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Effects of Aerobic Training on Airway


Inflammation in Asthmatic Patients
FELIPE AUGUSTO RODRIGUES MENDES1, FRANCINE MARIA ALMEIDA2, ALBERTO CUKIER3,
RAFAEL STELMACH3, WILSON JACOB-FILHO4, MILTON A. MARTINS2,
and CELSO RICARDO FERNANDES CARVALHO1
1
Department of Physical Therapy, School of Medicine, University of São Paulo, São Paulo, BRAZIL; 2Department of Medicine,
School of Medicine, University of São Paulo, São Paulo, BRAZIL; 3Pulmonary Department, School of Medicine, University
of São Paulo, São Paulo, BRAZIL; and 4Department of Geriatrics, School of Medicine, University of São Paulo, São Paulo,
BRAZIL

ABSTRACT
MENDES, F. A. R., F. M. ALMEIDA, A. CUKIER, R. STELMACH, W. JACOB-FILHO, M. A. MARTINS, and C. R. F. CARVALHO.
Effects of Aerobic Training on Airway Inflammation in Asthmatic Patients. Med. Sci. Sports Exerc., Vol. 43, No. 2, pp. 197–203, 2011.
Purpose: There is evidence suggesting that physical activity has anti-inflammatory effects in many chronic diseases; however, the role of
exercise in airway inflammation in asthma is poorly understood. We aimed to evaluate the effects of an aerobic training program on
eosinophil inflammation (primary aim) and nitric oxide (secondary aim) in patients with moderate or severe persistent asthma. Methods:
Sixty-eight patients randomly assigned to either control (CG) or aerobic training (TG) groups were studied during the period between
medical consultations. Patients in the CG (educational program + breathing exercises; N = 34) and TG (educational program + breathing
exercises + aerobic training; N = 34) were examined twice a week during a 3-month period. Before and after the intervention, patients
underwent induced sputum, fractional exhaled nitric oxide (FeNO), pulmonary function, and cardiopulmonary exercise testing. Asthma
symptom-free days were quantified monthly, and asthma exacerbation was monitored during 3 months of intervention. Results: At
3 months, decreases in the total and eosinophil cell counts in induced sputum (P = 0.004) and in the levels of FeNO (P = 0.009) were
observed after intervention only in the TG. The number of asthma symptom-free days and V̇O2max also significantly improved
(P G 0.001), and lower asthma exacerbation occurred in the TG (P G 0.01). In addition, the TG presented a strong positive relation-
ship between baseline FeNO and eosinophil counts as well as their improvement after training (r = 0.77 and r = 0.9, respectively).
Conclusions: Aerobic training reduces sputum eosinophil and FeNO in patients with moderate or severe asthma, and these benefits were
more significant in subjects with higher levels of inflammation. These results suggest that aerobic training might be useful as an adjuvant
therapy in asthmatic patients under optimized medical treatment. Key Words: ASTHMA, EXERCISE, EOSINOPHILS, SPUTUM,
NITRIC OXIDE, SYMPTOMS

A
sthma is a chronic inflammatory disorder of the flammation, asthma symptoms, and limitations in daily life,
airways involving many cells and cellular elements. physical activities, or exercise (10).
The chronic inflammation is associated with airway The effect of regular physical activity on the overall man-
hyperresponsiveness that leads to recurrent episodes of agement of asthma has been previously considered, and there
wheezing, breathlessness, chest tightness, and coughing is evidence suggesting that an increase in exercise capac-
(10). The clinical treatment of the disease is centered on ity improves psychosocial factors (14) as well as reduces
corticosteroids and bronchodilators to reduce airway in- exercise-induced bronchoconstriction (6) and corticosteroid
consumption (6,17). Moreover, recent studies have also shown
that asthmatic patients with higher exercise capacity present
Address for correspondence: Celso R. F. Carvalho, P.T., Ph.D., Depart-
lower risk of exacerbation (7). Taken together, these results
ment of Medicine, School of Medicine, University of São Paulo, Av.
Dr. Arnaldo 455, Room 1210, 01246-903, São Paulo, SP, Brazil; E-mail: may suggest a possible role for physical activity in attenua-
cscarval@usp.br. tion of allergic airway inflammation.
Submitted for publication March 2010. The anti-inflammatory effects of physical activity in
Accepted for publication June 2010. healthy subjects and in many chronic diseases have previ-
0195-9131/11/4302-0197/0 ously been described (9,11,13); however, its role in allergic
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ diseases such as asthma is poorly understood. Recent studies
Copyright Ó 2011 by the American College of Sports Medicine in experimental animal models of asthma have shown that
DOI: 10.1249/MSS.0b013e3181ed0ea3 aerobic training reduces eosinophil counts in the airways,

