Marcello Cottini Asma da

Sp. Immunologia Clinica

Allergologia esercizio fisico
Pneumologia
Bergamo

CORSO DI AGGIORNAMENTO
“I FENOTIPI DELL’ASMA’ ”
Arenzano 16 Febbraio 2008
 Exercise-induced
bronchospasm:
a different phenotype?
 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!
 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
Exercise-induced asthma (EIA), connotes transient
airflow obstruction associated with physical
exertion.
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
 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

DURING or AFTER ???
 The bronchospasm can occur also
during the exercise, especially during
prolonged exertion

Godfrey S, Bar-Yishay E, Exercise induced asthma revised, Respiratory Medicine 1993

 Asma da
esercizio
fisico
Aumento della
resistenza
inspiratoria (RLI)
durante e dopo
esercizio
prolungato
Suman et al., JAP 1999
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

Exercise-induced vocal
cord dysfunction
Pseudo-asthma: when cough, wheezing,
and dyspnea are not asthma.
Weinberger, Pediatrics Oct 2007

Exercise-induced vocal
cord dysfunction
 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
 Rahidi
Rashidi Wheeler morto per asma Wheeler
sul campo 03.08.01
 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

 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.
 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

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

 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!
 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 asthma

15 – 14%
579 ch.<12 yrs
playing
10 –
baseball
or soccer
5 –
80/579
Parents
reported
0
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

% of asthmatic children reporting to have

ready available a rescue medication
25 –
22%
579 ch.<12 yrs 20 –
playing
15 –
baseball
or soccer 10 – 18/80
Parents 5 –

reported 0
asthma
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
 For many years, it was generally assumed that this was
EFFECT OF EXERCISE TYPE
because the severity of exercise was also different.

Free-range running
Frequency and Severity ( 47% PEF )

of EIA Running on a treadmill

( 33% )
Cycling ( 25%)

Swimming,kayaking,walking (  15%)
Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976
 For many years, it was generally assumed that this was
EFFECT OF EXERCISE TYPE
because the severity of exercise was also different.

Free-range running
Is the increase in ventilation produced
Frequency and Severity
by exercise and not the kind of exercise
( 47% PEF )
that is crucial in EIA
of EIA Running on a treadmill
Any exercise can lead to EIA if ( 33% )
it is performed hard enough or
Cycling ( 25%)
long enough to increase the
amount of air being inhaled
Swimming,kayaking,walking (  15%)
Anderson, Br J Dis Chest 1975 ; Fitch, JAMA 1976
 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
Higher rates of hay fever.

Adverse effects on
the Clara cell
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.
Indoor swimming pools, water chlorination
and respiratory health

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
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.
Exercise-induced
Asthma :
Symptoms
Symptoms of EIA
Symptoms of EIA

può manifestarsi come

dolore toracico
Nudel Clin. Pediatr.
1987; 26: 388
 CHEST PAIN IN CHILDREN: DIAGNOSIS THROUGH
HISTORY AND PHYSICAL EXAMINATION
Evangelista JA, JPHC 2000; 14: 3

80 – 76%
 50 ch. 70 –
Chest pain in children
referred for 60 –
is rarely of
chest pain 50 –
cardiac origin
40 –
 Physical 30 –
examination 30 –
and ECG 20 – 12%
10 – 8% 4%
0 –
musculo- EIB gastric psycogenic
skeletal problem
pain
Exercise-induced
Asthma :
Pathophysiology
 Exercise-induced Asthma :
Pathophysiology

AIRWAY REWARMING HYPEROSMOLARITY

THEORY THEORY
 RESPIRATORY WATER LOSS

MUCOSAL COOLING MUCOSAL DEHYDRATION

VASOCONSTRICTION INCREASED OSMOLARITY

RAPID REWARMING MEDIATOR RELEASE

OF AIRWAYS

VASCULAR SMOOTH MUSCLE

ENGORGEMENT,EDEMA CONTRACTION, EDEMA

AIRWAY NARROWING
Anderson EJRD 1982; 63: 459 - Mc Fadden J. Clin. Invest. 1986; 78: 18
Anderson All. Proc. 1989; 10: 215
Increased urinary excretion of LTE4
after exercise

Reiss TF, Thorax 1997

Exhaled breath condensate cysteinyl leukotrienes are
increased in children with exercise-induced
bronchoconstriction

Maximal FEV1
decrease after
exercise in asthmatic
children with EIB at
baseline and after 3
days of treatment with
montelukast

Carraro S, JACI 2005

 Mechanisms Underlying the
Definition of Asthma
Risk Factors
(for development of asthma)

INFLAMMATION

Airway
Hyperresponsiveness Airflow Obstruction

Risk Factors Symptoms

(for exacerbations)
 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 defined as skin test reactivity may contribute to the

development of EIB in asthma, indipendently of AHR to metacholine
Exhaled breath condensate cysteinyl leukotrienes are
increased in children with exercise-induced
bronchoconstriction

Cys-LT levels in
EBC of asthmatic
children with EIB,
asthmatic children
without EIB, and
healthy control
children

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.

