See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/8882856

Metered Dose Inhaler with Spacer Versus Dry Powder Inhaler for Delivery of
Salbutamol in Acute Exacerbations of Asthma: A Randomized Controlled Trial

Article  in  Indian pediatrics · February 2004

Source: PubMed

CITATIONS READS

5 216

5 authors, including:

Rakesh Lodha Sushil Kumar Kabra

All India Institute of Medical Sciences All India Institute of Medical Sciences
539 PUBLICATIONS   6,655 CITATIONS    653 PUBLICATIONS   6,268 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Vitamin D in pediatric critical illness View project

Pneumocystis jirovecii pneumonia View project

All content following this page was uploaded by Sushil Kumar Kabra on 03 July 2016.

The user has requested enhancement of the downloaded file.

 Original Articles

Metered Dose Inhaler with Spacer Versus Dry Powder Inhaler for
Delivery of Salbutamol in Acute Exacerbations of Asthma:
A Randomized Controlled Trial
Rakesh Lodha, Gaurav Gupta, Bedanta Prakash Baruah, Rajiv Nagpal and S.K. Kabra
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar,
New Delhi 110 029, India.
Corrrespondence to: Dr S. K. Kabra, Department of Pediatrics, All India Institute of Medical
Sciences, Ansari Nagar, New Delhi 110 029, India. E-mail: [email protected]
Manuscript received: January 29, 2003, Initial review completed: April 8, 2003,
Revision accepted: June 20, 2003.

Background: Delivery of various drugs by aerosol inhalation is the mainstay of treatment of asthma.
Many delivery systems have been developed for children, each having its own advantages and
disadvantages. Studies comparing the clinical efficacy of metered dose inhalers (MDI) and dry
powder inhalers (DPI) in the treatment of acute exacerbations of asthma in children are limited. We
conducted a study to compare the response to salbutamol inhalation delivered by metered dose
inhaler with a spacer versus rotahaler (DPI) in children presenting with mild or moderate acute
exacerbations of asthma. Methods: Children in the age group of 5-15 years who presented with a
mild or moderate acute exacerbation of asthma were randomized to receive 400 µg salbutamol by
either a MDI with spacer or a DPI. The changes in the wheezing and accessory muscle scores, SaO2,
and PEFR were recorded and subjected to statistical tests for significance. Results: One hundred
and fifty three children were studied; 78 were assigned to the MDI-spacer group and 75 to rotahaler
(DPI) group. After receiving treatment, the PEFR improved by about 11% in both the groups. The
oxygen saturation increased by 2% in both the groups. Within each group, the improvement in PEFR,
SaO2, wheeze and accessory muscle score after the treatment was statistically significant. In both the
groups the children co-operated equally well. Conclusion: Metered dose inhaler with spacer and dry
powder inhaler have equal efficacy in delivering salbutamol in therapy of mild to moderate acute
exacerbations of bronchial asthma in children between 5-15 years of age.
Key words: Asthma, Acute exacerbation, Metered dose inhaler, Rotahaler, Spacer.

A STHMA is a clinical syndrome

characterized by increased responsive-
ness of the tracheobronchial tree to a variety of
symptoms depends upon the deposition of
adequate amount of drug in the lungs. This
depends to a large extent upon the delivery
stimuli, airway inflammation and airway system. Many delivery systems have been
obstruction that is reversible either developed for children, each having its own
spontaneously or with treatment. Aerosol unique advantages and disadvantages.
inhalation has long been recognized as the Prominent among them are pressurized
mainstay of treatment of asthma(1). The metered dose inhalers (MDI) with or without
success of therapy and subsequent relief of spacers, dry-powder inhalers (DPI) and