197

Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
expression of allergic cytokines (IL-4, IL-5, and IL-13), and Experimental Design
airway remodeling (30,27). In asthmatic patients, there are
The study was performed between two medical consul-
only two studies (16,4) evaluating the effect of aerobic
CLINICAL SCIENCES

tations to avoid changes in medication. Patients were ran-


training on inflammation, and the only observed effect was
domized (by drawing lots) into control (CG; N = 34) or
a reduction in the blood immunoglobulin E levels (16).
training (TG; N = 34; Fig. 1) groups. Both groups participated
Therefore, the aim of the present study was to evaluate the
in a 4-h educational program and a breathing exercise pro-
effect of an aerobic training program on airway inflamma-
gram, but only the TG participated in an aerobic training
tion and asthma symptoms in patients with moderate or se-
program individually on the basis of V̇O2max. Before and after
vere asthma.
the intervention, patients underwent induced sputum, frac-
tional exhaled nitric oxide (FeNO), pulmonary function, and
cardiopulmonary exercise testing. Asthma symptom-free days
METHODS were quantified monthly. To prevent issues of compliance, the
Patients transport costs for every patient were covered by the re-
searcher grants. Patients from both groups completed all 24
Sixty-eight patients (55 women and 13 men) with mod-
intervention sessions from either CG or TG.
erate or severe persistent asthma between 20 and 50 yr of
age were recruited at a university hospital. Asthma diagnosis
was based on the Global Initiative for Asthma (10). Patients
Educational Program
were under medical treatment for at least 6 months and were
considered clinically stable (i.e., no crises or changes in Both groups completed an educational program that
medication for at least 30 d). Patients diagnosed with car- consisted of two classes (once a week), and each class lasted
diovascular, pulmonary, or musculoskeletal diseases that 2 h. The core activity was based on an educational videotape
would impair exercise training were excluded from the about the ‘‘ABC of Asthma,’’ including information about
study. The clinic’s hospital ethics committee approved the asthma pathophysiology, medication skills, self-monitoring
study, and patients signed informed consent forms. Some techniques, and environmental control/avoidance strategies
patients (26/68) participated simultaneously in a study that (10,14,24). Patients’ doubts were addressed during an in-
was recently published (14). teractive discussion.

FIGURE 1—Study flow diagram.

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Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Breathing Exercise Program pressure of 12 cm H2O to avoid air contamination from the
nasal cavity. Exhaled mouth air was filtrated before being
Both groups were taught yoga breathing exercises in-
collected in the bag, and the expiratory pressure achieved by

