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Asthma: What are the Causes?

Asthma is a major health problem that affects at least 15 million people in the United States and is the most common chronic disease in childhood.1

The overall prevalence rate of asthma increased dramatically from the 1980s to the mid 1990s, up 52 percent for a rate of 52.6 cases per 1,000 in the 5 to 34-year-old age group.2 Because of this, it behooves us to consider, "What are the causes of asthma?"

The causes of asthma are multifactorial and might be divided into those that are underlying causes or risk factors, and those provocateurs that can trigger symptoms or exacerbations. In some cases there is overlap between these factors. That is to say, some triggers may actually become a cause and contribute to chronic asthma.

 Genetic causes

Most individuals with asthma have some family history of the disorder. In a recent study of asthma in children, prognostic risk factors for asthma included parental asthma and a history of allergic disease and atopy.3

Ethnic variations in the incidence of asthma also imply a genetic link. The incidence of asthma among Puerto Ricans is the highest (20.1 percent), followed by African Americans (9.1. percent), non-Hispanic whites (6.4 percent), and Mexican Americans (4.5 percent).4

Nevertheless, defining the exact genetics of this disorder has been elusive. It is thought that asthma is transmitted by multiple genes so that different genes lead to asthma in different individuals, and for some individuals multiple differing genes lead to the manifestation of asthma.5

A variety of study methods have resulted in inconclusive results. Using linkage analysis to investigate families with asthma has led to the identification of at least 10 regions of the genome that are related to asthma.

However, association studies, which look at the relationship between disease characteristics and the presence of certain DNA markers, have identified at least 25 genes associated with asthma, verified in six or more population groups, and another 54 genes associated with two to five population groups.5

One of the interesting findings in association studies is that the gene encoding for the beta-2 adrenergic receptor is located on chromosome 5q31. Variations in this receptor gene seem to be associated with different levels of responsiveness to beta agonists, the most commonly prescribed medication for the treatment of asthma.6

Based on this genetic research, it seems that there is some interaction between a genetic predisposition and the environment that ultimately leads to the development of asthma.5 

Infectious agents

Viral illnesses also can affect the development of asthma. For example, respiratory syncytial virus (RSV) may predispose individuals to the development of asthma, but there is evidence for and against this, since RSV is so common in early childhood that the association could be coincidental. In addition, individuals who develop atypical infections, such as Mycoplasma or Chlamydia, particularly if not treated promptly, may go on to develop asthma, which can be persistent.9

On the other hand, individuals who had measles during childhood seem to have a lower incidence of developing asthma, because measles may lead to a shift toward TH1 lymphocytes and away from TH2 lymphocytes. In the immune system, TH1 cells are associated with a non-allergic predisposition and TH2 cells are associated with an allergic predisposition, so the specific infectious agents that a person has been exposed to may affect whether they become allergic and asthmatic.

Similarly, individuals who have been raised on a farm, where they have had bacterial endotoxin exposure, seem to have a shift in their immunity toward TH1 lymphocytes and a non-allergic predisposition, and have a lower incidence of asthma.

This was first noted when the Berlin Wall came down, and it was found that the residents of Eastern Germany, where more people lived in farm houses with barns attached and where hygiene might be poorer, had a lower incidence of asthma than their genetically similar countrymen who lived in West Germany. West Germany had been westernized, had higher levels of hygiene, and more asthma.

This also is the origin of the "hygiene hypothesis," which implies that being overly clean may actually predispose to the development of asthma. There is further support for this in that children who attend day care centers at an early age have less asthma.1

Asthma: What are the Causes?

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