Anda di halaman 1dari 8

[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.

32]

Indian J Med Res 144, August 2016, pp 250-257


DOI: 10.4103/0971-5916.195040

Comparison of clinical effects of beclomethasone dipropionate &


budesonide in treatment of children with mild persistent asthma:
Adoubleblind, randomized, controlled study

Anju Singh1, Devki Nandan1, Vivek Dewan1 & Jhuma Sankar2

1
Department Pediatrics, Postgraduate Institute of Medical Education and Research and Dr.Ram Manohar
LohiaHospital & 2Department of Pediatrics, All India Institute of Medical Sciences, NewDelhi, India

Received September 4, 2015

Background & objectives: Various inhaled corticosteroids(ICSs) are available to control the symptoms
of asthma. Although beclomethasone dipropionate(BDP) and budesonide(BUD) are one of the oldest
ICSs, their wide availability and low cost make them attractive options in developing countries. Due
to lack of consensus on which of the two drugs is better for controlling mild persistent asthma, we
undertook this study to compare the efficacy of these two drugs by measuring the change in percentage
predicted forced expiratory volume in one second(FEV1) from baseline in children with mild persistent
asthma.
Methods: A doubleblind, randomized, parallel group study was conducted in children 715 yr of age
with newly diagnosed asthma. Of the 85 cases of mild persistent asthma, 42 received BUD while 43
received BDP at a dose of 400g/day using pressurized metereddose inhaler with valved spacer for two
months. The outcomes measured were change in FEV1, symptom scores and side effects.
Results: There was a significant(P<0.05) improvement in FEV1 in BUD group(98.434.63%) than in
BDP group(95.655.66%) at the end of two months of treatment. The mean symptom scores in BUD
group(0.281.22) and BDP group(0.431.52) were comparable after two months. No side effects were
seen in either group.
Interpretation & conclusions: FEV1 was significantly greater in BUD group than BDP group.
Improvement in symptoms and incidence of side effects were similar. Our findings indicate that both
BDP and BUD can be used effectively in the management of children with mild persistent asthma.[CTRI
No: CTRI/2013/03/003495].

Key words Beclomethasone dipropionatebudesonideforced expiratory volume in one secondmetered dose inhalermild persistent
asthmasymptom score

