- Email: [email protected]
Trends in Hospitalizations and Mortality From Asthma in Costa Rica Over a 12- to 15-year Period
Original Article
Trends in Hospitalizations and Mortality From Asthma in Costa Rica Over a 12- to 15-year Period Manuel Soto-Martínez, MDa,b, Lydiana Avila, MDa, Natalia Soto, MDb, Albin Chaves, MDc, Juan C. Celedón, MD, DrPHd,*, and Manuel E. Soto-Quiros, MD, PhDa,b,* San José, Costa Rica; and Pittsburgh, Pa
What is already known about this topic? Use of inhaled corticosteroids has been shown to reduce morbidity and mortality due to asthma in industrialized nations, for example, the United States. What does this article add to our knowledge? We show that nationwide efforts to standardize management and to increase the use of inhaled corticosteroids in subjects with persistent asthma probably contributed to marked decrements in hospitalizations and mortality due to asthma in Costa Rica, an economically developing Latin American country with universal health coverage. How does this study impact current management guidelines? This study emphasizes the importance of implementing current guidelines for asthma management, including educational programs and appropriate use of inhaled corticosteroids, in economically developing countries where this disease has become a significant public health problem. BACKGROUND: Little is known about trends in morbidity and/or mortality due to asthma in Latin America. OBJECTIVE: To examine trends in hospitalizations and mortality due to asthma from 1997-2000 to 2011 in Costa Rica. METHODS: The rates of hospitalization due to asthma were calculated for each sex in 3 age groups from 1997 to 2011. The number of deaths due to asthma was first calculated for all groups and then for each sex in 3 age groups from 2000 to 2011. All analyses were conducted over the entire period and separately for the periods before and after a National Asthma Program (NAP) in 2003. Data also were available for prescriptions for beclomethasone since 2004. All analyses were conducted by using Epi Info.
a
Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica b Department of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica c Department of Pharmaco-epidemiology, Caja Costarricense Seguro Social, San José, Costa Rica d Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pa * These authors contributed equally to this work. J. C. Celedón’s contribution to this work was supported by grants HL073373, HL079966, and HL117191 from the US National Institutes of Health and by an endowment from the Heinz Foundation. Conflicts of interest: J. C. Celedón has received research support from the National Institutes of Health, has received consultancy fees from Genentech, and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication August 1, 2013; revised September 17, 2013; accepted for publication September 19, 2013. Available online November 14, 2013. Corresponding author: Manuel E. Soto-Quiros, MD, PhD, Division of Pediatric Pulmonology, Hospital Nacional de Niños, PO Box 1654-1000, San José, Costa Rica. E-mail: [email protected]. 2213-2198/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2013.09.010
RESULTS: Substantial reductions were found in hospitalizations and deaths due to asthma in Costa Ricans (eg, from 25 deaths in 2000 to 5 deaths in 2011). Although, the percentage decrement in the rates of hospitalization for asthma in subjects <20 years old was similar before and after the NAP, the reduction in both deaths due to asthma and rates of asthma hospitalizations in older subjects were more pronounced after the NAP, when prescriptions for beclomethasone were also increased by approximately 129%. CONCLUSION: In Costa Rica, there was a marked decrement in hospitalizations and mortality due to asthma from 1997-2000 to 2011. In younger subjects, this is likely due to guidelines that, since 1988, recommend inhaled corticosteroids for persistent asthma. In older adults, the NAP probably enhanced reductions in hospitalizations and deaths due to asthma through inhaled corticosteroid use. Ó 2013 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2014;2:85-90) Key words: Asthma; Hospitalizations; Mortality; Costa Rica
The prevalence of asthma in Costa Rica is among the highest in the world.1,2 In a nationwide study of 2682 children ages 5-17 years, the estimated prevalence of physician-diagnosed asthma was 23% in 1989.2 Among Costa Rican children ages 13-14 years who participated in phase I of the International Study of Asthma and Allergies in Childhood in 1995, current wheeze was reported by approximately 24%.3 Eight years later, approximately 27% of children in the same age group reported current wheeze in phase III of the International Study of Asthma and Allergies in Childhood.3 Similarly, current wheeze was very frequently reported by parents of children ages 6 to 7 years in phase I (approximately 32%) and phase III (approximately 38%) of the International Study of Asthma and Allergies in Childhood.3 The causes of this high asthma burden are likely multifactorial and at least partly related to heredity and the “Westernized” lifestyle of contemporary Costa Ricans.1,4 85
86
SOTO-MARTÍNEZ ET AL
Abbreviations used COPD- Chronic obstructive pulmonary disease HNN- Hospital Nacional de Niños ICS- Inhaled corticosteroids NAP- National Asthma Program
Costa Ricans have had universal health coverage since the late 1940s. In Costa Rica, only 1 hospital provides tertiary level of care for childhood asthma by pulmonologists or allergists (Hospital Nacional de Niños in San José [HNN]). Pediatric specialists at the HNN have played a leading role in developing guidelines for the treatment of childhood asthma (first published in 1985, and first recommending the use of inhaled corticosteroids [ICS] by pulmonologists or allergists in 19885) and conducting 4 nationwide epidemiologic studies of childhood asthma in Costa Rica since 1989. In 2003, a National Asthma Program (NAP), which consisted of educational meetings at all major public health care centers, the HNN, and 4 tertiary-level hospitals for adults, was implemented in Costa Rica. This program emphasized early diagnosis by using ICS as first-line therapy for asthma control, early use of reliever medications (eg, albuterol) to treat exacerbations, appropriate referral to specialists for asthma care, and avoidance of common allergen sources (eg, cockroaches) or tobacco smoke. Concurrent with this program, general practitioners, pediatricians, and internists were first allowed to prescribe ICS for asthma (only pulmonologists or allergists could prescribe ICS before 2003). To date, little is known about temporal trends for morbidity and mortality in Latin American countries. In this study, we examined trends in hospitalizations due to asthma in Costa Rica over a 15-year period (1997-2011), including nearly equal periods of surveillance before and after implementation of the NAP in 2003. In addition, we assessed the number of deaths due to asthma in Costa Rica from 2000 to 2011.