INDIAN PEDIATRICS 15 VOLUME 41__JANUARY 17, 2004

LODHA, ET AL. METERED DOSE INHALER WITH SPACER VERSUS DRY POWDER INHALER

nebulizers. Studies comparing the clinical record the wheezing and accessory muscle
efficacy of MDI and DPI in the treatment of scores(4), oxygen saturation (SaO2) and PEFR
asthma in children are limited and none about using Wright’s mini peak flow meter. The
comparison in acute exacerbations. Therefore, child was then administered 400 µg of
we conducted a study to compare the response salbutamol by either a MDI with spacer or a
to salbutamol inhalation delivered by metered DPI (Rotahaler) by another author unaware of
dose inhaler with a spacer versus rotahaler (a the baseline characteristics. Children assigned
DPI) in children presenting with mild or to the MDI group received four 100 µg puffs
moderate acute exacerbation of asthma. of salbutamol using a 750 mL commercially
available spacer with valve (Cipla Ltd.,
Subjects and Methods Mumbai, India). It was ensured that the
The study was conducted in the Pediatric patients took 5 deep breaths following one
Chest Clinic of a tertiary care hospital in north actuation of the MDI into the spacer. Children
India. The study subjects were children in the assigned to rotahaler (Cipla Ltd., Mumbai,
age group of 5-15 years who presented with a India) group received 2 rotacaps (Cipla Ltd.,
mild or moderate acute exacerbation of Mumbai, India) each of 200 µg salbutamol.
asthma(2) and were cooperative enough to use Children performed 5 maximum inspiratory
a peak flow meter to measure the peak maneuvers after each dose. Thirty minutes
expiratory flow rate (PEFR). Mild exacerba- after treatment, the children were reevaluated.
tion was defined by presence of cough and Baseline parameters were compared for
wheezing without any form of distress, the two groups. The changes in the wheezing
cyanosis, increased respiratory rate, or and accessory muscle scores, SaO2, and PEFR
impairment of activity; ability to speak in full were recorded and subjected to statistical tests
sentences in between breaths, with PEFR for significance. Statistical package STATA
>80% of predicted value. Moderate 7.00 (Stata Corp, TX, USA) was utilized for
exacerbation was defined as cough, wheezing, this purpose.
with use of accessory muscles, increased
respiratory rate, and inability to talk in full Results
sentences, and PEFR 60-80% of predicted. One hundred and fifty three children were
For inclusion, other than clinical features of studied. Seventy-eight children were assigned
mild or moderate acute exacerbation, the to the MDI-spacer group and 75 to Rotahaler
PEFR had to be more than 60-80% of the group. The baseline characteristics are shown
values predicted for the height(3). Children in Table I. The proportion of boys was
with features of severe acute exacerbation or significantly more in the MDI-spacer group.
PEFR less than 60% of the predicted value or Percent predicted PEFR in both the groups
a lower respiratory tract infection were were similar. Children in the MDI-spacer
excluded. In addition, children who had group had a higher accessory muscle use
received a bronchodilator within the last 6 score.
hours of presentation were excluded.
After receiving treatment, the PEFR
The children were then randomized by improved by about 11% in each of the groups
using a random number table to receive (Table II). The oxygen saturation increased by
salbutamol by either a MDI with spacer or a 2% in both the groups. The accessory muscle
DPI. One of the authors examined the child to use scores were significantly less in the

INDIAN PEDIATRICS 16 VOLUME 41–JANUARY 17, 2004

LODHA, ET AL. METERED DOSE INHALER WITH SPACER VERSUS DRY POWDER INHALER

TABLE I–Baseline Characteristics of Study Population

Parameter MDI-spacer group Rotahaler group P value

(n = 78) (n = 75)

Male:Female 55:23 40:35 0.03

Age in years* 9 (8-10) 10 (9-11) 0.28
PEFR (liters/min)* 190 (170-210) 199 (170-207) 0.71
Percent predicted PEFR* 77.5% (73-83.9) 74.25% (71-78.1) 0.17
SaO2 (%)* 96 (95-96) 96 (95-96) 0.76
Wheeze score* 2 (1-2) 1(1-2) 0.19
Accessory muscle score* 1 (0-1) 0 (0-1) 0.04
*median (95% confidence interval).

TABLE II–Post-treatment Characteristics in the Two Groups

Parameter MDI-Spacer group Rotahaler group P value

(n = 78) (n = 75)

PEFR (Liters/min)* 217.5 (189.2-237.4) 210 (191.9-244.1) 0.11

Percent predicted PEFR* 87.7 (81.8-92.2) 83.3 (77.9-86.4) 0.09
% increase in PEFR after treatment* 11.2 (9.3-13.3) 11.1 (8.1-12.5) 0.63
SaO2 (%)* 97 (97-97) 98 (97-98) 0.09
Increase in SaO2 (%) after treatment* 2.06 (1.04-2.08) 2.08 (1.05-2.1) 0.13
Wheeze score* 1 (0-1) 1 (0-1) 0.14
Accessory muscle score* 0 (0-0) 0 (0-0) 0.02
* median (95% confidence interval).

rotahaler group. However, the wheeze scores allows adequate drug deposition in the lower
were comparable. respiratory tract without any significant
Within each group, the improvement in systemic side effects. However, despite
PEFR, SaO2, wheeze and accessory muscle adequate tuition many patients are unable to
score after the treatment were statistically use a pressurized inhaler efficiently, especially
significant. In both the groups the children co- children. Failure to co-ordinate inhaler
operated equally well. actuation with inspiration is the most
important error(1,5-7). Also they contain
Discussion lubricants that may cause broncho-
Delivery of drugs as aerosols, particularly constriction(8). The use of a spacer device
via metered dose inhalers, has been a major eliminates the need for any breath-hand
breakthrough in the treatment of asthma, as it co-ordination. But the side-effects of

