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To cite this Article:
Gimenez da Rocha D, Burch MO, Aparecida Teixeira Soares L, et al. Trajectory of the
response to bronchodilator and respiratory outcomes in adults with asthma-like
symptoms. Monaldi Arch Chest Dis doi: 10.4081/monaldi.2025.3116
©The Author(s), 2025
Licensee PAGEPress, Italy
Trajectory of the response to bronchodilator and respiratory outcomes
in adults with asthma-like symptoms
Daniel Gimenez da Rocha,1 Monique Olivia Burch,1 Luciana Aparecida Teixeira Soares,1
Jessica Regina Bertolino,1 Ana Lúcia Bergamasco Galastri,2
Daniel Antunes,1 Ronei Luciano Mamoni,2 Eduardo Vieira Ponte1
1Department of Internal Medicine, Jundiaí School of Medicine; 2Department of Pathology,
Jundiaí School of Medicine, Brazil
Correspondence: Eduardo Vieira Ponte, Department of Internal Medicine, Jundiaí School of
Medicine, Rua Francisco Telles, 250, Vila Arens II, Jundiaí-SP, ZIP 13.202-550, Brazil.
Tel.: 55 (11) 3395-2133. E-mail: evponte@yahoo.com.br
Contributions: DGR, ALBG, conceptualization, data curation, investigation, methodology,
project administration, resources, supervision, validation, visualization, roles/writing - original
draft, writing - review and editing; MOB, conceptualization, data curation, investigation,
methodology, resources, supervision, validation, visualization, roles/writing - original draft,
writing - review and editing; LATS, JRB, data curation, investigation, methodology, project
administration, resources, supervision, validation, visualization, roles/writing - original draft,
writing - review and editing; DA, data curation, investigation, methodology, resources,
supervision, validation, visualization, roles/writing - original draft, writing - review and editing;
RLM, formal analysis, funding acquisition, investigation, methodology, supervision, validation,
visualization, roles/writing - original draft, writing - review and editing; EVP,
conceptualization, data curation, formal analysis, funding acquisition, investigation,
methodology, project administration, resources, software, supervision, validation,
visualization, roles/writing - original draft; writing - review and editing
Conflict of interest: the authors declare no conflict of interest
Ethics approval and consent to participate: the institutional review board of the Jundiaí School
of Medicine approved the study, approval number 5.221.754.
Informed consent: all individuals included in the study signed the informed consent.
Availability of data and materials: all data underlying the findings are fully available.
Funding: FAPESP grant 2023/07590-0. FAPESP was not involved in the design of the study,
data collection, data analysis, interpretation of the data, preparation, review, and approval of
the manuscript.
Abstract
In the real world, health professionals need to care for individuals with asthma-like symptoms
who have a persistently negative bronchodilator response (BDR). Little is known about the
evolution of symptoms and lung function of these individuals because they are usually
excluded from studies on asthma. The aim of this study was to evaluate whether individuals
with asthma-like symptoms but with a persistently negative BDR have a different evolution of
symptoms and lung function compared to individuals with asthma proven by positive BDR.
This prospective cohort study included adults with asthma-like symptoms. Individuals
participated in two visits 12 months apart. They responded to questionnaires and underwent a
spirometry test. In individuals without airway obstruction in the first visit, those with asthma-
like symptoms and persistently negative BDR were less likely to lose forced expiratory volume
in the first second during follow-up or progress to airway obstruction at the final visit compared
to individuals with asthma proven by positive BDR. Among individuals with airway obstruction
at baseline, those with asthma-like symptoms and persistently negative BDR were less likely
to resolve the airway obstruction during follow-up compared to individuals with asthma
proven by positive BDR. In individuals with proven asthma, the emergence or persistence of
positive BDR during follow-up was accompanied by a worsening of asthma outcomes
compared to the remission of positive BDR. Thus, BRD is an accessible marker of disease
progression in individuals with asthma-like symptoms. In individuals with asthma proven by
positive BDR, the trend in BDR was associated with the evolution of symptoms and lung
function.
