1. health and fitness
2. disease
3. asthma

Original Research
ASTHMA
The Potential of a 2Tone Trainer To
Help Patients Use Their Metered-Dose
Inhalers*
Raid A.M. Al-Showair, PhD; Stanley B. Pearson, DPhil; and Henry Chrystyn, PhD
Background: Many patients have problems using the correct inhalation technique when they use
their metered-dose inhalers (MDIs). We have investigated whether a training aid (2Tone Trainer
[2T]; Canday Medical Ltd; Newmarket, UK) helps to maintain the correct inhaler technique after
patients leave the clinic
Methods: Ethics committee approval was obtained, and patients gave consent. Asthmatic patients
who had been prescribed an MDI had their inhalation technique assessed. Their peak inhalation
flow (PIF) when using their MDI, FEV1, and the Juniper asthma quality of life questionnaire
(AQLQ) score were measured. Those patients using the recommended MDI technique were the
good-technique (GT) group. The remainder were randomized to receive verbal training (VT) or
VT plus the 2T to improve their MDI technique. All patients returned 6 weeks later.
Results: There were 36, 35, and 36 asthmatic patients, respectively, who completed the GT, VT,
and 2T procedures. FEV1 did not change within all groups between visit 1 and 2. PIF and AQLQ
score did not change in the GT group. In the VT and 2T groups, the AQLQ score increased by
mean differences of 0.33 (95% confidence interval [CI], 0.14 to 0.53; p < 0.001) and 0.74 (95% CI,
0.62 to 0.86; p < 0.001). At visit 1, all patients in the VT and 2T groups inhaled > 90 L/min
decreasing to 12 patients and 1 patient, respectively, at visit 2 (p < 0.001 both groups). The
overall changes in the 2T group for PIF and AQLQ score, between visits 1 and 2, were
significantly (p < 0.001) greater than the corresponding changes in the VT group.
Conclusion: The 2T helps patients to maintain the recommended MDI technique posttraining
with improvements in AQLQ score.
(CHEST 2007; 131:1776 –1782)
Key words: asthma quality of life; metered dose inhaler; slow inhalation rate; 2Tone trainer
Abbreviations: AQLQ ⫽ asthma quality-of-life questionnaire; CFC ⫽ chlorofluorocarbon; GT ⫽ good technique;
MDI ⫽ metered-dose inhaler; PIF ⫽ peak inhalation flow; 2T ⫽ 2Tone Trainer; VT ⫽ verbally trained
inhaler (MDI) is the most
T hewidelymetered-dose
used inhaler device, but many patients do
not obtain full therapeutic benefit because their
inhalation technique is poor.1– 6 Training helps patients to use their inhalers,7,8 thereby justifying the
time and resources spent on the MDI technique.
*From the School of Pharmacy and Institute of Pharmaceutical
Innovation (Drs. Al-Showair and Chrystyn), University of Bradford, Bradford, UK; and the Department of Respiratory Medicine (Dr. Pearson), Leeds General Infirmary, Leeds, UK.
The 2Tone Trainers were donated by Canday Medical Ltd. Dr.
Al-Showair was financially supported by a scholarship from the
Saudi Arabian Government, and the study was part of his PhD
thesis. The authors have reported to the ACCP that no significant
conflicts of interest exist with any companies/organizations whose
products or services may be discussed in this article.
