...........

To::orol, a new long-acting bronchodilator for inhalation

P. Arvidsson, S. Larsson, C-G. Lofdahl, 8. Melander, L. W~hlander , N. Svedmyr

11 1WW long-acting bronchodilaror for inllalario11. P. 1\rvidsson, S. Depts of Pulmonary Medicine and Qinical Phar·
LOfdalll, B. Melandcr, L Wdlrlan.dt~r, N . Svedmyr. macology, Golhenburg University, Medical Dept,
T he aim or thJs s tudy was to evaluate If treatment with Inhaled CIBA-Geigy, Sweden.
Is appreciated by a.~tbmat lcs a nd whether lt ClHL'>CS taclty-
Conespondence: C-G. Lofdahl, Re~stromska
T wenty s!Jtble asthmatics wen Included In a r nndomlzed , Hospital, Box 17301, S-40264 Goteborg,
nd, crossover s tudy. They were treated for two weeks either with Sweden.
or snlbutamol, with one week washo ut lnbetween. T hey were
rormoterol or 200 Ill salbutamol twlc:e d ally and Instructed to Keywords: Aslhm a; fonnotcrol; salbutamol;
fdd.IUOn,ru sp ray doses on demand. On a diary card they recorded the symptom score; visual analogue scale.
o( doses, asthma symptoms and pea k expiratory now rule (PEFR)
e-very dose. For cr.d expiratory volume In one second (FEV 1) dose- Received: April, t989; accepted after revision:
curves ror salbutamol (total dose 1.3 mg) we re perrol'!11ed before November 10, 1988.
eac h treatment perlod to evaluate development or tachyphytuxls.
a !ilgnlnt'8nt di fference In favour o f rormoter ul concerning
P£ FR recordi ngs, s pray consumption, and prefllrence. Flneen
nr•• r.. rrHI rormoterol and twosalbutamot. The dose-response curves
'"· - "'"•"' and before, as well as after salbutamol were utmost
rormoterol the curve had changed ; both basal and ma:<t·
we re higher than before. Thus, no evidence Cif tachyp hylaxis
compared to the ordinary B-stimulant treatment.
f .. 1989, 2, 325-JJO,

nrmn•,.•·n• fumarate (BD-40A, YM-0 8316) is a new
~noc:cptor agonist which has been found in vitro
l 50 limes more potent than salbutamol on
smooth muscle (1, 2] and at least as 6-f
salbutamol and terbutaline [2]. In vivo am•
gave similar results [3, 4].
1986, formoterol has been registered for oral
on in Japan. However, as an inhalant this
has not been tested in Japan.
~ier ~tudy performed in Sweden has shown that
Jnhalcd, the potency of fonnotcrol is 5-15 Limes
or salbu~nmol , according to a double-blind, cumuJa·
~c:-rcsponse study, and studies in West Germany
Slf!lllar results rs, 6]. Mosl important, however, is
mg that the duration of effect or inhaled fomlOt·
is much longer than after equipotent doses of
Eight hours after administration, forced
. volume in one second (FEY,) was still sig-
•ncrcased compared with the basal value. and
approximately 75% of the maximum FEY 1 value.
lnhalnt•on of salbutamol, FEY , returned to the basal
afler <•pproximately 4 h (5, 61. In other studies. a
eftect nfter a single dose of inhaled forrnotcrol
shown after 12 h [7, 8).
prolonged bronchoclilating effect of inhaled
~ 11 "da'
Oter·nl , which has been demonstrated in studies over
Y ~n~er laboratory conditions, may be of great
81&n•ficance. The aim of the present study was
lO deJ.ennine whet11er patients would notice the prolonged
effect and appreciate it when formoterol was given in a
controlled study over a longer pcciod of time. We also
studied whether this long-lasting stimulation of the .131
adrenoceptors of the bronchi led to development of
increased tachyphylaxis during two weeks of treatment,
compared to their ordinary treatment with an inhaled 131 -
stimulant.
Patients
Twenty one patients with non-allergic bronchial asthma
using Bz·agonists by inhalation at least three times daily
were included in the trial. A reversibility of FEY 1 of at
least 20% after inhalation of a 131 -agonist was required on
the first day of the investigation. One patient was ex·
eluded as his reversibility was less than 20%. Twenty
patients are thus presented (table 1). Treatment with
lheophyUincs, inhaled steroids and inhaled anticholiner-
gics in unchanged dosage was allowed during the trial.
Oral 131 -agonists we~ withdrown. Thirteen patients used
oral theophylline, fifteen patients i nh:~ lcd corticostcroids
and two patients inhaled anticholincrgics.
Pregnant women, patients with serious diseases and
asthmatics on oral steroids or B-bloc.kers were excluded
from participation. Patients who were considered unable
to comply with the study protocol were not included.
326 P. ARV!DSSON ET Al.