CLINICAL SCIENCES
cluding Kapalabhati (fast expiratory breathing exercise fol-
the individual was monitored by a manometer. All collected
lowed by passive inhalation), Uddhiyana (full exhalation
samples were mixed up to 10 s before the determination
followed by a forced inspiration performed without air in-
of NO concentration by chemiluminescence (Sievers 280
halation (apnea)), and Agnisara (full exhalation followed by
NOA; Sievers Instruments, Boulder, CO) and analyzed up to
a sequence of retractions and protrusions of the abdominal
24 h after sample collection as previously described (2). The
wall in apnea) (14,29). A 30-min session was performed
equipment was calibrated before the start of each analysis.
twice a week for 3 months, and every exercise was executed
Clinical asthma symptoms were quantified by a daily di-
in sets of three with 2 min of exercise intercalated with 60 s
ary, including asthma symptoms such as cough, diurnal or
of rest (14).
nocturnal dyspnea, wheezing, and use of relief medication.
Aerobic Training Program A day free of asthma symptoms was considered when a
patient did not report any symptoms. All patients were fa-
Subjects from the TG completed an aerobic training pro- miliarized with the diary during the 30 d before the study.
gram for 30 min per session twice a week for 3 months in an The diary was filled out during the follow-up period, and
indoor treadmill. Aerobic exercise was initiated at 60% of symptom-free days were quantified monthly. Visits to an
V̇O2max in the first 2 wk and then increased to 70% V̇O2max emergency room and exacerbation of asthma symptoms
(14). After this increase, if the patient maintained two con- were also monitored in the daily diary. Asthma exacerbation
secutive exercise sessions without symptoms, then exercise was defined as worsening of asthma symptoms requiring
intensity was increased by 5% of cardiac frequency (until a the use of short-acting A2-agonist Q4 extra puffs per day for
maximal of 80% patient maximal cardiac frequency) by a minimum of 48 h.
using either treadmill speed or grade. The use of salbutamol Spirometry was performed before and after the inhalation
(200 Kg) before an exercise session was recommended only of 200 Kg of salbutamol (SensormMedics 229; Sensor-
if the peak expiratory flow (PEF) was G70% of the patient’s Medics Corp., Yorba Linda, CA), and technical procedures
best value. The safety of aerobic training was monitored by were performed as recommended by the American Thoracic
quantifying PEF and asthma symptoms at the end of every Society/European Respiratory Society (1). Predicted normal
exercise session. values were those proposed by Knudson et al. (12), and
a 12% and a 200-mL increase in FEV1 from baseline were
Assessments
characterized as a positive response to the bronchodilator.
Induced sputum. After premedication with 400 Kg of Cardiopulmonary exercise testing was evaluated by a
salbutamol, 3% of hypertonic saline was administered by symptom-limited treadmill test on a digital computer-based
inhalation over 15 min (20,21). The aerosol was generated by exercise system (SensormMedics 229) with breath-by-breath
an ultrasonic nebulizer (Ultraneb 99; DeVilbiss, Somerset, analysis according to the Balke-modified protocol (26).
PA) with an output of 2.4 mLIminj1 and a mass median A bronchodilator (200 Kg of salbutamol) was used 15 min
aerodynamic diameter of 4.5 Km as previously described before cardiopulmonary exercise testing to allow patients to
(20). The subjects were asked to blow their nose and to rinse reach maximal oxygen consumption. Aerobic impairment
their mouth with water and swallow it to reduce contamina- was classified according to Cooper et al. (5).
tion of the sputum specimen with postnasal drip and saliva.
Sputum samples were visually separated from saliva with the Statistical Analysis
help of an inverted microscope and divided into two aliquots.
The sample size of 46 patients (23 each group) was calcu-
One part was spread over a glass slide before fixation and
lated considering a decrease of 10% in eosinophil cell counts
staining (19,25). The slide was air dried, fixed, and stained
with a standard deviation of 12% as previously observed (15)
with Diff Quick (Sigma-Aldrich, São Paulo, Brazil). The
second aliquot was treated with 0.1% of dithiothreitol TABLE 1. Baseline anthropometric data, bronchodilator response, and corticosteroid
(Sigma-Aldrich), and the mixture was briefly stirred with a consumption in patients with persistent asthma.

