Chronic bronchitis and emphysema are two disorders that usually occur together and typically, but not exclusively, the result of cigarette smoking. Frequently, they are referred to collectively as chronic obstructive pulmonary disease (COPD). However, when used accurately, this term includes other chronic obstructive disorders such as asthma. Fortunately, it is usually easy to distinguish the two usages from the context.
In chronic bronchitis, there is long-term inflammation of the airways, accompanied by enlargement of the submucosal glands and hyperplasia of goblet cells. Copious secretion of mucus results. At the same time, the action of the cilia is impaired, so that the mucus is not readily cleared from the system. With time, a very abnormal epithelium develops.
Chronic bronchitis, with the inflamed, swollen, mucus-filled bronchi, makes breathing uncomfortable. But even greater difficulties in the airways are caused by the degeneration of the alveolar tissue, which is discussed in the next section. Recall slide #48 of lung tissue, in which you observed small bronchi and bronchioles. Note how the small airways are completely surrounded by alveoli. As this tissue disappears, the small airways lose important support. This is not a problem during inspiration because the pressure in the lungs is less than atmospheric. This tends to expand the airways. However, with expiration the pressure surrounding the airways is greater than atmospheric. Now, because the walls of the airways are weak and lack supportive tissue, the positive pressure tends to pinch them shut. This makes it hard to exhale, which cause even more effort, which raises the pressure around the airways even more, which causes even more collapse of the airways. This, of course, is not a pleasant sequence.
Emphysema is characterized by destruction of alveolar walls, leading to abnormally large air spaces within the lung (called pulmonary bullae, if larger than about a centimeter). In emphysema, however, the damage does not lead to fibrosis, but rather to the tissue of the lungs becoming progressively more flimsy.
One factor that can lead to emphysema is the unchecked breakdown of elastic connective tissue by proteases released by neutrophils, such as neutrophil elastase. Phagocytes accumulate in the lungs with smoking and engulf smoke particles. As this occurs, the phagocytes release proteases and toxic oxygen radicals that diffuse into the surrounding tissue.
Normally, the surrounding tissue is protected from the proteases by antiproteases (e.g. alpha-antitrypsin), which are released by macrophages. Sometimes an antiprotease is genetically deficient (fairly rare), in which case emphysema develops readily, especially with smoking.
In emphysema, the lack of tissue causes the lungs to be flaccid with a high compliance. While this makes inhalation easier, the patient must struggle constantly to exhale. Also, as discussed above, exhalation is made even more difficult because airways are no longer supported by as much surrounding tissue. Thus, when active contraction of expiratory muscles raises the intrapleural pressure, airways tend to be constricted or even collapse.
Exhalation is thus plagued by multiple problems:
The difficulties with exhalation tend to expand the chest, giving a high functional residual capacity (amount of air left in lungs at end of normal exhalation). But operating at high lung volumes is helpful because it helps keep the airways open. Asthmatics sometimes tend to breathe with a high functional residual capacity for the same reason. It can be most apparent in children.
Check out the chest X-ray and CT scan of a 59 year old woman with COPD.
The deterioration of the lung tissue also causes some regions to be much better ventilated than others. Likewise, blood flow is uneven due to destruction of capillaries. Difficulties of this sort are called mismatching of ventilation and perfusion. And any mismatching of ventilation and perfusion causes the partial pressure of oxygen in blood leaving the lungs to fall below the partial pressure that would occur with exact matching of ventilation and perfusion. In normal people, the mismatching is small and has a negligible effect on the blood gases. But in emphysema, and in many other respiratory disorders, mismatching of ventilation and perfusion is the most common causes of hypoxemia (a low level of oxygen in the blood). (Hypoxia, a more general term, refers to lack of oxygen at the tissue level.)
Smoking cessation is the most important therapy.
As with asthma, short-acting beta2 agonists (e.g. albuterol) traditionally have been used as "rescue" medications on an as needed basis. Also, short-acting anticholinergic drugs (e.g. ipratropium) are used, unlike the case with asthma. The effectiveness of medications, however, tends to be modest compared to that in typical asthma.
When COPD becomes moderate to severe, inhaled, long-acting beta2 agonists (e.g. salmeterol) and inhaled, long-acting anticholinergics (e.g. tiotropium) are routinely used. These improve the FEV1 and general quality of life, but do not seem to affect the course of the disorder. Effects on mortality are small and barely statistically significant.
While inhaled corticosteroids are the mainstay of asthma treatment, their use in COPD has been more controversial. Now the combination of an inhaled corticosteroid and a inhaled long-acting beta2 agonist is used (e.g. fluticasone and salmeterol). As with the above drugs, this combination improves the FEV1 and quality of life, but does not seem to affect the course of the disease and so far the effects on mortality have been barely statistically significant. In cases prone to severe exacerbations, sometimes an inhaled anticholinergic is added as well.
Dealing with infections, which can make the disorder worse and provoke serious exacerbations, is always very important.
Exercise intolerance is often the biggest complaint of patients with COPD. In general, the difficulties increase with the severity of the disorder, with severe COPD causing severe disability. Exercise training is usually helpful, unless there is some other disorder or circumstance that makes it impossible or unwise. For patients with moderate to severe COPD, designing an appropriate exercise regime and motivating the patients, who are likely to find the exercise unpleasant, usually requires a skilled team.
Oxygen therapy is only effective when the PaO2 falls below 55 to 60 mm Hg. And then it is an important part of the therapy.
Surgery is an option that involves a difficult weighing of benefits and problems. In lung reduction surgery, the most diseased part of a lung is removed, allowing the remaining better lung tissue to fill up the space. This removes lung tissue with the worst ventilation to perfusion ratios and expands the remainder. Sometimes a valve is put in a bronchus to shut off air flow to a region of the lung, but to allow drainage in the opposite direction. Lung transplants involve a long recovery and are comparatively expensive for their benefits.