Presentazione sul tema: "Asma da esercizio fisico"— Transcript della presentazione:
1Asma da esercizio fisico Marcello CottiniSp. Immunologia Clinica Allergologia Pneumologia BergamoAsma da esercizio fisicoCORSO DI AGGIORNAMENTO“I FENOTIPI DELL’ASMA’ ”Arenzano 16 Febbraio 2008
2Exercise-induced bronchospasm: a different phenotype?
3EIA è presente in circa il 70-80% dei bambini non in terapia con steroidi inalatori
4L’asma da sforzo allontana i bambini dallo sport!
5Exercise training on disease control and quality of life in asthmatic children Fanelli A, Med Sci Sports Exerc 2007Thirty-eight children with moderate to severe persistent asthma : control (N=17) training (N=21) groupsIn trained children:physiological variables at peak and submaximal exerciseSeverity of exercise-induced bronchoconstriction (EIB) and postexercise breathlessness Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores Daily doses of inhaled steroids
7Prolonged exercise of 5-to 10-min duration created bronchoconstriction 1962 : Jones and collegues reported that the effect of exercise on the asthmatic airway was dependent on the duration of activity.Prolonged exercise of 5-to 10-min duration created bronchoconstrictionJones RS, Br J Dis Chest 1962
8Asma da esercizio fisico Riduzione dei flussi espiratori dopo, ma non durante, esercizio fisico breve (6 min) preceduto da warm-up (W)Beck et al., JAP 1999
10The bronchospasm can occur also during the exercise, especially during prolonged exertion Godfrey S, Bar-Yishay E, Exercise induced asthma revised, Respiratory Medicine 1993
11Asma da esercizio fisico Aumento della resistenza inspiratoria (RLI) durante e dopo esercizio prolungatoSuman et al., JAP 1999
12Mistaken Diagnosis of EIB •Being unfit•Breathlessness in the overweight/obese•Vocal cord dysfunction•Exercise hyperventilation syndromeAre all often incorrectly diagnosed as EIB.For these disorders the symptoms occur DURING rather than AFTER exercise.
15Exercise-induced vocal cord dysfunction Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma Weinberger, Pediatrics Oct 2007Exercise-induced vocal cord dysfunction
16Exercise-induced vocal cord dysfunction Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma Weinberger, Pediatrics Oct 2007Exercise-induced vocal cord dysfunction
17Although most exacerbations are self- limited or subside readily with medication, sudden fatal asthma exacerbations occur in both competitive and recreational athletes, and can be precipitatedby sporting activityBecker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.J Allergy Clin Immunol 2004
19Rashidi Wheeler morto per asma sul campo 03.08.01 Rahidi Wheeler
2061 deaths over a 7-y period 81% < 21 y 57% elite athletes Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.J Allergy Clin Immunol 200461 deaths over a 7-y period81% < 21 y57% elite athletes
21Adolescenti a rischio: 10-14 anni fascia prevalente! Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.J Allergy Clin Immunol 2004Adolescenti a rischio: anni fascia prevalente!Non solo sport agonistico.
22Adolescenti a rischio: 10-14 anni fascia prevalente! Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.J Allergy Clin Immunol 2004Adolescenti a rischio: anni fascia prevalente!Non solo sport agonistico.Molti con asma lieve.
24Exercise-induced bronchospasm in children: effects of asthma severity The prevalence of EIB is greater in children with more severe asthma, and the intensity of response to exercise is not consistently related to the clinical severity of asthma.Cabral, AJRCCM 1999
25Adolescenti a rischio: 10-14 anni fascia prevalente! Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.J Allergy Clin Immunol 2004Adolescenti a rischio: anni fascia prevalente!Non solo sport agonistico.Molti con asma lieve.77% non in terapia di fondo per asma!
