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Chronic Inflammation

In asthma, the allergic inflammatory process never really stops. An important medical discovery made several years ago was that some inflammation is present in the bronchial tubes of people with asthma even when they feel well and when their breathing is normal. Medical researchers performed experiments to sample (biopsy) small pieces of the walls of the bronchial tubes. The samples were taken at times when the research participants were feeling well, free of asthma symptoms. Yet in the biopsied tissues, scientists found evidence of persistent inflammation of the bronchial tubes.

This suggests that airway inflammation in asthma is always present, at least to some degree. The inflammation may be so mild that it does not cause narrowing of the bronchial tubes. But the persistent presence of this inflammation is probably a major reason that the bronchial tubes are twitchy, or capable of narrowing abnormally. By understanding more about the multiple steps involved in this type of inflammation, physicians have developed treatments aimed at keeping it under control

The Allergy Connection

When most people think of allergies, they’re likely to think of sneezing and a runny or stuffy nose; red, itchy, watery eyes; or perhaps dry, red, itchy skin. But one theory about asthma is that it is also an allergic reaction — in this case, affecting the bronchial tubes.

In fact, allergic rhinitis (allergies of the nose), allergic conjunctivitis (allergies of the lining of the eyes), and allergic dermatitis (allergies of the skin, also called eczema) frequently occur together in various combinations both in individuals and in families, and they often occur together with asthma.

All these conditions share a common mechanism: They result from a specific type of allergic reaction. The tendency to make this specific type of allergic reaction is called atopy, and people who have this tendency are said to be atopic. Asthma accompanied by allergies is often referred to as atopic asthma or extrinsic asthma. The vast majority of children with asthma, and probably at least half of the adults with the disorder, have the atopic variety.

The allergic basis of asthma has provided insight into what proteins and cells are involved in the inflammation of the bronchial tubes. People who have allergies make a special kind of protein, called an antibody, which is precisely shaped to recognize and attach itself firmly to a particular allergen. This antibody belongs to the family of immune defenders called immunoglobulins. The defenders that are specifically designed to recognize allergens are referred to as immunoglobulin E (IgE). Let’s say you are allergic to dust mites; you make IgE antibodies that recognize the dust mite allergen.

The IgE antibodies do not roam freely in your breathing tubes but are firmly attached to immune system cells called mast cells. These cells are located mainly in parts of the body that regularly encounter substances from the outside world: the skin, intestinal tract, lining of the eyes (conjunctivae), nose, and breathing tubes.

In people with allergic asthma, the surface of each mast cell is coated with firmly attached IgE antibodies. All remains quiet until the IgE antibodies recognize and attach themselves to an allergen. Then, within seconds, an explosive reaction takes place (see Allergic Asthma ). The mast cell makes and releases a barrage of chemicals that carry out the inflammatory reaction. These chemicals include histamine (which you may be aware of if you are familiar with antihistamines for treating allergies), leukotrienes, and many others.

Together these inflammatory chemicals cause blood vessels to leak fluid, producing swelling in the breathing tubes. They stimulate the walls of the breathing tubes to secrete mucus. They also make the muscles surrounding the breathing tubes contract, narrowing these passageways. As if that weren’t enough, mast cells also call in reinforcements, other cells involved in allergic inflammation that travel from the blood to the site of the allergic reaction and make things worse. The most important of these reinforcements are blood cells called eosinophils. Like mast cells, they release chemicals that cause the airways to narrow.

Environmental Factors in Asthma

It is likely that inhaled substances are the most important environmental factors contributing to the development of asthma in people with a genetic predisposition to the disorder. Leading suspects include allergens (substances that cause an allergic reaction;tobacco smoke, air pollution, and infectious agents such as viruses.

Asthma most often develops during childhood following exposure to one or more of these environmental factors, but it can also develop in adulthood. People who smoke, are exposed to irritating chemicals in the workplace, or suffer a particularly nasty respiratory infection may develop asthma in adulthood. Hormone replacement therapy in menopausal women is another risk factor: The Nurses’ Health Study, a large epidemiological study that has collected information about women’s health issues since 1976, found that menopausal women who were currently using or who had used estrogen replacement therapy had a 50% greater risk of developing asthma than those who did not take hormones. Often, however, there is no identifiable cause of adult-onset asthma. In some cases, the problem may have been present in childhood but was undiagnosed, or it may have been present in childhood, become dormant around adolescence, then resurfaced in adulthood.