METHODS As part of the Costa Rican nationwide health care system, the Caja Costarricense del Seguro Social collects complete information on all hospitalizations and deaths that occur at public hospitals or health care centers (which care for approximately 4.5 million people). Information on hospitalizations and deaths due to asthma (as coded by the treating physicians) as well as prescriptions for 3 medications (beclomethasone, montelukast, and formoterol) approved by the Caja Costarricense del Seguro Social was obtained for patients of all ages from 2 databases maintained by the Health Statistics Division and the Epidemiology Division of the Caja Costarricense del Seguro Social. Age and sex were available for all individuals who were hospitalized for or died of asthma. We analyzed temporal trends in the rates of hospitalizations (from 1997 to 2011) and the number of deaths (from 2000 to 2011) due to asthma in Costa Rica. Rates of hospitalization due to asthma were calculated for each sex in 3 age groups: younger than 10 years old, 10 to 20 years old, and over 20 years old. Because of relatively small sample size and the observed age distribution, the number of deaths due to asthma was calculated for all age and sex groups, and then separately for each sex in 3 age groups: subjects younger than 5 years old, subjects ages 5-35 years old, and subjects older than 35 years. To further examine
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
mortality in older subjects, we also examined the number of deaths due to asthma in subjects older than 40 years. For the analysis of temporal trends in hospitalizations and mortality due to asthma, we first showed the results over the entire observation period (eg, from 1997 to 2011 for hospitalizations) and then separately for the periods before and after implementation of the NAP in 2003. We also examined the number of prescriptions issued for beclomethasone (from 2004 to 2011), montelukast (from 2005 to 2011), and formoterol (from 2006 to 2011) in Costa Rica. In secondary analyses of temporal trends for respiratory diseases other than asthma in Costa Rica, we examined the number of hospitalizations for bronchitis and bronchiolitis at the HNN from 2000 to 2011 as well as the number of hospitalizations for chronic obstructive pulmonary disease (COPD) in adults from 2002 to 2011. All analyses were conducted by using Epi Info 7 (US Centers for Disease Control, Atlanta, Ga).
RESULTS Between 1997 and 2011, there were 56,002 hospitalizations for asthma in Costa Rica. Of these 56,002 hospitalizations, 35,714 (64%) were for subjects younger than 20 years. The total number of asthma hospitalizations in Costa Rica in both children and adults decreased by approximately 53% from 1997 (n ¼ 5207) to 2011 (n ¼ 2459). The sex-adjusted rates of hospitalizations for asthma in Costa Rica in the 3 age groups from 1997 to 2011 are shown in Figure 1. Although the sex-adjusted rate of asthma hospitalizations was reduced in all 3 age groups from 1997 to 2011, the most substantial changes in absolute terms (given high baseline rates) occurred in children younger than 10 years old. In this age group, the rates of hospitalizations for asthma were reduced by approximately 57% in boys (from 46/ 10,000 to 20/10,000) and by approximately 54% in girls (from 35/10,000 to 16.2/10,000) between 1997 and 2011. Among subjects ages 10-20 years old, the rates of asthma hospitalizations were reduced by approximately 60% in male subjects (from 5.7/10,000 to 2.3/10,000) and by approximately 51% (from 5.7/10,000 to 2.8/10,000) in female subjects between 1997 and 2011. In adults older than 20 years, the rates of asthma hospitalizations were reduced by approximately 74% in male subjects (from 3.5/10,000 in 1997 to 0.9/10,000 in 2011) and by approximately 51% in female subjects (from 10.7/10,000 in 1997 to 5.2/10,000 in 2011). An increment in hospitalization rates for asthma in all age groups was noted from 2002 to 2003. During this period, hospitalizations for bronchitis at the HNN were essentially unchanged but the number of hospitalizations for bronchiolitis increased by 38.6% (from 796 to 1103). From 2002 to 2003, there was a slight reduction in the number of hospitalizations due to COPD in Costa Rican adults older than 20 years (889 vs 842). Among children (boys and girls) younger than 10 years and girls and women aged 10-20 years, there were similar decrements in the rates of asthma hospitalizations before (1997-2002) and after (2004-2011) implementation of the NAP. For example, although the rates of asthma hospitalizations in children younger than 10 years decreased by approximately 37% in boys (from 46.5/10,000 to 29.5/10,000) and by approximately 33% in girls (from 35/10,000 to 23.4/10,000) between 1997 and 2002, such rates decreased by approximately 34% in boys (from 30.4/10,000 to 20/10,000) and by approximately 30% in girls (from 23.1/10,000 to 16.2/10,000) between 2004 and 2011
J ALLERGY CLIN IMMUNOL PRACT VOLUME 2, NUMBER 1
SOTO-MARTÍNEZ ET AL
87
FIGURE 1. Age and sex-adjusted rates in Costa Rica of hospitalizations for asthma (1997-2011).