vortex mixer (25). Total cell counts were performed with a CG (n = 24) TG (n = 27) P

hemocytometer (Neubauer chamber) (22), and the cell sus- Anthropometric data
Gender (female/male)a 18/6 24/3 NS
pensions were adjusted to 1.0  106 mLj1 (8). Cells were Age (yr)b 36.0 (22.0–47.5) 37.9 (25.7–47.3) NS
classified as eosinophils, lymphocytes, neutrophils, macro- BMI (kgImj2)b 25.8 (18.2–29) 24.5 (19.4–29.2) NS
Bronchodilator respondersa 6 (27%) 3 (16%) NS
phages, squamous cells, goblet, and ciliated cells on the basis Long-acting A2-agonists (KgIdj1) 24 (12–39) 24 (12–36) NS
of their morphology by a single-blinded investigator. The in- Budesonide dosage (KgIdj1)b 800 (400–1600) 800 (400–1200) NS
vestigator who performed clinical tests had access to induced Data are expressed as median (95% CI), except for gender and bronchodilator re-
sputum data only at the end of the intervention program. sponders, which are presented as numbers of patients and percentages, n (%).
BMI, body mass index; NS, not statistically significant.
Fractional exhaled nitric oxide. Patients were ad- a
Chi-square test.
vised to blow into a Mylar bag, keeping the expiratory b
Mann–Whitney test.

EXERCISE ON ASTHMA AIRWAY INFLAMMATION Medicine & Science in Sports & Exercised 199

Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
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FIGURE 2—Percentages of cells in induced sputum before and after intervention. Eosinophils (A); total cells (B); macrophages (C); neutrophils (D).
*P e 0.05 compared with baseline and CG values (two-way repeated-measure ANOVA test). Boxes represent the 25th–75th percentiles, the line inside
the boxes represents the median, and the bars represent the 10th and 90th percentiles.

and considering the average number of eosinophils ob- The Fisher test was used to evaluate emergency room visits
served in our patients with moderate and severe asthma and asthma exacerbation. The linear correlation analysis was
(25). The statistical power normality was evaluated by using evaluated by the Spearman test. The statistical significance
the Kolmogorov–Smirnov test, and data were presented as level was set at 5% for all tests. Sigma Stat Software Package
medians with a 95% confidence interval (CI). The Mann– 3.5 was used for statistical analyses.
Whitney test was used to compare nonparametric data (age,
body mass index (BMI), and corticosteroid dosage), and the
RESULTS
chi-square test was used to evaluate gender and bronchodi-
lator response between groups at baseline. Induced sputum Seventeen patients (10 CG/7 TG) withdrew from the study
cellularity (primary outcomes), FeNO (secondary outcomes), because of health problems other than asthma, scheduling
and all other outcomes were assessed by a two-way repeated- difficulties, or personal problems. Fifty-one patients com-
measures ANOVA followed by a Holm–Sidak post hoc test. pleted the study (24 CG/27 TG). Before the study, both groups

FIGURE 4—Asthma symptoms during the study period. Values are


expressed as the mean number of symptom-free days per month with a
95% CI. Time points are as follows: 0 d, 1 month before intervention;
FIGURE 3—FeNO before and after the study. *P G 0.05 when com- 30 d, first month of intervention; 60 d, second month of intervention;
pared with CG and baseline values (two-way repeated-measure 90 d, third month of intervention. *P G 0.05 when compared with
ANOVA test). baseline and CG values (two-way repeated-measure ANOVA test).

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Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
TABLE 2. Pulmonary function and maximal aerobic capacity of adult asthmatic patients before and after the treatment program.
CG (n = 24) TG (n = 27)
Before After Before After P