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Previously, MDI technique assessment has heavily
focused on coordinating the dose release with the
start of an inhalation.1,2 However, studies have
shown that the coordination of the dose actuation
and inhalation is not important as long as the patient
is inhaling when a dose is released9,10 and that a slow
inhalation provides better lung deposition than a fast
Manuscript received November 21, 2006; revision accepted
January 23, 2007.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Henry Chrystyn, PhD, Professor of Clinical
Pharmacy, School of Pharmacy, University of Bradford, Bradford
BD7 1DP, UK; e-mail: [email protected]
DOI: 10.1378/chest.06-2765
Original Research
one of ⬎ 60 L/min.9 –11 Many patients did not use a
slow inhalation when they inhaled through their
MDI,4 and this error was more common than a
failure to coordinate.12,13
A review of the literature14 concluded that the
inhalation rate when using an MDI should be ⬍ 90
L/min, but most patients inhale faster.15,16 There
should, therefore, be an emphasis on training patients who have been prescribed MDIs to use a slow
inhalation, but this rate is difficult to define. Recently, a training aid has been introduced to help
patients obtain the most desirable inhalation rate
when using an MDI. This device, the 2Tone Trainer
(2T) [Canday Medical Ltd; Newmarket, UK], which
is shown in Figure 1, looks like an MDI but does not
have a canister, so that when it is used the patient
does not receive a dose. The patient information
leaflet provided with this training aid encourages
patients to practice using the device in the same way
that they would use their MDI. During use, this
training aid provides users with audible feedback
according to the patient’s inhalation rate. It makes a
two-tone sound when inhaling at ⬎ 60 L/min, one
tone when inhaling at between 30 and 60 L/min, and
no sound when inhaling at ⬍ 30 L/min. Patients are
advised to obtain the one-tone noise and thus become accustomed to the degree of inspiratory effort
they need to make to achieve this rate through an
MDI. By achieving this rate and performing a vital
capacity inhalation, the patient becomes aware that a
slow inhalation maneuver takes at least 5 s. The
cross-sectional view of the 2T in Figure 1 shows the
design that makes the audible noise during an inhalation. After MDI technique training, only 50% of
patients will use their MDI correctly a month later,17
thus requiring repeated training. Continued use of
the 2T at home after a training session may be a
solution to this problem.
Figure 1. The 2T (copyright Canday Medical Ltd, 2005).
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The aim of this study was to evaluate whether the
2T maintains the correct inhalation technique posttraining and whether continued use of the most
desirable inhalation technique, with emphasis on
using a slow inhalation flow, improves asthma healthcare outcomes. The study was integrated into the
usual management of the patients such that routine
practice was maintained.
Materials and Methods
Patients with asthma who were attending an outpatient clinic
were invited to take part in this study. The study received
approval from the local research ethics committee, and all
participating patients gave signed informed consent. Each patient
had to be receiving an inhaled corticosteroid from an MDI
without a spacer device. Those patients who had experienced an
acute exacerbation in the past 4 weeks were excluded from the
study. Patients who were deaf or unable to distinguish between
one and two tones with the 2T were also excluded.
At visit 1, the MDI techniques of all patients willing to take
part in the study were assessed, their current medications were
recorded, their FEV1 levels were measured, and they all completed the Juniper mini-asthma quality-of-life questionnaire
(AQLQ). The self-assessment version,18 using the standard scale
of 1 to 7 for each question, was used. In addition, patients were
asked to rate their asthma control using a 5-point Likert scale
(ranging from poor to excellent).
All patients were counseled on compliance with the prescribed
medication. Their peak inhalation flow (PIF) when using an MDI
was measured (In-Check Dial; Clement Clarke International Ltd;
Harlow, UK) set for an MDI. The maximum inhalation rate that
can be recorded is 120 L/min; thus, faster inhalation rates were
recorded as this value. Thus, although actual inhalation rates
were not always measured, all of those patients who inhaled too
fast could be identified. Those patients with a good technique
(GT) [which included good coordination, defined as actuating a
dose during the inhalation phase, and a slow inhalation rate of
⬍ 90 L/min] were placed into the GT group. All those patients
who met the criteria for coordination but inhaled too fast were
placed into the intervention group. All those patients who started
to inhale before actuating a dose (ie, poor coordination) were not
eligible for the study and were referred to the asthma nurse for
counseling about their MDI technique, according to routine
practice. The ethics committee would not allow any patient with
an incorrect technique to be recruited into a control group.
Subjects in the intervention group were randomly allocated into
the verbal training (VT) group or the 2T group. VT patients were
trained on the most desirable inhalation technique19 with emphasis on breathing out slowly as far as comfortable and actuating
a dose at or soon after the start of a slow inhalation. A slow
inhalation was defined as an inhalation that filled the lungs with
air that lasted 5 s (hence, a slow-vital capacity inhalation was
trained). Patients in the 2T group received the same VT as the VT
group and were trained how to use the 2Tone Trainer according
to the instructions on its patient information leaflet. All 2T
patients consistently made the one-tone noise when they used the
2T. They were advised to use the training device every morning
and night, to obtain the one-tone sound, and to use the same
inhalation procedure when they used their active MDI. All VT
and 2T group patients had their PIF through an MDI measured
at the end of the training session to ensure that they were all
inhaling at ⬍ 90 L/min through an MDI before they left the
clinic.