250
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

SINGH et al: BECLOMETHASONE DIPROPIONATE VS. BUDESONIDE IN MILD PERSISTENT ASTHMA 251

Asthma is a common childhood illness study to compare the clinical effects of the two drugs
characterized by chronic airway inflammation. This so as to help to develop standardized guidelines. The
chronic inflammatory nature of the disease needs to objective of our study was to compare the efficacy
be checked on time to prevent longterm irreversible of these two drugs in terms of improvement in
impairment of pulmonary function1. Uncontrolled pulmonary function in children with mild persistent
asthma reduces the quality of life of children by asthma, measured by change in predicted FEV1 from
retarding the growth2, inability to exercise3, loss of baseline.
sleep and frequent absences from school4. Material & Methods
There are various medications available to This parallel group doubleblind, randomized,
control the underlying inflammation such as inhaled controlled trial(RCT) was conducted in the
corticosteroids(ICSs), oral steroids, leukotriene department of Pediatrics, Dr.Ram Manohar Lohia
modifiers, chromones and theophylline. Of these, ICSs Hospital, NewDelhi, India between November
are considered as the most effective therapy for all 2011 and November 2012 after approval by the
levels of persistent asthma1. Their success is based on Institutional Ethical Committee. The trial was
their ability to improve asthma symptoms and quality registered in the Clinical Trials Registry of India No:
of life5, low systemic bioavailability and lesser side CTRI/2013/03/003495.
effects6. The various ICSs available are beclomethasone
dipropionate(BDP), budesonide(BUD), ciclesonide, Participants: Children with newly diagnosed mild
flunisolide, fluticasone and mometasone. Among these, persistent asthma aged 715 yr attending wards,
BUD and BDP are widely used in developing countries outpatient department and chest clinic were included
due to their better costbenefit ratio. However, it is still in this study. Mild persistent asthma was defined as
a matter of debate as to which of these two drugs is a asthma symptoms occurring more than once a week
better drug in terms of efficacy. Various invitro studies but not daily, exacerbations affecting activity and
have shown differences in their pharmacokinetic sleep, nocturnal symptoms greater than or equal to
properties. Receptor affinity of BDP is higher while once a month and FEV180 per cent of the predicted.
invitro potency of BUD is greater7,8. It is unclear Cases fulfilling the above definition and showing an
whether these differences translate into any clinical improvement of 12 per cent in FEV1 after 15min
significance. of administration of four separate doses of 100g of
salbutamol metered dose inhaler(MDI) with valved
The available data on the comparison of clinical spacer were considered eligible15. Children who
effects of these two drugs in children have mostly come received oral, parenteral or inhaled steroids during the
from small crossover studies that included less than last one month; children with any underlying chronic
30 children912. Majority of these studies have poorly illness including cystic fibrosis, pneumothorax, chronic
defined inclusion and exclusion criteria and have used suppurative lung disease, tuberculosis, congenital heart
different delivery devices with or without the spacers. diseases and any other chronic systemic illness; those
One of these studies has shown significantly higher unable to use inhaler with spacer or perform spirometry
forced expiratory volume in one second(FEV1) during and children with lower respiratory tract infections
BUD treatment12, while others have shown only slightly in the last one month were excluded from the study.
higher FEV1 during BUD treatment911. Ametaanalysis Written informed consent was obtained from parents
of crossover studies done in children and adults did not of all the children.
demonstrate a significant difference between BDP and
Interventionshow and when they were administered:
BUD for FEV1, morning peak expiratory flow(PEF),
Children with newly diagnosed asthma were randomly
evening PEF, asthma symptoms or rescue beta2
assigned to study(BDP) and control(BUD) groups.
agonist use, over a dose range of 4001000 g13.
Children allocated to BUD group received BUD
At present, BUD is being used for the treatment 200g one puff twice a dayb.i.d. and children in BDP
of mild persistent asthma in our hospital. However, group received BDP 200g one puff b.i.d. from an
the low cost and wide availability of BDP make it MDI with a valved spacer. Allocation of children to
an attractive alternative14. Moreover, due to lack of one of these groups was based on computergenerated
consensus on which of the two drugs is better for simple randomization by an independent person. After
controlling mild persistent asthma, We conducted this selecting the cases and recording the absolute and
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

252 INDIAN J MED RES, AUGUST 2016

percentage predicted values of FEV1, patients were and withdrawn from the study. Any patient developing
given these medicines for two months. acute exacerbation was advised to take 24 puffs of
salbutamol MDI with valved spacer every 20min for
Outcome measures: The primary outcome of our study
the first hour15 and immediately visit the emergency
was to compare the clinical effects of inhaled BDP and
department for further management. Oral steroids were
BUD by comparing the change in percentage predicted
allowed for acute exacerbation management.
FEV1 after two months of therapy. The secondary
outcomes were to compare symptom scoring for day Sample size: There are no previous studies on the
and night time symptoms, limitation in daily activities, comparison of BUD versus BDP in children with mild
absence from school, need for rescue salbutamol inhaler, persistent asthma. Therefore, we hypothesized that if a
number of exacerbations since the last visit, need for mean difference in FEV1 in BDP was lower than two
an emergency visit and incidence of side effects. The per cent in comparison to BUD, it would be considered
definitions used for this study were as follows: FEV1 noninferior to BUD. Sample size of 39 per group was
is the volume of air exhaled in the first second of a calculated based on the assumption of at least a mean
forceful expiration. Symptom score was done by the difference of two per cent in FEV1(%) at second month
end of each month using a validated Asthma Therapy between the two groups, a standard deviation(SD) of 32
Assessment Questionnaire (ATAQ)16,17. Major side or effect size of 0.67, a twosided alpha of 0.05, beta of
effects observed in the study were cough, hoarseness of 0.80, a power of 80 and 10 per cent as lost to follow up.
voice and candidiasis. These side effects were assessed Randomization:
clinically by history and physical examination on each
visit. Sequence generation:(i) Randomized sequence
The patients clinical history and physical was generated using computerized random number
examination findings were noted. We used vitalograph generator.(ii) Randomization list was prepared by
portable spirometer which was calibrated for volume biostatisticians not involved in the study and was kept
once daily with an airtight 3 l calibrated syringe with them.
with an accuracy of 15 ml18. Since valid spirometric Randomizationallocation concealment: Serially
measures are dependent on patients ability to perform numbered, sealed, identical opaque envelopes
properly a full, forceful and prolonged expiratory containing the random numbers were kept at the study
manoeuvres, spirometry was done after properly site as per the allocation sequence.
explaining the correct method to the patients, and the
best of three spirometry attempts was recorded. After Randomizationimplementation: The randomization
recording the absolute and percentage predicted was done as soon as the cases were enrolled in the
values of FEV1, patients were given the medicines study. The research staff assigned each case the next
for next two months which included random serial number corresponding to the randomization code
number coded MDI and salbutamol MDI(rescue of the intervention.
medication). The same type of valved spacers was Randomizationblinding: Aperson independent of the
used for the delivery of drug from the MDI. Parents study prepared the medicines. After removing their
were explained to maintain daily symptom diary labels, both the medicines were painted with red colour
for day and night symptoms, the number of acute and covered with similar coloured caps. Study labels
exacerbations, use of rescue medication, visits to the containing random numbers were put on the medicines.
emergency department, limitation in daily activities The treating paediatricians selected the cases, assessed
and absence from school. them and advised these medicines. The random number
Children were followed up at two weeks, first and coded medicines were distributed by the staff nurse.
second month. Compliance to medicines was checked Once the statistical analysis was done; the identity of
at every visit, as well as telephonically every week. the two drugs was revealed to the treating paediatrician
by the person who prepared the medicines. The
Every month symptom scoring and spirometry were
participants and the treating paediatrician both were
done. The patients were labelled as having controlled
blinded to the intervention.
asthma if ATAQ score and FEV1 showed improvement
during the two months follow up. Those who were not Statistical analysis: Data were collected using a
fulfilling these criteria were planned to be stepped up predesigned proforma. Statistical testing was conducted
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