Table 1. - Patient characteristics (n-20)
Mean Range
48 43~6
Age yrs
Duration of disease yrs 16 2-42
Basal FEY1 % predicted 44 14-78
Reversibility % 44 20-80
Seventeen of the patients were men and five were smokers.
Three patients had hypertension treated with diuretics or vera-
pamil. One patient had experienced slight cardiac decompensa-
tion, treated with a diuretic. FEY1: forced expiratory volume in
one second.
Methods
The study was carried out as a randomized, double-
blind crossover study with two weeks of treatment with
either inhaled salbutamol or inhaled formoterol and with
a washout period. of one week between treatment peri-
ods. The patients were examined before and after each
treatment period, with FEV1 dose-response curves for
salbutamol to evaluate tachyphylaxis. During the treat-
ment periods peak expiratory flow rate (PEFR) was
recorded by the patients themselves before each dose of
the study medication. They also recorded on a diary card
additional doses of the tested drugs and symptom scores.
Asthma symptoms were also recorded using visual ana-
logue scales at each visit, when side-effects were also
recorded. At the last visit, the patients were asked about
their treatment preference.
The study was approved by the Ethical Committee at
the University of Gothenburg.
mini peak_-flow ~eter was used. The patients were
thorough InStructions about the recording technique.
best of two values was recorded on a diary cant ln
way every additional dose was recorded. The vat
the last 10 days of each treatment were evalua~
Continuous recording of symptoms
The patients made subjective recordings of lhe
ity of their asthma every morning and evening on
diary card by using a four-grade scale:
0 = No symptoms, undisturbed sleep;
1 = Mild asthma, symptoms not interfering with
or sleep;
2 = Moderate asthma, symptoms only slightly .....,11arm
with activities and sleep;
3 = Severe asthma symptoms making daily ooutvtliiMII
impossible and seriously disturbing sleep.
Recordings made during the 10 last days of the
ment periods were used for the calculations.
Visual analogue scales
Before and after each treatment period the patients
asked about their subjective view of symptoms
duration of effect of the sn1dy medication. Visual
logue scales were used for this investigation. The
tients were asked to give their answers by
on a lOO mm long horizontal line. Separate
paper were used for each question. The four l•u~:.:~u~~J~t.;
asked are presented in figure 1.
Further interviews

PEFR values and need for additional doses ofbronchodi-
lators
PE~ was measured every morning and evening dur-
ing the study before lhe prescribed study medication was
taken. Recordings were also made before every addi-
tional dose (two puffs) of the study medication. A Wright
At each visit the patients were asked for any
effects that they considered attributable to the tested
They were also asked to give their opinion ,.,...,N•mnrw.-:
the duration of the effect by using a five-grade scale
the following alternatives; 0-2 h, 2-4 h, 4-6 h, 6-8 b.
and more than 8 h. At the last visit the patients welt
asked which treatment period they preferred.

How has your asthma been during the last 2 weeks,

compared with what lt Is usually like?

Much worse 1--------------------1 Much better

Have you had problems with shortness of breath
during the last 2 weeks?
A lot 1--------------------1 Not at all
How have you slept during the last 2 weeks?

Very badly Very well

How long-lasting has the effect of the spray been
during the last 2 weeks?

Very short Very long

Fig. I. - Visual analogue scales {0-1 00 mm).