The same environmental factors that are thought to incite asthmatic inflammation of the bronchial tubes in the first place can also cause subsequent asthma attacks. Learning to recognize and avoid your asthma triggers is an important part of managing the disorder

Asthma Genes

It has long been known that people inherit a tendency to develop asthma. The condition tends to run in families; if your brothers, sisters, or parents have asthma, you are more likely to develop it yourself.

The genetic contribution to asthma is far from simple, however. It’s almost certain that more than one gene — and by some estimates, as many as 10 genes — are responsible for the predisposition to asthma, and that these genes somehow interact to produce the disorder. Yet even if you are born with the genes predisposing you to asthma, you may never go on to develop the disease. This has been shown by studies of identical twins, who share the same genes. When one identical twin develops asthma, there is only a one-in-three chance that the other twin will develop it as well. Clearly, something in the environment must also be responsible for asthma.

A number of asthma-related genes have been discovered. Still other asthma genes are thought to exist, and it is unclear yet which ones are most significant. The research in this area continues, with the hope that better understanding of the genetic basis of asthma will lead to better treatments and potentially even a cure.

What Causes Asthma?

No one knows exactly what causes asthma. It is not even clear whether asthma is one disorder or a group of disorders with similar manifestations. Still, much has been learned about who is most likely to develop asthma and how an asthma attack occurs. To put it simply, a person becomes susceptible to developing asthma because of genes, but develops the disorder only after exposure to things in the environment that stimulate the immune system in such a way that airways become hypersensitive and prone to further attacks.

A simple example may help explain how genetic and environmental factors can interact to produce asthma. Suppose you inherit a tendency to be allergic to cockroaches. After many years of living in a single-family house, you move to an apartment complex. The good news is that you don’t have to mow the lawn anymore — but you may also find yourself living with cockroaches for the first time in your life. This can lead over time to an allergic irritation of your bronchial tubes. Once irritated or inflamed in this way, your bronchial tubes react not only to cockroaches but also to many other types of stimuli that typically make asthma worse, such as smoke, exercise, and respiratory infections. After many months or years of exposure, even if you move out of the apartment into one that doesn’t have a cockroach problem, this hypersensitivity of your airways — in other words, your asthma — may persist.

Airways Remodeling

In most cases, asthma is a variable condition characterized by intermittent and fully reversible airway narrowing. However, for some people, asthmatic inflammation of the airways leads to permanent changes. The bronchial tubes become narrower and less flexible, and do not return to normal. The term used for these permanent changes in airway wall architecture is airway remodeling.

The consequence of airway remodeling is reduced lung capacity, even when you are at your best. You may feel well, without coughing or wheezing, yet your breathing tests show a decreased capacity to expel air from your lungs. If the permanent narrowing is severe, even simple activities like climbing a flight of stairs can become an effort.

No one knows why airway remodeling happens in some people with asthma and not in others. One theory is that airway remodeling is most common in people with severe and longstanding asthma, especially if the disorder has not been treated with anti-inflammatory medications. Studies suggest that people with mild asthma tend to continue with mild asthma and are unlikely to develop permanent loss of lung function.

How Airways Narrow

During an asthma attack, some type of trigger causes your airway passages to narrow. Airway narrowing often involves two mechanisms, each of which requires separate treatment.

One component of airway narrowing is muscle contraction. The muscles surrounding the around your breathing tubes can contract quickly, in less than one minute, and squeeze the bronchial tubes so that they narrow. These breathing tubes are involuntary muscles, like the muscles that constrict pupils or move food through the intestines. When you encounter one of your asthma triggers, the muscles that form a ring muscles can also relax relatively quickly, in just a few minutes, either on their own or in response to medication. The terms used to describe these processes are bronchoconstriction or bronchospasm (when the tubes narrow) and bronchodilation (when they widen).