2680/579 14% % children with asthma A PILOT SURVEY OF ß2-AGONIST INHALER AVAILABILITY FOR CHILDREN WITH ASTHMA DURING ORGANIZED SPORTING EVENTS Cardona Ann. Allergy Asthma Immunol. 2004; 92: 340% children with asthma15 –10 –5 –14%579 ch.<12 yrs playing baseball or soccerParents reported asthma80/579
2718/80 22% 579 ch.<12 yrs playing baseball or soccer A PILOT SURVEY OF ß2-AGONIST INHALER AVAILABILITY FOR CHILDREN WITH ASTHMA DURING ORGANIZED SPORTING EVENTS Cardona Ann. Allergy Asthma Immunol. 2004; 92: 340% of asthmatic children reporting to have ready available a rescue medication25 –20 –15 –10 –5 –22%579 ch.<12 yrs playing baseball or soccerParents reported asthma18/80
28HistorySir John Floyer, who was himself asthmatic, first described the adverse effects of physical exercise on his asthma, noting that different types of exercise had greater or lesser adverse effects Floyer J, Sir. A treatise of the asthma. R Wilkin & W Innis, London, 1698
29Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976 For many years, it was generally assumed that this was because the severity of exercise was also different.( 47% PEF )( 33% )( 25%)( 15%)Anderson, Br J Dis Chest ; Fitch, JAMA 1976
30Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976 For many years, it was generally assumed that this was because the severity of exercise was also different.Is the increase in ventilation produced by exercise and not the kind of exercise that is crucial in EIA( 47% PEF )Any exercise can lead to EIA if it is performed hard enough or long enough to increase the amount of air being inhaled( 33% )( 25%)( 15%)Anderson, Br J Dis Chest ; Fitch, JAMA 1976
32Asmogenicità delle attività sportive (in ordine crescente) Gruppo di studio di Broncopneumologia pediatrica (SIP), 1994Nuoto BaseballPallanuoto CalcettoCanottaggio PallacanestroSci di fondo TennisPallavolo Atletica leggera(corsa veloce – 100 mt)Arti marziali CalcioDiscesa libera CiclismoMarcia Corsa libera
33Adverse effects on the Clara cell function Higher rates of hay fever.Adverse effects on the Clara cell function
34Indoor swimming pools, water chlorination and respiratory health During training and competition, higly trained swimmers inhale large amounts of air that floats just above the water surface.Therefore they are repetedly and stongly exposed to chlorine derivatives.
35Indoor swimming pools, water chlorination and respiratory health Airway inflammation in elite swimmers Piacentini G, JACI 2007EBC-LTB4 levels were 41.9 ± 14.3 pg/mL in swimmers and 5.1 ± 0.9 pg/mL in controls (P = .033), indicative of a neutrophilic inflammation, possibly accounting for airway tissue damageDuring training and competition, higly trained swimmers inhale large amounts of air that floats just above the water surface.Therefore they are repetedly and stongly exposed to chlorine derivatives.
38Symptoms of EIApuò manifestarsi come dolore toracico Nudel Clin. Pediatr ; 26: 388
39Chest pain in children is rarely of cardiac origin CHEST PAIN IN CHILDREN: DIAGNOSIS THROUGH HISTORY AND PHYSICAL EXAMINATIONEvangelista JA, JPHC 2000; 14: 3Chest pain in childrenis rarely ofcardiac origin80 –70 –60 –50 –40 –30 –20 –10 –0 –76%50 ch.referred for chest painPhysical examinationand ECG12%8%4%musculo-skeletalpainEIBpsycogenicgastricproblem
41Exercise-induced Asthma : Pathophysiology AIRWAY REWARMING THEORYHYPEROSMOLARITY THEORY
42RESPIRATORY WATER LOSS MUCOSAL COOLINGMUCOSAL DEHYDRATIONVASOCONSTRICTIONINCREASED OSMOLARITYRAPID REWARMINGOF AIRWAYSMEDIATOR RELEASEVASCULAR ENGORGEMENT,EDEMASMOOTH MUSCLE CONTRACTION, EDEMAAIRWAY NARROWINGAnderson EJRD 1982; 63: Mc Fadden J. Clin. Invest. 1986; 78: 18Anderson All. Proc. 1989; 10: 215