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Pulmonary function
FEV1 (L) 2.52 (1.3–3.2) 2.5 (1.3–3.5) 2.2 (1.2–3.2) 2.3 (1.0–3.4) 0.71
% predicted 85.5 (45.4–112.6) 84.4 (42.0–114.4) 79.9 (43.5–107.0) 79.6 (37.5–106.5) 0.89
FVC (L) 3.4 (2.3–4.3) 3.4 (2.4–4.60) 3.1 (1.9–4.1) 3.1 (2.4–4.3) 0.86
% predicted 90.0 (68.9–109.1) 92.1 (62.7–112.1) 94.0 (65.3–116.3) 96.2 (66.2–117.5) 0.83
FEV1/FVC 69.0 (48.7–89.4) 67.9 (49.5–89.1) 71.7 (53.4–87.7) 69.9 (46.6–92.3) 0.62
FEF25%–75% (LIsj1) 1.7 (0.4–3.8) 1.4 (0.4–4.0) 1.8 (0.532–4.0) 1.8 (0.3–4.5) 0.91
% predicted 40.0 (12.5–119.7) 37.0 (13.0–127.6) 54.7 (17.2–104.9) 54.4 (13.1–110.0) 0.89
Maximal aerobic capacity
V̇O2max (% predicted) 73.4 (52.5–98.3) 75.6 (57.6–99.5) 73.5 (43.6–96.3) 88.0 (64.9–109.3)* G0.001
Data are expressed as median (95% CI).
FEV1, forced expired volume in the first second; FVC, forced vital capacity; FEF, forced expiratory flow.
* P G 0.05 when compared with the intragroup value before treatment using a two-way repeated-measure ANOVA test.

were similar in gender, age, BMI, daily doses of cortico- after 60 and 90 d of aerobic training (24 d each) compared
steroids, and long-acting A2-agonists (P 9 0.05; Table 1), in- with baseline and CG values (P G 0.001; Fig. 4). During the
duced sputum celullarity (P 9 0.05; Fig. 2), FeNO (P 9 0.05; 3 months of intervention, the number of visits to the emer-
Fig. 3), asthma symptoms (P 9 0.05; Fig. 4), pulmonary gency room (4CG/1TG) and asthma exacerbations (7CG/1TG)
function (P 9 0.05; Table 2), and aerobic capacity (P 9 0.05; was lower in the TG compared with the CG (P G 0.01).
Table 2). All patients were under budesonide and long- Linear relationship among outcomes. The TG
acting A2-agonists prescription (Table 1), and both groups presented a strong linear relationship between the baseline
maintained the same medication dosage throughout the eosinophil counts (r = 0.90, P G 0.001) and their reduction
intervention. after exercise training ($ initial–final). Similar results were
Induced sputum cellularity. After training, only the observed in the FeNO levels (r = 0.76, P G 0.01). In addi-
TG presented a reduction in eosinophil and total cells counts tion, a negative linear relationship was observed between
compared with the baseline and the CG values (Fig. 2). No the baseline number of days without asthma symptoms and
changes were observed in macrophage, neutrophil, lym- an increase in symptom-free days after aerobic training
phocyte, and epithelial cell counts (squamous, goblet, and ($ initial–final) (r = j0.58, P = 0.003).
ciliated) between both groups after intervention (P 9 0.05).
The effect of training on FeNO. Before intervention,
DISCUSSION
patients from both groups presented, on average, a FeNO of
31.0 ppb (95% CI from 14.6 to 55.7), and 51% of the The results of the present study demonstrate that adults
patients (12 CG/16 TG) presented increased levels of FeNO with moderate or severe asthma who participated in an
(930 ppb). After intervention, the TG presented a decrease aerobic training program presented a decrease in eosinophil
in FeNO when compared with the baseline and the CG and total cell counts in the induced sputum as well as a
(Fig. 3; P = 0.009), and only 36% of patients from the TG reduction in FeNO levels and asthma symptoms. These
(10/27) had FeNO 930 ppb. The CG did not present any benefits were significantly associated with baseline values,
change in the FeNO after intervention (P 9 0.05). suggesting that the worse the airway inflammation and the
The effect of training on aerobic capacity and asthma symptoms were, the greater the improvement in-
pulmonary function. At baseline, 44% of the patients duced by aerobic training.
(22/51) presented V̇O2max values G70% of predicted. After The effect of physical fitness on airway inflam-
the study, only the TG showed an increase in V̇O2max mation. To the best of our knowledge, this study is the
compared with the CG (P G 0.001; Table 2) without changes first to verify a reduction in airway inflammation after aer-
in pulmonary function (Table 2). A positive response to obic training in asthmatic patients. Although the anti-
training (improvement in V̇O2max Q10%) was found in 24 inflammatory effects of physical activity in healthy subjects
patients (88%) who were considered ‘‘responders.’’ No and in many chronic diseases have previously been de-
patients presented a decrease in PEF Q15% or an increase scribed (9,11,13), its role on asthma, an airway inflamma-
in asthma symptoms after each exercise session. tory disease, is poorly understood. Recent experimental
Asthma symptoms. At baseline, the TG presented studies in animal models of asthma from our group sug-
16 dImonthj1 (from 4.0 to 28.3) without asthma symptoms gested that mice submitted to aerobic training presented
versus 14 dImonthj1 (from 5.2 to 24.7) for the CG (Fig. 4). decreases in the number of eosinophils, airway inflamma-
The CG had similar numbers of days without asthma symp- tion, and remodeling (27,30). In addition, those studies
toms after 30, 60, and 90 d (P 9 0.05). Nevertheless, the TG showed that these effects seem to occur in response to a
presented a significant increase in the number of days with- decreased expression of Th2 cytokines (IL-4, IL-5, and
out asthma symptoms after 30 d (20.0 d, 95% CI from IL-13) and NF-JB as well as an increased expression of
4.0 to 28.2, P G 0.001), and this difference was maintained anti-inflammatory cytokines IL-10 and IL-1ra.

