ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Epidemiology of asthma

Epidemiology of asthma
Literature review current through: Jan 2024.
This topic last updated: Oct 30, 2023.

INTRODUCTION — Asthma is a common, noncommunicable disease of the lungs affecting both children and adults. It has a global impact on health care utilization, quality of life, and mortality. The heterogeneous nature of the disease makes accurate assessment of prevalence challenging.

The definition of asthma and the identification of affected individuals for epidemiologic purposes and data on trends in asthma prevalence will be reviewed here. The definition, diagnosis, and treatment of asthma are discussed separately. (See "Natural history of asthma" and "Risk factors for asthma" and "Asthma in adolescents and adults: Evaluation and diagnosis" and "An overview of asthma management".)

DATA COLLECTION — Essential to any study of prevalence are the definition of the disease being studied and the methods available to identify affected individuals. Given the absence of a definitive laboratory test or biomarker for the diagnosis of asthma, many definitions and methods of data collection have been used and reported in epidemiologic studies; herein we discuss the most common. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Definition' and "Asthma in children younger than 12 years: Initial evaluation and diagnosis", section on 'Diagnosis'.)

Definition of asthma — The Global Initiative for Asthma (GINA) defines asthma as, "a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation [1]." This clinical definition is not easily translated into a form that can be used in population studies. A standard operational definition of asthma that can be used in all types of epidemiologic studies is lacking.

Ideally, because asthma can present in varied ways, it should be defined by a combination of symptoms, clinical diagnosis, pulmonary function tests (spirometry), or tests of either bronchial hyperresponsiveness (BHR) or reversibility of airway obstruction [2]. BHR may be performed with a variety of substances (eg, methacholine, histamine, mannitol, and even cold air). BHR with methacholine is the most widely used in epidemiologic and field studies [3,4]. A definition of asthma that was developed for epidemiologic studies to identify individuals with clinically important asthma combined wheezing in the past 12 months with BHR [5,6]. However, this approach has not proven feasible because of the need for equipment, trained personnel, and the time needed in performing BHR or reversibility testing.

A review of epidemiologic studies of asthma, which retrieved 1738 studies and included 117 for analysis, confirmed substantial heterogeneity in the definitions of asthma used by the various studies [2]. These studies included children, adolescents, and adults. For prevalence studies, the most frequently applied questionnaire was that from the Global Asthma Network (GAN) and International Study of Asthma and Allergies in Children (ISAAC), with 45 percent of the studies using a combination of two questions from ISAAC. Definitions used for epidemiologic studies and surveys are discussed in the next section.

Questionnaires — A variety of methods have been used to assess asthma prevalence, but each has intrinsic problems and biases. Epidemiologists primarily rely on historic or questionnaire sources to identify patients with asthma, but the various questionnaires used have assessed different symptoms, and case identification methods have varied among the following: direct physician diagnosis or surveys of population groups in which the definition was left to the patients, the parents of patients, or the report of the patient's clinician [7]. Data from large population-based surveys are obtained from these types of questions. For example, in NHANES, the question is "has a doctor or other health professional ever told you (or your child) that you (your child) have asthma?" [8]. Other large surveys, such as the Behavioral Risk Factor Surveillance System (BRFSS), the National Health Interview Survey (NHIS), and others use variations of this question. Other smaller studies have included objective tests of lung function and airway responsiveness in the identification of asthma.

A study that investigated the operational definitions of asthma in epidemiologic studies found that most studies used a combination of questions to identify asthma and the definitions could be categorized into three most common types:

Current asthma – This was generally defined by the affirmative response to variations of the questions of "do you (does your child) have asthma" or "have you (your child) been diagnosed with asthma by a clinician or health professional?" This is followed by an affirmative response to variations of the questions of "did you (did your child) have wheezing in the past 12 months?" or "do you (your child) still have asthma?" Some studies use medication used in the past 12 months in lieu of wheezing symptoms.

Lifetime asthma – This is defined as an affirmative response to "have you (your child) ever had asthma?"

Diagnosed asthma – This is defined by an affirmative response to variations of the question "have you (has your child) ever been diagnosed with asthma by a clinician or health professional?"

It is likely that some bias in reporting of cases is present in each method and that the biases in each approach are different. The table summarizes the potential problems of the various approaches to identifying persons with asthma (table 1).