43Increased urinary excretion of LTE4 after exercise Reiss TF, Thorax 1997
44Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstrictionMaximal FEV1 decrease after exercise in asthmatic children with EIB at baseline and after 3 days of treatment with montelukastCarraro S, JACI 2005
45Mechanisms Underlying the Definition of Asthma Risk Factors(for development of asthma)INFLAMMATIONAirwayHyperresponsivenessAirflow ObstructionSymptomsRisk Factors(for exacerbations)
46Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthmaPercentages of subjects with EIB according to the degree of blood eosinophilsEosinophils play a major role in the severity of exercise-induced bronchoconstriction in children with asthmaPediatr Pulmonol 2006
47Atopy may be related to exercise-induced bronchospasm in asthma Koh YI, Clin Exp Allergy 2002 Atopy defined as skin test reactivity may contribute to the development of EIB in asthma, indipendently of AHR to metacholine
48Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstrictionCys-LT levels in EBC of asthmatic children with EIB, asthmatic children without EIB, and healthy control childrenCarraro S, JACI 2005
49Emerging evidence indicates that injury to the airway epithelium is a key susceptibility factor for EIB. One consequence of epithelial injury is replacement of ciliated epithelial cells by mucin secreting cells.Anderson SD, Curr Allergy Asthma Rep Hallstrand TS, J Allergy Clin Immunol. 2005
50Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction Hallstrand TS, JACI May 2007
51Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction The release of MUC5AC may be mediated by the cysLT-associated activation of sensory airway nerves containing NKA
53Athletes and exercise-induced bronchoconstriction Same inflammation ??
54EIA and EIB: different phenotypes? JACI , June 2007EIA and EIB: different phenotypes?“We use the term exercise-induced bronchospasm (EIB) to describe the airway obstruction that occurs in association with exercise without regard to the presence of chronic asthma”.
56Up to 90% of subjects with asthma will have EIB Mc Fadden ER, NEJM 1994
57Factors that Exacerbate Asthma AllergensAir PollutantsRespiratory infectionsExercise and hyperventilationWeather changesSulfur dioxideFood, additives, drugs
58Method: sport-specific challenge testing in nonathletes Prevalence of EIAHallstrand found 9% of school children had EIA Hallstrand TS, J Pediatr 2002Rupp found 12% of school children had EIA Rupp NT, Ann Allergy 1993Method: sport-specific challenge testing in nonathletes
59% subjects with EIB KEEPING CHILDREN WITH EXERCISE-INDUCED ASTHMA ACTIVE Milgrom H Pediatrics 1999; 104 :3890 -80 -70 -60 -50 -40 -30 -20 -10 -% subjects with EIB90%40%6-12%GeneralpopulationRhinitisAsthmasubjects with
60Sinclair DG etal. Eur Respir et J 1995;8:1314-17 British study: EIA (>15% fall in FEV1) in 29/100 sequentially referred potential recruits with a history suggestive of asthma in childhood but no asthma symptoms or therapy in the last 4 years.Sinclair DG etal. Eur Respir et J 1995;8:
62FAMOUS ATHLETES WITH ASTHMA Mak Spitz: Munich 1972, 7 Gold medalsIndurain: 5 tours de France early 90sJackie Joyner-Kersee: heptathlon & long jump (6 olympic medals + 4 on world championship) Late 80s, early 90s
63Jackie Joyner-Kersee uses an asthma inhaler after winning the 800-meter race (part of the women's heptathlon) at the World Athletics Championships in Stuttgart, Germany, July 17, 1993.
65Delaying Decline in Pulmonary Function with Physical Activity A 25-Year Follow-up Physical activity is associated with a slower decline in pulmonary function and with lower mortalityPelkonen M, AJRCCM 2003
67Yep, this horse needed an inhaler treatment after a race-!