EXERCISE ON ASTHMA AIRWAY INFLAMMATION Medicine & Science in Sports & Exercised 201

Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
We are aware of only two studies aiming to evaluate the but the physiological basis of this perception has not been
anti-inflammatory effects of aerobic training in asthmatics systematically investigated (23). The current hypothesis to
patients (4,16). Morreira et al. (16) evaluated the effect of explain the benefits of physical activity in patients with
CLINICAL SCIENCES

aerobic training in 34 asthmatic children and did not ob- asthma is the decrease in minute ventilation, which reduces
serve changes on FeNO, blood eosinophils, eosinophil cat- the perception of breathlessness (23). In our study, patients
ionic protein, and C-reactive protein levels. In addition, who participated in the aerobic training program presented
they showed a reduction in total immunoglobulin E levels. an improvement in aerobic capacity and also a reduction in
Bonsignore et al. (4) evaluated the levels of FeNO in 50 airway inflammation, which might suggest another hypoth-
children with mild persistent asthma and did not show a esis for the reduction in asthma symptoms because of exer-
reduction in FeNO after aerobic training. The discrepancy cise training. We did not observe any effect in patients that
between our findings and those previously obtained by completed the yoga breathing exercises, and this may be
Morreira et al. (16) and Bonsignore et al. (4) may be ex- because we used only three exercises without increasing the
plained by exercise training, evaluated outcomes, and the grade of difficulty. In the present study, our strategy was to
patients’ disease severity. First, in our study, the intensity of follow-up with the CG twice a week, similar to the training
exercise during aerobic training was monitored and graded group, to reduce any possible bias toward a better treatment
by the cardiovascular response (heart rate), whereas in the between groups and not to compare yoga versus aerobic
studies of Morreira et al. (16) and Bonsignore et al. (4), training. On the basis of our results, we cannot assume that
the progression in exercise training was not precisely de- yoga is ineffective for asthmatic patients.
scribed. This difference may explain why the increase in It remains poorly understood which asthmatic patients
maximal aerobic capacity observed in our patients was at a benefit the most from exercise training. In our study, we ob-
similar level to that described in a recent systematic review served that patients with higher baseline scores, even when
(4.8 vs 5.5 mL O2Ikgj1minj1, respectively) (23). In con- they already received proper medical treatment, presented
trast, Bonsignore et al. (4) only observed an increase in the better improvement of asthma symptoms and airway inflam-
submaximal capacity (anaerobic threshold), and Morreira mation. These results seem relevant to clinical prescription
et al. (16) did not evaluate such parameters. of exercise training in this population; that is, they suggest
Second, to evaluate asthma inflammation, we quantified that aerobic training should be recommended to patients who
sputum eosinophil counts and FeNO levels and observed continue to experience either asthma symptoms or airway in-
a reduction in both parameters. Morreira et al. (16) evalu- flammation even after adequate medication. In addition, our
ated asthma inflammation by quantifying blood eosinophils, study also suggests that exercise training could be consid-
which is considered less accurate than sputum eosinophils ered a safe procedure for these patients because none of them
(20). In addition, Bonsignore et al. (4) did not evaluate eo- presented complications (increase in either asthma symptoms
sinophil counts, and asthma inflammation was quantified or decrease Q15% of PEF) after any of the exercise sessions.
only by measuring FeNO levels, which were not modified Certain limitations should be noted in our study. Our
after aerobic training. Third, our patients had moderate and results may not be considered as representative of the en-