SINGH et al: BECLOMETHASONE DIPROPIONATE VS. BUDESONIDE IN MILD PERSISTENT ASTHMA 253

with the Statistical Package for the Social Science respectively (Table II). When the two groups
systemversion SPSS 17.0 (Chicago, IL, USA). were compared, there was a significant (P<0.05)
Chisquare test and Fishers exact test(used where improvement in FEV1 in BUD group[mean difference:
expected frequency was<5) were used for categorical 2.78; 95% confidence interval(CI): -5.08 -0.48] as
variables and Wilcoxon ranksum test or Students compared to BDP group(Table II).
t test was used for continuous variables depending
on whether they were normally distributed or not. Secondary outcomes: The mean symptom score in BDP
Analysis was performed according to the intention to group at baseline was 4.300.75 and in BUD group
treat principle. was 4.280.85. On intergroup comparison of symptom
score after two months of treatment, improvement in
Results BDP(0.431.52) and BUD groups(0.281.22) was
Of the 90patients screened, 85 children with similar(mean difference: 0.15; 95% CI: -0.46 -0.76,
mild persistent asthma were enrolled and randomized. P=0.638) as shown in Table III. No side effects were
Forty three children received BDP, while 42 received observed in either group.
BUD. Three children were lost to follow up from BDP Some additional parameters were also observed
group and two from BUD group(Figure). The baseline in our study including PEF rate at the end of the first
demographic and clinical characteristics of the study and second month, number of acute exacerbations,
groups are presented in Table I. The two groups had limitation of physical activities, sleep disturbance,
comparable baseline characteristics including the school absenteeism, use of rescue medication
baseline spirometric parameters, i.e.FEV1. and visit to emergency department(Table III).
Primary outcomes: At the end of two months, There was significant improvement in PEF in
mean FEV1 in BDP group was 1.550.39 l, while both groupBDP(3.320.89 l, 3.681.19 l) and
in BUD group was 1.740.42 l with corresponding groupBUD(3.891.14 l, 4.121.10 l) after the
percentages of 95.655.66 and 98.434.63, first and second month of treatment. When both

