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Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard Allergy 2007: 62: 230–236 DOI: 10.1111/j.1398-9995.2007.01326.x Review article Access to inhaled corticosteroids is key to improving quality of care for asthma in developing countries Asthma is a worldwide public health problem affecting about 300 million people. The majority of persons living with asthma are in the developing world where there is limited access to essential drugs. The financial burden for persons living with asthma and their families, as well as for healthcare systems and governments, is very high. Inadequate treatment and the high cost of medications leads to disability, absenteeism and poverty. Despite the existence of effective asthma medications and international guidelines, and progress made in the implementation of such guidelines over the last decade, the high cost of essential asthma medications remains a major obstacle for patient access to treatment in developing countries.The International Union Against Tuberculosis and Lung Disease has evaluated this problem and created an Asthma Drug Facility (ADF) so that countries can purchase affordable, good quality essential drugs for asthma. The ADF uses pooled procurement along with other purchasing and supply strategies to obtain the lowest possible prices. Accompanied by the implementation of standardized asthma management, the increased affordability of drugs provided by the ADF should bring rapid and significant health and cost benefits for patients, their communities and governments. Asthma is a worldwide public health problem affecting about 300 million people. The majority of those living with asthma are in the developing world where there is limited access to essential drugs (1). The financial burden is very high for persons living with asthma, for their families, as well as for healthcare systems and governments (2–6). Costs increase dramatically when the quality of case management is poor (7). Inadequate treatment and high costs of medications lead to disability, absenteeism and poverty (8, 9). An effective case management strategy for the diagnosis, treatment and monitoring of asthma has been developed. It has been successfully evaluated in pilot studies conducted by the International Union Against Tuberculosis and Lung Disease (The Union) in health institutions in several developing countries (10, 11). Despite the existence of effective medications and international guidelines, and progress made in the implementation of such guidelines over the last decade, the continued high cost of essential asthma medications constitutes a major obstacle for patient access to treatment in the majority of developing countries. A key conclusion of the first World Asthma Meeting, a joint meeting in 1998 of experts from six scientific societies, was: ÔThere is a huge need for an international 230 N. Ait-Khaled, D. A. Enarson, K. Bissell, N. E. Billo International Union against Tuberculosis and Lung Disease (The Union), Paris, France Key words: asthma; developing countries; essential medicines; inhaled corticosteroids; quality of care. Prof. Nadia Ait-Khaled International Union against Tuberculosis and Lung Disease (The Union) 68, Boulevard Saint-Michel 75006 Paris France Accepted for publication 8 January 2007 action for making effective asthma therapy available in all countries all over the worldÕ (12). The increasing problem of asthma in developing countries Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) calculated the cumulative prevalence of asthma in children aged 13–14 years in 155 centres in 58 countries. The highest prevalence rates were found in Oceania (25.9%) and North America (16.5%), slightly lower rates in Latin America (13.4%), western Europe (13%), the eastern Mediterranean (10.7%), Africa (10.4%) and Asia Pacific (9.4%), and the lowest in South-East Asia (4.5%) and eastern Europe (4.4%). The prevalence of asthma is not only higher in industrialized countries, but also is already worryingly high in Latin America, in the eastern Mediterranean and in Africa (13–15). Conducted 5–6 years later using the same methodology, Phase III of the ISAAC study confirmed the high prevalence of asthma symptoms in some of the developing country centres. An increasing trend in asthma symptom prevalence was observed in the majority of centres in developing countries, particularly in the urban Improving quality of care for asthma centres, whereas a stabilization or decrease was observed in the majority of centres in industrialized countries (16). With the projected increase in the proportion of the world’s population that is urban from 45% to 59% in 2025, it is estimated that there may be an additional 100 million persons with asthma by 2025 (1). The moderate or high prevalence of asthma in some developing countries is already being reflected by a significant demand for health services. Thus, surveys conducted in several countries prior to the implementation of the ÔPractical Approach to Lung HealthÕ (PAL), a WHO initiative for the standardized management of respiratory diseases (17), demonstrated that asthma is the first cause of consultation for chronic respiratory disease in primary