EDITORIAL COMMENT

Risk Factors Associated

with the Development of Asthma
Ren-Bin Tang*
Department of Pediatrics, Taipei Veterans General Hospital,
and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.

Prevalence of Allergic Diseases

Asthma and allergic rhinitis are 2 of the most common allergic diseases worldwide. The prevalence of
these diseases appears to have increased significantly
1
in the past 2 centuries, and, indeed, in the past few
decades, a marked rise in the prevalence of allergic
diseases has been noted in industrialized countries and
in urban centers in less developed regions.2,3 Asthma
has become the most prevalent chronic disease,
4
especially in children.
In Taiwan, the prevalence of asthma and other
allergic diseases has been increasing, with surveys
documenting an asthma prevalence of 1.3% in 1974,
5.3% in 1987, and 8.7% in 2000.57 Trends towards an
increasing occurrence of asthma have not been limited
to Taiwan; indeed, such trends seem to be global, or
at least common to the industrialized countries in
which they have been studied. For example, reports
have indicated an increased prevalence of allergic
disease in Finland, Japan, Sweden, and the US. 1
Findings from a behavioral risk-factor surveillance
system indicate that approximately 7.2% of adults in
the US currently have asthma, and the overall lifetime
8
prevalence of asthma in adults is 11.0%.

Risk Factors for Asthma

Risk or trigger factors for asthma that are currently
under investigation include the following: genetic
atopic predisposition; early childhood allergen exposure
and sensitization; viral respiratory infections in young
children; maternal smoking during pregnancy; poor
diet; lack of breast-feeding; childhood obesity; certain
immunologic predisposition (Th2-prone); air pollu-

tion; and frequent immunization in childhood. It is

most likely that the causes of allergic diseases are multifactorial. Risk factors for asthma have been studied
extensively in school-age children; such evaluated
factors included dietary fatty acid, number of older
siblings, lack of breast-feeding, and atopy, which have
10
all been associated with asthma in older children.

The Hygiene Hypothesis

The hygiene hypothesis suggests that childhood asthma
develops as a result of decreased exposure to infectious
disease and other stimuli.9 As Westernization occurs,
the environment becomes cleaner, and we then lack
the immunologic and infectious stimuli needed for
our immune systems to shift from the helper T-cell
9
Th2 to Th1 response. Seropositivity for food-borne
and oro-fecal micro-organisms (e.g. hepatitis A virus,
Helicobacter pylori, and Toxoplasma gondii), which are
considered to be markers of poor hygiene, has been
associated with a reduced prevalence of atopy. In
contrast, colonization of the gut with Clostridium
difficile, a potential intestinal bacterial pathogen, in
early childhood may be associated with an increased
11
prevalence of atopy. For mycobacteria, measles and
respiratory viruses, studies demonstrate a significant
increase in atopy or allergic disease, and parasite
infections, which provide a strong Th2 stimulus, are
associated with reduced rather than enhanced allergen
sensitization. Nonetheless, available epidemiologic
evidence does not support a mechanism of early life
immune deviation. The principal environmental
influences on atopic disease are likely to occur
throughout life and involve interactions between
12,13
microbes and non-infective and lifestyle factors.

*Correspondence to: Dr. Ren-Bin Tang, Department of Pediatrics, Taipei Veterans General Hospital, 201,
Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
Received: November 8, 2004
Accepted: December 28, 2004
E-mail: rbtang@vghtpe.gov.tw

J Chin Med Assoc May 2005 Vol 68 No 5

2005 Elsevier. All rights reserved.

199

R.B. Tang

Analyses of patterns of risk factors for allergic

rhinoconjunctivitis and asthma in Europe have led to
conjecture about causes of the allergic disease epidemic:
the hygiene hypothesis. This hypothesis claims that
hygiene has removed a protective influence against
atopy and asthma that was once provided by exposure
to infections in early life. However, the hypothesis has
been questioned in the US, where allergic asthma since
the 1970s has increased in minorities living in poverty
and with suboptimal hygiene conditions (inner-city
14
asthma). Such a recent increase in respiratory allergies
among less-advantaged individuals in the US may be
due to several factors linked to Westernization (e.g.
declining exposure to food-borne and oro-fecal
infections); these factors first affected the richest
socioeconomic strata during the 19th century, expanded
th
to the middle classes during the first half of the 20
century, and eventually cascaded down to affect less15
16
advantaged Americans. Nja et al reported that a
history of otitis media in infancy seemed to be negatively associated with allergic sensitization in school-age
children of atopic parents, whereas a history of lower
respiratory tract infections was positively associated
with asthma in children of non-atopic parents.

