some of them had a history of asthma not only EIA

49 Our Experience with athletes for Olympics 2008 (Gallen Study ) According to our own experience Eucapnic Voluntary Hyperpnea test (EVH) is more sensitive test for exercise induced asthma than mannitol even in treatedt asthmatics. ti

50 Objective tests for Exercise Induced Asthma in Athletes Do we need these tests for EIA???

51 Experience from Olympic Games in Athens 2004 A reduction in applications for b2 agonists better evaluation for approvals Games IBAs Athletes Percent Salt Lake (notified) % (approved) % (rejected) % Athens (notified) % 4.4% (approved) % (rejected) %

52 Experience from Olympic Games in Athens in ,6% from all athletes suffer from bronchial asthma. But Asthma is not a problem for elite athletes. Elite athletes with asthma can be Olympic winners Early diagnosis based on objective tests and proper p treatment is helpful!!

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