68Racing Alaskan Sled Dogs as a model of “Ski Asthma” Davis MS, AJRCCM 2002 BAL obtained from dogs after the race had significantly higher macrophage and eosinophil counts compared with sedentary control dogs
70Identified by free running test ASTHMA SCREENING OF HIGH SCHOOL ATHLETES: IDENTIFYING THE UNDIAGNOSED AND POORLY CONTROLLED WITH FREE-RUNNING CHALLENGE Ann All Asthma Imm 2002; 88: 380801 student athletesquestionnaire and free running exercise challengeAsthma and EIAidentified byquestionnaire46 (5.7%)remaining 755Total49 (6.5%)801studentathletesIdentified byfree running test
71Perception of exercise induced asthma by children and their parents Modest specificity (82%) and low sensitivity (50%) of children’s descriptionsPanditi S, ADC 2003
72Ch Parents % 50 - 40 - 30 - 20 - 10 - 47% 45% 35% 35% 20% 17% WHEEZING DIFFERENCES BETWEEN CHILD AND PARENT REPORTSOF SYMPTOMS AMONG CHILDREN WITH ASTHMALara M Pediatrics 1998; 102 : E68ChParents%50 -40 -30 -20 -10 -47%97 ch. with asthmachild and parent interviewsexercise test45%35%35%20%17%NEVEROCCASIONALLYALWAYSWHEEZINGREPORTED WHEEZING DURING EXERCISE
73History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%)Tan RA, Ann Allergy Asthma Immunol 2002
74History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%)+Treat as ASTHMATan RA, Ann Allergy Asthma Immunol 2002
75Pulmonary Function Tests Flow-volume loop demonstrates flattened inspiratory loop when symptomatic.NormalVCD
76History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%)+-Treat as ASTHMAMC challenge; Exhaled nitric oxideTrial with ß2-agonists+Treat as EIATan RA, Ann Allergy Asthma Immunol 2002
77History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%)+-Treat as ASTHMAMC challengeTrial with ß2-agonists-++ExerciseTreat as EIATreat as EIA-+Treat as EIAOther diagnosesTan RA, Ann Allergy Asthma Immunol 2002
78Valutare il bambino mediante test da sforzo Per avviare il bambino asmatico allo sportValutare il bambino mediante test da sforzo
79Il test da sforzo appare particolarmente adeguato in età pediatrica poiché rappresenta uno stimolo fisiologico che riproduce circostanze di “vita reale”, quotidiane
80Test da sforzo eseguito in laboratorio Tapis RoulantVentilazione aumenta di più, bronco-ostruzione facile (V’O2 +10%)Per qualche paziente più facile da eseguire.Più difficile determinare intensità (watt)BiciclettaNon ha velocità e inclinazione, solo carico di lavoro (workload)Preferibile per pazienti con difficoltà di camminare/ correreFacile determinare intensità (watt)
81EXERCISE TESTING FEV1 in Litres Drop in FEV1 10% = positive test 54Normal subject3Drop in FEV1 10% = positive testFEV1 in Litres2Asthmatic patientSpirometryExercise181420Time in Minutes
82EIB after different exercise loads Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94:
83EIB after different exercise loads The most specific test is to test the athlete in the field in their sport;This is more specific than exercise testing in laboratory (but temperature and humidity cannot be controlled with exercise in the field).Rundell, Med Sci sports Exerc 1999Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94:
85ASMA DA SFORZO – PRECAUZIONI non eseguire il test se:presenza del medico per tutta la durata del testcardiomonitorsomministrare 2 stimolante spray e ossigeno se broncospasmo graveil paziente presenta broncospasmo a riposoPEFR o FEV1 < 70 % del predetto< 80 % dei valori usuali(in tal caso test di reversibilità)
86Anche il test della corsa libera è risultato valido e ripetibile, con il limite delle condizioni ambientali ( temp °C,umidità relativa < 40%)
87Exercise-induced bronchospasm in children: comparison of FEV1 and FEF25-75% responses FEF(25-75%) can decrease in response to exercise without changes in FEV(1), mainly in children with mild asthmaFonsega-Guedes, Pediatr Pulmonol 2003
89EIB could be excluded with a probability of 90% in asthmatic children with FeNO levels < 20 parts per billion (ppb) without current inhaled corticosteroid treatment, and < 12 ppb in children with current inhaled corticosteroid treatment.