healthcare settings and at the first level of referral in nine developing countries (18). Mortality rates (asthma death rate per 100 000 inhabitants) and fatality rate (asthma death rate per 100 000 asthmatics) are available for relatively few countries. These rates vary among countries and are not directly related to asthma prevalence. From 1985 to 1987, the estimated fatality rates in industrialized countries varied from 2 in the USA and Hong-Kong, to 7 in New Zealand, and more than 9 in Germany (19). These deaths occurred mainly among the young and in 50–60% of cases, at the patient’s home, after asthma attacks the severity of which were underestimated and under-treated, and in individuals who had not been given long-term treatment or had been given an inappropriate long-term treatment. For these reasons, in some countries this rate was much higher in disadvantaged population groups: it was three times higher among blacks than among whites in the USA, and five times higher in the Maori population than the European population in New Zealand (20). In most industrialized countries, the rising trend in mortality previously observed has stopped or has been reversed since 1990 (21). This decrease in mortality, despite a rise in prevalence, is probably linked to better use of inhaled corticosteroids among those who have access to such medication. This decrease was confirmed by estimations of the asthma fatality rate among patients of 5–34 years of age for the years 1996 and 1997 in several countries (1). Case fatality was low (<5) in most of industrialized countries, with variations from 1.6 in Finland and 4.6 in New Zealand, to 9.3 in Denmark. The highest fatality rates (>10) were found in several developing countries, such as Colombia (10), Mexico (14.5), South Africa (18.7) and China (36.7). Asthma morbidity has increased worldwide over the last 20 years (1), and is reflected in increased hospitalization. The dissemination of consensus recommendations seems to have stemmed this trend in some industrialized countries. But even in these countries, unplanned use of health services is higher among the poor. It has been linked to deficiencies in patient management, lack of access to care, absence or under-utilization of inhaled corticosteroids and lack of patient health education (22–24). The cost of asthma increases with ineffective management practices The cost of asthma (2) includes direct costs (e.g. the cost of medications, consultations, hospitalizations), indirect costs linked to loss of productivity (e.g. days absent from work or school, job losses, premature death), and intangible costs, which are often considerable but difficult to calculate (e.g. effects on family and social life, sporting activities, and professional or emotional repercussions). There is a lack of data regarding the overall cost of asthma morbidity and mortality in developing countries. The cost of the disease can only be estimated using data from industrialized countries. In industrialized countries, the rising trend in asthma morbidity over the last 20 years has been reflected in an increase in hospitalizations and healthcare costs. In 1990, it was estimated that annual asthma costs in the USA were US$ 640 per patient and that they represented 0.5– 1.0% of all USA healthcare expenditure. In 1998, the annual cost of asthma in the USA was estimated to be US$ 12.7 billion, more than twice the annual cost from 1990 (25). In 1999, the prevalence of asthma in Germany’s statutory health insurance system was 6.3% and the total cost of asthma amounted to €2.74 billion (26). Annual asthma costs vary among countries (27), from US$ 1315 in Sweden in 1975 to US$ 326 per patient in Australia in 1991. The cost of asthma per patient has consistently been found to be higher for the highest grade of severity and to rise dramatically with an increase in emergency room visits and hospitalizations (28–31). The total cost of asthma is estimated to be at least US$ 20 billion annually in developing countries alone. Although the disease is frequent, many cases do not receive adequate diagnosis and treatment, which exacerbates the condition and means additional costs. For more accurate estimations of the disease burden in developing countries; however, much more research into asthma costs for the individual and society as a whole is needed. The number of disability adjusted life years (DALYs) lost is a useful way to compare the relative importance of chronic respiratory diseases. Using this approach, it was estimated that respiratory diseases caused 15% of the global burden of disease in 1999, with chronic obstructive pulmonary disease (COPD) contributing 2.7% of the burden, tuberculosis 2.3% and asthma 0.9%. However, there were significant differences among regions of the world (32, 33). The number of DALYs lost worldwide due to asthma has been estimated at about 15 million/ year, which accounts for about 1% of all DALYs lost, Ôsimilar to that for diabetes, cirrhosis of the liver or schizophreniaÕ (1). 