When the lungs' airways are regularly assaulted by a troublesome irritant over a long time, as in cigarette smoking, they eventually respond in two ways. They become permanently inflamed, with fluid swelling the tissue that lines the airways. Since this narrows the airways, airflow resistance increases. The lungs also radically increase mucus production in a powerhouse attempt to clean out this irritant. In a two-pronged effort, the mucus glands grow several times their normal size and the goblet cells both become far more numerous and spread out to populate even the smallest airways.

In this early stage of chronic bronchitis, the excessive sputum does not yet block the patient's airways because the cough is still strong enough to move a great deal of it out of the lungs. Because this mucus is not permitted to stagnate in the airways, it has not yet become a hospitable site for bacterial growth. The impressive sputum reservoir that the lungs produce is still nonpurulent, a medical term meaning "without bacterial content." The airways are still sterile.

But gradual paralysis of the ciliathe tiny hair-like structures responsible for moving mucus up and out of the airwayspermits mucus to accumulate in smaller airways. Then air can no longer rush out of these airways fast enough to create a powerful cough. Eventually, the patient's cough becomes too weak to propel enough mucus out of his larger airways. Loss of the body's airway-clearing mechanism lets prodigious amounts of mucus stagnate in his lungs. This warm, dark, damp, and sticky environment is ideal for bacterial growth.

In the next stage of chronic bronchitis, then, bacteria colonize the airways. In this respect the airways now resemble the digestive tract, where bacteria are normally in permanent residence. But what is normal for the intestines is not so for the lungs. Once bacteria populate the airways, pulmonary infections become frequent. (Professionals in the field feel that continuous bacterial presence in the airways may actually perpetuate and worsen the mucus secretions. A vicious circle has developed.)

With each pulmonary infection, the dramatic increase in airway mucus production that would normally occur is added to an already huge mucus pool. Eventually, the peak excesses of mucus associated with respiratory infections begin to creep into the smallest airways, those crucial links to the air sacs. Little or no gas exchange occurs in these alveoli until the mucus recedes. As this periodic obstruction of the terminal and respiratory bronchioles becomes more widespread and slower to recede, air becomes trapped in the surrounding alveoli. These air sacs become permanently hyperinflated.

Deterioration of the elastic fibers in these air sac walls is given a big assist by the neutrophil-produced elastase increase that has been part of the inflammatory response for however many years the patient has been smoking. In the face of these combined forces, the progression of emphysema is inevitable. One chronic obstructive lung disease has now led to another.

This periodic obstruction gradually becomes permanent in more and more of the smallest airways. Then air can no longer reach the capillary blood in these air sac walls to deliver oxygen and remove carbon dioxide. A ventilation-blood flow imbalance has been created. This imbalance significantly reduces oxygen and raises carbon dioxide in the blood. In technical terms, the patient is now chronically hypoxic (low oxygen) and hypercapnic (high carbon dioxide).