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Archivos argentinos de pediatría
version ISSN 0325-0075
Arch. argent. pediatr. vol.110 no.5 Buenos Aires Oct. 2012
ORIGINAL ARTICLE
Healthcare Program for Children with Severe Asthma: impact analysis
Verónica Giubergia, MDa, Nora Fridman, BSb and Hebe González Pena, MDa
a. Department of
Neumonology.
b. Department of
Mental Health.
Hospital Nacional
de Pediatría "Prof.
Dr. Juan P. Garrahan".
Buenos Aires, Argentina.
E-mail: Verónica Giubergia, MD: verogiubergia@hotmail.com
Conflict of interest: None.
Received: 2-3--2012
Accepted: 5-16-2012
http://dx.doi.org/10.5546/aap.2012.382
SUMMARY
Introduction. Asthma is a major economic burden
to families and public healthcare since it leads
to a large number of emergency room (ER) visits and hospital admissions. Whereas healthcare
programs for children with asthma have proved
to be very effective to improve the course of the
disease, there is less information about programs
for children with severe asthma.
Objective. To comparatively analyze the impact
of the Healthcare Program for Children with Severe Asthma (Programa de Atención de Niños con
Asma Grave, PANAG).
Methods. This was a longitudinal, pre- and postintervention study. Two approaches were used to
compare the frequency of asthma exacerbations
and hospital admissions due to severe asthma in
a group of patients: regular follow-up in a public hospital (pre-intervention period, 18 months)
and follow-up while participating in PANAG
(post-intervention period, 18 months). During
the Program, patients received preventive treatment free of charge; educational activities were
also organized.
Results. Twenty children were included, 16 (80%)
out of the 20 were females, and the mean age was
13.3 years (SD 3.8). During the pre-intervention
period 59 asthma attacks were recorded; after
PANAG was implemented, they decreased to
26. This accounts for a significant reduction of
55% of asthma attacks (p= 0.0002). During the period previous to PANAG implementation, there
were 4 asthma-related hospital admissions. In the
period after the program implementation, there
was only one hospital admission.
Conclusions. The Healthcare Program for Patients with Severe Asthma is an effective strategy
to manage this disease. This healthcare program
is affordable to be used in a public hospital.
Key words: Severe asthma; Healthcare program; Asthma attacks; Exacerbation; Hospital admissions.
INTRODUCTION
Asthma is the most common
chronic disease in childhood.1
It has
a high impact on public health systems and results in a high number of
emergency room visits and hospital
admissions.2
The most important objective in
the treatment of asthma is to achieve total control of symptoms. Different
national and international consensus
and guidelines state that persistent
asthma should be treated with longacting preventive medications, generally related to the use of inhaled
corticosteroids (IC).2-4 These drugs decrease the frequency of asthma attacks
and improve lung function.5 However, the rate of patients who use IC on
a regular basis is low. It is estimated
that 41% of asthma patients in Europe,
35% in USA, 14% in Asia, and 5% in
Brazil use this medication.6,7
Patients diagnosed with severe
asthma, accounting for 5-7% of the
total number of children with asthma, are a small but very vulnerable
group.8 Non-compliance with prescribed medications leads to frequent
and severe exacerbations with a high
risk of hospital and intensive care admissions. These patients use ER services 15 times more and are admitted
to hospitals 20 times more than children with mild or moderate asthma.8 The higher the rate of hospital admissions due to asthma, the higher the
likelihood of having subsequent attacks. It has been suggested that there
is 30% likelihood of recurrence after
the first hospitalization, 46% after the
second one and 59% after the third
one.9
The implementation of interdisciplinary team care strategies for the follow-up of asthma patients has proven
to be very effective at improving longterm asthma control in these children.