(Figure 1). From 2000 to 2011, there was a parallel decrement in the number of hospitalizations for both bronchitis (by approximately 44%, from 34 to 19) and bronchiolitis (by approximately 8%, from 938 to 865) at the HNN. In contrast to our findings in subjects 20 years old and younger, the rates for asthma hospitalizations for subjects older than 20 years had a much more marked decrement after the NAP was implemented. Although the rates of hospitalizations for asthma in subjects 20 years old and older decreased by approximately 14% in men (from 3.5/10,000 to 3.0/10,000) and by approximately 11% in women (from 10.7/10,000 to 9.5/ 10,000) between 1997 and 2002, such rates decreased by 64% in men (from 2.5/10,000 to 0.9/10,000) and by 48% in women (from 10/10,000 to 5.2/10,000) between 2004 and 2011. Of note, the number of hospitalizations for COPD in Costa Rican adults 20 years and older decreased by approximately 47% (from 760 to 403) between 2004 and 2011. The number of deaths due to asthma decreased by 80% over a 12-year period (from 25 in 2000 to 5 in 2011), with a more marked reduction occurring after implementation of the NAP. Although the number of deaths due to asthma decreased by 16% between 2000 and 2002 (from 25 to 21), such numbers decreased by 58.3% between 2004 and 2011 (from 12 to 5). Although age- and sex-specific findings have to be interpreted with caution due to the small sample size, the most marked reduction in mortality due to asthma was observed in subjects older than 35 years (Figure 2). Among women older than 35 years, the number of deaths due to asthma decreased by 87% (from 15 to 2) between 2000 and 2011 (with an approximately 47% [from 15 to 8] decrement between 2000 and 2002, and a 50% decrement [from 4 to 2] between 2004 and 2011). Among men older than 35 years, the number of deaths due to asthma decreased by 75% (from 4 to 1) between 2000 and 2011 (with no change [from 4 to 4] between 2000 and 2002 but a 75% decrement [from 4 to 1] between 2004 and 2011). In contrast to our results for hospitalizations, no age and sex group (other than men older than 35 years) had a peak in deaths due to
asthma in 2003. When the analysis was restricted to subjects older than 40 years, we found that the number of deaths due to asthma in women decreased by 87% (from 14 to 2) between 2000 and 2011 (with an approximately 36% [from 14 to 9] decrement between 2000 and 2002 but a 60% decrement [from 5 to 2] between 2004 and 2011). Among men older than 40 years, the number of deaths due to asthma decreased by 75% (from 4 to 1) between 2000 and 2011 (with a 20% increment [from 4 to 5] between 2000 and 2002, but an 80% decrement [from 5 to 1] between 2004 and 2011). In parallel with a decrement in asthma hospitalizations in women older than 20 years old and a reduction in the number of deaths due to asthma, the number of prescriptions for ICS (beclomethasone) increased from 2004 to 2011 (Figure 3). For example, prescriptions for beclomethasone increased by 129% over this time period (from 291,834 prescriptions in 2004 to 668,468 prescription in 2011). In contrast, prescriptions for long-acting b-2 agonists and leukotriene inhibitors increased to a lesser extent between 2005 or 2006 and 2011 (likely due to their exclusive use by pulmonologists or allergists).
DISCUSSION We found substantial reductions in the rate of hospitalizations for and deaths due to asthma in Costa Ricans over a 12- to 15-year period (1997-2000 to 2011). Whereas, the percentage decrement in the rates of hospitalization for asthma in subjects 20 years old and younger was similar before and after implementation of the NAP, both the percentage reduction in the total number of deaths due to asthma in older subjects (either >35 years old or >40 years old) and the percentage decrement in the rates of asthma hospitalizations in subjects older than 20 years old were more pronounced after implementation of the NAP. In the absence of modifications to the coding system in Costa Rica in 2003, a change in diagnostic patterns and, for children younger than 10 years old, an upsurge in viral illnesses are the most likely explanation for the observed peak in hospitalizations
88
SOTO-MARTÍNEZ ET AL
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
A
B
FIGURE 2. The number of (A) female and (B) male deaths in Costa Rica attributable to asthma (2000-2011).
FIGURE 3. The number of prescriptions in Costa Rica for beclomethasone, formoterol, and montelukast (2004-2006 to 2011).
due to asthma in the year that the NAP was implemented. Because the prevalence of asthma in Costa Rican children and adolescents did not decrease from 1989 to 2003 (and, in fact, may have slightly increased),2,3 the sustained and relatively constant reduction in hospitalizations for asthma in children before and after the NAP was implemented (from 1997 to 2011) could be explained by improved disease management since at least the early 1990s, likely as a result of publication and regular updating of the national guidelines for pediatric asthma as well as increased awareness of childhood asthma by the general public
and health care providers as a result of large epidemiologic studies by the HNN, both of which preceded implementation of the NAP by at least 14 years. In contrast to our findings for hospitalizations for asthma in younger subjects, implementation of the NAP led to a more marked reduction in the rates of hospitalizations for asthma in subjects older than 20 years old. A change in diagnostic patterns (eg, diagnosing more adults with COPD instead of asthma after 2003) is not a probable explanation for this finding because the number of hospitalizations for COPD in Costa Rica actually
J ALLERGY CLIN IMMUNOL PRACT VOLUME 2, NUMBER 1
decreased between 2004 and 2011. Thus, the most plausible explanation for our results is improved asthma management in subjects older than 20 years as a result of the NAP, which first provided guidelines for the treatment of asthma in Costa Rican adults and, therefore, may have reduced heterogeneity in disease management among internists, pulmonologists, and allergists practicing at several institutions. Because Costa Rica is relatively small and has both socialized health care and a high literacy rate, improved awareness of the need for adequate and early treatment with ICS for subjects with persistent asthma is the most plausible cause for our overall results in children and adults, which are generally consistent with a previous report of the beneficial impact of ICS on hospitalizations for asthma in the 1990s in an industrialized nation (the United States).6 In contrast to our findings for hospitalizations for asthma, there was no consistent peak in deaths due to asthma in the year that the NAP was implemented. Because a marked reduction in asthma mortality occurred since the year after the NAP (2004), all or parts of the nationwide “asthma program” may have contributed to further reductions in