CHEST / 131 / 6 / JUNE, 2007
1777
Table 1—Visit 1 Data
GT Group VT Group 2T Group
(n ⫽ 36)
(n ⫽ 35) (n ⫽ 36)
Variables
Female gender
Age, yr
FEV1
% predicted
L
Mini-AQLQ
AQLQ
Symptoms
Environmental stimuli
Emotional function
Activity limitation
22
22
22
60.4 (15.1) 52.6 (15.7) 58.3 (13.7)
62.2 (25.4) 76.9 (24.1)† 71.4 (22.0)
1.60 (0.82) 2.10 (0.75)† 1.94 (0.76)
3.7 (1.1) 3.9 (1.0)
3.8 (1.1)
3.4 (1.0)
3.3 (1.6)
3.8 (1.6)
4.2 (1.5)
3.5 (1.2)
4.2 (1.5)
3.8 (1.5)
4.3 (1.4)
3.6 (1.3)
3.5 (1.3)
3.6 (1.4)
4.5 (1.5)
*Values are given as the mean (SD).
†p ⬍ 0.05 compared to GT group.
All patients returned 6 weeks later (visit 2). Their medication
was checked to ensure that no changes had been made, and their
PIF (In-Check Dial [set for an MDI]; Clement Clarke Ltd) and
their FEV1 were measured together with their AQLQ score.
Analysis (using the Shapiro-Wilks test) revealed a normal
distribution for all the AQLQ score values and the FEV1, but the
PIF values were not normally distributed. The AQLQ scores and
FEV1 values among the three groups were examined using
one-way analysis of variance with Bonferroni correction. PIF data
at visit 2 were continuous, so a Mann-Whitney test was used for
comparison between the groups. A ␹2 test was used for categoric
data. From previous data,15 it was estimated that 30 patients (plus
20%) would be required to reduce inhalation rates to ⬍ 90
L/min.
Discussion
Results
A total of 108 patients were recruited into the
study, and 107 adult asthmatic patients completed
the study. Thirty-six patients had been recruited into
the VT and 2T groups, but only 12 patients had been
recruited into the GT group from the first 130
consenting patients who were screened. Hence, 37%
of patients had coordination problems and were
referred to the practice nurse for routine training
and device selection. After this point, only those
patients who were eligible to enter the GT group
were recruited. To recruit the required 36 patients
Table 2—Categorization of the PIF Through an MDI
GT Group
into the GT group, 476 consenting patients had to be
screened. All study patients were using a short-acting
␤-agonist and an inhaled corticosteroid, and 17, 15,
and 18 patients, respectively, in the GT, VT, and 2T
groups had also been prescribed a long-acting ␤-agonist.
Visit 1 data (ie, baseline demographic data) are
described in Table 1; PIF values are shown in Table
2. The comparison of these demographic data from
visit 1 among the groups revealed no differences
between the ages and AQLQ scores of the patients.
The FEV1 values were lower in the GT group
compared with those in the other two. The baseline
PIFs of those patients in the VT and 2T groups were
significantly (p ⬍ 0.001) faster than those in patients
in the GT group. This was as expected due to the
study design.
Each individual’s PIFs and AQLQ scores for
visits 1 and 2 are shown in Figures 2 and 3,
respectively, and are summarized in Tables 2 and
3. Comparing the AQLQ scores between visits 1
and 2 (Table 4 and Fig 3), no patient in the GT
group recorded a difference of ⱖ 0.5. In contrast,
17 patients in the VT group and 30 patients in the
VT group recorded a difference of ⬎ 0.5 in their
AQLQ scores between visits 1 and 2. This is
reflected in their perception of asthma control,
which is described in Table 5.
VT Group
2T Group
Flow,
L/min
Visit 1
Visit 2
Visit 1*
Visit 2†
Visit 1*
Visit 2†
ⱖ 120
90–119
61–89
⬍ 60
0
0
24
12
0
0
24
12
30
5
0
0
4
8
15
8
27
9
0
0
0
1
7
28
*p ⬍ 0.001 compared to GT group for visit 1 data.