90Value of surrogate tests to predict exercise-induced bronchoconstriction in atopic childhood asthma Lex, Pediatr Pulmonol 2007All children with normal eNO levels (< or = 25 ppb) had normal lung function results after exercise; hence the negative predictive value (NPV) of eNO levels for prediction of EIB was 100%.
91Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthmaNishio K,J Asthma 2007Not only FEV1 but FEF25-75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children A low eNO is useful for a negative predictor for EIB
92Test di broncostimolazione positivo Asma bronchiale negli atleti Percorso diagnostico per le Olimpiadi di AteneTest di broncostimolazione positivo1) test metacolina:PD20 < 200 mcg2) test sforzo- < 10 % FEV1 v. b.3) test iperpnea vol. isocapnica < 10% FEV1 v.b.4) Aerosol ipertonico < 15% FEV1 v.b.Diagnosi di Iperreattività bronchiale Asma bronchiale - Terapia - Prevenzione
93EUCAPNIC VOLUNTARY HYPERVENTILATION 6min of hyperpnoeadry air4.9% CO210% fall in FEV1Specific for diagnosis of EIA (Rundell et al. 2004)Recommended by the IOC% Fall in FEV110203040506 minExerciseEVHn = 22
94Anderson et al. submitted IBAs USE SYDNEY vs ATHENSSYDNEY ATHENS 2004(notified) (approved)NOC IBAs PERCENT IBAs PERCENTNZL % %AUS % %UK % %USA % %CAN % %FIN % %Anderson et al. submitted
95Attuare la prevenzione non farmacologica Per avviare il bambino asmatico allo sportAttuare la prevenzione non farmacologica
96EIA:terapia non farmacologica SCHACHTER, E. N., E. LACH, and M. LEE The protective effect of a cold weather mask on exercised-induced asthma.Ann. Allergy 46:12–16, 1981.
97EIA:terapia non farmacologica A special warm-up routine has been shown to reduce the severity of EIA
98ALLENAMENTO INTERMITTENTE FRANÇOIS-PIERRE COUNIL, J Pediatr 2003 EIA:terapia non farmacologicaALLENAMENTO INTERMITTENTEEsecuzione,durante il preriscaldamento,di sprint brevi(10-12),della durata di secondi,intercalati da periodi di recupero di 1-2 min,per indurre refrattarietà all’EIA senza provocare broncoostruzione clinicamente significativaFRANÇOIS-PIERRE COUNIL, J Pediatr 2003
99ASMA DA SFORZO (EIA) - ALLERGIA esposizioneallergeniaumentoEIA infiammazionesforzo reattivitàbronchialeaspecifica
100ASMA DA SFORZO ED INQUINAMENTO ATMOSFERICO Bronchoconstriction in asthmatics exposed to sulfur dioxide during repeated exercise.RogerJ.Appl.Physiol. 1985Distribution of specific airway resistance (sRaw; cm H2O - s) inasthmatic subjects exposed, during exercise, to air (0.0 ppm) orSO2 (0.25, 0.5, and 1.0 ppm)
103Fish Oil Supplementation Reduces Severity of Exercise-induced Bronchoconstriction in Elite Athletes Mickleborough, American Journal of Respiratory and Critical Care Medicine 2003Supplementing the diet with n-3 PUFA represents a potentially beneficial treatment for elite athletes with EIB.