deaths due to asthma in Costa Rica over the 8-year period from 2004 to 2011. Given that ICS were more widely prescribed after 2003, improved treatment of older adults with severe asthma could chiefly account for the observed reduction in asthma mortality. The relatively larger impact of the NAP on deaths due to asthma in adults than in children may again be explained by a lack of uniform guidelines for asthma management in adults (including the elderly, who have the highest mortality risk) before 2003. According to the International Monetary Fund, Costa Rica is a developing (or less developed) country from an economical viewpoint.7 To our knowledge, this is the first report of the potential long-term impact of a national program on reducing asthma mortality in an economically less developed country whose physicians were given broad access to controller medications. Even though Costa Rica is not economically developed, its citizens enjoy free health care and have a high literacy rate (approximately 95%). Thus, our findings may not be generalizable to economically developing countries where health care access is currently limited or literacy is lower. However, our results are encouraging and, together with those from similar programs in the United States (eg, Easy Breathing8,9; Conn), suggest that education and appropriate use of ICS (by specialists, general practitioners, pediatricians, and internists) could reduce the emerging burden of asthma in economically developing countries that have attempted to implement universal health care in recent years (eg, Colombia and Mexico).9 Reducing hospitalizations and mortality due to asthma could not only alleviate major suffering but lead to significant cost savings.6,10-12 We recognize additional limitations to our findings. First, this is an ecologic study, and, thus, we cannot assess causation or exclude ecological fallacy. However, our findings are valuable and can be further tested in future studies in other nations in Latin America and elsewhere. Second, we lack data on prescriptions for ICS before 2004. However, we have shown a marked increment in the total number of prescriptions for ICS in Costa Rica after implementation of the NAP. Third, and as previously mentioned, misclassification of hospitalizations or deaths as due to asthma (or not) is possible in any epidemiologic study. However, this is unlikely to fully account for the magnitude of the observed reductions in asthma morbidity or mortality over time. Fourth, we are unable to separate the relative contributions of the
SOTO-MARTÍNEZ ET AL
89
separate components of the national guidelines for asthma management in children or the NAP (implemented in 2003, for both children and adults) to our findings. ICS were first recommended as treatment for persistent childhood asthma in Costa Rica in 1988.5 Although only approximately 8% of children who participated in a research study in 1989 were on ICS,2 approximately 33% of children who participated in a research study between 2001 and 2005 were on antiinflammatory medications (mostly ICS).13 Although we cannot show a direct causal link between the increased number of prescriptions for ICS and the observed reduction in deaths due to asthma after 2003, most deaths due to asthma in Costa Rica, as in the rest of Latin America,14 occur outside of the hospital, and it is thus plausible that increased use of ICS in ambulatory settings nationwide led to a reduced mortality due to asthma, particularly in older adults.15,16 In summary, there was a marked decrement in the rate of hospitalizations and mortality due to asthma in Costa Rica from 1997-2000 to 2011. The NAP sustained but did not accentuate the decrement in hospitalizations for asthma in subjects younger than 20 years old since 1997, which is likely due to previous nationwide efforts to improve the treatment of childhood asthma. However, the NAP may have enhanced reductions in hospitalizations for asthma in adults older than 20 years old and mortality due to asthma in older adults (>35 years old or >40 years old), likely because of guidelines that emphasized treatment with ICS for persistent asthma. Universal access to health care, coupled with implementation of nationwide programs that promote and facilitate use of ICS for persistent asthma may markedly benefit economically developing countries where asthma is a major problem. REFERENCES 1. Celedon JC, Soto-Quiros ME, Silverman EK, Hanson L, Weiss ST. Risk factors for childhood asthma in Costa Rica. Chest 2001;120:785-90. 2. Soto-Quiros ME, Soto-Martinez M, Hanson LA. Epidemiological studies of the very high prevalence of asthma and related symptoms among school children in Costa Rica from 1989 to 1998. Pediatr Allergy Immunol 2002;13:342-9. 3. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-43. 4. Hunninghake GM, Soto-Quiros ME, Lasky-Su J, Avila L, Ly NP, Liang C, et al. Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations. J Allergy Clin Immunol 2008;122:93-8, 98.e1-5. 5. Soto-Quiros M. Guia de Diagnostico y Tratamiento del Niño Asmatico. Guia Pediatrica Basica de Diagnostico y Tratamiento I Infecciones respiratorias Agudas II Asma BronquialApoyo a los Recursos Humanos en el Plan de Supervivencia Infantil PASCAP OPS/OMS; 1988. 6. Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997;277: 887-91. 7. International Monetary Fund. Costa Rica and the IMF. Available from: http:// www.imf.org/external/country/CRI/index.htm. Accessed September 12, 2013. 8. Cloutier MM, Hall CB, Wakefield DB, Bailit H. Use of asthma guidelines by primary care providers to reduce hospitalizations and emergency department visits in poor, minority, urban children. J Pediatr 2005;146:591-7. 9. Cloutier MM, Grosse SD, Wakefield DB, Nurmagambetov TA, Brown CM. The economic impact of an urban asthma management program. Am J Manag Care 2009;15:345-51. 10. Harju T, Keistinen T, Tuuponen T, Kivela SL. Hospital admissions of asthmatics by age and sex. Allergy 1996;51:693-6. 11. Haahtela T, Klaukka T, Koskela K, Erhola M, Laitinen LA. Working Group of the Asthma Programme in Finland. Asthma programme in Finland: a community problem needs community solutions. Thorax 2001;56:806-14. 12. Haahtela T, Tuomisto LE, Pietinalho A, Klaukka T, Erhola M, Kaila M, et al. A 10 year asthma programme in Finland: major change for the better. Thorax 2006;61:663-70.
90
SOTO-MARTÍNEZ ET AL
13. Hunninghake GM, Soto-Quiros ME, Avila L, Su J, Murphy A, Demeo DL, et al. Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood. J Allergy Clin Immunol 2007;120:84-90. 14. Neffen H, Baena-Cagnani CE, Malka S, Sole D, Sepulveda R, Caraballo L, et al. Asthma mortality in Latin America. J Investig Allergol Clin Immunol 1997;7:249-53.
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
15. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000;343: 332-6. 16. Suissa S, Ernst P. Use of anti-inflammatory therapy and asthma mortality in Japan. Eur Respir J 2003;21:101-4.