†p ⬍ 0.001 for visit 2 vs visit 1 within each group.
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Reviews from the past few years about inhaled
devices in the United Kingdom20 and the United
States21 have concluded that they are equivalent.
However, in the studies included in those reviews
patients were compliant and were trained how to use
the devices studied. Both reviews recommended that
it was essential that patients be trained to use these
devices according to the recommendations of the
manufacturer that are included in the patient information leaflet and that they be counseled on the
importance of compliance with their use. The MDI
is the only generic inhaled device on the market, but
only 7.6% of the patients willing to take part in the
study met the criteria for using the correct MDI
inhalation technique. The results highlight that, consistent with previous reports,12,13 not using a slowinhalation technique is the most common mistake
made by patients using an MDI. The improvements
shown in the VT group consolidate the health-care
gain when using the recommended inhalation technique. However, consistent with previous publications2,17 and routine clinical practice, many patients
in the VT group had forgotten or were uncertain how
to perform the slow-inhalation technique when they
Original Research
Peak Inhalation Flow (Lmin-1)
(a)
(b)
(c)
120
120
120
100
100
100
80
80
80
60
60
60
40
40
40
20
20
20
0
0
0
Visit 1
Visit 2
Visit 1
Visit 2
Visit 1
Visit 2
Figure 2. The PIF of each individual using an MDI in the (left, a) GT group, (middle, b) VT group,
and (right, c) 2T group.
returned to the clinic. All of the patients in the 2T
group inhaled more slowly, with a resultant highly
significant improvement in asthma quality of life.
There were no changes to patients’ prescriptions, so
any changes that occurred were presumably due to
differences in lung deposition. Improvements in
asthma quality of life and in the patient’s perception
of their asthma control without changing the dose
and without having to retrain the technique highlight
the potential of the 2T to decrease costs as well as to
improve health-care outcomes.
In this study, good coordination when using an
MDI was defined as dose activation during the
inhalation cycle, which included the standard splitsecond coordination between dose release and the
start of an inspiration together with coordination that
used a delayed actuation. Previous studies1– 6 have
focused on the split-second coordination between
dose release and inhalation, and have reported this as
the main problem with MDI users. Studies9,10 have
shown no difference in lung deposition or clinical
end points for a slow inhalation when the dose is
released either immediately at or just after the start
(b)
(c)
Asthma Quality of Life Score
(a)
of a slow inhalation. However, the majority of MDI
users inhale using a rate of ⬎ 90 L/min,15,16 and lung
deposition is higher when inhaling at a slow rate
compared with a fast rate.9,10 We have, therefore,
focused on training patients to inhale at a slower rate,
with emphasis on actuating a dose during the inhalation phase.
Drug particles emitted from an inhaler will deposit
into the lungs mainly by impaction and sedimentation. Although the faster the inhalation rate, the
greater the degree of impaction, it would be expected that there would be more sedimentation
when using a slow rate. There is, therefore, likely to
be more central lung deposition of the particles
emitted from an inhaler when using a fast rate
compared to a slow rate11 with less drug deposition
into the peripheral zone of the lungs.22 A 2005
report23 of lung deposition using three different
monosized particles has confirmed that there is more
peripheral penetration of smaller particles and that a
fast inhalation increases central lung deposition.
Although ␤-receptors are widely distributed
throughout the lungs,24 the surrounding airways
Visit 1
Visit 2
Visit 1
Visit 2
Visit 1
Visit 2
Figure 3. The AQLQ score of each individual using an MDI in the (left, a) GT group, (middle, b) VT
group, and (right, c) 2T group.