Table I. Comparison of baseline parameters of the study population


Parameters MeanSD Unadjusted OR/mean difference
Group BDP (n=40) Group BUD (n=40) (95% CI)
Age(yr)(meanSD) 10.362.26 10.083.24 0.28(0.961.52)
Sex
Male 25 29 1.27(0.762.12)
Female 15 11 1.27(0.762.12)
Height(cm), meanSD 135.1013.92 133.4613.46 1.64(4.467.74)
Weight(kg), meanSD 27.558.17 28.288.99 0.73(4.55 3.09)
Age of onset of asthma symptoms(yr), 5.283.62 4.643.55 0.64(0.96 2.24)
meanSD
Cough 40(100) 40(100)
Wheezing 20(50) 16(40) 0.81(0.521.28)
Breathlessness 33(82.5) 31(77.5) 0.86(0.521.42)
Chest pain 8(20) 13(32.5) 1.35(0.882.09)
Allergic rhinitis 13(32.5) 16(40) 1.17(0.761.82)
Sinusitis 1(2.5) 0(0.0) 0.32(0.018.22)
FEV1(l), meanSD 1.330.32 1.390.33 0.06(0.200.08)
FEV1(% predicted), meanSD 81.771.66 82.451.44 0.68(1.370.01)
Symptom score, meanSD 4.300.75 4.280.85 0.02(0.340.38)
Values in parenthesis are percentages. BDP, beclomethasone dipropionate; BUD, budesonide; FEV1, forced expiratory volume in one
second; OR, odds ratio; CI, confidence interval
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

254 INDIAN J MED RES, AUGUST 2016

90 patients screened

5 - Excluded
2 - Lower respiratory tract
infection in last one month
2 - Took oral steroid in last one
month
1 - Refusal to consent

85 randomized

42 BUD group 43 BDP group

2- Lost to follow 2 months follow up 3- Lost to follow up


up (went out of 2- Went out
station) of station
1- Staying far
off

40 completed 40 completed

Analysis

40 analyzed 40 analyzed

Figure. Flow chart, showing study design. BUD, budesonide; BPD, beclomethasone dipropionate.

groups were compared, BUD group had significantly Mild persistent asthma constitutes the largest
better improvement in PEF than BDP group(P<0.05) group of children with persistent asthma1. The previous
after first and second month (Table IV). However, clinical studies comparing inhaled BDP and BUD in
other additional parameters did not show significant asthmatic children have shown no clear advantage in
difference between the two groups(Table III). terms of efficacy of either drug912. However, many
Discussion clinicopharmacological studies have suggested that
BUD has better topical to systemic glucocorticoid
In this doubleblind, randomized, single centre activity ratio than BDP, and BUD may be preferred
study, greater improvement was reported in patients where high doses ICSs are required to control asthma19.
FEV1 treated with 400g/day of BUD MDI as
compared to 400g/day of beclomethasone MDI In 1982, Field and colleagues9 conducted a study
administered through valved spacer with comparable on 31 severely asthmatic children aged between 4 and
improvement in symptoms of asthma without any side 14 yr requiring regular inhaled steroid prophylaxis.
effect after two months of treatment. Fifteen children used BUD through pressurized aerosol
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

SINGH et al: BECLOMETHASONE DIPROPIONATE VS. BUDESONIDE IN MILD PERSISTENT ASTHMA 255

Table II. Primary outcome measures of the study population


Parameter MeanSD or n(%) Mean difference (95% CI)
Group BDP Group BUD
FEV1 baseline(l) 1.330.32 1.390.33 0.06(0.200.08)
Baseline(%) 81.771.66 82.451.44 0.68(1.370.01)
First month(l) 1.460.33 1.620.36* 0.16(0.01-0.31)
First month(%) 90.183.99 92.102.57 *
1.92(0.43-3.41)
Second month(l) 1.550.39 1.740.42* 0.19(0.37 0.01)
Second month(%) 95.655.66 98.434.63 2.78(5.08 0.48)
*
P<0.05 compared to BDP group. BDP, beclomethasone dipropionate; BUD, budesonide; OR, odds ratio; CI, confidence interval;
FEV1, forced expiratory volume in one second

Table III. Secondary outcomes of the study population


Parameter MeanSD or n(%) Unadjusted OR/mean
Group BDP (n=40) Group BUD (n=40) difference (95% CI)
Symptom score baseline 4.300.75 4.280.85 0.02(0.340.38)
Symptom score 1 month
st
0.751.06 0.480.75 0.27(0.680.14)
Symptom score 2nd month 0.431.52 0.281.22 0.15(0.460.76)
Number of acute exacerbations 2(5) 0
Rescue medication 5(12.5) 2(5) 0.55(0.171.80)
Emergency visits 1(2.5) 0
Limitations of physical activities 5(12.5) 2(5) 0.55(0.171.80)
Sleep disturbances 5(12.5) 2(5) 0.55(0.171.80)
School absenteeism 5(12.5) 2(5) 0.55(0.171.80)
Values in parenthesis are percentages. BDP, beclomethasone dipropionate; BUD, budesonide; OR, odds ratio; CI, confidence interval