 FORMOTEROL: A NI!W INHALED DRONCHOOILATOR 327

dose with a Yitalograph spirometer. The best of three

patieniS were treated with either salbut.amol from
8 erosol delivering I 00 ).1.8 per puff or formoterol
. Two puffs were given regularly morning
A spacer, Volumatic4P, was used for the
The patients were taught the correct inhala-
ue by an experienced assistant The patients
msiiJU~··"" to use additional inhalations when needed.
the washout period, the patients used their ordi-
medication.
studY the possibility of tachyphylaxis of the bron-
enCICCJ>tor·s, FEY1 dose-response curves for
butamol were recorded before and after each
period. The patieniS were asked to absmin
.......-,~ bronchodilators during 12 h before the dose-
tests and from oml theophyllines for 36 h before
They arrived at the laboratory at 7.30 am after
breakfast without coffee or tea. The patients rested
for 50 min and. basal values for FEYl were then
Two measurements were made wtth 20 rnin
Salbut.amol was then given in three doses
300 and 900 ).l.g, respectively) at intervals of 20
The inhaled doses were given by a dose aerosol
to a V olumatic~ spacer. Only 100 ).l.g salbutn-
cet(:asc:a illlo the space before each inhalation.
unrmJauorts were supervised by an experienced assis-
and the patient's mouth was rinsed with water after
inhalation. FEV 1 was recorded 12 min after each
values was used for calculations. lf the patient could not
abstain from inhaled bronchodilators during the night
before !he test, this was postponed.
Statistics
The results were analysed with regard to interactions,
period and treatment effects according to Hiu..s and
ARMrrAGE (9]. Thus, while all the results given are
based on the actually recorded unadjustcd figures, the
p-values presented for treatment effects ore adjusted for
period effects. Wilcoxon's mid rank-sum test was used
for comparisons between the sequences and p <0.05 was
chosen as the level of significance. The SAS programme
package was used for all the calculations.
Results
PEFR measurements
The highest and lowest PEFR values on each treat-
ment day were used in the calculation of data presented
in table 2. The table presents mean values for lhe last 10
days of each treatment period. Maximum and minimum
values were significantly higher during formoterol
treatment and the difference between maximum and
minimum values decreased significantly during formot-
erol treatment, showing a decrease in diurnal variation
during that treatment.

Table 2.- Daily PEFR values, number of additional doses and symptoms, during salbutamol and
formoterol treatment periods (mean±sEM)

Salburamol Formoterol Significance

Daily PEFR /·min·1 Maximal 344±22 357±21 p<0.05

Minimal 287±21 320±22 p<O.Ol
"Diurnal variation" 57±8 37±4 p<0.02

Additional doses Day ).55±0.33 0.78±0.32 p<0.001

(2 puffs each) Night 0.39±0.10 0.15±0.07 p<0.05
Total 1.94±0.35 0.92±0.33 p<O.Ol

Symptom score (0-3) Day 1.11±0.17 0 .77±0.13 p<0.05

Night 1.12±0.18 0.62±0.16 p<0.001
Total 1.11±0.16 0.69±0.14 p<O.Ol

Visual analogue scales (0-100 mm)

Asthma severity 55±5 71±3 p<O.Ol

Shortness of breath 52±5 74±4 p<O.OOl

Quality of sleep 64±6 77±5 p<0.05

Duration of
spray effect 55±4 78±3 p<O.OOl

PEFR: peak expiratory flow rate.

 328 P. ARVIDSSON ET AL.

Additional doses Durcstion of effect

Besides the regular inhalations of 2 puffs b.i.d. the
patients took. on average, 2 additional puffs 1.9 times
during 24 h when treated with salbutamol, whereas their
average number of additional dosage occasions during
24 h was 0.9 with formoterol. The number of additional
doses (2 puffs each) both at night and day was signifi-
cantly smaller during the formoterol treatment period
(table 2).
Symptom evaluation
The patient's awn opinion concerning the
..u~.....
effect of the tested drugs was estimated using -both···
analogue scales and a fi ve-grade scale. Acco~:ding
vL~ual analogue scales. the patients experienced
cantJy longer duration of effect with formotcrol
salbutnmol (table 2). There was also a significant
ence in favour of formoterol when the five-grade
was analysed (table 3). During formot.erol treatment,
patients estimated the duratiOn to be more lha:n
whereas during salbutamol treatment only three P3tillllfi!411
gave the same estimate.

Mean values for each patient during the last 10 days of

each treatment period were used for calculations of the Side-effects
values presented in table 3. When treated. these patients
had mild symptoms. reflected in low symptom scores. The patients had only slight complajnts. One
During both day and night. the symptom scores were on salbutamol complained of slight
significantly better dwing the formoterol lreatmenL pe- tachycardia, and another patient on salbutamol of
riod. The effect was most pronounced at night. ncss and coughing. On formoterol one patient cornpiJliftl•
of dryness of the mouth in the morning.
Table 3. - Subjective evaluation of spray
duration (number of patients)
Preferences
Spray duration Salbulamol Formoterol
After the last treatment period. we asked the
0- 2 h 1 0 which of the two treatment periods they preferred_.
2-4 h 6 1
4-c6 h 6 3 teen patients preferred the fonnoterol treatment
6-8 h 4 8 two patients preferred the salbutamol period and
>8 h 3 8 patients could not state a preference (p<O.O I).