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CHEST / 131 / 6 / JUNE, 2007
1779
Table 3—Mean Visit 2 Values and the Mean Differences Between Visits 2 and 1*
GT Group
Variables
Visit 2
FEV1, L
1.57 (0.73)
PIF, L/min
70.0 (55.0, 78.8)
Mini-AQLQ
3.7 (1.1)
AQLQ
Symptoms
3.5 (1.0)
Environmental
3.3 (1.5)
stimuli
Emotional function 3.9 (1.6)
Activity limitation
4.3 (1.5)
VT Group
2T Group
Difference†
Visit 2
Difference†
⫺0.03 (⫺0.12, 0.06)
NA
0.04 (⫺0.03, 0.11)
2.16 (0.74)
80.0 (60.0, 100.0)‡
4.2 (1.0)
0.04 (⫺0.07, 0.16)
⫺0.06 (⫺0.2, 0.09)
4.0 (1.1)
4.1 (1.5)
0.47 (0.22, 0.73)㛳
⫺0.11 (⫺0.32, 0.88)
4.7 (1.1)
4.2 (1.4)
1.10 (0.85, 1.29)¶
0.68 (0.45, 0.90)¶
0.1 (⫺0.11, 0.31)
0.07 (⫺0.07, 0.21)
4.2 (1.6)
4.7 (1.2)
0.41 (0.10, 0.72)#
0.43 (0.19, 0.67)㛳
4.2 (1.6)
5.0 (1.4)
0.60 (0.24, 0.97)㛳
0.46 (0.27, 0.66)¶
0.06 (⫺0.05, 0.17)
NA
0.33 (0.13, 0.53)㛳
Visit
Difference†
1.93 (0.63)
⫺0.01 (⫺0.11, 0.08)
50.0 (45.0, 55.0)§
NA
4.6 (1.0)
0.74 (0.61, 0.86)¶
*Values are given as the mean (SD) or median (interquartile range), unless otherwise indicated. NA ⫽ not applicable because most visit 1 values
for the VT and 2T groups are ⱖ 120 L/min.
†Values are given as the mean (95% confidence interval).
‡p ⬍ 0.01 (VT vs GT group).
§p ⬍ 0.001 (2T vs GT and VT groups).
㛳p ⬍ 0.01 compared to visit 1 (otherwise not significant).
¶p ⬍ 0.001 compared to visit 1 (otherwise not significant).
#p ⬍ 0.05 compared to visit 1 (otherwise not significant).
require the muscle to facilitate bronchodilation.
Deposition predominantly in the upper parts of the
conducting airways is more beneficial than deposition lower down for bronchodilation.23 However, a
previous study9 reported no difference in clinical end
points when a salbutamol MDI was used with fast
and slow inhalation rates, although total lung deposition was greater when using the slower rate. The
results of this more recent report9 could be due to
measurements at the top of the dose-response curve
in the areas where the salbutamol was deposited.
Thus, for a bronchodilator the inhalation rate when
using an MDI may not be clinically important because of the dose used.
Inflammation is reported to occur throughout the
lungs,25 and FEV1 measurements do not correlate
well with inflammation in the peripheral zones of the
lungs.26 A chlorofluorocarbon (CFC)-free MDI formulation of beclomethasone emits much smaller
particles than the CFC formulation, and the resultant lung deposition is much larger with greater
amounts in the peripheral areas.27 A study28 comparing therapeutically equivalent doses from these two
Table 4 —Patients With an Overall Change in Their
Mini-AQLQ Scores Between Visits 2 and 1*
AQLQ Score Change
⬍ ⫺0.5
⫺0.5–0.5
0.5–1
⬎1
GT Group
VT Group
2T Group
0
36
0
0
3
15
14
3
0
6
22
8
*Values are given as No. of patients. p ⬍ 0.001 for 2T vs GT group
and VT vs GT group; p ⫽ 0.012 for 2T vs VT group.
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MDI products has shown that the AQLQ score was
greater for the CFC-free formulation but that there
was no change in the FEV1. This could be due to the
greater deposition of the antiinflammatory agent into
the peripheral areas. This phenomenon, which has
been confirmed by the greater peripheral lung deposition when small particles are inhaled using a slow
inhalation,23 may be similar to what has occurred in
this study in that the slower inhalation allows the
steroid drug particles to penetrate deeper into the
peripheral areas. Thus, improvements would occur
in the smaller airways that would not necessarily be
picked up by the FEV1 measurements. The lack of
change in lung function measurements despite
changes in the AQLQ score has been reported in
other studies.29 –31
Compliance was not assessed, but this aspect of the
study was explained to all patients on entry to the study.
