Asthma in Children and Adolescents

Description

Causes

Asthma occurs in about five million American children and each year about 200,000 are hospitalized. It is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10 and about 80% develop symptoms before age five.

General Causes of Asthma

The mechanisms that cause asthma are complex and vary among population groups and even individuals. For example, asthma in children is highly associated with allergies. However, only a minority of children with allergies has asthma, and not all cases of asthma can be explained by allergic response. Other factors, such as genetics or environmental conditions are likely to be involved in the development of asthma. Most likely several genes are involved that make a child susceptible to environmental triggers, not only allergens, but also possibly infections, dietary patterns, or air pollution. Physical factors, particularly having smaller lungs, affect the chances for later asthma.

Factors Contributing to the Worldwide Increase of Asthma

From 1980 to 1994, asthma increased 160% in American children younger than 4 years and has also dramatically risen worldwide. Experts are puzzling over the cause of this phenomenon. Among the causes and factors that are suspects in the dramatic rise in asthma in children are the following:

• One 2000 study suggested that Western dietary habits (which commonly include more fast foods and less fruits, vegetables, fiber, minerals, and other nutrients) may contribute to the development of childhood asthma.
• Some experts observe that children are spending more time indoors watching television, playing video games, or using the computer and are, therefore, overexposed to indoor allergens.
• The trend of making homes more energy-efficient may result in dust mites being trapped inside them.
• Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
• Declining rates in nursing may be contributor. Breast milk contains important anti-inflammatory agents, such as omega-3 fatty acids, which might protect against asthma.
• Better hygiene and childhood immunizations have been associated with persistence of early immune factors that might increase the risk the risk for allergies and asthma. Important studies in 2002 and 2003, however, have found no association between vaccinations and allergic conditions or asthma.

The Allergic Response

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70% to 85% of children with asthma have allergies, with the risk being higher from seasonal allergies (e.g. hay fever) than perennial allergies (e.g., indoor allergies). (It should noted, however, that allergies are very common, and studies report that only 1% to 20% of children with allergic rhinitis actually develop asthma.)

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 the following:

• 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 present fewer problems.
• Molds.
• Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
• 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 were markedly increased and maximum tree pollen counts occurred two to four weeks earlier and mold counts two to three months earlier than in 1997.
• Food allergies. About 8% to 10% of children with asthma also have food allergies; these children also appear to have a high risk for very serious reactions to such foods. In infants and toddlers, allergy to eggs appears to be a major predictor of asthma.
• Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Of particular note, 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.

The Allergic Response. The allergic process, called atopy, and its connection to asthma are not completely understood. It 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. One description is as follows:

• 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, powerful agents of the inflammatory process.
• Interleukins 4, 9, and 13, for example, may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
• During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, over-produce mucus, and activate nerve endings in the airway lining.
• Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin 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.

Remodeling and Causes of Persistent Asthma

Over the course of 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 overgrowth of cells in the smooth muscles that line the airways and scarring in the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of asthma patients. VEGF is a powerful promoter of cell growth in blood vessel linings and some researchers believe it may be major factor in remodeling.

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 be passed to children from the mother than from the father. Both allergies and asthma are strongly associated with hereditary factors and they share certain genetic markers, but they are not always inherited together.

Research, then, on the genetics of these conditions is confusing and difficult. 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, then, could play a role in airway changes that occur after inflammation.

The Complex Role of Early Infections

The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma but the most common ones are unlikely to be causes of childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma.

Early Respiratory Infections as Causes of Asthma. Studies have found little evidence to suggest that most respiratory infections are important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which has been implicated in the development of asthma. RSV is the major viral cause of infant pneumonia. (Other respiratory infections may play an important role in many instances of adult-onset asthma.)

Common Respiratory Infections Worsen Asthma. It should be noted that even if the most common respiratory viruses, especially those that cause colds and flus, do not cause asthma in children, they can worsen asthma in children who have it.Rhinovirus, or the common cold virus, for example, has been reported to be the most common infectious agent associated with asthma attacks. In one study, it was associated with 61% of asthma exacerbations in children. Some research suggests that colds promote inflammation in patients with existing asthma and increase the intensity of airway responsiveness for weeks.

The Hygiene Theory: Early Infections as Protection Against Asthma. An increasingly important theory blames the dramatic increase in asthma on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called TH1 cells. As these cells build up, they replace other immune factors called TH2 cells, which react to allergens--a less serious threat to the body. Without infections to stimulate the production of the TH1 infection fighters, then the TH2 allergen fighters are not replaced and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

• Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
• In a 2002 study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had an 80% lower rates in allergies and asthma.
• A 2001 Swedish study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) carried in the infants intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic over-use and modern hygiene may specifically be reducing these helpful organisms. (Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.)

The standard vaccinations against serious childhood infections, according to important studies in 2002 and 2003, pose no risk for asthma. One of the studies even reported some lower risk for asthma and allergies in the second and third years after vaccinations. Infections killed thousands of children every year before immunization became widespread. Asthma, although serious, is rarely fatal in children. No one should stop giving their children vaccinations against childhood killers.

Other Contributing Medical Conditions

GERD. At least half of asthmatic patients also have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux which causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are as follows:

• Acid leaking from the lower esophagus in GERD stimulates the vagus nerves, which run through the gastrointestinal tract. These stimulated nerves in turn trigger the nearby airways in the lung to constrict, which causes asthma symptoms.
• Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be suspected as a contributor in the following asthmatic patients:

• Those who do not respond to asthma treatments.
• Those whose asthma attacks follow episodes of heartburn.
• Those whose attacks are worse after eating or exercise.
• Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in asthmatic patients.)

Treating GERD symptoms with anti-acid agents resolves asthma in some (but not all) patients who share both conditions.

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17% and 30% of asthmatic patients develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small 2000 study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-Induced Asthma

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

NSAIDs and Acetaminophen

About 10% of asthmatic adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition and is associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (e.g., Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. In fact, some asthmatic episodes have been linked to high consumption of acetaminophen among adults. And a study of children with asthma reported that those who took ibuprofen were less likely to be hospitalized for asthma than those taking acetaminophen. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Nocturnal Asthma

Asthma occurs primarily at night (called nocturnal asthma) in as many as 75% of asthma patients. Attacks often occur between 2 and 4 A.M. Factors that might play role in nocturnal asthma may include one or more of the following:

• Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways.
• Delayed allergic responses from exposure to allergens during the day.
• The wearing off of inhaled medications toward the early morning.
• An increase in acid reflux (back up of stomach acid) that causes airways to narrow.
• Postnasal drip that occurs during sleep.
• Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night.

Some experts believe that nocturnal asthma may actually be a unique form of asthma with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Click the icon to see an image of exercise-induced asthma.