Inadequate or insufficient drug treatment, poor monitoring during the
treatment period, low social and economic level, and age under 5 years are
factors that increase the risk of hospital admission of asthma patients that
are not part of a supervised follow-up
strategy.10
It has been shown that this type of interventions has a direct impact on the frequency of asthma attacks and hospital admissions. A reduction
of up to 42% has been observed in the frequency
of hospital admissions due to asthma attacks in
patients monitored under a special healthcare
program.11
The Healthcare Program for Children with Severe Asthma (PANAG, according to its acronym
in Spanish Programa de Atención de Niños con
Asma Grave) was implemented in the Department of Neumonology of Hospital Garrahan from
2008 with the objective of improving the quality
of life of children and reducing asthma exacerbations and hospital admissions. Some of PANAG
strategies included the free distribution of medications and the implementation of educational
sessions in charge of an interdisciplinary team of
professionals.
In this study, the Healthcare Program in Children with Severe Asthma was comparatively assessed to determine its impact on the frequency of
asthma attacks and hospital admissions.
MATERIAL AND METHODS
This was a longitudinal (pre- and post-intervention) study. The study hypothesis was based
on the fact that a special healthcare program for
patients with severe asthma could modify the frequency of exacerbations and hospital admissions
due to asthma attacks.
The objective of this study was to compare the
frequency of exacerbations and hospital admissions in a group of 20 patients diagnosed with severe asthma who were assigned to two different
follow-up strategies in the same hospital: regular
follow-up in a public hospital in the city of Buenos Aires (pre-intervention period, retrospective
phase) and follow-up based in the PANAG approach (post-intervention period, prospective
phase). The study lasted 3 years: pre-intervention
period (January 1st., 2007 to July 31st., 2008) and
post-intervention period (August 1st., 2008 to December 31st., 2009).
The study included both male and female children with a diagnosis of severe asthma as per the
Global Initiative for Asthma (GINA) (These were
daily symptoms, frequent exacerbations, usual
nocturnal symptoms, limitation of physical activity, forced expiratory volume in the 1st. second =60% than predicted at the time of diagnosis, and
need to use high doses of inhaled corticosteroids
[=800 µg of budesonide or a similar drug] to adequately manage the disease).12
Patients were followed up at the Department
of Neumonology for at least 6 months. Children
who were able to perform spirometry, were in follow-up during the 18 months prior to the beginning of the program, and continued the follow-up
for the next 18 months, were retrospectively included. Patients with obstructive disorders (i.e.,
obliterative bronchiolitis, bronchopulmonary dysplasia, cystic fibrosis) and children who discontinued their follow-up in the prospective phase
of the study were excluded.
During the pre-intervention period, patients
were regularly followed up, once a month or every two months, in an office where the clinical
course, frequency and type of exacerbations, and
asthma-related hospital admissions were carefully recorded on a specially designed case record form. All the patients had been prescribed
IC and long-acting bronchodilators (fluticasone
750/ salmeterol 75 µg/day, DS 250 µg/day). Patients could attend to an ER in case of clinical
deterioration. The cost of medications and the
metered dose inhaler (MDI) had to be covered by
the family.
During the implementation of the program
(post-intervention period), patients received free
of charge preventive medications at the same
dose they previously received (IC and long-acting bronchodilators) and MDIs. Visits took place
every month or every two months based on the
patient's evolution and they were monitored by a
neumonologist and a psychologist. Failure to assist to scheduled visits led to a phone call to the
family. Patients could attend the Department of
Neumonology from 8 AM to 4 PM, and the ER of
the Hospital from 4 PM to 8 AM.
All follow-up visits, exacerbations that required oral corticosteroids for at least 3 days
(whether patients attended ER or not), and asthma-related hospital admissions during the retrospective and prospective phases of the study were
recorded on the patient's case record forms.
Educational activities were targeted at patients
and parents, based on the four recommendations
from the U.S. National Institutes of Health (NIH):
basic information about the pathophysiology of
the disease, correct use of the medication, adequate technique and monitoring of symptoms,
and management of symptom-triggering factors.2
Four workshops were held. Parents and patients attended them and developed separate
activities. Medical information was provided,
as well as psychological approach based on requirements identified on previous anonymous surveys designed as part of the study protocol.
The information focused on fostering children's
commitment with their care, creating a space to
communicate their fears, fantasies and doubts.
The achievement of their children's autonomy
with respect to the compliance and commitment
with the treatment was promoted among parents
who attended the workshop. Adequate information about the disease and treatment was also
provided.