INDIAN PEDIATRICS 17 VOLUME 41–JANUARY 17, 2004

LODHA, ET AL. METERED DOSE INHALER WITH SPACER VERSUS DRY POWDER INHALER

Key Message
• Metered dose inhaler with spacer and dry powder inhaler have equal efficacy in delivering
salbutamol in therapy of mild to moderate acute exacerbation of bronchial asthma in children
5-15 years of age.

propellants and lubricants are not eliminated. persisted. This discrepancy may be avoided by
Static electricity accumulates on many poly use of composite scores for assessment of
carbonate and plastic spacers attracting drug severity(11).
particles that become charged when they are
A number of studies have been done to
produced by the MDI. Spacer made of anti-
compare the efficacy of the many inhalational
static material and washing them before use
systems available among adults. Most of them
may reduce this problem(9).
have shown that salbutamol administered by a
Dry powder inhalers (DPIs) provide an DPI is as efficacious as that by MDI(12-14).
alternative formulation for drug delivery to Two studies(15,16) found DPI to be more
the airways without the attendant problems of effective.
MDIs and are bioequivalent to them(10).
There are no studies to show the clinical
There is no need for any breath-hand actua-
efficacy of rotahaler in children with acute
tion. But the need for a minimum level of
exacerbations of asthma. Two studies
inspiratory flow for a DPI to be useful still
evaluated changes in the lung function tests
exists.
after administering the drug by either rotahaler
We observed that efficacy of salbutamol in or a MDI alone. Kemp, et al.(17) studied two
mild or moderate acute exacerbation of asthma groups of children with asthma. In first group,
was similar when the drug is delivered by the changes in lung function were studied after
MDI-spacer or a dry powder inhaler. The administration of a single dose of 100 µg or
increase in PEFR in the two groups was about 200 µg of salbutamol and no significant
11%. We used PEFR values predicted for differences were found. In the second group,
height to calculate the decrease in PEFR. the children received 200 µg of salbutamol for
While it is preferable to establish baseline 12 weeks. While there were no significant
PEFR values for a child, the same can be done differences between and pre- and post-treat-
only by repeated measures of PEFR. Most ment lung function tests, the children in the
patients do not monitor PEFR on a regular MDI group had higher number of acute
basis at home. So we did not use this exacerbations. The authors explained this by
parameter for our study and relied up on the fact that the children in the MDI group
percent predicted PEFR for categorization. had significantly lower mean baseline FEV1
Accessory muscle scores were higher in MDI when compared with the rotahaler group. In
group than Rotahaler group at baseline, while another study on 44 children, Bronksy, et al.
other parameters to assess severity were (18) observed that the two devices (rotahaler
comparable. There was significant improve- and MDI) were equally efficacious in
ment in the scores in both the groups; how- delivering salbutamol in exercise-induced
ever, the difference between two groups asthma(18).

INDIAN PEDIATRICS 18 VOLUME 41–JANUARY 17, 2004

LODHA, ET AL. METERED DOSE INHALER WITH SPACER VERSUS DRY POWDER INHALER

Alwarez, et al.(19) in an analysis of 10 EL, Chernick V, editors. Disorders of the

