Causes:

Asthma has dramatically risen worldwide over the past decades, particularly in developed countries, and experts are puzzled over the cause of this increase. The mechanisms that cause asthma are complex and vary among population groups and even from individual to individual. Many asthma sufferers have allergies, and some researchers are targeting common factors in both these conditions. Not all people with allergies have asthma, however, and asthma is not always due to an allergic response.

Asthma is most likely caused by a several factors that can include genes and environmental and biologic triggers (such as infections, dietary patterns, hormonal changes in women, and allergens).

The Allergic Response

Nearly half of adults with asthma have an allergy-related condition, which, in most cases developed first in childhood. (In patients who first develop asthma during adulthood, the allergic response usually does not play a strong causal role.)

The Allergic Process. The allergic process, called atopy, and its connection to asthma are not completely understood. The process involves various airborne allergens, or other triggers, that set off a cascade of events in the immune system, leading to inflammation and hyperreactivity in the airways. Here is an example of the allergic process:

• The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
• Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
• During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of several active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
• One specific cytokine, interleukin 5, attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

Over several years, the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

• Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.
• Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings, and some researchers believe it may be major factor in remodeling.

Environmental Factors

An asthma attack can be induced or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Important irritants or allergens include:

• Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
• Animal dander. Cats harbor significant allergens, which can even be carried on clothing; dogs usually cause fewer problems. People with asthma who already have pets and are not allergic to them probably have a low risk for developing allergies later on.
• Smoking, or exposure to secondhand smoke
• Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons. For example, in 1998, when the effects of El Nino were very strong, allergy and asthma attacks occurred earlier and were markedly increased.
• Molds might produce a worse asthma attack in adults than other allergens.
• Fungi
• Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
• Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. And, in people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

Genetic Factors

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to pass to children from their mother than from their father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

Contributing Medical Conditions

Infections. The role of infections in asthma is complicated. Respiratory infections may play a role in some cases of adult-onset asthma. In both children and adults with existing allergic asthma an upper respiratory tract infection often worsens an attack.

Researchers are particularly interested in the organisms Chlamydiapneumoniae and Mycoplasmapneumoniae adenovirus. They are major causes of both mild and serious respiratory infections and are becoming important suspects in many cases of severe adult asthma. (If such respiratory infections occur in young children, they are unlikely to affect adult-onset asthma.)

In any age group, respiratory infections worsen existing asthma in people who have it already. Rhinovirus (the common cold virus) has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma exacerbations in children and 44% in adults. Some research suggests that colds promote allergic inflammation and increase the intensity of airway responsiveness for weeks.