Integration games, group discussions, roleplaying, poster design, drawings and collages
were organized and planned accordingly. The
focus was on difficulties related to treatment adherence, forgetfulness to take or dropping medication, underestimation of the severity of the
disease, rebelliousness, anger and tiredness as a
result of the disease, misinterpretation of medical
indications, fear of discrimination, asthma attacks
and death. Aspects related to physical activity
were also reinforced.
Drugs were provided to patients by the hospital pharmacy.
STATISTICS
The statistical analysis was performed with
the software Stata 9.0 (Stata-Corp, College Station, TX). Value distribution within each outcome
was described by means of measures of central
tendency and scattered plots or categorically, as
appropriate.
Categorical outcomes were reported as proportions and compared using the chi-square (?²)
test. Continuous outcomes were compared with
Student's t test for paired data or with Wilcoxon
signed-rank test. P values lower than 0.05 were
statistically significant.
RESULTS
Twenty children diagnosed with severe asthma were included in this study. Sixteen (80%) out
of 20 were females, and their mean age was 13.3
years (SD 3.8). The mean age at the onset of symptoms was 1.5 years (SD 1).
Eight (40%) of these children had been admitted to the intensive care unit because of a severe
asthma attack. Five (62%) of them required mechanical ventilation (average 5 days, SD 2) and
two underwent a tracheostomy.
At the beginning of the study, patients had adequately controlled severe asthma since they had
been treated for at least 6 months. The lung function was within near to normal parameters. Children had mild obstructive ventilatory disorder, evidenced only by a mild reduction of the forced
expiratory volume in the 1st second (FEV1) and
forced vital capacity ratio, with FEV1 and mean
and maximal forced expiratory flow values within normal parameters. Table 1 shows the general
characteristics of this population.
Table 1. Clinical and functional characteristics of the
patients (n= 20)

A reduction in the number of asthma attacks and asthma-related hospital admissions was observed. During the pre-intervention period, 90% of children (n= 18) had 59 attacks. During the PANAG implementation period, 90% of children (n= 18) had 26 asthma exacerbations (p= 0.0002) (Table 2). There were no patients with a higher number of attacks during the follow-up period under the program.
Table 2. Asthma attacks and hospital admissions due to asthma, pre- and post-implementation of PANAG (n= 18)

In 77% of cases (n= 14), a decrease in the frequency of asthma attacks was observed, and 22% (n= 4) had an identical number of exacerbations (Figure 1).
Figure 1. Number of asthma attacks per patient. Pre- post-
PANAG (n= 18) period

Regarding asthma-related hospital admissions, 20% of the population (n= 4) required to be hospitalized because of an asthma attack during the period previous to PANAG. In the period post PANAG implementation, only one patient required hospitalization (p= 0.02) (Table 2). There were no patients who required mechanical ventilation or to be admitted to the intensive care unit during the study period.
DISCUSSION
Healthcare programs for patients with severe
asthma based on the free administration of medications and the promotion of education are beneficial for the evolution of asthma, with a reduction
of symptoms. Similar results were observed in
this study. The findings were as expected given
the proven efficacy of asthma treatment with IC;
it has been now possible to quantify the benefits
of a healthcare program in a group of children
diagnosed with severe asthma assisted at a public hospital.
Even though it is estimated that only 20%
of asthma children progress into a more severe
asthma condition, this low percentage of patients
has a remarkable impact on all healthcare systems due to the high rate of symptoms they have.
Approximately 80% of the resources allocated to
asthma treatment are for the management of these group of patients.13
Children with severe asthma
have frequent exacerbations and asthma attacks,
severe enough to lead to hospitalizations.9,14,15 Previous observations have revealed that these attacks would be directly related to the high degree
of airway inflammation present in these subjects.16
The decrease in the frequency of asthma attacks and hospital admissions is the main objective of asthma management programs. Previous
experiences in other countries of the region, i.e.
Brazil, under-score that the cause of the decrease
in the number of hospital admissions is explained
by the accessibility to treatment access that these
programs offer.17,18 Limited access to medication
and the irregular follow-up have been related to
the unfavorable course of the disease in asthma
patients.10 In this study, it is quite likely that the
high rate of exacerbations was related, among
other reasons, to the difficult access to medication
because of its high cost.