Differenc e between drugs (p<O.OOl).

Mean values for visual analogue scale recordings before
and after each treatment are presented in table 2. The
parameters, asthma severity, quality of night sleep, and
breathlessness were significantly better during formot-
erol treatment.
Studies of tachyphylaxis.
Figure 2 shows the mean FEV1 dose-response curvetl•
for 20 patients. The curves before and after the ~alb•il.l
mol treatment period are almost identical, showing
indication of a change in the 62-adrenoceptor resJpoll~!l

FEV
2.2
1 Salbutamol Formoterol

1.7

1.2
0 100 400 1300 0 100 400 1300
Cumulative dose (J.!Q)
Pig. 2. - Mean dose-response curves for cumulative doses of s~Jbutamol perfonned before (o ) and after (•) 2 weeks of trealtllent
with salbutamol or fonnoterol. FEV 1: forced expiratol}' volume in one second.
 FORMOTEROL: A NP.W INHALP.D BRONCHODILAT0R
thl} fomlotcrol treatment period lhc FEY, curve
approximately the same level as the curves re-
before and after the salbutamol treatment period.
treatment for two weeks with fonnoterol both tlte
and maximal FEY, value were higher than the values
before the fonnotcrol treatment pedod. TI1Us,
was no indication that fonnoterot produced a more
Ulchyphylrutis to B2 -adrcnoceptor stimulation
bronchial muscle of asthmatics than the B'l·
agonists normally used. e.g. salbutamol.
stuctied separately the live patients who were
with inhaled corticosteroids. Their dose-
curves showed the same pattcm as those of the
group, i.e there was no indication of tac.hyphy-
ln thl'se patients either.
Discussion
study has demonslrated that the prolonged effect
formoterol shown in acute studies is also
longer periods or clinical use. The pa-
the long duration of effect and stated !hat
lasted considerably longer than that of salbu-
also noted the longer duration of action or
os a need for fewer additional inhalations.
patients included in this study had moderate to
severe asthma as evidenced by basal FEY, values,
no bronchodilators had been given since the previ-
No patients with the most severe form of
ipated, as patients on oral steroids were not
The reason for their exclusion was the diffi-
ot studying patients with very severe asthma. as
rend to be unstable and unable to complete a
study. This means, however. that we do not
whether patients with more severe asthma will find
as advantageous as the patients in the present
lll'nranht~ilators with a prolonged effect on the bron-
.::~tt,r.•n.nr~>ntnr~may involve a greater risk of
ylaxis compared to the short-acting drugs. Stud-
tachyphylaxis to this new bronchodilator are
essential. In this study, with a limited number
, no evidence of tachyphylaxis to formoterol
compared to their ordinary treatment with a
Fourteen days of treatment is a rather short
probably long enough for a study of tachy-
Tachyphylaxis to 62-agonists develops very
after the start of ttcatment in almost all re-
studied, except the bronchial 62-adrenoceptors
patients (11- 15]. It has been shown that healthy
develop tachyphylaxis to the bronchial effects of
lsts (contrary to asthmatics) even after one week
I 12). It is therefore likely that tachyphylaxis
. developed in this group of patients within 14
•f such a development were to occur. The patients
study are now on continuous formoterol therapy
one year and will be followed with repeated dose-
curves to elucidate this matter further.
patients were treated with inhaled corticostcr-
>Which is the standard treatment of asthma of this
329
severity in Sweden. Inhaled corticostcroids are the rec-
ommended second choice after inhaled B1 adrenoceptor
ogonists for the treatment of asthma. This may have
blunted the development of tachyphylaxis [ 12]. How-
ever, separate evatuntion of patients without inhaled
corticosteroid treatment did not indicate tachyphylaxis.
Moreover. as this is the recommended treatment for this
type of patiem. our data elucidate the most important
question, namely, whether a long-acting B.z-adrenoceplor
agonist such as fonnoterol induces tachyphylaxis in the