Key words: airway inflammation, bronchial hyperresponsiveness, airway remodeling, airway
smooth muscle, bronchodilator response.
Introduction
Studies indicate that the intrinsic contractility of human airway smooth muscle cells (ASM) is
not different between individuals with asthma and healthy individuals [1], but inflammatory
mediators produced in the airways of asthmatic individuals stimulate these cells to proliferate
[2,3]. The consequences of ASM hyperplasia and hypertrophy are bronchial hyper-
responsiveness (BHR), loss of lung function and irreversible airway obstruction [4].
Guidelines require evidence of BHR or bronchodilator response (BDR) for the diagnosis of
asthma [5]. More than 200 ml and 12% increase of Forced Expiratory Volume in the first
second (FEV1) after bronchodilator in the spirometry test is evidence of BDR, but 36 to 83% of
individuals with asthma have negative BDR in a single test [6-8]. Studies have shown that
asthmatics with negative BDR have less eosinophilic airway inflammation [9,10]. In these
individuals, the guidelines recommend repeating spirometry later to try to detect the presence
of immediate BDR; or perform a bronchoprovocation test with methacholine to investigate
BHR, but this last test is rarely available in clinical practice.
In the real world, health professionals need to care for individuals with asthma-like symptoms
who have a persistently negative BDR on repeated spirometry. Little is known, however, about
the evolution of symptoms and lung function of these individuals, because they are usually
excluded from studies on asthma. Therefore, the primary objective of this study was to evaluate
whether individuals with asthma-like symptoms but with a persistently negative BDR have a
different evolution of symptoms and lung function compared to individuals with asthma
proven by positive BDR. The secondary objective was to evaluate, in individuals with asthma
proven by a positive BDR, if the evolution of BDR during follow-up is associated with the
variation in the symptom score and lung function.
Materials and Methods
We conducted this prospective cohort study in Jundiaí, a 400,000-inhabitant city in southeast
Brazil. We screened consecutive individuals attending a scheduled spirometry test requested
by physicians from any of the 42 public health facilities in the municipality; therefore, the
sample is representative of the population of users of the public health service. The recruitment
period was from January 2021 to July 2022.
We included individuals aged 18 years or older reporting typical asthma symptoms for two
years or more. We excluded current smokers; smoking history above 5 pack-years; pregnant
women; history of tuberculosis treatment; thoracic surgery; exposure to indoor air pollution;
occupational risk factors for COPD or pneumoconiosis; and those unable to achieve American
Thoracic Society (ATS) requirements in the spirometry test. All individuals included in the study
signed the informed consent. The institutional review board of the Jundiaí School of Medicine
approved the study, approval number 5.221.754.
Individuals participated in two study visits twelve months apart. In each study visit, they
attended a consultation with a chest physician, responded study questionnaires and underwent
a spirometry test. Between study visits, individuals had one intermediate consultation with
their referring physician. The researchers did not inform the referring physician about the
hypothesis and purpose of the research.
Study procedures and definitions
In both study visits, the chest physician in charge of the research interviewed the volunteers,
obtained clinical and demographic information, reviewed prescriptions and inspected
medicines to record the drugs that individuals were taking during the preceding eight weeks.
The record of pharmacological treatment considered the drugs and the quantity actually used.
We instructed in advance that individuals bring to the study visit the prescriptions and
medications so that the chest physician in charge of the research could confirm the patient's
report. A trained healthcare professional applied the Asthma Control Test (ACT). This
questionnaire measures the severity of asthma symptoms in a scale from five to 25, highest
values indicating less symptomatology. The 19-point score discriminates controlled from
uncontrolled symptoms [11]. In each study visit, individuals underwent a spirometry test with
a Koko PDS® equipment and repeated the test twenty minutes after 400 mcg of salbutamol
administration to measure the immediate BDR. Salbutamol was administered through a spacer.