Patients in the GT group had more severe asthma than
those in the two intervention groups, and thus could be
from a different population. It may be that patients
with more severe asthma may be targeted more often
Table 5—Patient Perception of Asthma Control
GT Group
VT Group
2T Group
Asthma Control Visit 1 Visit 2 Visit 1 Visit 2 Visit 1 Visit 2*
Poor
Fair
Good
Very good
Excellent
5
12
15
4
0
5
11
19
1
0
4
11
10
7
3
0
14
11
6
4
4
15
10
6
1
0
6
17
12
1
*p ⬍ 0.05 (visit 2 vs visit 1).
Original Research
for inhaler technique training or that these patients
focus more on their inhalation technique than other
patients. The lack of change in the AQLQ score and the
PIF in the GT group suggests that any study effect
should have been small. However, it would be expected
that AQLQ score changes in patients in the GT group
would be smaller than those in patients with milder
forms of asthma.
A change of 0.5 in the AQLQ score32,33 is regarded
as being clinically significant34; 30 of 36 patients who
used the 2T exceeded this change, thereby highlighting the benefit of using this training aid without any
change to their prescription. The results also demonstrate the importance of using a slow inhalation
with an MDI. The 2T belongs to the patient and is
relatively inexpensive. The cost is offset by the
improvement in the patient’s asthma care outcomes
and by the prevention of retraining in the inhalation
technique at subsequent clinic visits.
ACKNOWLEDGMENT: We thank all of those patients who
took part in the study and all of the staff in the chest outpatient
clinic at Leeds General Infirmary.
References
1 Paterson IC, Crompton GK. Use of pressurized aerosols by
asthmatic patients. BMJ 1976; 1:76 –77
2 Crompton GK. Problems patients have using their pressurised aerosol inhalers. Eur J Respir Dis 1982; 63(suppl):
101–104
3 Pederson S, Frost L, Arnfred T. Errors in inhalation technique and efficiency in inhaler use in asthmatic children.
Allergy 1986; 41:118 –124
4 Larsen JS, Hahn M, Ekholm B, et al. Evaluation of conventional press-and-breathe metered-dose inhaler technique in
501 patients. J Asthma 1994; 31:193–199
5 Lenney J, Innes JA, Crompton GK. Inappropriate inhaler use:
assessment of use and patient preference of seven inhalation
devices. Respir Med 2000; 94:496 –500
6 Lahdensuo A, Muittari A. Bronchodilator effects of a fenoterol
metered dose inhaler and fenoterol powder in asthmatics with
poor inhaler technique. Eur J Respir Dis 1986; 68:332–335
7 Horsley MG, Bailie GR. Risk factors for inadequate use of pressurized aerosol inhalers. J Clin Pharm Ther 1998; 13:139–143
8 Orehek J, Gayrard P, Grimaud C, et al. Patient error in use of
bronchodilator metered aerosols. BMJ 1976; 1:76
9 Tomlinson HS, Corlett SA, Allen MB, et al. Assessment of
different methods of inhalation from salbutamol metered
dose inhalers by urinary drug excretion and methacholine
challenge. Br J Clin Pharmacol 2005; 60:605– 610
10 Newman SP, Pavia D, Garland SP, et al. Effects of various
inhalation modes on deposition of radioactive pressurised
aerosols. Eur J Respir Dis 1982; 63(suppl):57– 69
11 Newman SP, Steed K, Hooper G, et al. Comparison of
gamma scintigraphy and a pharmacokinetic technique for
assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler. Pharm Res 1995;
12:231–236
12 Ressor Nimmo CJ, Chen DNM, Martinusen SM, et al.
Assessment of patient acceptance and inhalation technique of
a pressurized aerosol inhaler and two breath-actuated devices. Ann Pharmacother 1993; 27:922–927