To ensure study accuracy, questionnaire-defined asthma and BHR can be validated against respiratory clinician assessment of current asthma [9]. For example, the Tasmanian Asthma Survey (TAS) questionnaire for adults and the International Study of Asthma and Allergies in Children (ISAAC) questionnaire for children identified subjects with symptoms (eg, wheeze, wheezy breathing) in the past year [10]. In a validation study, the TAS and ISAAC surveys were administered to 93 and 361 participants, respectively [9]. BHR testing was then conducted using hypertonic saline, and subjects were interviewed by one of two respiratory physicians who were blinded to the results of the questionnaires and BHR testing. A clinician diagnosis of "current asthma" was defined as a history of wheeze suggestive of a clinical diagnosis of asthma within the past 12 months.

Using the clinician's diagnosis as the "gold standard," questionnaire responses alone were found to be sensitive (0.80 for adults, 0.85 for children) and specific (0.97 for adults, 0.81 for children) [9]. Questionnaire response plus BHR was found to have high specificity (0.99 for adults, 0.94 for children) but low sensitivity (0.37 for adults, 0.47 for children). This study, however, did not incorporate a previous asthma diagnosis to the definitions of asthma, particularly for the children.

GLOBAL VARIATION — Worldwide, it is estimated that approximately 260 million individuals have asthma [11], although the prevalence varies among countries [12-17]. A portion of the variability may be attributable to use of different definitions and ascertainment methods; genetics and variation in environmental exposures (eg, poor air quality) likely also contribute.

Three large multicenter studies, the Global Asthma Network (GAN), the International Study of Asthma and Allergies in Children (ISAAC), and the European Community Respiratory Health Survey (ECRHS) have examined worldwide variations in asthma prevalence.

GAN and ISAAC examined the prevalence of asthma symptoms using standardized simple surveys which were conducted among representative samples of school children in two age groups (six to seven and 13 to 14 years) in 61 countries [10,12,17,18]. In a subset, a video asthma questionnaire was also administered.

For the GAN surveys conducted from 2015 to 2020, there was marked variation in the prevalence of "wheeze in the last 12 months" [17]. As an example, in the younger age group, the prevalence of wheeze ranged from 3 to 23.2 percent with lowest rates in Russia, India, and Kosovo and highest rates in Costa Rica, New Zealand, Thailand, and Taiwan. In the older age group, the difference in prevalence between countries ranged from 3.7 to 21.4 percent, with lowest rates in India and Greece and the highest rates in Argentina, Costa Rica, Syria, South Africa, and Honduras.

For asthma prevalence, variations were smaller than for "wheeze in the last 12 months" [12,17]. For example, among six- to seven-year-olds, prevalence of ever having asthma ranged from 3.9 percent in Southeast Asia and the Western Pacific to 9.2 percent in central America; among 13- to 14-year-olds, prevalence ranged from 12.3 percent in Southeast Asia and the Western Pacific to 26.1 percent in Africa and the Eastern Mediterranean. This is a significant decrease in variation compared with the prior ISAAC study [12]. This may reflect a general trend towards more homogeneous worldwide exposures to risk factors such as air pollution and Western diet; however, low income and low-middle income countries continue to show a decreased burden of disease. Somewhat paradoxically, within specific countries, subjects from lower socioeconomic strata have a greater prevalence of asthma [19,20].

The GAN survey of adults included assessment of the prevalence of wheeze, asthma, hay fever, and eczema in adults from 43 centers in 17 countries [16]. Similar to the report in children, the prevalence of wheeze varied widely, ranging from 3.4 to 6.0 percent from centers in India, Taiwan, Kosovo, Nigeria, and Russia to 17 to 33 percent from centers in Honduras, Costa Rica, Brazil, and New Zealand. The prevalence of ever having asthma ranged from 1.3 to 3 percent from centers in Kosovo, India, Russia, Nigeria, Iran, and Cameroon to 13 to 29 percent from centers in Saudi Arabia, New Zealand, Honduras, and Costa Rica.

The asthma burden was higher in female participants and in higher income countries. Current severe asthma symptoms were commonly reported (range 15 to 63.9 percent) among participants with wheeze in the past 12 months across all centers, suggesting poor asthma control.

The prevalence of asthma in the United States is estimated at 25 million based on data from the National Health Interview Survey [21].

Potential reasons for variation in asthma prevalence have been hypothesized, but none is fully explanatory:

The rate of asthma increases as communities adopt western lifestyles and become urbanized. However, this observation does not fully explain the international patterns of asthma prevalence.

The increase in the prevalence of asthma has been associated with an increase in atopic sensitization and is paralleled by similar increases in other allergic disorders such as eczema and rhinitis. (See "Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors", section on 'Since 1960'.)