We advised individuals to discontinue bronchodilators in the 24 hours prior to carrying out
the study spirometry. The spirometer was calibrated daily with a 3-liter syringe. Trained
respiratory therapists executed the spirometry tests according to the ATS protocol. Briefly, all
tests had at least three reproducible curves; all curves would need to have retro-extrapolated
volume below 5% and end of the curve in a plateau. The researcher in charge evaluated all
spirometry exams for quality. Individuals who were unable to perform spirometry according
to ATS criteria were excluded from the study. The criteria for positive BDR in the spirometry
test were FEV1 variation after bronchodilator greater than 12% and 200 ml.
The chest physician in charge of the research identified individuals with asthma-like symptoms
through an in-depth interview, physical examination and review of medical records. Some
clinical evidence of asthma-like symptoms were recurrent wheezing, cough or dyspnea lasting
longer than two years, lability of symptoms, symptoms improvement after ICS maintenance
therapy, and symptoms relief after bronchodilator. It was crucial for the individual's inclusion
in the study that there was evidence of typical asthma-like symptoms for at least 2 years.
Individuals with asthma-like symptoms and a positive BDR in at least one of the two spirometry
tests performed during the study were labeled as ¨Asthma¨. Individuals with a negative BDR in
both spirometry tests performed during the study were named “Asthma-like symptoms”. To
meet the main objective of the study, we compared the evolution of symptoms and lung
function between these two groups.
Subsequently, individuals with “Asthma” were grouped according to the evolution of their
BDR during follow-up in the study. Individuals with a positive BDR at the first study visit but
negative BDR at the second study visit were named “Remission of BDR”. Individuals with
negative BDR on the first study visit who presented positive BDR on the second visit were
labeled ¨Emergence of BDR¨. Individuals with positive BDR at both study visits were called
¨Persistently positive BDR¨. To meet the secondary objective of the study, we compared the
evolution of symptoms and lung function between the group “Remission of BDR” and the other
two groups.
We computed comorbidities whenever the individual reported current use of any
pharmacological therapy for the referred illnesses [12].
Statistical analyses
The primary outcome was loss of lung function. Loss of more than 200 ml in FEV1 between
the first and last study visits defined loss of lung function because this amount of loss is large
enough to ensure that it is not random according to data from two Brazilian cohorts. [13,14].
Secondary outcomes were variation in the intensity of respiratory symptoms (any improvement
or worsening of the ACT score) and airway obstruction at the final study visit. Criterion of
airway obstruction was FEV1/FVC ratio below the lower limit of normality.
We calculated a minimum sample of 93 individuals in each group considering that 70% of
individuals in the ¨Asthma¨ group would lose lung function over one year of follow-up; and
50% in the ¨Asthma like symptoms ¨ group. The basis for this estimate comes from a Brazilian
cohort, which showed that 70% of adults with asthma lose lung function over one year [13].
The alfa error was set in 0.05 and the power was 80%. It is relevant that the descriptive and
comparative analyses were stratified by the presence of pre-BD airway obstruction at baseline,
because individuals with airway obstruction are more likely to have positive BDR [15]. We
applied the Chi-Square test to compare nominal variables between two groups, while the
Mann-Whitney test compared ordinal and continuous variables. We used binary logistic
regression analyzes to measure the risk of loss of lung function (dependent variable) in
individuals with ¨Asthma-like symptoms¨ compared to individuals with ¨Asthma¨ (independent
variable). A similar model was used to assess whether the independent variable was associated
with the variation of symptoms score during follow-up (V2 ACT score - V1 ACT score) and
airway obstruction at the last study visit (SPSS 25, IBM, Armonk, New York). We adjusted the
analyzes for age, gender, lung function at baseline, symptoms score at baseline and asthma
maintenance therapy at baseline because these covariates might modify the relationship
between the dependent and independent variables [16-19]. In individuals with ¨Asthma¨,
binary logistic regressions assessed whether the groups with ¨Persistence¨ or ¨Emergence¨ of
BDR had worse asthma outcomes compared to the group with ¨Remission of BDR¨.
The method of data entry into the regression model was the Backward Likelihood Ratio. The
level of significance required for a given variable to remain in the model was 0.10. We used
the Hosmer-Lemeshow test (HL) to measure goodness-of-fit, and the Tolerance test (Tol) and
Variance Inflation Factor (VIF) to measure collinearity. Data and model fitted together (HL >
0.05) and we observed no collinearity (Tol > 0.10 and VIF < 10).
