Slide1:
Marcello Cottini
Sp. Immunologia Clinica Allergologia Pneumologia Bergamo Asma da esercizio fisico CORSO DI AGGIORNAMENTO
“I FENOTIPI DELL’ASMA’ ”
Arenzano 16 Febbraio 2008
Exercise-induced bronchospasm: a different phenotype?: Exercise-induced bronchospasm: a different phenotype?
Slide3: EIA è presente in circa il 70-80% dei bambini non in terapia con steroidi inalatori
L’asma da sforzo allontana i bambini dallo sport! : L’asma da sforzo allontana i bambini dallo sport!
Exercise training on disease control and quality of life in asthmatic children Fanelli A, Med Sci Sports Exerc 2007: Exercise training on disease control and quality of life in asthmatic children Fanelli A, Med Sci Sports Exerc 2007 Thirty-eight children with moderate to severe persistent asthma : control (N=17) training (N=21) groups
In trained children:
physiological variables at peak and submaximal exercise
Severity of exercise-induced bronchoconstriction (EIB) and postexercise breathlessness
Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores
Daily doses of inhaled steroids
Slide6: Exercise-induced asthma (EIA), connotes transient airflow obstruction associated with physical exertion.
Slide7: 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 bronchoconstriction Jones RS, Br J Dis Chest 1962
Slide8: Asma 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
Slide9: DURING or AFTER ???
Slide10: The bronchospasm can occur also during the exercise, especially during prolonged exertion Godfrey S, Bar-Yishay E, Exercise induced asthma revised, Respiratory Medicine 1993
Slide11: Asma da esercizio fisico
Aumento della resistenza inspiratoria (RLI) durante e dopo esercizio prolungato Suman et al., JAP 1999
Slide12: Mistaken Diagnosis of EIB
•Being unfit
•Breathlessness in the overweight/obese
•Vocal cord dysfunction
•Exercise hyperventilation syndrome
Are all often incorrectly diagnosed as EIB.
For these disorders the symptoms occur DURING rather than AFTER exercise.
Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Weinberger, Pediatrics Oct 2007: Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Weinberger, Pediatrics Oct 2007 Exercise-induced vocal cord dysfunction
Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Weinberger, Pediatrics Oct 2007: Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Weinberger, Pediatrics Oct 2007 Exercise-induced vocal cord dysfunction
Slide17: Although most exacerbations are self-
limited or subside readily with medication, sudden fatal asthma exacerbations occur in both competitive and recreational athletes, and can be precipitated
by sporting activity
Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.
J Allergy Clin Immunol 2004
Slide19: Rahidi Wheeler Rashidi Wheeler morto per asma sul campo 03.08.01
Slide20: Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.
J Allergy Clin Immunol 2004 61 deaths over a 7-y period 81% < 21 y 57% elite athletes
Slide21: Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.
J Allergy Clin Immunol 2004 Adolescenti a rischio: 10-14 anni fascia prevalente!
Non solo sport agonistico.
Slide22: Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.
J Allergy Clin Immunol 2004 Adolescenti a rischio: 10-14 anni fascia prevalente!
Non solo sport agonistico.
Molti con asma lieve.
Exercise-induced bronchospasm in children: effects of asthma severity: Exercise-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
Slide25: Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience.
J Allergy Clin Immunol 2004 Adolescenti a rischio: 10-14 anni fascia prevalente!
Non solo sport agonistico.
Molti con asma lieve.
77% non in terapia di fondo per asma!
Slide26: 579 ch.<12 yrs playing baseball or soccer
Parents reported asthma % children with asthma 15 –
10 –
5 –
0 14% 80/579 A PILOT SURVEY OF ß2-AGONIST INHALER AVAILABILITY FOR CHILDREN WITH ASTHMA DURING ORGANIZED SPORTING EVENTS Cardona Ann. Allergy Asthma Immunol. 2004; 92: 340
Slide27: 579 ch.<12 yrs playing baseball or soccer
Parents reported asthma 22% 18/80 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 medication 25 –
20 –
15 –
10 –
5 –
0
History: History Sir 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
Slide29: For many years, it was generally assumed that this was because the severity of exercise was also different.
Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976
( 47% PEF ) ( 33% ) ( 25%) ( 15%)
Slide30: For many years, it was generally assumed that this was because the severity of exercise was also different.
Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976
( 47% PEF ) ( 33% ) ( 25%) ( 15%) Is the increase in ventilation produced by exercise and not the kind of exercise that is crucial in EIA Any exercise can lead to EIA if it is performed hard enough or long enough to increase the amount of air being inhaled
Slide32: Asmogenicità delle attività sportive (in ordine crescente) Gruppo di studio di Broncopneumologia pediatrica (SIP), 1994 Nuoto Baseball
Pallanuoto Calcetto
Canottaggio Pallacanestro
Sci di fondo Tennis
Pallavolo Atletica leggera
(corsa veloce – 100 mt)
Arti marziali Calcio
Discesa libera Ciclismo
Marcia Corsa libera
Slide33: Higher rates of hay fever. Adverse effects on the Clara cell function
Slide34: Indoor 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.
Slide35: Indoor 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. Airway inflammation in elite swimmers Piacentini G, JACI 2007
EBC-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 damage
Slide36: Exercise-induced Asthma : Symptoms
Slide37: Symptoms of EIA
Slide38: Symptoms of EIA può manifestarsi come dolore toracico Nudel Clin. Pediatr. 1987; 26: 388
Slide39: CHEST PAIN IN CHILDREN: DIAGNOSIS THROUGH HISTORY AND PHYSICAL EXAMINATION
Evangelista JA, JPHC 2000; 14: 3 50 ch.
referred for chest pain
Physical examination
and ECG 80 –
70 –
60 –
50 –
40 –
30 –
30 –
20 –
10 –
0 – 76% 12% 8% 4% musculo-
skeletal
pain EIB gastric
problem psycogenic
Slide40: Exercise-induced Asthma : Pathophysiology
Slide41: HYPEROSMOLARITY THEORY AIRWAY REWARMING THEORY Exercise-induced Asthma : Pathophysiology
Slide42: RESPIRATORY WATER LOSS MUCOSAL COOLING VASOCONSTRICTION RAPID REWARMING
OF AIRWAYS VASCULAR ENGORGEMENT,EDEMA
AIRWAY NARROWING MUCOSAL DEHYDRATION INCREASED OSMOLARITY MEDIATOR RELEASE SMOOTH MUSCLE CONTRACTION, EDEMA
Anderson EJRD 1982; 63: 459 - Mc Fadden J. Clin. Invest. 1986; 78: 18
Anderson All. Proc. 1989; 10: 215
Slide43: Reiss TF, Thorax 1997
Slide44: Maximal FEV1 decrease after exercise in asthmatic children with EIB at baseline and after 3 days of treatment with montelukast
Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction
Carraro S, JACI 2005
Mechanisms Underlying the Definition of Asthma: Mechanisms Underlying the Definition of Asthma Risk Factors
(for development of asthma)
INFLAMMATION Airway
Hyperresponsiveness Airflow Obstruction Risk Factors
(for exacerbations) Symptoms
Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma : Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma Percentages of subjects with EIB according to the degree of blood eosinophils
Eosinophils play a major role in the severity of exercise-induced bronchoconstriction in children with asthma
Pediatr Pulmonol 2006
Atopy may be related to exercise-induced bronchospasm in asthma Koh YI, Clin Exp Allergy 2002: Atopy 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
Slide48: Cys-LT levels in EBC of asthmatic children with EIB, asthmatic children without EIB, and healthy control children
Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction
Carraro S, JACI 2005
Emerging 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.: Emerging 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. 2005 Hallstrand TS, J Allergy Clin Immunol. 2005
Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction: Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction Hallstrand TS, JACI May 2007
Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction: Role 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
Mucus plugging in fatal asthma: Mucus plugging in fatal asthma Mucus plugs
Slide53: Athletes and exercise-induced bronchoconstriction Same inflammation ??
Slide54: JACI , June 2007 “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”.
EIA and EIB: different phenotypes?
Slide55: Exercise-induced Asthma : Prevalence
Up to 90% of subjects with asthma will have EIB: Up to 90% of subjects with asthma will have EIB Mc Fadden ER, NEJM 1994
Factors that Exacerbate Asthma: Factors that Exacerbate Asthma Allergens
Air Pollutants
Respiratory infections
Exercise and hyperventilation
Weather changes
Sulfur dioxide
Food, additives, drugs
Prevalence of EIA: Hallstrand found 9% of school children had EIA Hallstrand TS, J Pediatr 2002
Rupp found 12% of school children had EIA Rupp NT, Ann Allergy 1993
Method: sport-specific challenge testing in nonathletes Prevalence of EIA
Slide59: KEEPING CHILDREN WITH EXERCISE-INDUCED
ASTHMA ACTIVE Milgrom H Pediatrics 1999; 104 :38 100 -
90 -
80 -
70 -
60 -
50 -
40 -
30 -
20 -
10 -
0 6-12% 40% 90% % subjects with EIB General
population Rhinitis Asthma subjects with
Slide60:
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;8:1314-17
Prevalence of EIA: Prevalence of EIA
FAMOUS ATHLETES WITH ASTHMA: FAMOUS ATHLETES WITH ASTHMA
Slide63: Jackie 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.