TRENDS

Prevalence trends in United States — Data from the Centers for Disease Control and Prevention (CDC) have shown that the prevalence of asthma increased in the United States from the early 1980s to the early 2000s and subsequently decreased slightly [22-25]. In 2018, the prevalence of asthma in the United States was estimated to be 7.9 percent, with the prevalence in children <18 years slightly higher than in adults (8.4 versus 7.7 percent) (figure 1) [20].

The prevalence statistics for current asthma in the United States have been updated by the CDC (figure 1) [20]:

Among children, the prevalence of asthma increases from the younger age groups to the older age groups: Children in the age group 0 to 4 years had a prevalence of 3.8 percent (standard error [SE] 0.49), age group 5 to 11 years had a prevalence of 8.1 percent (SE 0.60), and age group 12 to 17 years had a prevalence of 9.9 percent (SE 0.73).

In children <18 years, asthma is more common in boys (8.3 percent) compared with girls (6.7 percent); however, in adults, asthma is more common in women (9.8 percent) compared with men (5.5 percent).

Females (9.3 percent) tend to have more current asthma than males (6.4 percent).

While asthma is more common in children and adolescents, asthma also affects older adults. As noted above, the distribution of asthma differs by age and sex, with it being more common in boys in the younger ages but more common in girls in the older ages (figure 2).

Black persons (10.1 percent) have more current asthma than White persons (8.1 percent).

Hispanic Americans (6.4 percent), as a group, had lower current asthma prevalence than White persons. However, within the Hispanic group, Puerto Ricans (12.8 percent) had a higher prevalence than Mexicans (5.1 percent).

Current asthma prevalence was highest in those from areas with the lowest annual household income (11.7 percent) compared with those from areas with higher household income.

Several explanations for the observed increase in prevalence from the early 1980s to early 2000s have been suggested. Increased clinician and public awareness of the signs and symptoms of asthma could have led to a change in diagnostic recognition and accuracy. It is also likely that changes in the risk factors thought to cause and worsen asthma (eg, obesity, tobacco smoke exposure, low vitamin D levels, and occupational exposures) are responsible for much of the increase in asthma prevalence. (See "Risk factors for asthma" and "Obesity and asthma".)

Changes in asthma prevalence have been documented since the 1980s (figure 3):

During the period from 1982 to 1992, the overall annual age-adjusted prevalence rate of self-reported asthma increased by 42 percent, from 34.7 to 49.4 per 1000. For the younger age group 5 to 34 years, where the diagnosis of asthma is thought to be more accurate, the rate increased from 34.6 to 52.6 per 1000, an increase of 52 percent. Since that time, the prevalence of asthma has increased more gradually [26-28].

Since 2001, the prevalence of asthma has increased more gradually. In 2001, about 20 million, or 7.3 percent of the population had asthma, whereas in 2017, about 25 million, or 8 percent of the population had asthma (figure 3). This increase has occurred in all races and ethnicities in the United States (figure 4).

Health care utilization related to asthma has also changed over time. In general, physician office visits, emergency department visits, and hospitalizations have decreased since the early 2000s, in contrast to increases in asthma prevalence.

In 2001, asthma-related physician office visits were 409.7 per 10,000 population. This has varied over time, and the rate in 2016 was 307.8 per 10,000 population (figure 5).

Asthma-related emergency department visits have remained relatively stable between 2001 and 2016 (figure 6).

Asthma-related hospitalizations fell from 13 per 10,000 population in 2010 to 5.9 per 10,000 population in 2016 (figure 7), although it is unclear how much of an effect the change in coding from ICD-9 to ICD-10 had in the decrease in rates.

Global prevalence trends — As noted above, asthma prevalence varies around the world (see 'Global variation' above). While most countries saw an increase in prevalence of asthma in the decades before 2000, data since then has shown differing trends between countries. While asthma prevalence continued to rise after 2000 in some countries, such as Italy [29] and Sweden [30], other countries, such as Denmark [31] and Korea [32], have seen a plateau of prevalence from data through 2010 and 2014, respectively.

The reasons for the plateau and potential decrease in prevalence of asthma in some countries remain unclear. It has been hypothesized that the rapidly changing exposures and lifestyles led to asthma developing in susceptible individuals in the latter half of the past century, but the proportion of the population that is susceptible to developing asthma is now reaching capacity [33]. We have postulated that progressive decreases in serum vitamin D levels as a result of elimination of cod liver oil intake, increased time spent indoors (television, air conditioning) and the introduction of sun screen usage has led to progressive vitamin D deficiency and subsequent increased allergy and asthma [34]. The trends in vitamin D levels exactly mirror the trends in asthma and allergy prevalence. It is also possible that better understanding of risk factors other than vitamin D levels and faster dissemination of this information to the public has contributed to these changes in the trends. (See "Risk factors for asthma", section on 'Vitamin D'.)