Likewise, these strategies oriented to reinforcing the correct use of the preventive medication
and the different devices reduce asthma-related
deaths.19 In this study, during the post-intervention
period, compliance, technique and access to medication were thoroughly supervised in each visit.
A decrease in the frequency of asthma attacks and
hospital admissions was observed, which confirms
previously published observations.20
As far as the impact of educational programs
on the course of asthma, studies that compared
groups with and without intervention showed
a decrease in the average of asthma attacks and
hospital admissions in those who participated in
educational programs. Non-compliance with the
treatment and the consequent deceit to the physician concerning the use of medication is frequent
even in patients with severe asthma, especially
if they are adolescents.21 Continuous education
is highly important to promote treatment adherence. Adequately informed parents become
highly valuable health agents, making it possible for children to adhere to the proposed treatment
regimen continuously over time. When dealing
with adolescents, information should first be targeted to patients so that they take responsibility
for their own health.21 It has also been suggested
that the stronger the interaction with patients, the
better the results that will be obtained. Parents
and children are more careful to closely monitor symptoms and implement an early treatment.
These approaches can avoid visits to the ER, and
possibly, hospitalizations.11
It has been shown that educational activities
which include the four items proposed by the
NIH are highly effective.2,11 Frequent individual
sessions are more effective than isolated group
sessions because the information provided is customized and planned taking into account each patient's needs.11,22
Both approaches were used in this study.
Based on individual surveys, the information required by each patient was designed and then
implemented during the patient's office visits.
Concepts were reinforced with workshops every
six months, where parents and patients had an active participation.
Cost reduction was not one of the objectives of
the study, but due to the significant decrease in
the frequency of asthma attacks and hospital admissions observed post PANAG implementation,
it is estimated that the amount spent in the program, including medication distribution and the
physician-hours used, was less than the expenses
incurred by the patients during the pre-intervention period, as previously published.18,23
Some methodological observations should be
made. Since the program included the administration of medication free of charge, because of
ethical considerations it was not possible to do
a prospective, randomized study with a control
group that would not be supported by the program. At the onset of the study, patients enrolled
were adequately controlled because they had
been receiving treatment for at least 6 months.
The enrolment of patients with uncontrolled asthma would have biased results favoring the prospective phase.
These findings show that organized care of patients with chronic diseases, as severe asthma, is a
proven and highly effective strategy for the management of these disorders. It is a model of care
that can be easily put into practice in a public hospital and that requires few human and economic
resources for its implementation. This strategy,
which included the participation of a psychologist and neumonologists and the collaboration of
other professionals as needed, together with the
active participation of the hospital as the medication supplier, has significantly decreased the
frequency of asthma exacerbations and asthmarelated hospital admissions.
As a result of these favorable findings, this approach has been implemented in a public hospital
as a special healthcare program.
Acknowledgements
To Adriana González, Bachelor of Kinesiology, and to Liliana del Valle Rodríguez, Bachelor of Science in Nursing, for their valuable participation in the different activities developed in the Healthcare Program for Children with Severe Asthma (PANAG).
1. Lai CK, Beasley R, Crane J, Foliaki S, et al. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009;64(6):476-83.
2. NAEPP3 Science base committee. Expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007;120(suppl):S94-S138.
3. Comité Nacional de Neumonología Pediátrica. Sociedad Argentina de Pediatría. Consenso Nacional Asma Bronquial en la Infancia: Criterios de diagnóstico y tratamiento 2007. (2ª parte). Arch Argent Pediatr 2008;106(2):162-175.
4. British Guidelines on the Management of Asthma. British Thoracic Society. [Accessed on: May 28, 2012]. Available at: http://www.sign.ac.uk/guidelines/published/numlist.html.
5. De Benedictis F, Bush A. Corticosteroids in Respiratory Diseases in Children. Am J Respir Crit Care Med 2012; 185:12-23.
