Restrictive lung disease is distinguished from the obstructive lung diseases by having a normal FEV1/FVC ratio. In other words, an expiration can occur at the normal rate. The airways are not obstructed. However, the lungs cannot inflate to a normal volume, giving an abnormally low FVC. In contrast to asthma and chronic bronchitis and emphysema, the lungs have a low compliance. They are stiff and difficult to inflate, and this is one reason why the patient has dyspnea (shortness of breath). However, in addition the diffusion of oxygen from the alveoli to the blood is typically impaired.
Before looking at some of the causes of restrictive lung disease, let's first examine the normal healing that follows damage.
The delicate tissue of the lungs can be readily damaged by infections and various environmental factors. Cytomegalovirus, for example, is one of a number of viruses that attack the epithelial cells of the alveoli. It is often prominent when the immune system is compromised, as in AIDS or in a patient receiving immunosuppressive drugs.
The type I cells are usually those most likely to be damaged. Fortunately, the alveolar epithelium regenerates readily, but only if the connective tissue matrix remains intact. Type II cells migrate to sites of damage, divide and develop into type I cells.
If the connective tissue matrix is not too badly damaged, it might be repaired, and the alveoli return more or less to their normal condition. But beyond a certain point, the damage cannot be repaired and the healing does not reproduce the normal structure of the lung. The fibroblasts secrete excessive type I collagen and proteoglycans, creating nonfunctional scar tissue.
With prolonged, repeated insults to the lung tissue, a serious, abnormal situation can develop in which fibroblasts create fibrosis and thus restrictive lung disease.
Why might fibroblasts secrete excessive connective tissue? The prevailing view is that abnormal wound healing and/or excessive injury by inhaled particles and substances drives the pathology. The process starts as inhaled particles reach the alveoli and cause damage. Then they are phagocytized by macrophages and removed as usual. The macrophages also secrete growth factors which begin the repair process by stimulating fibroblasts. This is the normal process for removing substances and repairing damagage. But results become pathological when combined with other factors.
First, there appear to be abnormalities in the replenishment of type I cells by type II cells. This creates a situation in which the steady, excessive stimulation by stressful substances creates the abnormal fibrosis.
Second, impaired mucosal defense mechanisms in the smallest airways can play an important role. For example, one genetic factor can be an abnormality in one of the mucus genes, which can lead to impaired mucosal defense and inflammation. Factors such as this can slow the removal of stressful factors, such as various inhaled particles, viral infections or tobacco smoke. This leads to prolonged action of the stressful factors, leading to abnormal fibrosis.
When the environmental particles are silica, the resulting disorder is silicosis, which is characterized by nodules of dense, fibrous tissues.
Another important example is asbestosis, which results from long-term inhalation of asbestos dust. While in developed countries, asbestos is much more carefully controlled than earlier, cases still appear since they can show up 30 years after the occupational exposure.
One type of restrictive lung disease that shows up for unknown reasons is idiopathic pulmonary fibrosis.
As the name implies, the cause of idiopathic pulmonary fibrosis is unknown. It tends to appear in people over 50 years old. There is at least some connection to smoking. Unlike asthma and COPD, there is little inflammation. Extensive fibrosis develops in the interstitial spaces between alveoli. Survival following diagnosis may be only three years, although some patients can live considerably longer.
Genetic factors include genes involved in the replenishment of the epithelial cells, and the abnormality in the mucus gene mentioned above.
The CT scan at the right shows the extensive fibrosis in idiopathic pulmonary fibrosis. Note that, in addition to the fibrosis, there is a large emphysematous bulla present.
Sarcoidosis is an inflammatory disorder of unknown ethiology. But an exaggerated cellular immune response to antigens is probably involved in some way. The disorder is characterized by accumulations of macrophages termed granulomas. However, these lack the caseous (cheese-like) interior of granulomas found in tuberculosis. The granulomas in sarcoidosis are found most commonly in mediastinal lymph nodes and the lungs, but can occur in various other organs as well. The disorder often shows up in young adults and is not linked with smoking.
In the lungs the granulomas are scattered throughout the interstitial spaces. Thus, sarcoidosis often presents as a restrictive lung disease, with the reduced FVC and compliance, as discussed above. But sometimes, if large granulomas push against bronchi, there are obstructive symptoms. Symptoms develop slowly and may include fever, malaise and weight loss.
The CT scan to the right shows hilar adenopathy (enlargement of gland, such as lymphatic). The patient was a 39 year old female, and the pathology was revealed initially in a routine pre-employment x-ray before the patient had any symptoms.
Complete recovery is common in mild cases, with only about 10% of the patients going on to serious disability.
Note that infant respiratory distress syndrome, which occurs in premature infants who lack sufficient surfactant, is also a restrictive lung disease.