Mortality — The Global Burden of Disease (GBD) report estimates that asthma accounts for approximately 420,000 deaths per year worldwide [35]. While this is <1 percent of all deaths, avoidable factors (eg, under prescription of inhaled glucocorticoids, insufficient access to emergency medical care or specialist care) still play a part in most asthma deaths [35]. According to the GBD report, age-standardized death rates from asthma decreased substantially in most countries from 2001-2005 to 2011-2015. Other reports also support a decline in death rates since the 1980s and 1990s [36-38].

The annual death rate from asthma in the United States increased from 1982 to 2001 but has since declined, similar to international data (figure 8) [27]. As an example, the overall mortality rate was 15.09 per million in 2001 and 9.86 per million in 2017 [39]. Consistently higher rates have been reported for African Americans than for White Americans, but not for Hispanic ethnicity, except those from Puerto Rico [27]. This difference in death rates is thought to be due both to socioeconomic factors and to differences in access to medical care [26,40].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in adolescents and adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)" and "Patient education: Trigger avoidance in asthma (Beyond the Basics)")

SUMMARY

Epidemiologists rely on historic or questionnaire sources, sometimes supplemented with lung function data, to identify patients with asthma. Some bias in ascertainment and reporting of cases is associated with each of the various approaches and these biases differ among the approaches (table 1). (See 'Questionnaires' above.)

There is no single definition of asthma that is used universally in epidemiologic studies. Most commonly, "current asthma" is the definition used for these studies and national surveys. (See 'Definition of asthma' above.)

The International Study of Asthma and Allergies in Children (ISAAC) has confirmed wide variations in the prevalence of asthma symptoms in children worldwide. Similarly, the European Community Respiratory Health Survey (ECRHS) has documented broad variation in asthma symptoms in adults from different countries in Europe. The reasons for variability across countries remain unclear. (See 'Global variation' above.)

Based on data from the Centers for Disease Control, the prevalence of asthma increased by more than 45 percent in the United States from 1982 to 1992. During the years 2001 through 2009, the prevalence of asthma increased more gradually, and has remained stable to slightly decreasing from 2009 to 2016. (See 'Prevalence trends in United States' above.)

It has been hypothesized that the rapidly changing exposures and lifestyles led to asthma developing in susceptible individuals in the latter half of the past century. However, the factors that contribute to the plateau and apparent decrease in asthma prevalence since then have not been elucidated. (See 'Global prevalence trends' above.)

Based on survey data, asthma accounts for approximately 420,000 deaths per year worldwide. While this is <1 percent of all deaths, avoidable factors contribute to many asthma deaths. (See 'Mortality' above.)

