(Chest. 2002;121:329-333.)
© 2002
American College of Chest Physicians
The Risk of Hospitalization and Near-Fatal and Fatal Asthma in Relation to the Perception of Dyspnea*
Rasmi Magadle, MD;
Noa Berar-Yanay, MD and
Paltiel Weiner, MD
*
From the Department of Medicine A, Hillel-Yaffe, Medical Center, Hadera, Israel.
Correspondence to: Paltiel Weiner, MD, Department of Medicine A, Hillel-Yaffe Medical Center, Hadera, Israel 38100
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Abstract
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Background: A life-threatening asthma attack is still
of major concern. One of the main goals in treating patients with
asthma is identification of the patients at risk of having these
attacks. It has been shown that patients who have a near-fatal asthma
attack have a blunted perception of dyspnea (POD). The purpose of this
study is to measure the POD in patients with asthma, and to relate POD
to life-threatening attacks within a 24-month follow-up period.
Methods: The POD was scored using the Borg scale during
breathing against a progressive load at 1-min intervals, in order to
achieve mouth pressure up to 30 cm H2O, in 113 consecutive
asthmatic patients with stable asthma attending an outpatient clinic.
All patients were invited to regular follow-up every 3 months for up to
24 months, and all hospitalizations and near-fatal and fatal asthma
attacks were recorded. The prebronchodilator morning peak expiratory
flow rate (PEFR), daily regular treatment, and ß2-agonist
consumption were recorded in a diary card for the first 4 weeks.
Results: Seventeen patients (15%) had high POD compared to
the normal subjects, 67 patients (59%) had POD within the normal
range, and 29 patients (26%) had lower-than-normal POD. In the
patients with low POD, there was a tendency for higher age, higher
female/male ratio, and a longer duration of disease. The rate of severe
asthma was higher in the low-POD group than in the normal-POD group,
but did not differ from the rate in the high-POD group. The mean daily
ß2-agonist consumption in the patients with low POD was
significantly lower (p < 0.01) than in the patients with high POD,
although the mean PEFR was lower in the low-POD group. During the 2
years of follow-up, the patients in the low-POD group had statistically
significantly more emergency department (ED) visits, hospitalizations,
near-fatal asthma attacks, and deaths compared to the normal-POD and
high-POD groups.
Conclusions: Approximately 26% of
the referral subjects with asthma had low POD when compared to healthy
matched subjects. Patients with low POD had statistically significantly
more ED visits, hospitalizations, near-fatal asthma attacks, and deaths
during the follow-up period. Reduced POD may predispose patients to a
life-threatening attack.
Key Words: asthma life-threatening asthma attack perception of dyspnea
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Introduction
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From
1.1 to 7.0% of patients with asthma die from an asthma
attack.1
2
3
It is hard to predict which asthma patients
will have a fatal or near-fatal asthma attack. In both fatal and
near-fatal asthma, there is a female predominance,4
5
history of frequent hospital admissions and emergency department (ED)
visits,6
noncompliance,7
psychosocial
abnormalities,8
and socioeconomic factors linked to poverty.9
In
addition, Kikuchi et al10
reported in 1994 a
significantly decreased response to inspiration against resistance
and to hypoxic hypercapnia in 11 patients with near-fatal asthma.
This observation that most patients with near-fatal asthma have blunted
perception of dyspnea (POD) suggests that a dysfunction in these
defense mechanisms may play a role in near-fatal asthma.
Fatal or near-fatal asthma is undoubtedly severe asthma, but
it may not have been manifested in poor lung function or in terms of
disturbing the patient very much, leading to consultation with a
doctor. In the Barcelona soybean epidemic,11
patients with
near-fatal asthma had fewer symptoms and had attended EDs significantly
less than asthmatic patients who did not have near-fatal asthma.
The prognosis of patients with near-fatal asthma is not good. The
in-hospital mortality rate is 16.5% in patients who require mechanical
ventilation, and an additional 14% of patients die during the
following period.12
We hypothesized that assessment of the
POD in patients with asthma will identify patients at risk of having
fatal or near-fatal asthma attacks.
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Materials and Methods
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One hundred thirteen patients with stable asthma attending an
outpatient clinic (54 male and 59 female patients) were recruited for
the study. Our outpatient clinic receives only patients who are
referred by their primary physician, and therefore may have more
complicated conditions than patients with asthma alone. All
patients satisfied the American Thoracic Society definition of asthma,
with symptoms of episodic wheezing, coughing, and shortness of breath
responding to bronchodilators, and reversible airflow obstruction
documented in at least one previous pulmonary function
study.13
Their characteristics are summarized in Table 1
. All patients were tested at baseline and were followed up for at least
24 months. The severity of asthma was defined according to spirometric
values.14
Patients with a history of near-fatal asthma
attacks were excluded from the study, because these patients are known
to have an excessive risk for further fatal or near-fatal attacks.
Near-fatal attacks were defined as attacks of asthma requiring
treatment with mechanical ventilation or resulting in unconsciousness
and severe respiratory failure.