Results
We screened 3,626 individuals referred for spirometry test during the recruitment period.
Various respiratory and non-respiratory morbidities justified the request for spirometry by the
referring physician. We did not enroll 1,891 individuals without asthma-like symptoms and
341 individuals aged bellow 18 years old. Five hundred and twelve individuals were not
included because they met any exclusion criteria. Thus, we enrolled 882 individuals, but we
lost the follow-up of 182. Seven hundred individuals completed all study visits, of which 437
without airway obstruction in the first study visit (110 individuals with “Asthma” and 327 with
“Asthma-like symptoms”) and 263 with airway obstruction (133 individuals with “Asthma”
and 130 with “Asthma-like symptoms”).
Table 1 shows baseline characteristics of individuals without airway obstruction. Individuals
with ¨Asthma-like symptoms¨ had higher pre-BD lung function valuescompared to individuals
with ¨Asthma¨, whilst all other characteristics were similar between groups. Table 2 shows
that, among individuals with airway obstruction, those with ¨Asthma-like symptoms¨ were
older, had more comorbidities, used a greater amount of asthma maintenance therapy and had
a lower post-bronchodilator FEV1 value at baseline compared to individuals with ¨Asthma¨.
Among individuals without airway obstruction, the dose variation of inhaled corticosteroids
maintenance therapy from the first to the second study visit was similar (p 0.34) between
individuals with ¨Asthma-like symptoms¨ [0 (-320, 0) mcg per day] and those with asthma
proven by positive BDR [0 (-240, 200) mcg per day]. In individuals with airway obstruction,
the variation in inhaled corticosteroid dose was also similar between the groups [0 (0, 400) &
0 (0, 400) mcg per day; p 0.86].
Table 3 presents the longitudinal data of individuals without airway obstruction at baseline.
Compared to individuals with ¨Asthma¨, those with ¨Asthma-like symptoms¨ were less likely
to lose FEV1 during follow-up or evolve to pre-BD airway obstruction at the final study visit.
Table 4 describes that, among individuals with airway obstruction at baseline, those with
¨Asthma-like symptoms¨ were less likely to resolve the airway obstruction during follow-up
compared to individuals with ¨Asthma¨.
In individuals with ¨Asthma¨, the emergence or persistence of positive BDR during follow-up
was accompanied by worsening of asthma outcomes compared to the remission of positive
BDR (Table 5).
Discussion and Conclusions
This study shows that, in the absence of airway obstruction at baseline, individuals with
asthma-like symptoms and persistently negative BDR had more favorable outcomes compared
to individuals with asthma proven by positive BDR. We are unaware of research that has
investigated the disease progression of these individuals who are not usually included in
studies on asthma. We did not perform a methacholine bronchoprovocation test to confirm
the diagnosis of asthma, therefore, we preferred to label individuals with persistently negative
BDR as ¨Asthma-like symptoms¨. It is meaningful that only individuals with typical asthma
symptoms, according to the careful assessment of experienced pulmonologists, were included
in the study; even so, we cannot rule out the possibility that few of them might have another
illness simulating asthma. This limitation does not reduce the importance of the results and
conclusions, as the intention of the study was to evaluate the disease progression of a
population that frequently presents to healthcare professionals. We believe this information
will help plan the management of the disease of these individuals.
In individuals with airway obstruction at baseline, those with asthma-like symptoms and
persistently negative BDR had worse lung function and greater use of maintenance therapy at
the initial study visit compared with individuals with asthma proven by positive BDR. During
follow-up, individuals with persistently negative BDR had a lower chance of resolving their
airway obstruction. We hypothesize that the persistently negative BDR in these individuals
results from the control of eosinophilic inflammation due to the use of a high dose of inhaled
corticosteroids, while the persistence of airway obstruction during follow-up might be due to
underlying airway remodeling. This hypothesis is supported by studies that demonstrated less
eosinophilic inflammation and greater concentration of biomarkers of airway remodeling in
the airways of asthmatic individuals with little response to BD when compared to asthmatic
individuals with an intense response to BD [9,10,15].