  1. 2023 Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. www.ginasthma.org/2023-gina-main-report (Accessed on May 15, 2023).
  2. Sá-Sousa A, Jacinto T, Azevedo LF, et al. Operational definitions of asthma in recent epidemiological studies are inconsistent. Clin Transl Allergy 2014; 4:24.
  3. Kennedy SM, Contreras GR. Measurement of nonspecific bronchial responsiveness in epidemiologic studies: methacholine challenge testing in the field. Occup Med 1993; 8:303.
  4. Chan-Yeung M. Spirometry and tests of bronchial hyperresponsiveness in population studies. Int J Tuberc Lung Dis 2000; 4:633.
  5. Toelle BG, Peat JK, Salome CM, et al. Toward a definition of asthma for epidemiology. Am Rev Respir Dis 1992; 146:633.
  6. Pekkanen J, Pearce N. Defining asthma in epidemiological studies. Eur Respir J 1999; 14:951.
  7. Weiss ST, Speizer FE. Epidemiology and natural history. In: Bronchial Asthma Mechanisms and Therapeutics, 3rd ed, Weiss EB, Stein M (Eds), Little, Brown, Boston 1993. p.15-25.
  8. Centers for Disease Control and Prevention. Asthma: Survey questions. https://www.cdc.gov/asthma/questions.htm (Accessed on September 15, 2020).
  9. Jenkins MA, Clarke JR, Carlin JB, et al. Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma. Int J Epidemiol 1996; 25:609.
  10. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet 1998; 351:1225.
  11. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396:1204.
  12. Lai CK, Beasley R, Crane J, et al. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009; 64:476.
  13. Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur Respir J 1996; 9:687.
  14. Patel SP, Järvelin MR, Little MP. Systematic review of worldwide variations of the prevalence of wheezing symptoms in children. Environ Health 2008; 7:57.
  15. National Cooperative Group on Childhood Asthma, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Chinese Center for Disease Control and Prevention. [Third nationwide survey of childhood asthma in urban areas of China]. Zhonghua Er Ke Za Zhi 2013; 51:729.
  16. Mortimer K, Lesosky M, García-Marcos L, et al. The burden of asthma, hay fever and eczema in adults in 17 countries: GAN Phase I study. Eur Respir J 2022; 60.
  17. García-Marcos L, Asher MI, Pearce N, et al. The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study. Eur Respir J 2022; 60.
  18. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J 1998; 12:315.
  19. Wang D, Xiao W, Ma D, et al. Cross-sectional epidemiological survey of asthma in Jinan, China. Respirology 2013; 18:313.
  20. Centers for Disease Control and Prevention. Most recent national asthma data. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm (Accessed on September 15, 2020).
  21. National Health Interview Survey. Current Asthma Population Estimates — in thousands by Age, United States, 2018. https://www.cdc.gov/asthma/nhis/2018/table3-1.htm (Accessed on March 09, 2020).
  22. Weiss KB, Wagener DK. Asthma surveillance in the United States. A review of current trends and knowledge gaps. Chest 1990; 98:179S.
  23. Centers for Disease Control and Prevention (CDC). Asthma--United States, 1982-1992. MMWR Morb Mortal Wkly Rep 1995; 43:952.
  24. Akinbami LJ, Simon AE, Rossen LM. Changing Trends in Asthma Prevalence Among Children. Pediatrics 2016; 137.
  25. Mazurek JM, Syamlal G. Prevalence of Asthma, Asthma Attacks, and Emergency Department Visits for Asthma Among Working Adults - National Health Interview Survey, 2011-2016. MMWR Morb Mortal Wkly Rep 2018; 67:377.
  26. Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma--United States, 1980-1999. MMWR Surveill Summ 2002; 51:1.
  27. Moorman JE, Rudd RA, Johnson CA, et al. National surveillance for asthma--United States, 1980-2004. MMWR Surveill Summ 2007; 56:1.
  28. Centers for Disease Control and Prevention (CDC). Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001--2009. MMWR Morb Mortal Wkly Rep 2011; 60:547.
  29. Maio S, Baldacci S, Carrozzi L, et al. Respiratory symptoms/diseases prevalence is still increasing: a 25-yr population study. Respir Med 2016; 110:58.
  30. Backman H, Räisänen P, Hedman L, et al. Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016-results from three population surveys. Clin Exp Allergy 2017; 47:1426.
  31. de Korte-de Boer D, Mommers M, Gielkens-Sijstermans CM, et al. Stabilizing prevalence trends of eczema, asthma and rhinoconjunctivitis in Dutch schoolchildren (2001-2010). Allergy 2015; 70:1669.
  32. Kim BK, Kim JY, Kang MK, et al. Allergies are still on the rise? A 6-year nationwide population-based study in Korea. Allergol Int 2016; 65:186.
  33. Baïz N, Annesi-Maesano I. Is the asthma epidemic still ascending? Clin Chest Med 2012; 33:419.
  34. Litonjua AA, Weiss ST. Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 2007; 120:1031.
  35. The Global Burden of Disease. The Global Asthma Report 2018: Asthma Mortality. http://www.globalasthmareport.org/burden/mortality.php (Accessed on March 09, 2020).
  36. Wijesinghe M, Weatherall M, Perrin K, et al. International trends in asthma mortality rates in the 5- to 34-year age group: a call for closer surveillance. Chest 2009; 135:1045.
  37. Centers for Disease Control and Prevention (CDC). Asthma mortality and hospitalization among children and young adults--United States, 1980-1993. MMWR Morb Mortal Wkly Rep 1996; 45:350.
  38. Centers for Disease Control and Prevention (CDC). Asthma mortality -- Illinois, 1979-1994. MMWR Morb Mortal Wkly Rep 1997; 46:877.
  39. Centers for Disease Control and Prevention (CDC). Mortality Data for asthma. https://www.cdc.gov/asthma/data-visualizations/mortality-data.htm (Accessed on March 03, 2020).
  40. Weiss KB, Gergen PJ, Crain EF. Inner-city asthma. The epidemiology of an emerging US public health concern. Chest 1992; 101:362S.
Topic 573 Version 24.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