Table IV. Peak expiratory flow values of the study population


Parameter MeanSD or n(%) Mean difference (95% CI)
Group BDP Group BUD
PEF baseline(l) 3.190.80 3.460.94 0.27(0.110.66)
Baseline(%) 82.021.89 82.371.48 0.35(0.401.10)
First month(l) 3.320.89 3.891.14* 0.57(0.121.02)
First month(%) 90.93.11 92.21.87 *
1.30(0.162.44)
Second month(l) 3.681.19 4.121.10 *
0.44(0.07 0.95)
Second month(%) 95.756.04 98.623.99* 2.87(0.595.15)
*
P<0.05 compared to BDP group PEF, peak expiratory flow; BUD, budesonide; CI, confidence interval; BDP, beclomethasone
dipropionate

with a spacer inhaler, while 12 used BDP through BUD9. In another study conducted by Springer etal.10
Rotahaler. FEV1 and symptom score in the BUD group on 10 asthmatic children in each group who were
were83.422.9l and 13.616.5, while the values of already on treatment with steroids were given a total
the same parameters in BDP group were78.525.1l daily dose of 400g each of BDP and BUD through
and 17.219.3, respectively. This comparison did not a conventional pressurized aerosol without a spacer.
show any significant difference although there was The comparison of FEV1 and symptom score between
a consistent tendency towards greater benefit from the two groups showed no significant difference10. In a
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