Trends in Hospitalizations and Mortality From Asthma in Costa Rica Over a 12- to 15-year Period Manuel Soto-Martínez, MDa,b, Lydiana Avila, MDa, Natalia Soto, MDb, Albin Chaves, MDc, Juan C. Celedón, MD, DrPHd,*, and Manuel E. Soto-Quiros, MD, PhDa,b,* San José, Costa Rica; and Pittsburgh, Pa
What is already known about this topic? Use of inhaled corticosteroids has been shown to reduce morbidity and mortality due to asthma in industrialized nations, for example, the United States. What does this article add to our knowledge? We show that nationwide efforts to standardize management and to increase the use of inhaled corticosteroids in subjects with persistent asthma probably contributed to marked decrements in hospitalizations and mortality due to asthma in Costa Rica, an economically developing Latin American country with universal health coverage. How does this study impact current management guidelines? This study emphasizes the importance of implementing current guidelines for asthma management, including educational programs and appropriate use of inhaled corticosteroids, in economically developing countries where this disease has become a significant public health problem. BACKGROUND: Little is known about trends in morbidity and/or mortality due to asthma in Latin America. OBJECTIVE: To examine trends in hospitalizations and mortality due to asthma from 1997-2000 to 2011 in Costa Rica. METHODS: The rates of hospitalization due to asthma were calculated for each sex in 3 age groups from 1997 to 2011. The number of deaths due to asthma was first calculated for all groups and then for each sex in 3 age groups from 2000 to 2011. All analyses were conducted over the entire period and separately for the periods before and after a National Asthma Program (NAP) in 2003. Data also were available for prescriptions for beclomethasone since 2004. All analyses were conducted by using Epi Info.
a
Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica b Department of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica c Department of Pharmaco-epidemiology, Caja Costarricense Seguro Social, San José, Costa Rica d Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pa * These authors contributed equally to this work. J. C. Celedón’s contribution to this work was supported by grants HL073373, HL079966, and HL117191 from the US National Institutes of Health and by an endowment from the Heinz Foundation. Conflicts of interest: J. C. Celedón has received research support from the National Institutes of Health, has received consultancy fees from Genentech, and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication August 1, 2013; revised September 17, 2013; accepted for publication September 19, 2013. Available online November 14, 2013. Corresponding author: Manuel E. Soto-Quiros, MD, PhD, Division of Pediatric Pulmonology, Hospital Nacional de Niños, PO Box 1654-1000, San José, Costa Rica. E-mail: [email protected]. 2213-2198/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2013.09.010
RESULTS: Substantial reductions were found in hospitalizations and deaths due to asthma in Costa Ricans (eg, from 25 deaths in 2000 to 5 deaths in 2011). Although, the percentage decrement in the rates of hospitalization for asthma in subjects <20 years old was similar before and after the NAP, the reduction in both deaths due to asthma and rates of asthma hospitalizations in older subjects were more pronounced after the NAP, when prescriptions for beclomethasone were also increased by approximately 129%. CONCLUSION: In Costa Rica, there was a marked decrement in hospitalizations and mortality due to asthma from 1997-2000 to 2011. In younger subjects, this is likely due to guidelines that, since 1988, recommend inhaled corticosteroids for persistent asthma. In older adults, the NAP probably enhanced reductions in hospitalizations and deaths due to asthma through inhaled corticosteroid use. Ó 2013 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2014;2:85-90) Key words: Asthma; Hospitalizations; Mortality; Costa Rica
The prevalence of asthma in Costa Rica is among the highest in the world.1,2 In a nationwide study of 2682 children ages 5-17 years, the estimated prevalence of physician-diagnosed asthma was 23% in 1989.2 Among Costa Rican children ages 13-14 years who participated in phase I of the International Study of Asthma and Allergies in Childhood in 1995, current wheeze was reported by approximately 24%.3 Eight years later, approximately 27% of children in the same age group reported current wheeze in phase III of the International Study of Asthma and Allergies in Childhood.3 Similarly, current wheeze was very frequently reported by parents of children ages 6 to 7 years in phase I (approximately 32%) and phase III (approximately 38%) of the International Study of Asthma and Allergies in Childhood.3 The causes of this high asthma burden are likely multifactorial and at least partly related to heredity and the “Westernized” lifestyle of contemporary Costa Ricans.1,4 85
86
SOTO-MARTÍNEZ ET AL
Abbreviations used COPD- Chronic obstructive pulmonary disease HNN- Hospital Nacional de Niños ICS- Inhaled corticosteroids NAP- National Asthma Program
Costa Ricans have had universal health coverage since the late 1940s. In Costa Rica, only 1 hospital provides tertiary level of care for childhood asthma by pulmonologists or allergists (Hospital Nacional de Niños in San José [HNN]). Pediatric specialists at the HNN have played a leading role in developing guidelines for the treatment of childhood asthma (first published in 1985, and first recommending the use of inhaled corticosteroids [ICS] by pulmonologists or allergists in 19885) and conducting 4 nationwide epidemiologic studies of childhood asthma in Costa Rica since 1989. In 2003, a National Asthma Program (NAP), which consisted of educational meetings at all major public health care centers, the HNN, and 4 tertiary-level hospitals for adults, was implemented in Costa Rica. This program emphasized early diagnosis by using ICS as first-line therapy for asthma control, early use of reliever medications (eg, albuterol) to treat exacerbations, appropriate referral to specialists for asthma care, and avoidance of common allergen sources (eg, cockroaches) or tobacco smoke. Concurrent with this program, general practitioners, pediatricians, and internists were first allowed to prescribe ICS for asthma (only pulmonologists or allergists could prescribe ICS before 2003). To date, little is known about temporal trends for morbidity and mortality in Latin American countries. In this study, we examined trends in hospitalizations due to asthma in Costa Rica over a 15-year period (1997-2011), including nearly equal periods of surveillance before and after implementation of the NAP in 2003. In addition, we assessed the number of deaths due to asthma in Costa Rica from 2000 to 2011.
