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Original Articles Indian Pediatrics 2001; 38: 24-28 |
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Randomized
Comparison of a Dry Powder Inhaler and Metered Dose Inhaler |
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Manuscript received: March 9, 2000; Initial review completed: April 19, 2000; Revision accepted: July 24, 2000. Objective: Comparison of the clinical efficacy of a transparent, DPI (transparent Rotahaler) with MDI and spacers in childhood asthma. Design: Open, randomized, crossover trial. Setting: Out patient clinic of a referral pediatric center. Methods: Thirty (mean 6.1 ± 2.7 years) children with moderate persistent asthma were randomized to receive long-term medications by a DPI or a metered dose inhaler with spacer for six weeks and then crossed over to receive the same drugs for another period of six weeks after an initial run in period of one week for training in inhalation techniques. The preventative therapy consisted of inhaled Beclomethasone dipropionate (600 mcg/day) and Salbutamol as per requirement. The patients were monitored by a symptom diary, weekly PEFR, and PEFR variability by the parental record of PEFR measurements at home with Mini Wright’s Peakflow meter in accordance with the Consensus guidelines. Results: Comparisons made on weekly symptom scores, PEFR at interval visits, PEFR variability, additional beta sympathomimetic use and acute exacerbations of asthma did not reveal any statistically significant differences during the two treatment periods (>0.05). Conclusion: Metered dose inhaler and dry powder inhaler have equal efficacy in anti-inflammatory therapy of bronchial asthma in children. Key words: Asthma, Dry powder inhaler, Metered dose, Peak expiratory flow rate.
THE last decade has seen introduction of a large number of inhalation devices for drug delivery to the lower respiratory tract in patients with respiratory disease. Children with asthma have a specific problem with inhalation medication becuase they cannot coordinate inhalation with actuation of the devices(1). Several solutions have been offered to overcome this problem including breathing through a large volume spacer, breath actuated devices, accuhalers or turbohalers and the use of nebulizers. Dry powder inhalers such as diskhalers which provide ready to use drug doses in blister packs or rotahalers in which a powdered aerosol is generated once the patient inhales through it have also been introduced(2). A new cocoa based inhalation device has been used in Australia which is more child friendly(3). Nebulizers are far more expensive and bulky. Recently, a transparent rotahaler (Fig. 1) has been introduced in India in which special care has been taken to prevent development of moisture which was found to make the drug capsule soggy in an earlier model. The device which is available now has the advantage of being small and portable. It is transparent so the patient can actually observe the inhalation drug disappearing and does not require any co-ordination between breathing and actuation. We report the results of a randomized controlled trial comparing efficacy and safety of this dry powder inhaler with conventional metered dose inhaler with spacer in treatment of children with asthma.
A sample of 30 children with newly diagnosed moderate persistent asthma who were not in acute exacerbation, who were started on inhalation therapy for the first time were randomized (computer generated sequence) to receive their long term medica-tion by a dry powder inhaler (transparent Rotahaler; Cipla Ltd). or by a metered dose inhaler with spacer (750 ml valved spacer by Cipla Ltd). The sample size was estimated at an accrual rate of 100 new patients per year for this randomized controlled crossover trial at an a of 0.05 and power of 80%. A sample of 28 patients was considered adequate to detect a difference of 10% in the primary outcome measures at six data recordings at weekly intervals(4). Transparent rotahaler is a dry powder inhaler made form synthetic polycarbonate material (Fig. 1). It has a mouth piece, a space for the drug rotacap insertion and a fin which when rotated leads to opening of the rotacap. After the rotacap has been opened, the patient inspires through the mouth piece and can actually see the drug disappearing from the rotachamber. The patients were included after an initial run in period of one week for training of the inhalation techniques. Beclomethasone dipropionate 600 micrograms per day was administered in three divided doses and Salbutamol as needed (PRN basis). The treatment of patients with one form of inhala-tion system was continued for six weeks before being crossed over to receive the same drugs by the other delivery device. Throughout the period of the study the patient/parent recorded their symptoms at home on a diary sheet. A symptom score based on symptoms of cough (nocturnal or day time), wheezing, breathing difficulty, exercise intolerance and aditional bronchodilator use was calculated at the time of weekly visit to the clinic. This score (as described under the section of outcome measurements) has been in use in this department for the last three years and has been validated in relation to pulmonary function tests and a quality of life scale in a study carried out in the department. The parents were asked to keep a record of morning and evening PEFR with the help of a mini Wright’s peak flow meter, which was provided to them for the study period. The patients were followed up in the clinic at weekly intervals with complete physical examination and record of any extra medica-tion use or any emergency room visits. The following outcome measurements were compared between the two groups: 1. Mean weekly symptom scores Presence of each of the symptoms of cough, wheezing, breathing difficulty, exercise intolerance and use of rescue puffs of salbutamol was given a score of one or zero depending on their presence or absence every day for a period of one week. The patients marked a positive or a negative sign on their diary score sheets every day against each symptom. The score was calculated at the time of visit to the clinic. Thus, a maximum score of 35 and a minimum of zero could be assigned to any patient at the end of one week. 2. Mean weekly PEFR 3. Averaged PEFR % variability PEFR was measured at home and record kept by the parents at 8 am and 3 pm every day as the best of three efforts. PEFR variability was calculated as follows: {PEFR variability = (PEFR 8 am – PEFR 3 pm)}/ Mean PEFR of the two records expressed as percentage}. An average of the seven days record was taken. 4. Emergency room visits for exacerbation of asthma The data was compared using Students ‘t’ test for comparison of means and analysis of variance for incremental data. A written informed consent was obtained in all cases by the parents. Prior approval of ethics committee of the Institute was also obtained.