6. Rabe K, Adachi M, Lai C. Worldwide severity and control of asthma in children and adults: The global asthma insights and reality surveys. J Allergy Clin Immunol 2004,114:40-7.
7. Neffen H, Fritscher C, Schacht F, Levy G, et al and the AIRLA Survey Group: Asthma control in Latin America: the asthma insights and reality in Latin America (AIRLA) survey. Rev Panam Salud Publica 2005;17:191-197.
8. The ENFUMOSA cross sectional European Multicenter Study of the Clinical Phenotype of Chronic Severe Asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003;22:470-7.
9. Brandão HV, Cruz CS, Guimarães A, Camargos PAM, Cruz AA. Predictors of hospital admission due to asthma in children and adolescents enrolled in an asthma control program. J Bras Pneumol 2010;36(6):700-6.
10. Brandão HV, Cruz CMS, Santos Junior IS, Ponte EV, et al. Hospitalizations for asthma: impact of a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol 2009;35(8):723-9.
11. Coffman J, Cabana MD, Halpin HA, Yelin EH. Effects of asthma education on children's use of acute care services: A meta-analysis. Pediatrics 2008;121:575.
12. Global Initiative for Asthma, National Heart, Lung, and Blood Institute. Global strategy for asthma management and prevention. [Accessed on: May 28, 2012]. Available at: http://www.ginasthma.org.
13. Smith DH, Malone DC, Lawson KA, Okamoto LJ, et al. A national estimate of the economic costs of asthma. Am J Respir Crit Care Med 1997;156(3 Pt 1):787-93.
14. Adams RJ, Smith BJ, Ruffn RE. Factors associated with hospital admissions and repeat emergency department visits for adults with asthma. Thorax 2000;55(7):566-73.
15. Bousquet J, Gaugris S, Kocevar VS, Zhang Q, et al. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial. Clin Exp Allergy 2006;36(2):249.
16. Louis R, Lau LC, Bron AO, Roldaan AC, et al. The relationship between airways infammation and asthma severity. Am J Respir Crit Care Med 2000;161(1):9-16.
17. Brandão HV, Cruz CS, Pinheiro MC, Costa EA, et al. Risk factors for ER visits due to asthma exacerbations in patients enrolled in a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol 2009;35(12):1168-73.
18. Ponte E, Franco RA, Souza-Machado A, Souza-Machado C, Cruz AA. Impact that a program to control severe asthma has on the use of Unifed Health System resources in Brazil. J Bras Pneumol 2007;33(1):15-19.
19. Sin DD, Tu JV. Inhaled corticosteroid therapy reduces the risk of rehospitalization and all-cause mortality in elderly asthmatics. Eur Respir J 2001;17(3):380-5.
20. Cabral AL, Carvalho WA, Chinen M, Barbiroto RM, et al. Are International asthma guidelines effective for lowincome Brazilian children with asthma? Eur Respir J 1998;12(1):35-40.
21. Chandler M, Grammer LC, Patterson R. Noncompliance and prevarication in life threatening adolescent asthma. N E Reg Allergy Proc 1986;7:367-70.
22. Teach SJ, Crain EF, Quint DM, Hylan ML, Joseph JG. Improved asthma outcomes in a high-morbidity pediatric population: results of an emergency department based randomized clinical trial. Arch Pediatr Adolesc Med 2006;160(5):535-41.
23. Franco R, Santos AC, do Nascimento HF, Souza-Machado C, et al. Cost-effectiveness analysis of a state funded program for control of severe asthma. BMC Public Health 2007;7:82.