METHODS As part of the Costa Rican nationwide health care system, the Caja Costarricense del Seguro Social collects complete information on all hospitalizations and deaths that occur at public hospitals or health care centers (which care for approximately 4.5 million people). Information on hospitalizations and deaths due to asthma (as coded by the treating physicians) as well as prescriptions for 3 medications (beclomethasone, montelukast, and formoterol) approved by the Caja Costarricense del Seguro Social was obtained for patients of all ages from 2 databases maintained by the Health Statistics Division and the Epidemiology Division of the Caja Costarricense del Seguro Social. Age and sex were available for all individuals who were hospitalized for or died of asthma. We analyzed temporal trends in the rates of hospitalizations (from 1997 to 2011) and the number of deaths (from 2000 to 2011) due to asthma in Costa Rica. Rates of hospitalization due to asthma were calculated for each sex in 3 age groups: younger than 10 years old, 10 to 20 years old, and over 20 years old. Because of relatively small sample size and the observed age distribution, the number of deaths due to asthma was calculated for all age and sex groups, and then separately for each sex in 3 age groups: subjects younger than 5 years old, subjects ages 5-35 years old, and subjects older than 35 years. To further examine
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
mortality in older subjects, we also examined the number of deaths due to asthma in subjects older than 40 years. For the analysis of temporal trends in hospitalizations and mortality due to asthma, we first showed the results over the entire observation period (eg, from 1997 to 2011 for hospitalizations) and then separately for the periods before and after implementation of the NAP in 2003. We also examined the number of prescriptions issued for beclomethasone (from 2004 to 2011), montelukast (from 2005 to 2011), and formoterol (from 2006 to 2011) in Costa Rica. In secondary analyses of temporal trends for respiratory diseases other than asthma in Costa Rica, we examined the number of hospitalizations for bronchitis and bronchiolitis at the HNN from 2000 to 2011 as well as the number of hospitalizations for chronic obstructive pulmonary disease (COPD) in adults from 2002 to 2011. All analyses were conducted by using Epi Info 7 (US Centers for Disease Control, Atlanta, Ga).
RESULTS Between 1997 and 2011, there were 56,002 hospitalizations for asthma in Costa Rica. Of these 56,002 hospitalizations, 35,714 (64%) were for subjects younger than 20 years. The total number of asthma hospitalizations in Costa Rica in both children and adults decreased by approximately 53% from 1997 (n ¼ 5207) to 2011 (n ¼ 2459). The sex-adjusted rates of hospitalizations for asthma in Costa Rica in the 3 age groups from 1997 to 2011 are shown in Figure 1. Although the sex-adjusted rate of asthma hospitalizations was reduced in all 3 age groups from 1997 to 2011, the most substantial changes in absolute terms (given high baseline rates) occurred in children younger than 10 years old. In this age group, the rates of hospitalizations for asthma were reduced by approximately 57% in boys (from 46/ 10,000 to 20/10,000) and by approximately 54% in girls (from 35/10,000 to 16.2/10,000) between 1997 and 2011. Among subjects ages 10-20 years old, the rates of asthma hospitalizations were reduced by approximately 60% in male subjects (from 5.7/10,000 to 2.3/10,000) and by approximately 51% (from 5.7/10,000 to 2.8/10,000) in female subjects between 1997 and 2011. In adults older than 20 years, the rates of asthma hospitalizations were reduced by approximately 74% in male subjects (from 3.5/10,000 in 1997 to 0.9/10,000 in 2011) and by approximately 51% in female subjects (from 10.7/10,000 in 1997 to 5.2/10,000 in 2011). An increment in hospitalization rates for asthma in all age groups was noted from 2002 to 2003. During this period, hospitalizations for bronchitis at the HNN were essentially unchanged but the number of hospitalizations for bronchiolitis increased by 38.6% (from 796 to 1103). From 2002 to 2003, there was a slight reduction in the number of hospitalizations due to COPD in Costa Rican adults older than 20 years (889 vs 842). Among children (boys and girls) younger than 10 years and girls and women aged 10-20 years, there were similar decrements in the rates of asthma hospitalizations before (1997-2002) and after (2004-2011) implementation of the NAP. For example, although the rates of asthma hospitalizations in children younger than 10 years decreased by approximately 37% in boys (from 46.5/10,000 to 29.5/10,000) and by approximately 33% in girls (from 35/10,000 to 23.4/10,000) between 1997 and 2002, such rates decreased by approximately 34% in boys (from 30.4/10,000 to 20/10,000) and by approximately 30% in girls (from 23.1/10,000 to 16.2/10,000) between 2004 and 2011
J ALLERGY CLIN IMMUNOL PRACT VOLUME 2, NUMBER 1
SOTO-MARTÍNEZ ET AL
87
FIGURE 1. Age and sex-adjusted rates in Costa Rica of hospitalizations for asthma (1997-2011).