All patients were invited to have regular follow-up every 3 months and
were required to be compliant with the recording of prebronchodilator
morning peak expiratory flow rates (PEFRs), daily regular treatment,
and ß2-agonist consumption on a diary card for
the first 4 weeks. The study protocol was approved by the institutional
ethics committee, and informed consent was obtained from all the
subjects.
Tests
Spirometry
FVC and FEV1 were measured three times on
a computerized spirometer (Compact; Vitalograph; Buckingham England),
and the best trial is reported.
POD
The sensation of dyspnea was measured while the subject breathed
through a device similar to that proposed by Nickerson and
Keens.15
Subjects inhaled through a two-way valve
(Hans-Rudolph; Kansas City, MO), the inspiratory port of which was
connected to a chamber and plunger to which weights could be added
externally. The subjects breathed against a progressive load at 1-min
intervals, in order to achieve mouth pressures of 0 (no load), 5, 10,
20, and 30 cm H2O. After breathing for 1 min at
each level of threshold load, in a protocol similar to the one
previously described by Kikuchi and coworkers,10
with
resistive loads, using a method recently published by Larson
and associates16
with the same device as ours, using
threshold loads, the subjects rated the sensation of difficulty in
breathing (dyspnea) using the modified Borg scale.17
This
is a linear scale of numbers ranking the magnitude of difficulty in
breathing, ranging from 0 (none) to 10 (maximal).
Data Analysis
Normal POD was defined as mean ± 1 SD of 100 age- and
sex-matched normal subjects. Comparisons of dyspnea score and follow-up
hospital visits were carried out using the two-way repeated-measures
analysis of variance.
 |
Results
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The data of the POD in the patients with asthma were compared to
the data received from 100 age- and sex-matched normal subjects.
Seventeen patients (15%) had high POD compared to the mean ± 1 SD
POD of normal subjects, 67 patients (59%) had POD within the normal
range, and 29 patients (26%) had lower-than-normal POD. The mean Borg
scores during breathing against load in the normal subjects was 0.2,
1.7, 2.7, 3.8, and 4.8 while breathing against loads of 0, 5, 10, 20,
and 30 cm H2O, respectively (Fig 1 ). The mean Borg score during breathing against load in the asthma
patients with within-normal POD was somewhat lower than in normal
subjects, but with no statistical significance. The mean Borg score
during breathing against a load in the asthma patients with low POD was
significantly lower (p < 0.005) than in the normal subjects (0.1,
0.9, 1.2, 1.8, and 2.4 while breathing against loads of 0, 5, 10, 20,
and 30 cm H2O, respectively). The mean Borg score
during breathing against a load in the asthma patients with high POD
was also significantly higher (p < 0.001) than in the normal
subjects (0.5, 2.8, 4.0, 5.8, and 6.4 while breathing against loads of
0, 5, 10, 20, and 30 cm H2O, respectively).

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Figure 1.. The mean POD of the 17 patients with high POD, the
67 patients with normal POD, and the 29 patients with lower-than-normal
POD, as compared to the data (mean ± 1 SD) received from 100 age- and
sex-matched normal subjects.
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There was a tendency for higher age, higher female/male ratio, and a
longer duration of asthma in the patients with low POD (Table 1)
. The
rate of severe asthma was higher in the low-POD group than in the
normal-POD group, but did not differ from that in the high-POD group
(15% and 24%, respectively). However, no correlation was found in the
whole group for POD vs FEV1 % (Fig 2
), POD vs age, and POD vs duration of asthma. In addition, it could be
suggested that low POD was associated with a history of ED visits and
hospitalizations.

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Figure 2.. The relation between the FEV1 and the
POD (sum of the Borg score while breathing against loads of 0, 5, 10,
20, and 30 cm H2O) in the whole group of asthma patients.
Near-fatal asthma attacks are indicated by reticulated circles, and
deaths are indicate by black circles. Patients with no fatal or
near-fatal attacks are indicated by open circles. pred = predicted.
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During the 4 weeks of follow-up, the mean daily
ß2-agonist consumption in the patients with low
POD was significantly lower (p < 0.01) than in the patients with
high POD, although the mean PEFR was lower in the low-POD group. It was
also lower than that in the normal-POD group, but it did not reach
statistically significance (Table 2
).
During the 2 years of follow-up, the patients in the low-POD group had
statistically significantly more ED visits (p < 0.001 and
p < 0.01), hospitalizations (p < 0.001 and p < 0.001),
near-fatal asthma (p < 0.001 and p < 0.001), and deaths
(p < 0.001 and p < 0.001), compared to the normal-POD and the
high-POD groups, respectively (Table 3
). Three patients died at home. One patient died during an asthma
attack, the second patient was found dead in his bed and no autopsy was
performed, and the cause of death for the third patient could not be
determined. The three remaining patients in the low-POD group died
during hospitalization for acute asthma, with mechanical ventilation.