1. Lai CK, Beasley R, Crane J, Foliaki S, et al. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009;64(6):476-83. [ Links ]
2. NAEPP3 Science base committee. Expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007;120(suppl):S94-S138. [ Links ]
3. Comité Nacional de Neumonología Pediátrica. Sociedad Argentina de Pediatría. Consenso Nacional Asma Bronquial en la Infancia: Criterios de diagnóstico y tratamiento 2007. (2ª parte). Arch Argent Pediatr 2008;106(2):162-175. [ Links ]
4. British Guidelines on the Management of Asthma. British Thoracic Society. [Acceso: 28 de mayo de 2012]. Disponible en: http://www.sign.ac.uk/guidelines/published/numlist.html. [ Links ]
5. De Benedictis F, Bush A. Corticosteroids in Respiratory Diseases in Children. Am J Respir Crit Care Med 2012;185:12-23. [ Links ]
6. Rabe K, Adachi M, Lai C. Worldwide severity and control of asthma in children and adults: The global asthma insights and reality surveys. J Allergy Clin Immunol 2004,114:40-7. [ Links ]
7. Neffen H, Fritscher C, Schacht F, Levy G, et al and the AIRLA Survey Group: Asthma control in Latin America: the asthma insights and reality in Latin America (AIRLA) survey. Rev Panam Salud Publica 2005;17:191-197. [ Links ]
8. The ENFUMOSA cross sectional European Multicenter Study of the Clinical Phenotype of Chronic Severe Asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003;22:470-7. [ Links ]
9. Brandão HV, Cruz CS, Guimarães A, Camargos PAM, Cruz AA. Predictors of hospital admission due to asthma in children and adolescents enrolled in an asthma control program. J Bras Pneumol 2010;36(6):700-6. [ Links ]
10. Brandão HV, Cruz CMS, Santos Junior IS, Ponte EV, et al. Hospitalizations for asthma: impact of a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol 2009;35(8):723-9. [ Links ]
11. Coffman J, Cabana MD, Halpin HA, Yelin EH. Effects of asthma education on children's use of acute care services: A meta-analysis. Pediatrics 2008;121:575. [ Links ]
12. Global Initiative for Asthma, National Heart, Lung, and Blood Institute. Global strategy for asthma management and prevention. [Acceso: 28 de mayo de 2012]. Disponible en: http://www.ginasthma.org. [ Links ]
13. Smith DH, Malone DC, Lawson KA, Okamoto LJ, et al. A national estimate of the economic costs of asthma. Am J Respir Crit Care Med 1997;156(3 Pt 1):787-93. [ Links ]
14. Adams RJ, Smith BJ, Ruffn RE. Factors associated with hospital admissions and repeat emergency department visits for adults with asthma. Thorax 2000;55(7):566-73. [ Links ]
15. Bousquet J, Gaugris S, Kocevar VS, Zhang Q, et al. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial. Clin Exp Allergy 2006;36(2):249. [ Links ]
16. Louis R, Lau LC, Bron AO, Roldaan AC, et al. The relationship between airways infammation and asthma severity. Am J Respir Crit Care Med 2000;161(1):9-16. [ Links ]
17. Brandão HV, Cruz CS, Pinheiro MC, Costa EA, et al. Risk factors for ER visits due to asthma exacerbations in patients enrolled in a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol 2009;35(12):1168-73. [ Links ]
18. Ponte E, Franco RA, Souza-Machado A, Souza-Machado C, Cruz AA. Impact that a program to control severe asthma has on the use of Unifed Health System resources in Brazil. J Bras Pneumol 2007;33(1):15-19. [ Links ]
19. Sin DD, Tu JV. Inhaled corticosteroid therapy reduces the risk of rehospitalization and all-cause mortality in elderly asthmatics. Eur Respir J 2001;17(3):380-5. [ Links ]
20. Cabral AL, Carvalho WA, Chinen M, Barbiroto RM, et al. Are International asthma guidelines effective for low-income Brazilian children with asthma? Eur Respir J 1998;12(1):35-40. [ Links ]
21. Chandler M, Grammer LC, Patterson R. Noncompliance and prevarication in life threatening adolescent asthma. N Engl Reg Allergy Proc 1986;7:367-70. [ Links ]
22. Teach SJ, Crain EF, Quint DM, Hylan ML, Joseph JG. Improved asthma outcomes in a high-morbidity pediatric population: results of an emergency departmentbased randomized clinical trial. Arch Pediatr Adolesc Med 2006;160(5):535-41. [ Links ]
23. Franco R, Santos AC, do Nascimento HF, Souza-Machado C, et al. Cost-effectiveness analysis of a state funded program for control of severe asthma. BMC Public Health 2007;7:82. [ Links ]