(Figure 1). From 2000 to 2011, there was a parallel decrement in the number of hospitalizations for both bronchitis (by approximately 44%, from 34 to 19) and bronchiolitis (by approximately 8%, from 938 to 865) at the HNN. In contrast to our findings in subjects 20 years old and younger, the rates for asthma hospitalizations for subjects older than 20 years had a much more marked decrement after the NAP was implemented. Although the rates of hospitalizations for asthma in subjects 20 years old and older decreased by approximately 14% in men (from 3.5/10,000 to 3.0/10,000) and by approximately 11% in women (from 10.7/10,000 to 9.5/ 10,000) between 1997 and 2002, such rates decreased by 64% in men (from 2.5/10,000 to 0.9/10,000) and by 48% in women (from 10/10,000 to 5.2/10,000) between 2004 and 2011. Of note, the number of hospitalizations for COPD in Costa Rican adults 20 years and older decreased by approximately 47% (from 760 to 403) between 2004 and 2011. The number of deaths due to asthma decreased by 80% over a 12-year period (from 25 in 2000 to 5 in 2011), with a more marked reduction occurring after implementation of the NAP. Although the number of deaths due to asthma decreased by 16% between 2000 and 2002 (from 25 to 21), such numbers decreased by 58.3% between 2004 and 2011 (from 12 to 5). Although age- and sex-specific findings have to be interpreted with caution due to the small sample size, the most marked reduction in mortality due to asthma was observed in subjects older than 35 years (Figure 2). Among women older than 35 years, the number of deaths due to asthma decreased by 87% (from 15 to 2) between 2000 and 2011 (with an approximately 47% [from 15 to 8] decrement between 2000 and 2002, and a 50% decrement [from 4 to 2] between 2004 and 2011). Among men older than 35 years, the number of deaths due to asthma decreased by 75% (from 4 to 1) between 2000 and 2011 (with no change [from 4 to 4] between 2000 and 2002 but a 75% decrement [from 4 to 1] between 2004 and 2011). In contrast to our results for hospitalizations, no age and sex group (other than men older than 35 years) had a peak in deaths due to
asthma in 2003. When the analysis was restricted to subjects older than 40 years, we found that the number of deaths due to asthma in women decreased by 87% (from 14 to 2) between 2000 and 2011 (with an approximately 36% [from 14 to 9] decrement between 2000 and 2002 but a 60% decrement [from 5 to 2] between 2004 and 2011). Among men older than 40 years, the number of deaths due to asthma decreased by 75% (from 4 to 1) between 2000 and 2011 (with a 20% increment [from 4 to 5] between 2000 and 2002, but an 80% decrement [from 5 to 1] between 2004 and 2011). In parallel with a decrement in asthma hospitalizations in women older than 20 years old and a reduction in the number of deaths due to asthma, the number of prescriptions for ICS (beclomethasone) increased from 2004 to 2011 (Figure 3). For example, prescriptions for beclomethasone increased by 129% over this time period (from 291,834 prescriptions in 2004 to 668,468 prescription in 2011). In contrast, prescriptions for long-acting b-2 agonists and leukotriene inhibitors increased to a lesser extent between 2005 or 2006 and 2011 (likely due to their exclusive use by pulmonologists or allergists).
DISCUSSION We found substantial reductions in the rate of hospitalizations for and deaths due to asthma in Costa Ricans over a 12- to 15-year period (1997-2000 to 2011). Whereas, the percentage decrement in the rates of hospitalization for asthma in subjects 20 years old and younger was similar before and after implementation of the NAP, both the percentage reduction in the total number of deaths due to asthma in older subjects (either >35 years old or >40 years old) and the percentage decrement in the rates of asthma hospitalizations in subjects older than 20 years old were more pronounced after implementation of the NAP. In the absence of modifications to the coding system in Costa Rica in 2003, a change in diagnostic patterns and, for children younger than 10 years old, an upsurge in viral illnesses are the most likely explanation for the observed peak in hospitalizations
88
SOTO-MARTÍNEZ ET AL
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
A
B
FIGURE 2. The number of (A) female and (B) male deaths in Costa Rica attributable to asthma (2000-2011).
FIGURE 3. The number of prescriptions in Costa Rica for beclomethasone, formoterol, and montelukast (2004-2006 to 2011).
due to asthma in the year that the NAP was implemented. Because the prevalence of asthma in Costa Rican children and adolescents did not decrease from 1989 to 2003 (and, in fact, may have slightly increased),2,3 the sustained and relatively constant reduction in hospitalizations for asthma in children before and after the NAP was implemented (from 1997 to 2011) could be explained by improved disease management since at least the early 1990s, likely as a result of publication and regular updating of the national guidelines for pediatric asthma as well as increased awareness of childhood asthma by the general public
and health care providers as a result of large epidemiologic studies by the HNN, both of which preceded implementation of the NAP by at least 14 years. In contrast to our findings for hospitalizations for asthma in younger subjects, implementation of the NAP led to a more marked reduction in the rates of hospitalizations for asthma in subjects older than 20 years old. A change in diagnostic patterns (eg, diagnosing more adults with COPD instead of asthma after 2003) is not a probable explanation for this finding because the number of hospitalizations for COPD in Costa Rica actually
J ALLERGY CLIN IMMUNOL PRACT VOLUME 2, NUMBER 1
decreased between 2004 and 2011. Thus, the most plausible explanation for our results is improved asthma management in subjects older than 20 years as a result of the NAP, which first provided guidelines for the treatment of asthma in Costa Rican adults and, therefore, may have reduced heterogeneity in disease management among internists, pulmonologists, and allergists practicing at several institutions. Because Costa Rica is relatively small and has both socialized health care and a high literacy rate, improved awareness of the need for adequate and early treatment with ICS for subjects with persistent asthma is the most plausible cause for our overall results in children and adults, which are generally consistent with a previous report of the beneficial impact of ICS on hospitalizations for asthma in the 1990s in an industrialized nation (the United States).6 In contrast to our findings for hospitalizations for asthma, there was no consistent peak in deaths due to asthma in the year that the NAP was implemented. Because a marked reduction in asthma mortality occurred since the year after the NAP (2004), all or parts of the nationwide “asthma program” may have contributed to further reductions in