Vaccination
Anecdotal case reports and uncontrolled observational
studies in the medical literature claim that vaccines
cause chronic diseases such as asthma, multiple sclerosis, chronic arthritis, and diabetes. Several biologic
mechanisms have been proposed to explain how
vaccines might cause allergic or autoimmune diseases.
For example, allergic diseases might be caused by
the prevention of early childhood infections (the hygiene hypothesis), thus causing prolongation of
immunoglobulin E (IgE)-promoting Th2 responses.
However, vaccines do not prevent most common
childhood infections, and large well-controlled
epidemiologic studies do not support the hypothesis
17
that vaccines cause allergies.

Testing for Allergens

Differentiating between allergic and nonallergic diseases
involves detailed history taking, physical examination,
and either in vivo or in vitro testing for relevant allergens.
Skin testing is the most widely used diagnostic test for
allergies.18 However, because of its high percentage of
false positives, and certain contraindications such as
skin problems and antihistamine interference, other

200

diagnostic tests for allergies have been proposed. The

multiple allergosorbent chemiluminescent assay,
radioallergosorbent test, and Pharmacia CAP SystemTM
(Pharmacia Diagnostics, Uppsala, Sweden), have all
1922
demonstrated good agreement with skin tests.
The house dust mites Dermatophagoides
pteronyssinus and D. farinae, which are inhaled
allergens, are the major allergens detected in Taiwan
in both children and adults.23,24 A good correlation
between the immunodot assay and skin testing was
confirmed in asthmatic children. Further, the
electroblotting technique is fast, convenient, and highly
suitable for both allergen composition studies and
2426
screening for antibody specificity.
Mean levels of
mite-specific IgE were not significantly related to the
age of onset and severity of asthmatic symptoms, but
were significantly different between individuals with
5
current asthma and those with previous asthma. Fungi
are well known as allergens that cause allergic rhinitis
27,28
and allergic asthma in Taiwan.
Penicillium citrinum
and Aspergillus fumigatus are prevalent indoor airborne
fungal species that have been implicated in human
29,30
respiratory allergic disorders.
In addition, pollen
and food allergens both show significant differences
in incidence among different age groups. Crab meat,
milk, and egg white are all associated with a significantly
greater incidence of allergic disease in the 2- to 6-yearold age group than other age groups.31

Correlation Between Risk Factors and

Asthma
The article by Chiang et al32 in this issue of the journal
illustrates many of the difficulties that arise in a study
attempting to evaluate the correlation between risk
factors for and the development and severity of asthma.
The article describes symptoms in 579 asthmatic
patients of various ages, and documents that levels of
specific IgE antibodies to house dust mites bear no
relation to the severity of asthma. Nonspecific trigger
factors were analyzed by questionnaire, but these
factors were not well defined, because of a lack of
symptom provocation by the factors or by inhaled
allergens; generally, such symptom provocation is the
most reliable way of demonstrating clinically relevant
32
sensitization in atopic patients with asthma.

Asthma: A Multifactorial Condition

Asthma is a multifactorial lung disease that is often
associated with familial, allergenic, socioeconomic,

J Chin Med Assoc May 2005 Vol 68 No 5

Risk factors for asthma

psychologic, and environmental factors. Asthma affects proportionately more children than adults,
but morbidity and mortality are, to some extent,
preventable with improved medical, environmental,
and self-management.

References
1. Peterson B, Saxon A. Global increases in allergic respiratory
disease: the possible role of diesel exhaust particles. Ann
Allergy Asthma Immunol 1996;77:26370.
2. Sly RM. Changing prevalence of allergic rhinitis and asthma.
Ann Allergy Asthma Immunol 1999;82:23352.
3. Magnus P, Jaakkola JJ. Secular trend in the occurrence of
asthma among children and young adults: critical appraisal of
repeated cross sectional surveys. BMJ 1997;314:17959.
4. Tang RB, Kho BJ. A survey of childhood asthma in the
northern area of Taiwan. J Chin Med Assoc 1980;27:6137.
5. Tang RB, Tsai LC, Hwang HM, Hwang BT, Wu KG, Hung
MW. The prevalence of allergic disease and IgE-antibodies to
house dust mite in school children in Taiwan. Clin Exp Allergy
1990;20:338.
6. Chen CF, Wu KG, Hsu MC, Tang RB. Prevalence and
relationship between allergic diseases and infectious diseases.
J Microbiol Immunol Infect 2001;34:5762.
7. Hsieh KH, Shen JJ. Prevalence of childhood asthma in Taipei,
Taiwan, and other Asian Pacific countries. J Asthma 1988;25:
7382.
8. Rhodes L, Moorman JE, Redd SC, Mannino DM. Asthma
prevalence and control among adults United States, 2001.
MMWR Morbid Mortal Wkly Rep 2003;52:3814.
9. OConnell EJ. Pediatric allergy: a brief review of risk factors
associated with developing allergic disease in childhood. Ann
Allergy Asthma Immunol 2003;90:538.
10. Haby MM, Peat JK, Marks GB, Woolcock AJ, Leeder SR.
Asthma in preschool children: prevalence and risk factors.
Thorax 2001;56:58995.
11. Linneberg A, Ostergaard C, Tvede M, Andersen LP, Nielsen
NH, Madsen F, Frolund L, et al. IgG antibodies against
microorganisms and atopic disease in Danish adults: the
Copenhagen Allergy Study. J Allergy Clin Immunol 2003;111:
84753.
12. Kemp A, Bjorksten B. Immune deviation and the hygiene
hypothesis: review of the epidemiological evidence. Pediatr
Allergy Immunol 2003;14:7480.
13. Pickup J. Too clean for our own good?: current issues in
home hygiene. J Fam Health Care 2002;12:159.
14. Matricardi PM, Bouygue GR, Tripodi S. Inner-city asthma and
the hygiene hypothesis. Ann Allergy Asthma Immunol 2002;
89:6974.
15. Liu AH, Szefler SJ. Advances in childhood asthma: hygiene
hypothesis, natural history, and management. J Allergy Clin
Immunol 2003;111:78592.