256 INDIAN J MED RES, AUGUST 2016

study by Baran etal11 on 21 chronic asthmatic children, References


aged 414 yr who were on regular ICSs for their 1. National Heart, Lung and Blood Institute. Bethesda, MD:
control, BUD group received 100g b.i.d. through National Asthma Education and Prevention Program, c2001.
spacer inhaler, while BDP group received 100g b.i.d. Expert Panel Report 3: Guidelines for the Diagnosis and
through dry powder inhaler. On analysis, it was found Management of Asthma Summary Report 2007. Available
that compared with placebo, FEV1 was significantly from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.
better with BUD(P<0.05), but no significant effect htm, accessed on August 2, 2012.
could be detected with BDP11. 2. HauspieR, SusanneC, AlexanderF. Maturational delay and
temporal growth retardation in asthmatic boys. JAllergy Clin
Our study also reflected improvement in the quality Immunol 1977; 59 :2006.
of life of the asthmatic children, especially those 3. CoughlinSP. Sport and the asthmatic child: a study of
receiving BUD. In the BUD group, though there was exerciseinduced asthma and the resultant handicap. JR Coll
a reduction in sleep disturbance, school absenteeism, Gen Pract 1988; 38 :2535.
limitation of physical activities, less number of children 4. Anderson HR, Bailey PA, Cooper JS, Palmer JC, West S.
requiring emergency visits and rescue medication, Morbidity and school absence caused by asthma and wheezing
but this difference was not significant. There was a illness. Arch Dis Child 1983; 58 :77784.
significant increase in PEF at the end of the first and 5. JuniperEF, KlinePA, VanzieleghemMA, RamsdaleEH,
second month in the group receiving BUD. However, OByrnePM, HargreaveFE. Effect of longterm
daily home monitoring of PEF rate was not possible as treatment with an inhaled corticosteroid(budesonide)
patients could not purchase the peak flow meter. on airway hyperresponsiveness and clinical asthma in
nonsteroiddependent asthmatics. Am Rev Respir Dis 1990;
The strengths of our study were the study design, 142 :8326.
proper blinding and objective primary outcome. It was 6. Reiser J, Warner JO. Inhaled glucocorticoids in childhood
an adequately powered RCT in children with mild asthma. In: GodfreyS,editor. Glucocorticoids in childhood
persistent asthma and the results favoured BUD which asthma. Amsterdam: Exerpta Medica; 1987. p.7884.
is commonly prescribed in most regions of the world. 7. DaleyYatesPT, PriceAC, SissonJR, PereiraA, DallowN.
Thus, our results can be generalized to most settings. Beclomethasone dipropionate: absolute bioavailability,
However, one important limitation of our study was the pharmacokinetics and metabolism following intravenous,
short follow up period of two months during which we oral, intranasal and inhaled administration in man. Br J Clin
did not expect the compliance to be as poor as would Pharmacol 2001; 51 :4009.
be the case in case of a lengthier time period. 8. DonnellyR, SealeJP. Clinical pharmacokinetics of inhaled
budesonide. Clin Pharmacokinet 2001; 40 :42740.
In conclusion, our study showed improvement in
9. Field HV, Jenkinson PMA, Frame MH, Warner JO. Asthma
patients FEV1 treated with 400g/day of BUD MDI treatment with a new corticosteroid aerosol, budesonide,
as compared to 400g/day of beclomethasone MDI administered twice daily by spacer inhaler. Arch Dis Child
administered through spacer with valve over a period 1982; 57 :8646.
of two months. However, comparable improvement in 10. SpringerC, AvitalA, MaayanC, RoslerA, GodfreyS.
symptoms of asthma was observed in both the groups. Comparison of budesonide and beclomethasone dipropionate
No significant safety concerns were identified. BUD for treatment of asthma. Arch Dis Child 1987; 62 :8159.
was found to be slightly more effective than BDP. It 11. BaranD. Acomparison of inhaled budesonide and
can be suggested that both BDP and BUD can be used beclomethasone dipropionate in childhood asthma. Br J Dis
effectively in the management of children with mild Chest 1987; 81 :1705.
persistent asthma. 12. Nicolaizik WH, Marchant JL, Preece MA, Warner JO.
Endocrine and lung function in asthmatic children on inhaled
Acknowledgment corticosteroids. Am J Respir Crit Care Med 1994; 150 :6248.
Authors acknowledge DrT.P. Yadav and the hospital 13. Adams N, Bestall JM, Jones PW. Inhaled beclomethasone
administration for providing inhalers, Sister Chanci as the nursing versus budesonide for chronic asthma. Cochrane Database
staff for the distribution of medicines and the pharmacist Shrimati Syst Rev 2002;(1): CD003530.
Sagar for the preparation of the drug. Authors thank Shrimati Parul
Takkar for helping in statistical analysis and Dr.Neha Patharia for 14. Kercsmar CM. Wheezing in older children: Asthma. In:
collection of review material. ChernickV, BoatTF, WilmottRW, BushA, editors. Kendig
and Chernicks disorders of the respiratory tract in children.
Conflicts of Interest: None. 8thed. Philadelphia: Saunders; 2012. p.70130.
[Downloaded free from http://www.ijmr.org.in on Saturday, July 15, 2017, IP: 36.86.56.32]

SINGH et al: BECLOMETHASONE DIPROPIONATE VS. BUDESONIDE IN MILD PERSISTENT ASTHMA 257

15. Global Strategy for Asthma Management and Prevention, FittermanL, BergerM, etal. Association of asthma control
Global Initiative for Asthma(GINA) 2006; c2002. Available with health care utilization and quality of life. Am J Respir
from: http://www.ginasthma.org, accessed on August 20, Crit Care Med 1999; 160 : 164752.
2012. 18. MillerMR, HankinsonJ, BrusascoV, BurgosF, CasaburiR,
16. Asthma Therapy Assessment Questionnaire. New Jersey: Merck CoatesA, etal. Standardisation of spirometry. Eur Respir J
Sharp and Dohme Corp; c20082010. Available from: http://www. 2005; 26 :31938.
asthmacontrolcheck.com/asthma_control/asthmacontrolcheck/ 19. BrogdenRN, McTavishD. Budesonide. An updated review
consumer/index.jsp, accessed on August 20, 2012. of its pharmacological properties, and therapeutic efficacy in
17. Vollmer WM, Markson LE, OConnor E, Sanocki LL, asthma and rhinitis. Drugs 1992; 44 :375407.

Reprint requests: DrDevki Nandan, Department of Pediatrics, PGIMER and


Dr. RML Hospital, NewDelhi 110001, India
email:devkinandan2002@yahoo.com

Anda mungkin juga menyukai