deaths due to asthma in Costa Rica over the 8-year period from 2004 to 2011. Given that ICS were more widely prescribed after 2003, improved treatment of older adults with severe asthma could chiefly account for the observed reduction in asthma mortality. The relatively larger impact of the NAP on deaths due to asthma in adults than in children may again be explained by a lack of uniform guidelines for asthma management in adults (including the elderly, who have the highest mortality risk) before 2003. According to the International Monetary Fund, Costa Rica is a developing (or less developed) country from an economical viewpoint.7 To our knowledge, this is the first report of the potential long-term impact of a national program on reducing asthma mortality in an economically less developed country whose physicians were given broad access to controller medications. Even though Costa Rica is not economically developed, its citizens enjoy free health care and have a high literacy rate (approximately 95%). Thus, our findings may not be generalizable to economically developing countries where health care access is currently limited or literacy is lower. However, our results are encouraging and, together with those from similar programs in the United States (eg, Easy Breathing8,9; Conn), suggest that education and appropriate use of ICS (by specialists, general practitioners, pediatricians, and internists) could reduce the emerging burden of asthma in economically developing countries that have attempted to implement universal health care in recent years (eg, Colombia and Mexico).9 Reducing hospitalizations and mortality due to asthma could not only alleviate major suffering but lead to significant cost savings.6,10-12 We recognize additional limitations to our findings. First, this is an ecologic study, and, thus, we cannot assess causation or exclude ecological fallacy. However, our findings are valuable and can be further tested in future studies in other nations in Latin America and elsewhere. Second, we lack data on prescriptions for ICS before 2004. However, we have shown a marked increment in the total number of prescriptions for ICS in Costa Rica after implementation of the NAP. Third, and as previously mentioned, misclassification of hospitalizations or deaths as due to asthma (or not) is possible in any epidemiologic study. However, this is unlikely to fully account for the magnitude of the observed reductions in asthma morbidity or mortality over time. Fourth, we are unable to separate the relative contributions of the
SOTO-MARTÍNEZ ET AL
89
separate components of the national guidelines for asthma management in children or the NAP (implemented in 2003, for both children and adults) to our findings. ICS were first recommended as treatment for persistent childhood asthma in Costa Rica in 1988.5 Although only approximately 8% of children who participated in a research study in 1989 were on ICS,2 approximately 33% of children who participated in a research study between 2001 and 2005 were on antiinflammatory medications (mostly ICS).13 Although we cannot show a direct causal link between the increased number of prescriptions for ICS and the observed reduction in deaths due to asthma after 2003, most deaths due to asthma in Costa Rica, as in the rest of Latin America,14 occur outside of the hospital, and it is thus plausible that increased use of ICS in ambulatory settings nationwide led to a reduced mortality due to asthma, particularly in older adults.15,16 In summary, there was a marked decrement in the rate of hospitalizations and mortality due to asthma in Costa Rica from 1997-2000 to 2011. The NAP sustained but did not accentuate the decrement in hospitalizations for asthma in subjects younger than 20 years old since 1997, which is likely due to previous nationwide efforts to improve the treatment of childhood asthma. However, the NAP may have enhanced reductions in hospitalizations for asthma in adults older than 20 years old and mortality due to asthma in older adults (>35 years old or >40 years old), likely because of guidelines that emphasized treatment with ICS for persistent asthma. Universal access to health care, coupled with implementation of nationwide programs that promote and facilitate use of ICS for persistent asthma may markedly benefit economically developing countries where asthma is a major problem. REFERENCES 1. Celedon JC, Soto-Quiros ME, Silverman EK, Hanson L, Weiss ST. Risk factors for childhood asthma in Costa Rica. Chest 2001;120:785-90. 2. Soto-Quiros ME, Soto-Martinez M, Hanson LA. Epidemiological studies of the very high prevalence of asthma and related symptoms among school children in Costa Rica from 1989 to 1998. Pediatr Allergy Immunol 2002;13:342-9. 3. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-43. 4. Hunninghake GM, Soto-Quiros ME, Lasky-Su J, Avila L, Ly NP, Liang C, et al. Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations. J Allergy Clin Immunol 2008;122:93-8, 98.e1-5. 5. Soto-Quiros M. Guia de Diagnostico y Tratamiento del Niño Asmatico. Guia Pediatrica Basica de Diagnostico y Tratamiento I Infecciones respiratorias Agudas II Asma BronquialApoyo a los Recursos Humanos en el Plan de Supervivencia Infantil PASCAP OPS/OMS; 1988. 6. Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997;277: 887-91. 7. International Monetary Fund. Costa Rica and the IMF. Available from: http:// www.imf.org/external/country/CRI/index.htm. Accessed September 12, 2013. 8. Cloutier MM, Hall CB, Wakefield DB, Bailit H. Use of asthma guidelines by primary care providers to reduce hospitalizations and emergency department visits in poor, minority, urban children. J Pediatr 2005;146:591-7. 9. Cloutier MM, Grosse SD, Wakefield DB, Nurmagambetov TA, Brown CM. The economic impact of an urban asthma management program. Am J Manag Care 2009;15:345-51. 10. Harju T, Keistinen T, Tuuponen T, Kivela SL. Hospital admissions of asthmatics by age and sex. Allergy 1996;51:693-6. 11. Haahtela T, Klaukka T, Koskela K, Erhola M, Laitinen LA. Working Group of the Asthma Programme in Finland. Asthma programme in Finland: a community problem needs community solutions. Thorax 2001;56:806-14. 12. Haahtela T, Tuomisto LE, Pietinalho A, Klaukka T, Erhola M, Kaila M, et al. A 10 year asthma programme in Finland: major change for the better. Thorax 2006;61:663-70.
90
SOTO-MARTÍNEZ ET AL
13. Hunninghake GM, Soto-Quiros ME, Avila L, Su J, Murphy A, Demeo DL, et al. Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood. J Allergy Clin Immunol 2007;120:84-90. 14. Neffen H, Baena-Cagnani CE, Malka S, Sole D, Sepulveda R, Caraballo L, et al. Asthma mortality in Latin America. J Investig Allergol Clin Immunol 1997;7:249-53.
J ALLERGY CLIN IMMUNOL PRACT JANUARY/FEBRUARY 2014
15. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000;343: 332-6. 16. Suissa S, Ernst P. Use of anti-inflammatory therapy and asthma mortality in Japan. Eur Respir J 2003;21:101-4.