Anderson SD, Curr Allergy Asthma Rep. 2005 Hallstrand TS, J Allergy Clin Immunol. 2005
 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

The release of MUC5AC may be

mediated by the cysLT-associated
activation of sensory airway nerves
containing NKA
Mucus plugging in fatal asthma

Mucus plugs
Athletes and exercise-induced
bronchoconstriction

Same inflammation ??
 JACI , June 2007

EIA 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”.
Exercise-induced
Asthma :
Prevalence
Up to 90% of subjects with
asthma will have EIB

Mc Fadden ER, NEJM 1994

 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
KEEPING CHILDREN WITH EXERCISE-INDUCED
ASTHMA ACTIVE Milgrom H Pediatrics 1999; 104 :38

100 -
90 -
% subjects with EIB 90%
80 -
70 -
60 -
50 -
40 - 40%
30 -
20 -
10 - 6-12%
0
General Rhinitis Asthma
population
subjects with
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
FAMOUS ATHLETES WITH ASTHMA
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

Physical activity is associated

with a slower decline in
pulmonary function and with
lower mortality

Pelkonen M, AJRCCM 2003

 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
Exercise-induced
Asthma :
diagnosis
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

Asthma and EIA
Total identified by 49 (6.5%)
801 questionnaire
student 46 (5.7%)
athletes

remaining 755 Identified by

free running test
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

DIFFERENCES BETWEEN CHILD AND PARENT REPORTS
OF SYMPTOMS AMONG CHILDREN WITH ASTHMA
Lara M Pediatrics 1998; 102 : E68
% Ch
50 - Parents
 97 ch. with 47% 45%
asthma 40 - 35% 35%
30 -
 child and
20 - 20% 17%
parent
interviews
10 -
 exercise test 0
NEVER OCCASIONALLY ALWAYS
WHEEZING
REPORTED WHEEZING DURING EXERCISE
History and/or p.e. compatible
with EIA

Spirometry (FEV1 reversibility > 12%)

Tan RA, Ann Allergy Asthma Immunol 2002

 History and/or p.e. compatible
with EIA

Spirometry (FEV1 reversibility > 12%)

+
Treat as ASTHMA

Tan RA, Ann Allergy Asthma Immunol 2002

 Pulmonary Function Tests

• Flow-volume loop demonstrates flattened

inspiratory loop when symptomatic.

Normal VCD
 History and/or p.e. compatible
with EIA

Spirometry (FEV1 reversibility > 12%)

+
Treat as ASTHMA -
MC challenge; Trial with ß2-agonists
Exhaled nitric oxide
+
Treat as EIA

Tan RA, Ann Allergy Asthma Immunol 2002

 History and/or p.e. compatible
with EIA

Spirometry (FEV1 reversibility > 12%)

+
Treat as ASTHMA -
MC challenge Trial with ß2-agonists
- + +
Exercise Treat as EIA Treat as EIA
+ -
Treat as EIA Other diagnoses Tan RA, Ann Allergy Asthma Immunol 2002
 Per avviare il bambino
asmatico allo sport

Valutare il bambino
mediante test da
sforzo
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
Tapis Roulant Bicicletta

• Ventilazione aumenta di • Non ha velocità e

più, bronco-ostruzione inclinazione, solo carico di
facile (V’O2 +10%) lavoro (workload)
• Per qualche paziente più • Preferibile per pazienti
facile da eseguire. con difficoltà di
camminare/ correre
• Più difficile determinare • Facile determinare
intensità (watt) intensità (watt)
 EXERCISE TESTING
5

4
Normal subject
FEV1 in Litres

3
Drop in FEV1  10% = positive test

2 Asthmatic patient
Spirometry
Exercise
1
0 8 14 20

Time in Minutes
EIB after different exercise loads

130
85% load
95% load
120

FEV1 % predicted
110

100

90

80
Salbutamol
inhalation
70 Exercise

-6 0 3 6 10
Minutes

Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94: 750-755

EIB after different exercise loads

130
The most specific test is to85%
test
load the
95% load
athlete in the field in
120
their sport;
This is more specific110than exercise

FEV1 % predicted
testing in laboratory (but temperature
and humidity cannot be100 controlled with
exercise in the90 field).

80
Salbutamol
Rundell, Med Sci sports
70
Exerc
Exercise
1999 inhalation

-6 0 3 6 10
Minutes

Carlsen KH, Engh G, Mørk M. Respir Med 2000; 94: 750-755

 ASMA DA SFORZO – PRECAUZIONI

 non eseguire il test se:

 il paziente presenta broncospasmo a riposo
 PEFR o FEV1 < 70 % del predetto
< 80 % dei valori usuali
(in tal caso test di reversibilità)

 presenza del medico per tutta la durata del test

 cardiomonitor
 somministrare 2 stimolante spray e ossigeno se
broncospasmo grave
 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

FEF(25-75%) can decrease in response to

exercise without changes in FEV(1), mainly
in children with mild asthma

Fonsega-Guedes, Pediatr Pulmonol 2003

 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.
 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%.
 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
 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
EUCAPNIC VOLUNTARY
HYPERVENTILATION