clinical situation. However, studies of tachyphylaxis to
t11is dntg in mild asthmatics without previous steroid or
Bz-stimulanl therapy would be of interest.
The dose of formoterol used in this study, 12 ~g. was
chosen to be approximately equipotent with 200 ll& of
salbutamol, with regard to the maximum bronchodilating
effecL Actually, 200 J.L& salbutamot is somewhat more
potent. This has been shown in a double-blind cumula-
tive dose-response comparison to salbutamol in asthmat-
ics [5). Available data indicate tllatthe duration of effect
of l 2 jlg fonnoterol would be I2 h [7, 8]. For this reason
two administrations a day were chosen for continuous
use in this study. On average, the patients used formot-
crol once more per day. Our patients are used to talring
bronchodilators pr:ophylacticaJly when attacks can be
anticipated, as for example before physical exercise. The
dose used may, therefore, have been slightly higher than
was actually needed. However. on the basis of data from
this study. regular dosage of 12 Jl& formoterol 3 times
dally can be expected to be a reasonable recommenda-
tion for asthmatics witll moderate to severe asthma.
However, several patients in this study felt well on only
two doses of fonnoterol a day. lt was not the original
intention of the present study to compare formoterot with
recommended salbutamol dosage. Such a comparison
seems possible, however. since the patients in this study
took 200 J.L& salbutamot approximately 4 times daily, on
average, which is in fact the recommended regular dose
[16J. Our results indicate that 12 1.18 fonnoterol 3 times
daily is clearly superior to 200 jlg salbutamol 4 times
daily with regard to symptom relief and improved PEFR
values.
The crossover design may give rise to certain prob-
lems [9, lOJ. In this study a tendency towards interaction
between treatment and treatment order was noticed, witll
respect to the dose-response recordings. This means that
it cannot be ascertained that the change toward.-; "im-
provement'' of the dose-response curves for FEY after
the rormotcrot treatment period wns in fact caused by the
therJpy. However. this is highly likely, since the same
pattern wa$ evident when tlte results from Ule lirst treat·
mcnt period were analysed as a study with parallel groups.
We are therefore inclined to believe !hat tlle high bnS31
values for FEV 1 after formoterol thernpy were caused by
remaining bronchodilatalion after the last dose. given
about 12 h before the test.
It has been stated that a long-acting inhaled bronchocli-
huor would improve astllma therapy significantly I 171.
This p::tpcr supports this assumption. The patients did not
only notice the prolonged erfect of fomloterol, but also
sUited that tlleir asthma was better controlled during both
 330 P. ARVIDSSON ET AL.
night and day. Furthermore, they slept better and it was
objectively demonstrated that their pulmonary function
was improved. The view that long-acting bronchodila-
tors are a major improvement appeared to be shared by
the patients, as they strongly preferred this therapy.
Such clear-cut results are uncommon even in placebo-
controlled studies and it should be borne in mind that the
comparison made in this study was with an active treat-
ment, once a therapeutic breakthrough.
Acknowlrdgernents: We \hank B. Boquist and B.
Oiofsson for e:~~pert technical assistance during \he
study.
References
I. ldo H. - Comparison of oction of BD 40A and some other
B-adrcnoceplor stimul1111ts on the isolated ltnchea. 1111d alrin of
the guinea-pig. Arz~im-Forsch (D,ug Res). 1976, .526, 839-842.
2. Decker N. Quennedey MC, Rouo1 B, Schwnrt7. I, Velly J.
- Effect of N-amkyl :;ubstitution of ll agonisls on alpha nnd
beta-odrenoccptor sublypes: phamu1cologic.1J studies ond bind-
ing nssoys. J Phrnm Pharmocol. 1982, 34, 107- 112.
3. Id a H. - Cardiorcspimtory activities of 3-formyl:unino-4-
hydroxy -aJpha-(N - 1-methyl-2 -p-melhoxyphcnetylamin·
omethyl)-ben7.yhdcohol-hemifumamt (BD 40A) and some other
B-adrcnoceptor stimulants in conscious guine:~-pigs. Arzm:im-