A cross-sectional study by Denlinger et al observed that the intensity of bronchodilator
response in individuals with severe asthma was associated with self-reported exacerbations in
the previous year [20]. We observed, in individuals with asthma proven by positive BDR, that
the ¨emergence¨ or ¨persistence¨ of positive BDR during follow-up was accompanied by
worsening of asthma outcomes compared to the remission of positive BDR. Compared to
Denlinger's study, our study has the quality of its prospective design and greater external
validity, as it included individuals from all spectrums of asthma severity. Studies would need
to investigate whether immediate BDR could be used as an additional information to guide the
titration of asthma maintenance therapy. The methacholine bronchoprovocation test is a useful
tool to guide asthma maintenance therapy in adults and children [21,22], but the lack of
availability of the broncoprovocation test makes its use in clinical practice unfeasible.
It is relevant that individuals with COPD probably did not contaminate the group with airway
obstruction and negative BDR because we excluded individuals exposed to risk factors for
COPD and the prevalence of alpha-1-antitrypsin deficiency is usually very low [23]. Positive
aspects of this study were the enrollment of individuals from various primary and secondary
outpatient health facilities, the prospective design and adjusting analyzes for confounding
variables. Individuals maintained regular follow-up of asthma with their referring physician
between the study visits; thus, the management of asthma during the study matches real life
experiences. At the baseline visit, the ¨Asthma¨ and ¨Asthma-like symptoms¨ groups differed
with regard to some variables such as age, maintenance therapy and values of some spirometry
test parameters. These differences, however, did not bias the conclusions because the binary
logistic regressions were adjusted for covariates that could interfere with the interpretation of
the results. The researchers carefully quantified maintenance therapy used by study individuals
during the eight weeks preceding each of the two study visits, but they did not monitor
maintenance therapy over the one year between visits. We do not foresee, however, any reason
to suspect that there was a bias in the management of asthma during the follow-up, because
the dozens of referring physicians who managed asthma maintenance therapy during the
period between study visits were not aware of the study hypothesis. Finally, we adopted the
criteria of BDR recommended in GINA, but some societies have recently proposed new
guidelines for BDR [5,24].
We conclude that, in the absence of airway obstruction at baseline, individuals with asthma-
like symptoms and persistently negative BDR have a more favorable evolution of lung function
compared to individuals with ¨Asthma¨ proven by positive BDR. In clinical practice, this
information may help plan disease management in this understudied population. In individuals
with airway obstruction at baseline, the presence of asthma-like symptoms and negative BDR
was associated with a lower chance of resolving the airway obstruction. Studies need to
investigate whether these individuals have asthma with dominance of airway remodeling and
little eosinophilic inflammation. Finally, in individuals with asthma proven by positive BDR,
the trend in immediate BDR during follow-up was associated with the evolution of symptoms
and lung function.
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Table 1. Baseline characteristics of individuals without pre-bronchodilator (BD) airway
obstruction in the first study visit grouped according to the trajectory of immediate response
to bronchodilator (BDR).
Asthma *
(N = 110)
Asthma-like
Symptoms
**
(N = 327)
p
Age in years – median (IQ)
56 (44-67)
56 (42-66)
0.39
Female gender - n (%)
88 (80)
265 (81)
0.76
Body mass index – median (IQ)
31 (27-35)
30 (26-34)
0.14
Smoking history, pack-years – median (IQ)
0 (0-0)
0 (0-0)
0.65
Diabetes mellitus and/or systemic arterial
hypertension - n (%)
53 (48)
165 (51)
0.64
Depression - n (%)
18 (16)
49 (15)
0.74
Asthma maintenance therapy according to the GINA,
n (%)
Step 1 or 2
Step 3 or 4
Step 5
36 (33)
56 (51)
18 (16)
93 (28)
165 (51)
69 (21)
0.47
Controlled symptoms of asthma, ACT > 19 – n (%)
48 (44)
154 (48)
0.45
FVC % predict, pre-BD – median (IQ)
84 (75-95)
90 (80-101)
<
0.01
FVC % predict, post BD – median (IQ)
92 (83-103)
91 (81-103)
0.85
FEV1 % predict, pre-BD – median (IQ)
80 (70-90)
85 (76-99)
<
0.01
FEV1 % predict, post BD – median (IQ)
88 (78-102)
89 (78-103)
0.59
* Individuals with asthma-like symptoms and positive BDR in any of the spirometry tests
performed during the study. ** Individuals with asthma-like symptoms and persistently
negative BDR on spirometry performed during the study.