• 6min of hyperpnoea
– dry air 50
– 4.9% CO2

% Fall in FEV1
40

• 10% fall in FEV1 30

20
• Specific for diagnosis of EIA
(Rundell et al. 2004) 10

0
• Recommended by the IOC n = 22

6 min 6 min
EVH Exercise
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

 Per avviare il bambino
asmatico allo sport

Attuare la
prevenzione non
farmacologica
 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.
 EIA:terapia non farmacologica

A special warm-up routine has been shown

to reduce the severity of EIA
 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 FRANÇOIS-PIERRE COUNIL,
refrattarietà all’EIA senza J Pediatr 2003
provocare broncoostruzione
clinicamente significativa
 ASMA DA SFORZO (EIA) - ALLERGIA

esposizione
allergeni

aumento
EIA
 infiammazione

sforzo  reattività
bronchiale
aspecifica
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)
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.
 Per avviare il bambino
asmatico allo sport

Pianificare la
protezione
farmacologica
 TERAPIA E PREVENZIONE
DELL’ASMA DA SFORZO
1. Premedicazione

• ß2-agonisti
• Cromoni
• Montelukast
 TERAPIA E PREVENZIONE
DELL’ASMA DA SFORZO
2. Terapia di fondo

• Steroidi inalatori
• Montelukast
 TERAPIA E PREVENZIONE
DELL’ASMA DA SFORZO
1. Premedicazione

• ß2-agonisti
• Cromoni
• Montelukast
 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

• Hancox RJ, AJRCCM 2002 (salbutamol)

• Nelson JA, NEJM 1998 (salmeterol)

• Garcia R, J Invest All Clin Immunol 2001

(formoterol)
 Asma da esercizio fisico
L’effetto del salmeterolo e la sua durata si
attenuano col trattamento cronico

Nelson et al., NEJM 1998

 Risposta alla metacolina
L’effetto protettivo del salmeterolo si
riduce nel tempo

Cheung et al AJRCCM 1998

 Tolerance to the bronchoprotective effect of salmeterol
in adolescents with exercise induced asthma
Simons, Pediatrics 1997;99:665
• SLM 50 mcg once daily vs
Placebo Salmeterol
PL+ daily inhaled steroids
40
therapy

P = 0.0001
• Exercise at 1 and 12 hours
35

P = 0.0002

P = 0.0002
30
after drug, on day 1 and 28 25
20

ns
15
10
5

The duration of the broncho- 0

protective effect decreases -5

-10 AM PM AM PM
during regular treatment with
salmeterol despite
1 day 28 day
concomitant use of inhaled
steroids
 TERAPIA E PREVENZIONE
DELL’ASMA DA SFORZO
1. Premedicazione

• ß2-agonisti
• Cromoni
• Montelukast
51%
 TERAPIA E PREVENZIONE
DELL’ASMA DA SFORZO
2. Terapia di fondo

• Steroidi inalatori
• Montelukast
 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

four trials involving children

Inhaled corticosteroids
used for 4 weeks or more
before exercise testing
significantly attenuated
exercise-induced
bronchoconstriction
 In asthmatic patients ICSs not only attenuate
exercise-induced bronchospasm but also improve
arterial blood oxygenation during exercise

JACI 2007
 50%

J ALLERGY CLIN IMMUNOL MAY 2006

51%
 New Treatments for Exercise-induced
Asthma : MONTELUKAST

Montelukast for the treatment of mild asthma and EIB

Leff, NEJM 1998
• 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
 Montelukast vs salmeterol in patients with asthma
and exercise-induced bronchoconstriction
Villaran, J Allergy Clin Immunol 1999;104:547

• 197 patients, 15-45 yrs 30

Montelukast 10 mg od
• Mild asthma Salmeterol 50 mcg bid
% drop FEV1
• MNT or SLM for 8 wks
• Exercise challenge 25 p<0.001
ns p<0.001
at definite times
20-24 h after dosing
20

The effect of montelukast

was greater than salmeterol15
over a period of 8 weeks Basal Day 3 Week 4 Week 8
 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
 Effect of different
antiasthmatic
treatments on
exercise-induced
bronchoconstriction
in children with
asthma
Stelmach, JACI in Press
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

 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

• 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)
 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.
 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.
Concentrazioni urinarie al di sopra delle quali un
laboratorio accreditato dal CIO deve dichiarare i
risultati

• Salbutamolo > 1000 ng/ml

• Efedrina > 10 ng/ml
• Metilefedrina > 10 ng/ml
• Catina > 5 ng/ml
• Pseudoefedrina > 25 ng/ml
• Fenilpropanolamina > 25 ng/ml

• *Dal 2004 pseudoefedrina e fenilpropalanina non sono proibite

ma incluse nel programma di monitoraggio WADA
 Corticosteroidi
Norme WADA - CIO

Assolutamente vietati
per via sistemica
-------------------------

Ammessi solamente per via inalatoria per la

terapia dell’asma bronchiale e delle
allergopatie
 CONTROINDICAZIONI

• Uso di respiratori subacquei

• Attività fisica in alta quota
• Sport motoristici
• Asma grave persistente
What About More Information?

 macottini@alice.it