An evaluation of the acidogenic potential of asthma inhalers
Introduction
Asthma and vigilance in its treatment is steadily increasing in children. It is estimated that approximately 1.5 million (at least one in seven) children between 2 and 15 years have asthma symptoms requiring treatment in the United Kingdom.16 In the ISAAC study of 12–14-year-old UK children 15.8% used inhalers.12
The usual treatment for asthma is a combination of regular anti-inflammatory medication to suppress the inflammatory response (preventor/controller medication) and drugs used to reverse bronchospasm (reliever medication). Drugs licensed in the United Kingdom for use in children include: (i) preventor medication: disodium chromoglycate and glucocorticoids (beclamethasone dipropionate, budesonide and fluticasone propionate) and (ii) reliever medications: β2 agonists, anti-cholinergics and theophyllines. The inhaled route is currently accepted as the most effective for asthma management. There are three main methods for dispersing medication into an aerosol for inhalation: by using a pressurised metered dose inhaler (MDI), dry powder inhaler (DPI) or a nebuliser. Individual patient factors and inhaler device can both affect drug delivery.4 To coordinate actuation and inspiration precisely enough with an MDI, to inhale forcefully enough when wheezy to use a DPI, or to manipulate the complicated mechanics of some inhalers, may prove very difficult in a young child.2 Almost 30% of adult asthmatics have inadequate MDI technique10 and 80% of the drug is deposited in the oropharynx.4 The delivery of drugs in particle sizes within the respirable range also varies widely among inhaler devices. Patients may change inhaler devices several times in order to achieve a therapeutic effect; this invariably changes the effectiveness of treatment and creates a potential for unwanted local and systemic effects.
There is a growing body of evidence from epidemiological and clinical studies to suggest that dental disease in the asthmatic child population is increasing. The reported oral findings include increased incidence of dental caries, tooth wear, gingivitis, oral candidiasis, and an altered salivary composition and flow rate.7., 14., 15., 17., 18., 20., 21. One of the difficulties in determining the most likely reason for an increased caries experience in asthmatic children relates to the complexity of combinations of asthma disease severity and medication usage over time. Alterations in the type of inhaler device, route of administration, dosage and frequency of inhaler use are all possible contributors. Results from prospective cohort studies investigating the relationship between medication-controlled asthma and oral diseases remain inconclusive.
A lack of consensus in the dental literature provided an opportunity to investigate the possible link between asthma inhalers and dental disease. The asthma inhaler medication itself may be acidic and alter the oral homeostasis when inhaled. The DPIs have a lower pH than their MDI counterparts. Many of them contain lactose monohydrate as a carrier vehicle in proportions of 12–25 mg per dose. The role of pH and titratable acidity of asthma inhalers and potentially cariogenic lactose-based dry powder formulations in the development of dental caries and tooth surface loss remains to be proven.
To date only two in vivo studies on oral pH changes following inhaler use have been conducted. Kargul et al.11 utilised the touch electrode (TE) technique to investigate the effect on salivary pH (SpH) and plaque pH (PpH) in 30 asthmatic children between the ages of 6 and 14 years, regularly using two MDIs, β2 agonist (salbutamol) and corticosteroid (fluticasone propionate) in conjunction with a volumatic spacer device. A significant decrease in both PpH and SpH was observed over 30 min following inhaler use. Another very similar PpH study14 on 10 healthy non-medicated adults with normal salivary outputs, who inhaled two doses of fluticasone propionate Diskhlaer® (containing 25 mg lactose monohydrate), budesonide Turbohaler® (no lactose carrier), and beclamethasone dipropionate Accuhaler® (containing 8 mg lactose monohydrate) DPIs. Statistically significant drops in PpH from baseline were observed with all three inhalers. These studies suggest that the decrease in pH could be the direct result of the asthma medication itself and that the continuous use of inhaled dry powder corticosteroids containing lactose11., 14. may be one factor for an increased caries risk seen in asthmatic patients. These authors suggest that inhalers are capable of reducing oral pH though only selected inhalers and very different study samples were investigated in each study.
From the above studies it is not clear which of the following factors is largely responsible for changes in oral pH following inhaler use: the generic drug, the vehicle of delivery (MDI/DPI), or the DPI lactose content. The full range of asthma inhalers available for use in children in the UK has not been subjected to such acidogenic tests. The aims of the present study were therefore to investigate the inherent pH and titratable acidity of all commercially available paediatric asthma inhalers in the United Kingdom and then to assess the in vivo acidogenic potential (SpH and PpH tests) of these inhalers in a group of healthy adult volunteers.
Section snippets
Test inhalers
Asthma inhalers, according to generic drug, commonly used in children were identified for this study. The final choice was made with reference to the latest British National Formulary recommendations.3 The range of inhalers according to category of medication (preventor/reliever), generic drug (glucocorticoids/disodium chromoglycate/β2 agonists/combination medication) and vehicles of delivery (MDI/DPI) included the following:
Preventors:
- •
Glucocorticoids
- (i)
Beclamethasone dipropionate: MDI: Becotide®
- (i)
Inherent pH and titratable acidity
The mean pH of all inhalers tested can be observed in Table 1. A lack of significant differences in overall mean pH and titratable acidity was observed among generic drugs. However, a highly significant difference (P<0.005) in overall mean pH was observed between the vehicles of delivery: MDIs (n=10, mean inherent pH=6.45±0.21) and DPIs (n=8, mean inherent pH=5.06±0.34). Similar observations were made for each generic MDI/DPI pair. Collectively, lactose-based DPIs tended to have lower inherent
Discussion
The inherent pH of the DPIs was consistently and significantly lower than their MDI counterparts for all inhalers tested. Most dry powder inhalers produced pH values below pH 5.5, indicative of their potential to dissolve enamel hydroxyapatite (Table 1). These findings are in agreement with those of O’Sullivan et al.17 The measurement of titratable acidity gives an indication of the buffer capacity of a solution. Solutions with a higher titratable acidity have a higher buffer capacity and are
Acknowledgements
This study was partly funded by The British Dental association/Glaxo SmithKline young scientist award and partly by Mr Huw Richardson, a private citizen, residing in Leeds, UK.
References (22)
- et al.
Inhaled corticosteroid aerosols and candidiasis
Br. J. Dis. Chest
(1979) - et al.
Statistical methods for assessing agreement between two methods of clinical measurement
Lancet
(1986) - et al.
Patient compliance with inhaled medication: does combining beta-agonists with corticosteroids improve compliance
Eur. Resp. J.
(1994) - British National Formulary. A joint publication of the British Medical Association and the Royal Pharmaceutical Society...
- The use of inhaled corticosteroids in adults with asthma. Drugs Ther Bull...
- et al.
An evaluation of the cariogenic potential of baby and infant fruit drinks
Br. Dent. J.
(1989) - et al.
Plaque acidity models for cariogenicity testing—some theoretical and practical observations
J. Dent. Res.
(1986) - et al.
Inhalational and topical steroids, and oral candidosis: a mini review
Oral Dis.
(2001) - et al.
Laboratory studies of the dental properties of soft drinks
Br. J. Nutr.
(1989) - et al.
Human plaque acidity models
J. Dent. Res.
(1986)
Does patient education work
Br. J. Hosp. Med.
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