J Chin Med Assoc May 2005 Vol 68 No 5

16. Nja F, Nystad W, Hetlevik O, Lodrup Carlsen KC, Carlsen KH.

Airway infections in infancy and the presence of allergy and
asthma in school age children. Arch Dis Child 2003;88:5669.
17. Offit PA, Hackett CJ. Do vaccines cause allergic or autoimmune
diseases? Pediatrics 2003;111:6539.
18. Tang RB, Chang HN, Lin FM, Chang YF, Chou NS, Lin CY.
Serum IgE, skin and radioallergosorbent tests for house dust
and mites in asthmatic children. J Asthma 1986;23:2459.
19. Tang RB, Wu KG. Total serum IgE, allergy skin testing, and
the radioallergosorbent test for the diagnosis of allergy in
asthmatic children. Ann Allergy 1989;62:4325.
20. Tsai LC, Tang RB, Hung MW, Chen HM, Hwang LA.
Correlation between serum IgE and specific IgE antibody titer
to house dust mite in children with asthma. J Asthma 1988;25:
713.
21. Tang RB, Wu KG, Hwang BT. Comparison between skin
testing and in vitro testing for diagnosis of allergen in asthmatic
children. J Chin Med Assoc 1994;54:24650.
22. Tang RB, Chen BS, Chen SJ, Wu KG, Hwang B. Determination
of the food specific IgE antibodies: comparison of MAST-CLA
and CAP systems. J Chin Med Assoc 1996;57:21923.
23. Tang RB, Tsai LC, Chao PL, Hung MW. Significance of
specific IgG subclass antibodies to house dust mites in asthmatic
children. J Chin Med Assoc 2000;63:4406.
24. Tsai LC, Chao PL, Shen HD, Tang RB, Chang TC, Chang
ZN, Hung MW, et al. Isolation and characterization of a novel
98-kd Dermatophagoides farinae mite allergen. J Allergy Clin
Immunol 1998;102:295303.
25. Tang RB, Tsai LC, Hung MW, Hwang B, Wu KG. Detection
of house dust mite allergens and immunoblot analysis in
asthmatic children. J Asthma 1988;25:838.
26. Chao PL, Peng HJ, Tang RB, Hung MW, Tsai LC. Serum
specific IgE reactivity to recombinant Der f 11 in asthmatic
children. J Asthma 2001;38:3918.
27. Shen HD, Choo KB, Tang RB, Lee CF, Yeh JY, Han SH.
Allergenic components of Candida albicans identified by
immunoblot analysis. Clin Exp Allergy 1989;19:1915.
28. Tang RB, Shen HD, Chen SJ, Lee CY. Detection of IgE
reactivity to fungus antigens by immunoblotting in allergic
diseases in children. J Chin Med Assoc 2003;66:4539.
29. Chou H, Chang CY, Tsai JJ, Tang RB, Lee SS, Wang SR, Peng
HJ, et al. The prevalence of IgE antibody reactivity against the
alkaline serine protease major allergen of Penicillium
chrysogenum increases with the age of asthmatic patients. Ann
Allergy Asthma Immunol 2003;90:24853.
30. Lai HY, Tam MF, Tang RB, Chou H, Chang CY, Tsai JJ, Shen
HD. cDNA cloning and immunological characterization of a
newly identified enolase allergen from Penicillium citrinum
and Aspergillus fumigatus. Int Arch Allergy Immunol 2002;
127:18190.
31. Lee CS, Tang RB, Chung RL. The evaluation of allergens and
allergic diseases in children. J Microbiol Immunol Infect 2000;
33:22732.
32. Chiang CH, Wu KM, Wu CP, Yan HC, Perng WC. Evaluation
of risk factors for asthma in Taipei City. J Chin Med Assoc 2005;
68:2049.

201