RCTs observed that in stable asthma in Respiratory Tract in children. 4th Edition,
Philadelphia; W B Saunders & Company; 1983.
children, salbutamol administered via pMDI
p. 521.
is as effective as DPIs. No additional clinical
benefit was found in either case. Singh and 4. Bentur L, Canny GJ, Shields MD, Kerem E,
Schuh S, Reisman JJ, et al. Controlled trial of
Kumar compared the clinical efficacy of a
nebulized albuterol in children younger than 2
transparent, DPI (transparent Rotahaler) with years of age with acute asthma. Pediatrics 1992;
MDI and spacer in moderate persistent 89: 133-137.
childhood asthma(20). The two groups of
5. Epstein SW, Manning CPR, Ashley MJ, Corey
children received both inhaled steroids and PN. Survey of the clinical use of pressurized
bronchodilators through either of the devices aerosol inhalers. Can Med Assoc J 1979; 120:
for 6 weeks and then were crossed over to the 813-816.
other group. Comparisons made on weekly 6. Shim CH, Williams MH. The adequacy of
symptom scores, PEFR at interval visits, inhalation of aerosol from canister nebulizers.
PEFR variability, additional bronchodilator Am J Med 1980; 69: 891-898.
use and acute exacerbations of asthma did not 7. Chen SH, Yin TJ, Huang JL. An exploration of
reveal any statistically significant differences the skills needed for inhalation therapy in school
during the two treatment periods. children with asthma in Taiwan. Ann Allergy
Asthma Immunol 2002; 89: 311-315.
We studied the efficacy of the two devices
8. Yarborough J, Mansfield LE, Ting S. Metered
in only acute exacerbations and only for
dose inhaler induced bronchospasm in asthmatic
bronchodilators. Based on our findings and patients. Allergy 1985; 55: 25-27.
review of literature, we conclude that metered
9. Callaghan C, Barry P. Spacer devices in the
dose inhaler with spacer and dry powder
treatment of asthma. BMJ 1997; 314: 1061-
inhaler have equal efficacy in therapy of l062.
bronchial asthma in children
10. Hindle M, Newton DAG, Chrystyn H. Dry
Contributors: RL, SKK designed and coordinated the powder inhalers are bioequivalent to MDIs.
study and prepared the manuscript. GG, BPB, RN Chest 1995; 107: 629-633.
were involved in collection of data. GG and BPB were
11. Wood DW, Downes JJ, Lecks HI. A clinical
also involved in preparation of manuscript. SKK will
scoring system for the diagnosis of respiratory
act as the guarantor of the study.
failure. Am J Dis Child 1972: 123; 227-228.
Funding: None.
12. Bronksy E, Bucholtz GA, Busse WW,
Competing interests: None stated. Chervinksy P, Condemi J, Ghafouri MA, et al.
REFERENCES Comparison of inhaled salbuteral powder and
aerosol in asthma. J Allerg Clin Immunol 1987;
1. Crompton GK. Problems patients have using 79: 741-747.
pressurized aerosol inhalers. Eur J Resp Dis
1982; 63 (Suppl): 101-104. 13. Sovijarvi ARA, Lahdensuo A, Muitari A.
Bronchodilating effect of salbutamol inhalation
2. Warner JO, Naspitz CK. Third International powder and salbutamol aerosol after metha-
Pediatric Consensus statement on the Manage- choline-induced bronchoconstriction. Curr Ther
ment of Childhood Asthma. International Res 1982; 32: 565-573.
Pediatric Asthma Consensus Group. Pediatr
14. Tukainen H, Terho EO. Comparison of inhaled
Pulmonol 1998; 25: 1-17.
salbutamol powder and aerosol in asthmatic
3. Bierman CW, Pearlman DS. Asthma-average patients with low peak expiratory flow level. Eur
(50%) pulmonary values in children. In: Kendig J Clin Pharmacol 1985; 27: 645-647.

INDIAN PEDIATRICS 19 VOLUME 41–JANUARY 17, 2004

 LODHA, ET AL. METERED DOSE INHALER WITH SPACER VERSUS DRY POWDER INHALER

15. Muittari A, Ahonen A. Comparison of the 18. Bronksy EA, Spector SL, Pearlman DS, Justus
bronchodilator effect of inhaled salbutamol SE, Bishop AL. Albuterol aerosol versus
powder and pressurized salbutamol aerosol. rotacaps in exercise-induced bronchospasm. J
Curr Ther Res 1979; 25: 804-808. Asthma 1995; 32: 207-214.
16. Golish J, Curtis-McCarthy P, McCarthy K, 19. Negro Alwarez JM, Miralles Lopez JC, Felix
Kavuru M, Wagner W, Beck G, et al. Albuterol Toledo R, Pagan Aleman JA, Garcia Selles FJ,
delivered by MDI, MDI + spacer, and rotahaler Lopez Sanchez JD, et al. pMDIs versus DPIs
device-A comparison of efficacy and safety. J to rapid-acting b2 agonists for asthma in
Asthma 1998; 35: 373-379. children. Allergol Immunopathol 2002; 20: 245-
249.
17. Kemp JP, Furukawa CT, Bronksy EA,
Grossman J, Lemanske RF, Mansfiedl I, et al. 20. Singh M, Kumar L. Randomized comparison of
Albuterol treatment for children with asthma-a a dry powder inhaler and metered dose inhaler
comparison of inhaled powder and aerosol. J with spacer in management of children with
Allergy Clin Immunol 1989; 83: 687-702. asthma. Indian Pediatr 2001; 38: 24-28.

INDIAN PEDIATRICS 20 VOLUME 41–JANUARY 17, 2004

View publication stats