severe persistent asthma, whereas Bonsignore et al. (4) tire population of patients with moderate or severe per-
studied patients with a mild disease severity, and Morreira sistent asthma because we evaluated 42% (68 from 160
et al. (16) did not report the patients’ severities. patients) of the patients assessed for eligibility in the study
Asthma symptoms and exacerbation. There are (Fig. 1). Furthermore, it is important to note that not all
few randomized and controlled trials investigating the effect subjects from the aerobic training group showed improve-
of physical training on asthma symptoms (14,23,28) and ment in the inflammatory markers. Most the patients (88%)
exacerbation (7), and these issues remain controversial. Al- were considered responders to aerobic training (improve-
though those outcomes were not the main issue in our study, ment in V̇O2max Q10%): 80% of them presented a reduction
it is appropriate that they would be investigated simulta- in at least one inflammatory outcome (either eosinophilG3%
neously with airway inflammation because asthma symptoms [3] or FeNOG30 ppb [18]), and 16% presented a reduction
and exacerbation are the main complaints in clinical practice. in both parameters.
In our study, we observed that an improvement in aerobic Second, although both groups completed 24 intervention
capacity increased the number of asthma symptom-free days sessions and received the same educational program, they
(Fig. 4) reported by the patients 30 d after of the beginning of were not exposed to a similar amount of attention during
exercise training program, and this was maintained until the each intervention session (30 min CG vs 60 min TG).
end of the program. We also observed that patients from the However, our experimental design is an improvement over
TG had less asthma exacerbation and fewer visits in the previous studies where the CG only received usual care
emergency room than patients in the CG. Interestingly, a very (23). Third, because there was no previous study evaluating
recent study suggests that asthmatic women with higher phys- the effect of aerobic training on airway inflammation, the
ical activity levels present a reduced risk of exacerbation (7). sample size was calculated on the basis of the study of
Subjectively, many asthmatic patients report a reduction Minoguchi et al. (15), where the sputum eosinophil counts
in asthma symptoms after improvement in physical fitness, were similar to our patients (25). Fourth, pulmonary function

202 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

Copyright © 2011 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
and cardiopulmonary tests were conducted by the same in- might be useful as an adjuvant therapy in asthmatic patients
vestigator in charge of aerobic training. However, sputum under optimized medical treatment.
eosinophil counts and FeNO levels were determined by a

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blinded investigator. Finally, patients were followed for a This study was supported by FAPESP grants 2002/08422-7.
short-term period, and further studies are required to un- Felipe A. R. Mendes, Francine M. Almeida, Alberto Cukier, Rafael
derstand long-term effects. Stelmach, Wilson Jacob-Filho, Milton A. Martins, and Celso R. F.
Carvalho did not receive funding either from the National Institutes
In conclusion, our results suggest that aerobic training of Health (NIH) or the Wellcome Trust, Howard Hughes Medical In-
reduces sputum eosinophil counts and FeNO levels in stitute (HHMI).
patients with moderate or severe asthma, and these bene- C. R. F. Carvalho and M. A. Martins are established investigators
of the CNPq.
fits were more significant in subjects with higher levels of The results of the present study do not constitute endorsement
inflammation. These results suggest that aerobic training by the American College of Sports and Medicine.

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EXERCISE ON ASTHMA AIRWAY INFLAMMATION Medicine & Science in Sports & Exercised 203

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