Delaying Decline in Pulmonary Function with Physical Activity A 25-Year Follow-up : Delaying Decline in Pulmonary Function with Physical Activity A 25-Year Follow-up Pelkonen M, AJRCCM 2003 Physical activity is associated with a slower decline in pulmonary function and with lower mortality
Slide68: Racing 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
Slide69: Exercise-induced Asthma : diagnosis
Slide70: ASTHMA SCREENING OF HIGH SCHOOL ATHLETES: IDENTIFYING THE UNDIAGNOSED AND POORLY CONTROLLED WITH FREE-RUNNING CHALLENGE Ann All Asthma Imm 2002; 88: 380 801 student athletes
questionnaire and free running exercise challenge Total 801
student
athletes Asthma and EIA
identified by
questionnaire
46 (5.7%)
remaining 755 Identified by
free running test 49 (6.5%)
Perception of exercise induced asthma by children and their parents: Perception of exercise induced asthma by children and their parents Modest specificity (82%) and low sensitivity (50%) of children’s descriptions
Panditi S, ADC 2003
Slide72: 50 -
40 -
30 -
20 -
10 -
0 % 47% 20% 35% 35% 45% 17% NEVER OCCASIONALLY ALWAYS REPORTED WHEEZING DURING EXERCISE WHEEZING DIFFERENCES BETWEEN CHILD AND PARENT REPORTS
OF SYMPTOMS AMONG CHILDREN WITH ASTHMA
Lara M Pediatrics 1998; 102 : E68 97 ch. with asthma
child and parent interviews
exercise test
Slide73: History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%) Tan RA, Ann Allergy Asthma Immunol 2002
Slide74: History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%) Treat as ASTHMA + Tan RA, Ann Allergy Asthma Immunol 2002
Slide75: Pulmonary Function Tests Flow-volume loop demonstrates flattened inspiratory loop when symptomatic.
Normal VCD
Slide76: History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%) - + Trial with ß2-agonists MC challenge; Exhaled nitric oxide Treat as EIA + Tan RA, Ann Allergy Asthma Immunol 2002 Treat as ASTHMA
Slide77: History and/or p.e. compatible with EIA Spirometry (FEV1 reversibility > 12%) - + Trial with ß2-agonists MC challenge Treat as EIA Treat as EIA Exercise Treat as EIA Other diagnoses + - + + - Tan RA, Ann Allergy Asthma Immunol 2002 Treat as ASTHMA
Slide78: Per avviare il bambino asmatico allo sport Valutare il bambino mediante test da sforzo
Slide79: Il test da sforzo appare particolarmente adeguato in età pediatrica poiché rappresenta uno stimolo fisiologico che riproduce circostanze di “vita reale”, quotidiane
Test da sforzo eseguito in laboratorio: Test da sforzo eseguito in laboratorio Tapis Roulant
Ventilazione aumenta di più, bronco-ostruzione facile (V’O2 +10%)
Per qualche paziente più facile da eseguire.
Più difficile determinare intensità (watt)
Bicicletta
Non ha velocità e inclinazione, solo carico di lavoro (workload)
Preferibile per pazienti con difficoltà di camminare/ correre
Facile determinare intensità (watt)
Slide81: Time in Minutes FEV1 in Litres 1 2 3 4 5 Asthmatic patient Normal subject Exercise 8 14 20 0 EXERCISE TESTING Drop in FEV1 10% = positive test Spirometry
EIB after different exercise loads: EIB after different exercise loads Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94: 750-755
EIB after different exercise loads: EIB after different exercise loads Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94: 750-755 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 1999
Slide85: ASMA DA SFORZO – PRECAUZIONI non eseguire il test se:
presenza del medico per tutta la durata del test
cardiomonitor
somministrare 2 stimolante spray e ossigeno se broncospasmo grave
il paziente presenta broncospasmo a riposo
PEFR o FEV1 < 70 % del predetto
< 80 % dei valori usuali
(in tal caso test di reversibilità)
Slide86: Anche il test della corsa libera è risultato valido e ripetibile, con il limite delle condizioni ambientali ( temp. 20-24°C,umidità relativa < 40%)
Exercise-induced bronchospasm in children: comparison of FEV1 and FEF25-75% responses: Exercise-induced bronchospasm in children: comparison of FEV1 and FEF25-75% responses Fonsega-Guedes, Pediatr Pulmonol 2003 FEF(25-75%) can decrease in response to exercise without changes in FEV(1), mainly in children with mild asthma
Slide89: EIB 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.