www.chestjournal.org
Downloaded From: http://journal.publications.chestnet.org/ on 10/21/2014
13 Hesselink AE, Penninx BWJH, Wijnhoven HAH, et al.
Determinants of an incorrect inhalation technique in patients
with asthma and COPD. Scand J Prim Health Care 2001;
19:255–260
14 Pauwels R, Newman S, Borgstrom L. Airway deposition and
airway effects of antiasthma drugs delivered from metereddose inhalers. Eur Respir J 1997; 10:2127–2138
15 Chrystyn H, Brownlee K, Chetcuti P, et al. Inhalation rates of
asthmatic children (child) and adults and of chronic obstructive pulmonary disease (COPD) patients through inhalers
[abstract]. Am J Respir Crit Care Med 2002; 105(suppl):A190
16 Broeders MEAC, Molema J, Hop WC, et al. Inhalation
profiles in asthmatic and COPD patients: reproducibility and
effect of instruction. J Aerosol Med 2003; 16:131–141
17 Shim C, Williams MH. The adequacy of inhalation of aerosol
from canister nebulizers. Am J Med 1980; 891– 894
18 Juniper EF, Guyatt GH, Cox FM, et al. Development and
validation of the Mini Asthma Quality of Life Questionnaire.
Eur Respir J 1999; 14:32–38
19 Hindle M, Newton DAG, Chrystyn H. Investigations of an
optimal inhaler technique with the use of urinary salbutamol
excretion as a measure of relative bioavailability to the lung.
Thorax 1993; 48:607– 610
20 Brocklebank D, Ram F, Wright J, et al. Comparison of the
effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.
Health Technol Assess 2001; 5:1–149
21 Dolovich MB, Ahrens MB, Hess DR, et al. Device selection
and outcomes of aerosol therapy: evidence-based guidelines:
American College of Chest Physicians/American College of
Asthma, Allergy, and Immunology. Chest 2005; 127:335–371
22 Farr SJ, Rowe AM, Rubsamen R, et al. Aerosol deposition in
the human lung following administration from a microprocessor controlled pressurised metered dose inhaler. Thorax
1995; 50:639 – 644
23 Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung
deposition and bronchodilator response as a function of
␤2-agonist particle size. Am J Respir Crit Care Med 2005;
172:1497–1504
24 Carstairs JR, Nimmo AJ, Barnes BJ. Autoradiographic visualisation of ␤-adrenoceptor subtype in human lung. Am Rev
Respir Dis 1985; 132:541–547
25 Kraft M, Djukanovic R, Wilson S, et al. Alveolar tissue
inflammation in asthma. Am J Respir Crit Care Med 1996;
154:1505–1510
26 Rand Sutherland E, Martin RJ, Bowler RP, et al. Physiologic
correlates of distal lung inflammation in asthma. J Allergy
Clin Immunol 2004; 113:1046 –1050
27 Leach CL, Davidson PJ, Boudreau RJ. Improved airway
targeting with the CFC-free HFA-beclomethasone metereddose inhaler compared with CFC-beclometasone. Eur Respir
J 1998; 12:1346 –1353
28 Juniper EF, Price DB, Stampone PA, et al. Clinically important improvements in asthma-specific quality of life, but no
difference in conventional clinical indexes in patients changed
from conventional beclomethasone dipropionate to approximately half the dose of extrafine beclomethasone dipropionate. Chest 2002; 121:1824 –1832
29 Gonzalez-Martin G, Joo I, Sanchez I. Evaluation of the
impact of a pharmaceutical care program in children with
asthma. Patient Educ Couns 2003; 49:13–18
30 Rowe BH, Oxman AD. Performance of an asthma quality of
life questionnaire in an outpatient setting. Am Rev Respir Dis
1993; 148:675– 681
31 Stahl E, Postma DS, Juniper EF, et al. Health-related quality
of life in asthma studies: can we combine data from different
countries? Pulm Pharmacol Ther 2003; 16:53–59
CHEST / 131 / 6 / JUNE, 2007
1781
32 Juniper EF, Guyatt GH, Epstein RD, et al. Evaluation of
impairment of health-related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax
1992; 47:76 – 83
33 Juniper EF, Guayatt GH, Ferrie PJ, et al. Measuring
1782
Downloaded From: http://journal.publications.chestnet.org/ on 10/21/2014
quality of life in asthma. Am Rev Respir Dis 1993;
147:832– 838
34 Juniper EF, Guyatt GH, Willan A, et al. Determining a
minimal important change in disease-specific quality of life
instrument. J Clin Epidemiol 1994; 102:16 –17
Original Research