231 Ait-Khaled et al. Cost-effective standardized case management is possible International guidelines have been widely disseminated throughout the world (34). Several national consensus documents, recommendations and guides have also been published. The cost-effectiveness of inhaled drugs, in particular inhaled corticosteroids, has been demonstrated in many countries and is well known by health workers. Costs associated with asthma can be reduced by appropriate case management and the introduction of high-dose inhaled corticosteroids for patients with persistent asthma. The number of hospital days for such patients can be reduced by up to 80%, which entails a significant reduction in costs for the health services (35). The Union Asthma guide, published in 1996 (36) and revised in 2005 (37), proposes a technical package for asthma management, based on the management model developed for tuberculosis control, known as the DOTS strategy (internationally-recommended tuberculosis control strategy), which is implemented within the clinical general health services. This standardized asthma management approach recommends the use of two drugs, both of which are included in the World Health Organization’s Model List of Essential Medicines: inhaled beclomethasone 250 lg per puff and inhaled salbutamol 100 lg per puff (Fig. 1). As for tuberculosis information systems, the use of a register is recommended for asthma management. Each new patient with persistent asthma is registered, and key information about his or her initial status and status during follow up is entered into the register. Case notification and patient outcome can therefore be routinely analysed using the register. Pilot studies of The Union asthma management approach were conducted in Algeria, Morocco, Vietnam and Syria from 1998 to 1999. The 1-year follow up of 167 patients (11) found that the severity of asthma had decreased dramatically for the majority of patients (Fig. 2), and the number of emergency visits and hospitalizations had decreased by more than 70% (Fig. 3). Thus, the implementation of standardized management of asthma using effective essential medicines can significantly reduce costs for patients, their families, societies and governments. In addition, by increasing the quality of services for respiratory patients, it will enhance the credibility of public health services in general, and attract more patients with respiratory symptoms, in particular, those with chronic cough. Low affordability of essential asthma drugs is a key barrier for standardized case management Despite the demonstrated cost-effectiveness of standardized asthma management using high-dose inhaled beclomethasone, this medicine has not been available in a large number of developing countries in recent years. In other developing countries, it is available but not affordable for the majority of patients. In a 1998 Union study, inhaled beclomethasone was found to be consistently available in only four of the eight countries surveyed. The cost of inhaled beclomethasone varied more than fivefold and for inhaled salbutamol more than threefold. In general, the highest prices were observed in the poorest countries. In all but two Figure 1. Four-step approach to asthma with chlorofluorocarbons (CFC)-free inhalers; beclomethasone 250 lg and salbutamol 100 lg. 232 Improving quality of care for asthma Change in asthma severity before and after standardised management for the 167 patients still on followup after one year Proportion of patients 60 50 40 Before 30 After 20 10 0 intermittent mild moderate persistent persistent Asthma severity severe persistent Figure 2. Asthma treatment efficacy with essential asthma drugs. Implementation of The Union Asthma Guide (Algeria, Morocco, Syria and Vietnam). Nb events 160 ER visits Hospitalisation 140 Cost of drugs for one year in 1998 for 1 case of moderate persistent asthma compared with the monthly salary of a nurse Drug cost 120 Algeria 100 Vietnam Syria 80 Guinea 60 Mali 40 Ivory Coast Burkina Faso 20 0 Nurse's salary Turkey 0 Before 50 100 150 200 250 300 350 After Figure 4. Low affordability of asthma drugs. Figure 3. Treatment cost-effectiveness with asthma essential drugs. Implementation of The Union guide (Algeria, Morocco, Syria and Vietnam). countries, the cost of 1 year of treatment for a case of moderate persistent asthma exceeded the monthly salary of a nurse. In addition, patients did not have health insurance in six of these countries (38). It is clear that under these conditions the patients could not be treated with inhaled steroids (Fig. 4). The next survey, conducted in eastern Europe, showed that inhaled beclomethasone was generally unavailable in Azerbaijan, Georgia and the Russian Federation. In six other countries, however, drugs were available and affordable. The situation was particularly positive in Poland, where 1 year of treatment for one case of moderate persistent asthma with drugs produced in Poland cost only US$ 20 (8). In 2002 and 2003, The Union surveyed drug prices in several other countries (8). Results confirmed large variations in drug prices. For example, the price of one inhaler with 200 doses of inhaled beclomethasone 250 lg was US$ 62 in Kuwait, US$ 25 in Sudan, US$ 32 in France and $ 4 in Algeria. The same price variation was observed for salbutamol within countries (US$ 2.20 to US$ 8.75). The average price for 1 year of treatment for one case of moderate persistent asthma