Slide90: Value of surrogate tests to predict exercise-induced bronchoconstriction in atopic childhood asthma
Lex, Pediatr Pulmonol 2007 All 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%.
Slide91:
Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthma
Nishio K,J Asthma 2007 Not 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
Slide92: Asma bronchiale negli atleti Percorso diagnostico per le Olimpiadi di Atene Test di broncostimolazione positivo
1) test metacolina:PD20 < 200 mcg
2) 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
Slide93: 6min of hyperpnoea
dry air
4.9% CO2
10% fall in FEV1
Specific for diagnosis of EIA (Rundell et al. 2004)
Recommended by the IOC EUCAPNIC VOLUNTARY HYPERVENTILATION
Slide94: IBAs USE SYDNEY vs ATHENS SYDNEY 2000 ATHENS 2004
(notified) (approved)
NOC IBAs PERCENT IBAs PERCENT
NZL 31 21.1% 11 11.3%
AUS 128 20.7% 65 13.7%
UK 62 19.9% 62 23.3%
USA 112 18.9% 50 9.1%
CAN 55 18.6% 11 4.1%
FIN 10 14.3% 4 6.6%
Anderson et al. submitted
Slide95: Per avviare il bambino asmatico allo sport Attuare la prevenzione non farmacologica
Slide96: EIA: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.
Slide97: EIA:terapia non farmacologica A special warm-up routine has been shown to reduce the severity of EIA
Slide98: EIA:terapia non farmacologica ALLENAMENTO INTERMITTENTE
Esecuzione,durante il preriscaldamento,di sprint brevi(10-12),della durata di 20-30 secondi,intercalati da periodi di recupero di 1-2 min,per indurre refrattarietà all’EIA senza provocare broncoostruzione clinicamente significativa FRANÇOIS-PIERRE COUNIL, J Pediatr 2003
Slide99: ASMA DA SFORZO (EIA) - ALLERGIA infiammazione reattività
bronchiale
aspecifica sforzo aumento
EIA
Slide100: ASMA DA SFORZO ED INQUINAMENTO ATMOSFERICO Bronchoconstriction in asthmatics exposed to sulfur dioxide during repeated exercise.
Roger
J.Appl.Physiol. 1985 Distribution of specific airway resistance (sRaw; cm H2O - s) in
asthmatic subjects exposed, during exercise, to air (0.0 ppm) or
SO2 (0.25, 0.5, and 1.0 ppm)
Slide103: Fish Oil Supplementation Reduces Severity of Exercise-induced Bronchoconstriction in Elite Athletes
Mickleborough, American Journal of Respiratory and Critical Care Medicine 2003
Supplementing the diet with n-3 PUFA represents a potentially beneficial treatment for elite athletes with EIB.
Slide104: Per avviare il bambino asmatico allo sport Pianificare la protezione farmacologica
TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO: TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazione
ß2-agonisti
Cromoni
Montelukast
TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO: TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO 2. Terapia di fondo
Steroidi inalatori
Montelukast
TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO: TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazione
ß2-agonisti
Cromoni
Montelukast
Long-acting beta-agonists: Long-acting beta-agonists Prevention of EIA in pediatric asthma patients: a comparison of two salmeterol powder delivery devices. Bronsky,Pediatrics 1999
Evidence of the rapid protective effect of formoterol dry-powder inhalation against EIA in athletes with asthma. Ferrari, Respiration 2000
ß2-Agonist Tolerance and EIB: ß2-Agonist Tolerance and EIB
Hancox RJ, AJRCCM 2002 (salbutamol)
Nelson JA, NEJM 1998 (salmeterol)
Garcia R, J Invest All Clin Immunol 2001 (formoterol)
Slide110: Nelson et al., NEJM 1998 Asma da esercizio fisico
L’effetto del salmeterolo e la sua durata si attenuano col trattamento cronico
Risposta alla metacolina L’effetto protettivo del salmeterolo si riduce nel tempo: Risposta alla metacolina L’effetto protettivo del salmeterolo si riduce nel tempo Cheung et al AJRCCM 1998
Slide112: Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise induced asthma
Simons, Pediatrics 1997;99:665 SLM 50 mcg once daily vs PL+ daily inhaled steroids
therapy
Exercise at 1 and 12 hours
after drug, on day 1 and 28
The duration of the broncho-protective effect decreases
during regular treatment with salmeterol despite concomitant use of inhaled steroids Mean Fall FEV1 % P = 0.0001 P = 0.0002 P = 0.0002 ns 1 day 28 day
TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO: TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO Premedicazione
ß2-agonisti
Cromoni
Montelukast
Slide114: 51%
TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO: TERAPIA E PREVENZIONE DELL’ASMA DA SFORZO 2. Terapia di fondo
Steroidi inalatori
Montelukast
Slide116:
Bambini 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.
Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction Koh, Cochrane Database of Systematic Reviews 2007 : Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction Koh, Cochrane Database of Systematic Reviews 2007 Inhaled corticosteroids used for 4 weeks or more before exercise testing significantly attenuated exercise-induced bronchoconstriction four trials involving children
Slide118: JACI 2007 In asthmatic patients ICSs not only attenuate exercise-induced bronchospasm but also improve arterial blood oxygenation during exercise
Slide119: J ALLERGY CLIN IMMUNOL MAY 2006 50%
Slide120: 51%
New Treatments for Exercise-induced Asthma : MONTELUKAST: New Treatments for Exercise-induced Asthma : MONTELUKAST Montelukast for the treatment of mild asthma and EIB
Leff, NEJM 1998
Slide122: Montelukast for the treatment of mild asthma and EIB
Leff, NEJM 1998
Montelukast inhibits EIB in 6-to 14-year-old children with asthma Kemp, J Pediatr 1998
Montelukast versus salmeterol in patients with asthma and EIB Villaran, JACI 1999
Comparison of montelukast versus budesonide in the treatment of EIA Vidal, AAAI 2001
Montelukast compared with salmeterol to prevent EIB
Edelman,Ann Intern Med 2000
Comparative effects of LABA and INI-LT on EIB
Coreno, JACI 2000
Slide123: % drop FEV1 p<0.001 p<0.001 Week 4 Day 3 Basal Montelukast 10 mg od
Salmeterol 50 mcg bid ns Week 8 Montelukast vs salmeterol in patients with asthma
and exercise-induced bronchoconstriction
Villaran, J Allergy Clin Immunol 1999;104:547 197 patients, 15-45 yrs
Mild asthma
MNT or SLM for 8 wks
Exercise challenge
at definite times
20-24 h after dosing
The effect of montelukast
was greater than salmeterol
over a period of 8 weeks
Prolonged Effect of Montelukast in Asthmatic Children With EIB, Pediatr Pulmonol, 2005: Prolonged 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
Prolonged Effect of Montelukast in Asthmatic Children With EIB Kim Pediatr Pulmonol, 2005: Miglioramento significativo per tutti i parametri considerati
Massima caduta di FEV1
Score sintomatologico
Tempo di recupero
Nel gruppo crossover, dopo 8 settimane di washout, tutti i parametri rimanevano persistentemente e significativamente migliorati rispetto ai valori basali Prolonged Effect of Montelukast in Asthmatic Children With EIB Kim Pediatr Pulmonol, 2005
Slide127: Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma Stelmach, JACI in Press
Slide128: Montelukast administered in the morning or evening to prevent exercise-induced bronchoconstriction in children
Montelukast, taken for 2 weeks, is equally effective in exercise-induced bronchoconstriction when dosing either in the morning or in the evening
Pajaron-Fernandez, Pediatr Pulmonol 2006
Slide129: A 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. Bronchoconstriction
provoked by exercise in a high-particulate-matter environment
is attenuated by montelukast. Inhal Toxicol 2005;17:99–105.
STEP 2 : Adulti: STEP 2 : Adulti Nei 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 principale
Alcuni 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)
Slide131: Montelukast does not affect exercise performance at
subfreezing temperature in highly trained non-asthmatic
endurance athletes
Sue-Chu Int. J. Sports. Med. 2000; 21: 424 Compared to placebo, montelukast did not increase physiologic performance variables, or increase the mean running time to exhaustion
these findings do not suggest the need for disallowing the use of this drug by asthmatic athletes.
Slide133: OLYMPIC MOVEMENT ANTI-DOPING CODE
APPENDIX A
PROHIBITED CLASSES OF SUBSTANCES AND PROHIBITED METHODS
1 January 2003
I. PROHIBITED CLASSES OF SUBSTANCES b
Prohibited substances in class A.b include the following examples with both their L and D-isomers
formoterol***, 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.
Corticosteroidi Norme WADA - CIO: Corticosteroidi Norme WADA - CIO
Assolutamente vietati
per via sistemica
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Ammessi solamente per via inalatoria per la terapia dell’asma bronchiale e delle allergopatie
CONTROINDICAZIONI: CONTROINDICAZIONI Uso di respiratori subacquei
Attività fisica in alta quota
Sport motoristici
Asma grave persistente
What About More Information?: What About More Information? macottini@alice.it