The other component of airway narrowing is inflammation, a biological process in which the body tries to heal various injuries, irritations, or infections. Inflammation generally involves some swelling caused by leakage of fluid from the blood vessels, and an influx of specialized cells to the scene of an injury or infection.
In asthma, inflammatory cells come out of the blood and take up residence in the walls of the bronchial tubes. These inflammatory cells contain powerful chemicals that can cause the walls of the bronchial tubes to swell and produce extra mucus, or phlegm. (Mucus that is coughed up is called sputum, although most people use mucus, phlegm, and sputum interchangeably.) The mucus can plug the bronchial tubes, leaving little room for air to move in and out. Both the swelling of the airway walls and the accumulation of excess mucus can contribute to the breathing problems of asthma. Unlike muscle contraction around the bronchial tubes, inflammation of the bronchial tube walls takes many hours or even days to subside.

Medications used to treat asthma focus on these two mechanisms of airway narrowing. Some drugs are designed to relax the muscles surrounding the airways; others reduce inflammation of the breathing tubes. Some do both.

Twitchy Airways

Normally when you inhale, air passes easily from your nose and mouth into the trachea, which branches into the two bronchial tubes, or bronchi, that feed the right and left lungs. These primary bronchi divide into smaller and smaller branches, or segmented bronchi, ultimately narrowing into small stems called bronchioles that terminate in microscopic sacs, or alveoli. These tiny sacs cluster around the bronchioles in a configuration that resembles bunches of grapes
With each intake of breath, your airways dilate and the alveoli expand to admit air, providing oxygen to networks of tiny blood vessels in the alveolar walls. Exhale, and the alveoli shrink, forcing exhaled gas — and with it, carbon dioxide — into the bronchioles, back through the bronchi and trachea, and out of your body.

If you have asthma, much of the time your airways are fully open, and at those times you can breathe normally. At other times, however, your airways become constricted and breathing becomes difficult, so bad at times that you may feel as though you are trying to breathe through a straw while a gorilla sits on your chest.

The variable narrowing of the breathing tubes that can come and go over a period of minutes, hours, or days is called reversible airway narrowing and is one of the hallmarks of asthma. This variability distinguishes asthma from other lung diseases, such as emphysema and chronic bronchitis, which cause permanent breathing problems that occur day in and day out.
Airways narrow in asthma because they are hypersensitive, or — to use a less medical-sounding term — "twitchy." Having twitchy airways doesn’t mean that they feel twitchy; it means that there is an underlying tendency for the airways to react by narrowing when they encounter certain stimuli, such as cat dander or cold air. These stimuli are known as asthma triggers, because they cause symptoms to flare up (see Asthma Triggers). If you have asthma, the potential for airway narrowing is always there: Your airways remain hypersensitive or "twitchy" even when you feel well. Asthma thus involves intermittent airway narrowing but persistent vulnerability to that narrowing — a concept that is central to both the understanding of this disorder and its treatment.

What Is Asthma?

Asthma is a disorder that intermittently causes shortness of breath and difficulty breathing, although the exact type and severity of symptoms vary from person to person. Some people with asthma have cough, wheezing, and trouble breathing nearly every day. Others feel perfectly well in between occasional attacks of chest congestion and wheezing. Some Olympic athletes with asthma experience only a tightness in the chest during world-class athletic competition. Other people have such severe asthma attacks after exercising that they require emergency treatment. All people with asthma share something in common, however: breathing passageways that periodically become abnormally narrow.

More than 20 million people in the United States — about 7% of the population — have asthma (see Asthma in America, below). Most people tend to think of asthma as a childhood disease, for good reason: Most cases of asthma are diagnosed by age five. Nonetheless, adults of any age may develop asthma, although the likelihood of developing it becomes increasingly rare the older you get. Studies indicate that as many as 10% of people over 65 have asthma, higher than the prevalence of asthma in childhood. If you are an adult with asthma, it is likely that you have had the disorder for a long time and will continue to deal with it for the rest of your life.

For reasons that are unclear, children with asthma often grow out of their illness, usually around adolescence. If the condition develops or persists into adulthood, though, it is rare that asthma just goes away. But the condition can be managed. In fact, if you have asthma, you can anticipate being free of symptoms and fully active almost all the time.