Table 2. Baseline characteristics of individuals with pre-bronchodilator (BD) airway
obstruction in the first study visit grouped according to the trajectory of immediate response
to bronchodilator (BDR).
Asthma *
(N =133)
Asthma-
like
Symptoms
**
(N = 130)
p
Age in years – median (IQ)
53 (40-63)
59 (47-71)
< 0.01
Female gender - n (%)
95 (71)
83 (64)
0.19
Body mass index – median (IQ)
28 (24-34)
28 (24-31)
0.23
Smoking history, pack-years – median (IQ)
0 (0-0)
0 (0-0)
0.14
Diabetes mellitus and/or systemic arterial hypertension
- n (%)
47 (35)
66 (51)
0.01
Depression - n (%)
21 (16)
19 (15)
0.79
Asthma maintenance therapy according to the GINA,
n (%)
Step 1 or 2
Step 3 or 4
Step 5
34 (26)
64 (48)
35 (26)
19 (15)
51 (39)
60 (46)
< 0.01
Controlled symptoms of asthma – n (%)
52 (40)
58 (46)
0.38
FVC % predict, pre-BD – median (IQ)
81 (68-96)
86 (71-
100)
0.12
FVC % predict, post BD – median (IQ)
91 (80-103)
89 (74-
102)
0.10
FEV1 % predict, pre-BD – median (IQ)
59 (46-74)
63 (51-77)
0.30
FEV1 % predict, post BD – median (IQ)
73 (58-86)
66 (53-81)
0.03
* Individuals with asthma-like symptoms and positive BDR in any of the spirometry tests
performed during the study. ** Individuals with asthma-like symptoms and persistently
negative BDR on spirometry performed during the study.
Table 3. Binary logistic regression analyzes to evaluate whether the trajectory of immediate response to bronchodilator (BDR) is associated
with respiratory outcomes during the follow-up, in individuals without pre-bronchodilator (BD) airway obstruction at baseline.
Odds Ratio (95 Confidence Interval)
Crude
p
Adjusted
p
Worsening of ACT score *
Asthma a
Asthma-like symptoms b
-
0.80 (0.46-1.41)
0.45
-
0.78 (0.44-1.38)
0.39
> 200 ml FEV1 decline - pre-BD **
Asthma a
Asthma-like symptoms b
-
0.60 (0.39-0.93)
0.02
-
0.41 (0.25-0.66)
< 0.01
> 200 ml FEV1 decline - post BD **
Asthma a
Asthma-like symptoms b
-
0.60 (0.39-0.93)
0.02
-
0.52 (0.32-0.84)
< 0.01
Emergence of pre-BD airway obstruction **
Asthma a
Asthma-like symptoms b
-
0.30 (0.16-0.57)
< 0.01
-
0.42 (0.21-0.83)
< 0.01
Emergence of post-BD airway obstruction **
Asthma a
Asthma-like symptoms b
-
0.67 (0.22-1.99)
0.47
-
0.81 (0.24-2.77)
0.74
* Adjusted for age, gender, ACT score at baseline and asthma maintenance therapy at baseline. **Adjusted for age, gender, equivalent lung-
function parameter at baseline and asthma maintenance therapy at baseline. a Individuals with asthma-like symptoms and positive BDR in any
of the spirometry tests performed during the study. b Individuals with asthma-like symptoms and persistently negative BDR on spirometry
performed during the study.