Forscll (Drug Res), 1916, 726, 1337-1340.
4. Wasserman MA, Griffm RL. - A new and highly potent
bronchoselective beta-adrenergic stimulant. Pharmacologist,
1980, 22, 202.
5. Lofdahl CG, Svedmyr N. - Formotcrol fumarate, a new
31 -adrenoceptor agonist.
6. Lofdahl CG, Svedmyr N. - Effcel and dunnion of inhaled
fonnoterol, a new Bt·adrenoceptor agonist, compBTed tO S11lbu-
tamol in asthmatic patients. Acta PJrarmacol Toxicol, 1986.
(Suppl. 52), 229.
7 . .....:: Bcrg A, Bcrdel D. - In: Comparison of a new B-
ugomsl with snlbutnmol in the treatment of bronchospasm in
asthmatic children. XIT World Congress lnterasma. Barcelona,
1987, Abstract.
8. Noho D. Rolke M. - In: Compt~tison of the bronchodi-
lator effect or fomtoterol and fenoterol over a 12-hour period.
XIT World Congress 1nrcrasma. fbrcelonu. 1987, Abstract.
9. Hills M, Armitagc P. - The tWo·pcriod cross-over tri;1l.
Br J C/in Plwmtlcol, 1979. 8, 7-20.
10. Vere DW. -Validity of cross-over trials. Br J Clin Phar-
mocol, 1979, 8, 5-6.
ll. Svedmyr N. - Is belo-adrcnoceplor sensitivity a limiting
factor in asthma thernpy? In: Perspectives in asthma U. Bcta-
adrenoceptors in asthma. J. Moreley cd., Academic Press, Lon-
don. 1984, pp. 181-199.
12. Holga tc ST. Baldwin CJ, Tattcrsfield AE. _ B-ac~ten
agonist resislance in normal human airways. Lancet
375-377. ' 1917•
13. Harvey JE, Baldwin CJ, Wood PJ, Albcni KO
T altersfield AE. - Airway and metabolic rc.~ponsiv
intravenous salbutamol in asthma: effect of regular~
salbutamol. Clin Sci. 1981, 60, 579-585.
14. Harvey JE. Taucrsfield AE. - Airway response
10
lam.o l: o(fcct or regular salbutamol inhalnt.ions in normli)
and nsthmntic subjects. Thorax, 1982, 37, 280-287.
15. Larsson S, Svcdmyr N. 'T'hiringer G. - L:\Ck of br
B1 -adrcnoceptor resi~tnnce in nsthmatics during long-term
ment with tcrbutnline. J Allergy Clin lmm.unol, 19n, 59, 93-~
16. Ulfdnhl CG, Svedmyr N . - Bronchodil:l[ors. /n: Ph
cotherpy of respiratory disea.tes. J. Wilson ed., WiUiarna llill
WUkins. Sydn.ey, 1987, pp. 60-77.
17. Svcdmyr N, Ulfdahl CO.- Physiology and ph.umacoltt;.
nctics or bcln-odrcnergic agonist$./n: Drug therapy rur IISI!una.
J.W. Jcnnc and S. Murphy eds, Ockkcr, New York, l987 - ·
177-211. • ..,...
Le formt)le:ro/, UII II()UVeau brondwdilatateur aaction proro,~;
en inlwlotion. Um! comparoison pendOJIJ deux j'eiTUJines, ~
etude de la tachypllylaxie. P. Arvidsson, S. Lor.rso11 , C.(f.
LO[dahl, 8 . MeiOJuler. L. W4Jrlander. N. Sved.myr.
RESUME: L'objcctif de COliC etude est d'c!va.luer si lo lta!to.
mcnt nu moyen du fonnoterol en inhalation est bien nppr6ci6
par les asthmatiqucs, et s'il provoque une tnchyphyhuie. Noua
nvons introduit 20 osthmatiqucs en etat sLoblc dans w1c &ucll
rnndomis~. en double anonymot, ayee permutation CTOis~c. 0.
ont ete trru l~ pendnnr deux sem aincs, soit pnr le fomtoL«<~
soil par le salbutamol, ovec une semaine intcmHI<II~tlrc cfe
wa.shout. On leur a donne 12 ~g de formoterol ou 200 J.l& cfl
salbutnmol deux fols par jour et on leur a doMe corrune
struction d'utiliser des doses complementaires d'aerosols a 11
dcmandc. lis ont note sur uno fiche d'observation quotidiCIUIJ
le nombre de doses utilis~es. les symptOmes nsthmatiques, ainsl
que le DEP avant chaque dose. Les courbes dose-rl!ponse du
YEMS pour le salbutamol (dose totale l.3 mg) ont e~ real is&~
avant et apres chaque periode de traitement, pour evaluet ..
devcloppement d'une tachyphylaxie. On a note une dlff~
signilicative en favcur du fonnotcrol en cc qui conceme let
symptomes, les enregisltemenlS du DEP, la consomnnllion
d'acrosols, et la preference. Quinze patients preferaient le formo-
terol et deux le salbutamol. Les courbes dose-rcponse real~
avant formoterol ainsi qu'avant et apres salbutamol, s'av~re:nl
quasiment identiques. Apres formoterol, la courbe s'est modi·
fice, Ios valeurs basales et maximales elant plus 6Jev6el
qu'auparavant. On n'a done trouve aucune preuve de tochyphY•
laxie par comparaison avec un traitement beta-stimulant clll•
sique.
Eur Respir J., 1989, 2, 325-330.