It was also noticed that the patients with high POD had significantly
more ED visits (p < 0.05) than the patients with normal POD, but not
hospitalizations, near-fatal asthma attacks, or deaths.
 |
Discussion
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In this study, we found that approximately 60% of patients with
asthma referred to our outpatient clinic had normal POD, approximately
26% of the patients had low POD, and the rest of the patients had high
POD, when compared to healthy matched subjects. Patients with low POD
tend to be older, have a longer duration of asthma, a higher
female/male ratio, a low daily ß2-agonist
consumption, and statistically significantly more ED visits,
hospitalizations, near-fatal asthma attacks, and deaths during the
follow-up period.
In the management of bronchial asthma, the subjects POD serves as one
of the most important indexes used to guide treatment. It is well
documented that large variations in perception of respiratory symptoms
may be observed from one asthmatic patient to another18
;
in 60% of asthma patients, there is no correlation between the POD and
simultaneous peak flow measurements.19
Among the factors
that can affect POD related to bronchoconstriction are changes in lung
volume, speed of bronchoconstriction, anxiety level, duration of
asthma, airway inflammation, and age.20
21
22
23
24
Low POD may result in undertreatment of asthma, delay modification in
treatment,25
and even predispose patients to fatal asthma
attacks.10
One might think that the severity of the airway
obstruction caused the patients death. However, death occurred in
patients with FEV1 measurements from 53 to 77%
of predicted normal values.
The low-POD patients tended to be older and female, and to have more
airway obstruction than patients in the other groups. The latter
accentuates how low the POD actually was, because usually patients have
more dyspnea when they have more airway obstruction.
To investigate the ability of patients to perceive respiratory
sensation, either bronchoprovocation testing or resistance/threshold
load testing have been used.26
We prefer the latter test
because very often only a few concentrations can be administered during
the bronchoprovocation test, whereas assessment of the relation between
respiratory sensation and the physical change requires an adequate
number of observations over a wide range of stimulus intensity.
It has been shown that there is a close relationship between the
sensation of breathlessness and respiratory muscle force, relative to
respiratory muscle strength, both in normal subjects and in patients
with severe lung function impairment.25
Thus, it could be
argued that our assessment of POD, which compares breathlessness to
absolute load rather than that relative to strength, might
underestimate POD in subjects with strong respiratory muscles while
overestimating POD in subjects with weak respiratory muscles.
Furthermore, since our technique does not take intrinsic positive
end-expiratory pressure into account, it might overestimate POD in
severely obstructed, dynamically hyperinflated subjects.27
Since our low-POD patients tended to be older and female, and have more
airway obstruction than our normal-POD or high-POD patients, we believe
that any error resulting from variations in respiratory muscle strength
and dynamic hyperinflation would only tend to bring POD estimates
closer to normal.
There are relatively few assessments of mortality from asthma in the
general population. Although fatal asthma is, almost by definition,
difficult, approximately half of those who die have mild or moderate
disease on postmortem review.28
Campbell and
associates6
found that those who died were more likely to
be women, to have more comorbidities, to have made more visits to the
doctor in the 12 months prior to the attack, to have better
self-management skills, and more likely to be receiving nebulized
ß-agonists. Suggestions also have been made that near-fatal asthma
attacks are associated with previous hospital admissions for
asthma,29
increased airway responsiveness and poor
control,5
poor compliance,5
and a hyperacute
form of attack.
The observation made by Kikuchi et al,10
that most
patients with near-fatal asthma had a decreased hypoxic response
accompanied by a blunted POD, suggested that a dysfunction in these
defense mechanisms may play a role in near-fatal asthma. A blunted POD
also was detected by others4
5
in association with fatal
asthma. Published data30
suggest that blunted POD
is found in patients with stable and unstable asthma and is correlated
with the degree of sputum eosinophilia. Although the factors that
influence perception of asthma are poorly understood, it seems that low
POD is not usually an inborn defect but an acquired and changeable
defect.5
18
Although there have been many epidemiologic studies of fatal or
near-fatal asthma, the precise mechanisms of life-threatening attacks
were not completely elucidated, and concerns about deaths from asthma
still exist. Most of the deaths are avoidable if the patients are
adequately followed up and treated.31
To prevent death
from asthma, it is important to identify patients who may be at risk of
a fatal attack. Unfortunately, a history of a near-fatal asthma attack
that required hospitalization and mechanical ventilation is the
strongest single predictor of subsequent death from
asthma.8
The present study shows that patients with low
POD, even without a history of near-fatal asthma, are at an increased
risk of future hospitalization, a near-fatal asthma attack, or even
death from an asthma attack.
The POD is not readily measured in patients with asthma. However, the
findings of previous studies and ours have important implications for
the prevention of death from asthma. Patients with a low POD should be
monitored carefully and more often, and should be educated in
self-management. Measurement of the POD should be performed at least
once in all asthma patients, to identify those at high risk for a fatal
attack. Either technique, the method of breathing against added
resistance or added threshold loads, or the methacholine
bronchoprovocation test, may be used to identify these patients.
 |
Footnotes
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Abbreviations: ED = emergency department;
PEFR = peak expiratory flow rate; POD = perception of dyspnea
Received for publication November 28, 2000.
Accepted for publication August 23, 2001.
 |
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