Table 4. Binary logistic regression analyzes to evaluate whether the trajectory of immediate response to bronchodilator (BDR) is associated
with respiratory outcomes during the follow-up, in individuals with pre-bronchodilator (BD) airway obstruction at baseline.
Odds Ratio (95 Confidence Interval)
Crude
p
Adjusted
p
Worsening of ACT score *
Asthma a
Asthma-like symptoms b
-
1.46 (0.75-2.83)
0.26
-
1.21 (0.60-2.41)
0.60
> 200 ml FEV1 decline - pre BD **
Asthma a
Asthma-like symptoms b
-
1.07 (0.62-1.87)
0.80
-
1.22 (0.67-2.21)
0.52
> 200 ml FEV1 decline - post BD **
Asthma a
Asthma-like symptoms b
-
1.16 (0.67-2.01)
0.60
-
1.16 (0.65-2.05)
0.62
Resolution of pre-BD airway obstruction **
Asthma a
Asthma-like symptoms b
-
0.65 (0.35-1.22)
0.18
-
0.52 (0.26-1.07)
0.08
Resolution of post BD airway obstruction **
Asthma a
Asthma-like symptoms b
-
0.44 (0.26-0.76)
< 0.01
-
0.76 (0.60-0.97)
0.04
* Adjusted for age, gender, ACT score at baseline and asthma maintenance therapy at baseline. **Adjusted for age, gender, equivalent lung-
function parameter at baseline and asthma maintenance therapy at baseline. a Individuals with asthma-like symptoms and positive BDR in any
of the spirometry tests performed during the study. b Individuals with asthma-like symptoms and persistently negative BDR on spirometry
performed during the study.
Table 5. Binary logistic regression to assess whether the trajectory of the immediate response to the bronchodilator (BDR) is associated with
the trend in symptoms and lung function in individuals with asthma proven by positive response to bronchodilator (BDR).
Odds Ratio (95 Confidence Interval)
Crude
p
Adjusted
p
Worsening of ACT score *
Remission of BDR (n = 99)
Emergence of BDR (n = 85)
Persistently positive BDR (n = 59)
-
2.21 (1.19-4.11)
0.93 (.44-1.96)
0.01
0.84
-
2.16 (1.15-4.05)
0.,82 (0.38-1.78)
0.01
0.61
> 200 ml FEV1 decline - pre-BD **
Remission of BDR (n = 99)
Emergence of BDR (n = 85)
Persistently positive BDR (n = 59)
-
13.07 (6.86-24.92)
2.70 (1.33-5.46)
< 0.01
< 0.01
-
14.79 (7.34-29.82)
4.48 (2.02-9.96)
< 0.01
< 0.01
> 200 ml FEV1 decline - post BD **
Remission of BDR (n = 99)
Emergence of BDR (n = 85)
Persistently positive BDR (n = 59)
-
0.65 (0.37-1.13)
0.98 (0.56-1.74)
0.10
0.95
-
0.71 (0.39-1.27)
0.80 (0.44-1.47)
0.25
0.48
Pre BD airway obstruction at the last study visit **
Remission of BDR (n = 99)
Emergence of BDR (n = 85)
Persistently positive BDR (n = 59)
-
6.41 (3.51-11.69)
3.53 (2.10-5.94)
< 0.01
< 0.01
-
15.49 (5.87-40.86)
9.69 (4.32-21.71)
< 0.01
< 0.01
Post BD airway obstruction at the last study visit **
Remission of BDR (n = 99)
Emergence of BDR (n = 85)
Persistently positive BDR (n = 59)
-
2.18 (1.25-3,80)
3.14 (1.75-5.62)
< 0.01
< 0.01
-
2.95 (1.41-6.17)
3.66 (1.70-7.88)
< 0.01
< 0.01
Comparison within three groups requires a p-value below 0.017 for statistical significance - Bonferroni correction. * Adjusted for age, gender,
ACT score at baseline and asthma maintenance therapy at baseline. **Adjusted for age, gender, equivalent lung-function parameter at baseline
and asthma maintenance therapy at baseline
