In some people—but not all—asthma is associated with allergy. And while some individuals outgrow asthma, others acquire it later in life. These diverse patterns make some experts think that asthma should be viewed not as a single entity but rather as a group of similar conditions with one common factor. And that one factor uniting the various forms of this airway disease may well be an abnormality of the airway smooth muscle cell.

The airway smooth muscle extends from the trachea (windpipe) to deep down in the lungs. When we breathe in any kind of irritant—chemical, smoke, or dust, for example—the smooth muscle constricts, narrowing the airway. If you have asthma, inhaling such an irritant causes an even more intense constriction, blocking the flow of air.

The explanation for this appears to lie in an abnormality of the smooth muscle cells. These cells contain reduced levels of an essential protein called C/EBP alpha, which keeps inflammation in check. Inadequate levels of C/EBP alpha make the smooth muscle more likely to constrict and narrow the airways.

More than just inflammation
Researchers have long regarded asthma as an inflammatory disease. But, as it turns out, it is not as simple as that. During an asthma attack, the immune system unleashes a number of different weapons. Among them are 2 types of helper T cells, Th1 and Th2. Helper T cells stimulate other immune cells to make antibodies, which help destroy foreign substances. T cells also produce proteins known as cytokines, which help trigger an immune system attack on invading substances.

All these components participate in the inflammatory process of asthma. Numerous studies have shown that people with asthma have more Th2 cells and their respective cytokines than do people without asthma.

But asthma involves more than just inflammation produced by Th2 cells. And that brings us back to the abnormal activity of cells in the airway smooth muscle, and raises the question: Does airway inflammation make these cells overreact, or do these abnormal smooth muscle cells in people with asthma prompt an inflammatory response in the airways?

Under the microscope
It was once thought to be too risky to remove airway smooth muscle cells from people with asthma so that the cells could be examined. But more recently, investigators have been able to take a closer look at the cells, thanks to volunteers who have been willing to undergo biopsy (removal of a small sample of tissue) and bronchoscopy (an examination of the airways with a special instrument called a bronchoscope).

Comparison of airway smooth muscle cells from individuals with asthma and individuals without asthma has revealed something very interesting: The cells from the asthma group reproduce much faster than those from the non-asthma group. That may well explain why people with asthma have more smooth muscle in their airways.

And here is another interesting fact: When some of those smooth muscle cells in asthma sufferers were removed by applying high heat, both asthma symptoms and lung function improved.

One clue leads to another . . . and another
These findings suggest that cells in the airway’s smooth muscle can create an environment that stimulates airway inflammation and airway remodeling. Airway remodeling refers to the structural changes created as a result of long-term inflammation. The airway wall becomes thicker, thereby narrowing the airway itself. That, in turn, leads to airway obstruction—a dangerous situation.

Also important are the reduced levels of the C/EBP?alpha protein in people with asthma. The lack of this protein could explain most of the features of asthma, helping scientists understand the disease better. Because C/EBP?alpha levels are only abnormal in asthma, not in the respiratory diseases emphysema or chronic obstructive pulmonary disease (COPD), the presence or absence of this protein can help nail down the diagnosis of asthma early on.

In addition, if defective levels of C/EBP alpha are indeed proven to be at the root of asthma, it’s possible that restoring those levels could be a new avenue of treatment for asthma.