varied from US$ 688 in Kuwait to US$ 36 for country buying generics (with an order of at least 10 000 inhalers of each drug). Several other studies have highlighted the problem of low affordability of asthma drugs. Preliminary results from the Global Asthma Survey on Practice (GASP), an audit of emergency room treatment of asthma in several countries in 2003, showed that the main factor associated with emergency visits is low affordability for patients of the drugs used for long-term treatment of asthma (39). Other studies have found that emergency admissions are associated with patientsÕ lack of or poor health insurance 233 Ait-Khaled et al. coverage for asthma medications (40, 41) and with socioeconomic deprivation (23, 40). It is evident, then, that affordable essential asthma drugs are still not reaching patients in developing countries and that the low affordability of essential asthma drugs remains the main barrier for the adequate management of asthma. Improving access to affordable medications In order to improve the access and affordability of essential asthma medicines in low- and middle-income countries, The Union has created the Asthma Drug Facility (ADF; 42, 43). The ADF has drawn lessons from The Union’s experiences in medicine procurement in the 1990s (44) and the Stop TB Partnership’s Global Drug Facility (GDF), created in 2001 (45). Countries or organizations within countries can purchase affordable, good quality essential medicines for asthma through the ADF. The ADF uses pooled procurement and other purchasing and supply strategies to obtain the lowest possible prices. Delivery is organized by the ADF’s procurement agent. As the implementation of quality healthcare services is a key concern of the ADF and The Union, technical resources and monitoring will also be provided and clients will be required to submit reports on patient management. The ADF supplies the following inhaled drugs in CFCfree and CFC-containing formulations: salbutamol 100 lg, terbutaline 250 lg, beclomethasone 250 lg, budesonide 200 lg and fluticasone 125 lg. These are available as pressured meter-dose inhalers propelled either by chlorofluorocarbons (CFCs) or hydrofluoroalkanes (HFAs). In accordance with the Montreal Protocol on Substances that Deplete the Ozone Layer, and its subsequent amendments, many industrialized countries have now stopped producing and importing CFC-containing products. For asthma treatment, the Protocol required that CFC-containing inhalers be phased out in the majority of countries by 2005 (46, 47). In parallel, HFA-propelled asthma inhalers have been produced. Studies of the bioavailability, pharmacokinetics, efficacy, improvement in quality of life and toxicity of HFA inhalers have been conducted mainly on salbutamol and beclomethasone. HFA formulations of salbutamol have been judged comparable with those containing CFCs (48–51). How- ever, HFA beclomethasone has proved effective and less toxic at lower doses: the dose equivalence between HFAbeclomethasone and CFC-beclomethasone is approximately 2 to 1 (52–59). Thus, the number of puffs per day for HFA-beclomethasone (Fig. 1) becomes half of the number recommended for CFC-beclomethasone in The Union guide (37). As the prices obtained by the ADF for these two beclomethasone inhalers are very similar, the use of HFA inhalers will significantly decrease the price of treatment. Two studies comparing the cost and effectiveness of these two formulations of beclomethasone (CFC and HFA at half the dose) have shown that HFA beclomethasone is more cost-effective (60, 61). Conclusion World Health Organization has recently highlighted the importance of chronic diseases, notably with its publication ÔPreventing chronic diseases: a vital investmentÕ (62). However, there are today many competing public health priorities (AIDS, tuberculosis, malaria, avian flu, etc.). It is difficult to convince donors and governments that chronic respiratory diseases, such as asthma, represent a huge burden to healthcare systems all over the world. This challenge was emphasized at the launch of the Global Alliance against Chronic Respiratory Diseases (GARD) in Beijing on the 28 of March 2006 (63). The availability of affordable CFC-free asthma medicines through the ADF (leading to annual treatment costs for one case of persistent asthma of <30 USD) and the introduction of standardized case management will allow governments to save millions in costs for medicines and unnecessary emergency room visits and hospitalizations. Clinical services will be able to provide a more complete response for patients presenting with respiratory problems. This should improve the credibility of the public health sector and other services that can provide quality asthma care, thus strengthening health systems in general. Most importantly, affordable asthma drugs will contribute to poverty alleviation by reducing the burden on governments, hospitals, persons and families affected by asthma. Improved access and standardized management should be advocated by all those interested in public health with as much force, enthusiasm and perseverance as is dedicated to AIDS, tuberculosis and malaria (43). 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