104Pianificare la protezione farmacologica Per avviare il bambino asmatico allo sportPianificare la protezione farmacologica
105TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazioneß2-agonistiCromoniMontelukast
106TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO 2. Terapia di fondoSteroidi inalatoriMontelukast
107TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazioneß2-agonistiCromoniMontelukast
108Long-acting beta-agonists Prevention of EIA in pediatric asthma patients: a comparison of two salmeterol powder delivery devices Bronsky,Pediatrics 1999Evidence of the rapid protective effect of formoterol dry-powder inhalation against EIA in athletes with asthma Ferrari, Respiration 2000
109ß2-Agonist Tolerance and EIB Hancox RJ, AJRCCM 2002 (salbutamol)Nelson JA, NEJM 1998 (salmeterol)Garcia R, J Invest All Clin Immunol (formoterol)
110Asma da esercizio fisico L’effetto del salmeterolo e la sua durata si attenuano col trattamento cronicoNelson et al., NEJM 1998
111Risposta alla metacolina L’effetto protettivo del salmeterolo si riduce nel tempo Cheung et al AJRCCM 1998
112Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise induced asthma Simons, Pediatrics 1997;99:665SLM 50 mcg once daily vs PL+ daily inhaled steroidstherapyExercise at 1 and 12 hoursafter drug, on day 1 and 28The duration of the broncho-protective effect decreasesduring regular treatment with salmeterol despite concomitant use of inhaled steroidsP =P =P =Mean Fall FEV1 %ns1 day day
113TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazioneß2-agonistiCromoniMontelukast
115TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO 2. Terapia di fondoSteroidi inalatoriMontelukast
116Bambini con broncostruzione indotta da esercizio fisico La broncostruzione indotta dall’esercizio fisico è espressione di asma non adeguatamente controllato.Bambini con broncostruzione indotta dall’esercizio fisico dovrebbero essere trattati come pazienti con asma persistente.
117four trials involving children Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction Koh, Cochrane Database of Systematic Reviews 2007four trials involving childrenInhaled corticosteroids used for 4 weeks or more before exercise testing significantly attenuated exercise-induced bronchoconstriction
118In asthmatic patients ICSs not only attenuate exercise-induced bronchospasm but also improve arterial blood oxygenation during exerciseJACI 2007
119J ALLERGY CLIN IMMUNOL MAY 2006 50%J ALLERGY CLIN IMMUNOL MAY 2006
121New Treatments for Exercise-induced Asthma : MONTELUKAST Montelukast for the treatment of mild asthma and EIBLeff, NEJM 1998
122Montelukast for the treatment of mild asthma and EIB Leff, NEJM 1998Montelukast inhibits EIB in 6-to 14-year-old children with asthma Kemp, J Pediatr 1998Montelukast versus salmeterol in patients with asthma and EIB Villaran, JACI 1999Comparison of montelukast versus budesonide in the treatment of EIA Vidal, AAAI 2001Montelukast compared with salmeterol to prevent EIBEdelman,Ann Intern Med 2000Comparative effects of LABA and INI-LT on EIBCoreno, JACI 2000
123Montelukast vs salmeterol in patients with asthma and exercise-induced bronchoconstrictionVillaran, J Allergy Clin Immunol 1999;104:54715202530197 patients, yrsMild asthmaMNT or SLM for 8 wksExercise challengeat definite times20-24 h after dosingThe effect of montelukastwas greater than salmeterolover a period of 8 weeksMontelukast 10 mg odSalmeterol 50 mcg bidnsp<0.001p<0.001% drop FEV1The maximal percent fall in FEV1 after exercise decreased significantly from pre-randomization baseline to week 8 in both treatment groups (p< 0.001). The mean maximal percent fall decreased (improved) from 33.1% to 15.9% after 8 weeks on montelukast, and from 30.9% to 20.2% after 8 weeks on salmeterol. The improvement (decrease) was significantly (p=0.001) larger in the montelukast treatment group (mean decrease =17.2 % [52% inhibition vs baseline]) than in the salmeterol treatment group (mean decrease=10.7 % [35% inhibition vs baseline]). Throughout the study, the improvement in maximal percent fall in FEV1 was greater with montelukast treatment than with salmeterol treatment. The estimated treatment difference was -3.1 % at day 3 (p= 0.123), -8.8 % at week 4 (p<0.001) and -7.2 % at week 8 (p=0.001). The mean decrease in maximal percent fall in FEV1 with salmeterol was most pronounced at day 3 compared with weeks 4 and 8. In the montelukast group, the decrease remained stable from day 3 through week 8 1.Since maximal percent fall in FEV1 was the primary endpoint in this study, a further analysis of interaction between treatment effect and the various demographic subgroups was performed. All tests of interaction revealed no significant effect, demonstrating that the effect of both therapies was consistent over the various subgroups including gender, age, ethnicity and concomitant use of inhaled steroids 1.BasalDay 3Week 4Week 8