A total of 32 cases were enrolled. Two patients however dropped out, one belonging to each group. Both the cases dropped out because they were unable to maintain weekly visits to the clinic as required for study follow up. With the given sample size the power of the study was more than 80%. The mean age of recruited children was 6.1 ± 2.7 years. Comparison of Outcome Measurements There was no difference in the mean symptom score, PEFR % between the two groups at the time of entry into the study. PEFR variability also was similar during the first week of follow up. Table I gives the comparison of symptom scores at each visit while using a Dry Powder Inhaler (DPI) or Metered Dose Inhaler (MDI). The mean scores were not statistically different in the two groups at all time intervals except at the fifth visit in the DPI group where the scores were higher (p<0.05). Mean PEFR percentage at each visit and PEFR variability were not statistically different at all intervals in both the groups (Table I). There was no significant difference in the frequency of acute exacer-bations requiring emergency room visits which were two in number in each case. None of the children developed oral candidiasis or tremors. Two patients belonging to DPI group reported something sticking to the throat but they did not discontinue the medicine.
The inhalation route is widely used for the treatment of asthma because the administered drugs have a high therapeutic index as they reach their target directly(5). Inhalation route has become cornerstone of therapy of asthma according to all major international guidelines of management(6,7). To penetrate the con-ducting airways, the respiratory aerosol should have optimum particle size and particle velocity to minimize deposition in the pharyngeal airways. Pressurized inhalers were the first reliable metered dose devices available and are still widely used; however, they require a high degree of hand lung co-ordination. Moreover, MDI suspensions would have to be reformulated in the near future as they contain chlorofluorocarbons (CFC’s) which affect the stratosphere(8,9). Several other inhalation devices have been developed such as spacers, dry powder inhalers and breath actuated devices which have been shown to increase lung deposition in poor co-ordinators. Children with asthma are expected to make mistakes in use of MDIs due to their psycho-motor immaturity because they require co-ordination between actuation and inhalation. This problem had been circumvented by addition of a valved spacer device with which there is no need for such co-ordination. However, this addition makes the inhalation system more bulky and more expensive and decreases portability. Dry powder inhalers have been shown to be bioequivalent to metered dose inhaler(1). The present open randomized trial has shown that transparent rotahaler which is a much smaller device is as effective as MDI with spacer for the control of asthma symptoms as well as for improvement in objective parameter for respiratory obstruction such as PEFR and PEFR variability (which assesses bronchial hyper reactivity). The lower cost of therapy with this system makes it a preferred choice because inhaled anti-inflammatory therapy in asthma has to be continued for long periods of time. The familiies of the patients were able to experience greater mobility due to smaller size of the device. Since each inhalation requires loading the device with the rotacaps this could minimize the misuse of aerosol as has been reported with MDI’s which are ready to use and just require compression of the cylinder for dose delivery. MDI and spacer are however indispensable in the acute situation when the patient is experiencing an exacer-bation(11). In this situation, rotahaler has not been tried. Transparent rotahaler can thus be recom-mended as a cost effective and environment friendly alternative to CFC containing metered dose inhaler with spacer for administering preventative therapy to children with spacer for administering preventative therapy to children with asthma. However, the choice should be left to the child.
Dr. S.K. Gambhir helped in the training of the inhalation techniques. Mrs. Parveen Sachdev helped in performing PEFR measurements. Contributors: MS designed the study, monitored patients, analyzed data and drafted the manuscript. LK did critical review of the manuscript. Competing interests:
None stated
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