125Prolonged Effect of Montelukast in Asthmatic Children With EIB, Pediatr Pulmonol, 2005 Studio in doppio cieco (n=64) Montelukast contro placebo per 8 settimane, seguito da crossover di parte del gruppo trattato (28/40) per ulteriori 8 settimane
126Miglioramento significativo per tutti i parametri considerati Prolonged Effect of Montelukast in Asthmatic Children With EIB Kim Pediatr Pulmonol, 2005Miglioramento significativo per tutti i parametri consideratiMassima caduta di FEV1Score sintomatologicoTempo di recuperoNel gruppo crossover, dopo 8 settimane di washout, tutti i parametri rimanevano persistentemente e significativamente migliorati rispetto ai valori basali
127Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma Stelmach, JACI in Press
128Pajaron-Fernandez, Pediatr Pulmonol 2006 Montelukast administered in the morning or evening to prevent exercise-induced bronchoconstriction in childrenMontelukast, taken for 2 weeks, is equally effective in exercise-induced bronchoconstriction when dosing either in the morning or in the eveningPajaron-Fernandez, Pediatr Pulmonol 2006
129A recent study reported that montelukast provided greater protection against bronchoconstriction after exercise during high PM1 than low PM1 exposure (approximately 90% vs. approximately 35%)Rundell KW, Spiering BA, Baumann JM, Evans TM. Bronchoconstrictionprovoked by exercise in a high-particulate-matter environmentis attenuated by montelukast. Inhal Toxicol 2005;17:99–105.
130STEP 2 : AdultiNei pazienti con asma lieve persistente, le basse dosi di corticosteroidi inalatori sono più efficaci delle altre opzioni terapeutiche (A)Esiste tuttavia una eterogeneità di risposta al trattamento con i diversi farmaci antiasmatici, da valutare in ogni singolo caso con metodi oggettivi (B); in tal caso, le altre opzioni terapeutiche possono essere considerate in alternativa all’opzione principaleAlcuni tipi di asma (asma da sforzo, asma del bambino, asma di recente insorgenza) e la presenza contemporanea di asma e rinite, rispondono bene agli antileucotrieni (B)
131Montelukast does not affect exercise performance at subfreezing temperature in highly trained non-asthmaticendurance athletesSue-Chu Int. J. Sports. Med. 2000; 21: 424Compared to placebo, montelukast did not increase physiologic performance variables, or increase the mean running time to exhaustionthese findings do not suggest the need for disallowing the use of this drug by asthmatic athletes.
133OLYMPIC MOVEMENT ANTI-DOPING CODE APPENDIX APROHIBITED CLASSES OF SUBSTANCES AND PROHIBITED METHODS1 January 2003I. PROHIBITED CLASSES OF SUBSTANCESbProhibited substances in class A.b include the following examples with both their L and D-isomersformoterol***, salbutamol***, salmeterol*** and terbutaline*** … and related substances*** permitted by inhaler only to prevent and/or treat asthma and exercise-induced asthma.Written notification by a respiratory or team physician that the athlete has asthma and/or exercise-induced asthma is necessary to the relevant medical authority prior to competition.At the Olympics Games, athletes who request permission to inhale a permitted beta-2agonist, will be assessed by an independent medical panel.* For salbutamol, a concentration in urine greater than 1000 nanograms permillilitre of non-sulphated salbutamol constitutes a doping violation.
135Corticosteroidi Norme WADA - CIO Assolutamente vietatiper via sistemicaAmmessi solamente per via inalatoria per la terapia dell’asma bronchiale e delle allergopatie
136CONTROINDICAZIONI Uso di respiratori subacquei Attività fisica in alta quotaSport motoristiciAsma grave persistente
137What About More Information? In a moment I’ll take your questions. But I don’t want to leave you without giving you some sources of additional information.Reprints of the Clinical Therapeutics meta-analysis are available on request by contacting the ACAAI through the Web sites listed above. The July 2001 Annals supplement, with proceedings of the 2000 consensus conference, also is available on the Web sites listed above.That same conference is available in an on-line CME course you can access through our Web site at:Press space bar