63. Chronic restrictive lung diseases
Introduction
Diseases that affect the lung interstitium usually cause reduced compliance (increased stiffness) of the lung. This increases the work of breathing, leading to dyspnoea. Several parts of the interstitium is involved in gas exchange, like the alveolar epithelium and vessels, so diseases of the interstitium affect the gas exchange as well, causing V/Q mismatches and therefore possibly respiratory failure.
Pulmonary hypertension occurs because the whole lung becomes hypoxic, which induces vasoconstriction. This can again lead to cor pulmonale. Advanced stages of these diseases cause destruction and scarring of the lung, which is called end-stage or honeycomb lung.
Four categories of chronic interstitial lung diseases exist: Fibrosing type, granulomatous type, eosinophilic type and smoking-related type.
Fibrosing diseases
Idiopathic pulmonary fibrosis (IPF) is a lung disorder with unknown etiology, hence the name. It’s characterised by progressive bilateral interstitial fibrosis. Patients are usually male and old.
Nonspecific interstitial pneumonia (NSIP) is another chronic bilateral interstitial lung disease with unknown etiology. It has a much better prognosis than IPF. Histology shows that the interstitium is chronically inflamed and fibrotic.
Cryptogenic organizing pneumonia also has unknown etiology. Histology shows plugs of loose connective tissue in small airways and alveoli. There’s no interstitial fibrosis.
Pneumoconiosis is a group of occupational lung diseases that occur due to inhalation of mineral dusts. The three most important mineral dusts are coal dust, silica crystals and asbestos fibres, which cause coal worker’s pneumoconiosis, silicosis and asbestosis, respectively. Dust particles between 1-5 μm sediment in the alveoli, causing damage. Clearance of dust from the bronchi and airways is no problem – they have kinocilia. Clearance of dust from the alveoli however takes years, and is done by macrophages that carry them to regional lymph nodes. The main tissue reaction to mineral dust is fibrosis.
Anthracosis is something you’ve probably seen a lot already in autopsy and pathohistology. Anthracosis is the harmless accumulation of carbon pigment in lung and hilar lymph nodes that can be seen in anyone who lives in or near a city.
Coal worker’s pneumoconiosis (CWP) occurs in two forms, simple and complicated forms. Simple CWP just cause a small decrease in lung function, but complicated CWP causes progressive massive fibrosis, pulmonary hypertension and cor pulmonale.
Silicosis is the most prevalent chronic occupational disease in the world. The inhaled silica crystals activate macrophages, which secrete factors that promote fibrosis. They develop progressive massive fibrosis, pulmonary hypertension and cor pulmonale. Silicosis also predisposes to tuberculosis, so-called silicotuberculosis. For histology, see the slide.
Asbestosis is the interstitial fibrotic disease associated with asbestos exposure, and the consequences are similar as for the other pneumoconioses. Asbestos exposure also drastically increases the risk of lung carcinoma, laryngeal carcinoma and mesothelioma as well. Asbestos is composed of many thin, long mineral fibres, which macrophages has much bigger problems dealing with than small particles.
Granulomatous diseases
Sarcoidosis isn’t a restrictive lung disease, it’s a multisystem disease that has effect on the lung as well. Sarcoidosis causes noncaseating granulomas in many organs, including the lung. In 10% of patients are the granulomas replaced by interstitial fibrosis, resulting in a special morphology called honeycomb lung. Fibrosis causes the usual symptoms of restrictive diseases, ending with cor pulmonale.
Hypersensitivity pneumonitis is an immune-mediated disease that affects the alveoli. Both type III and IV hypersensitivity occur in the disease, which is provoked by allergens like moldy hay and bird poop. If the patient has continued exposure to the allergen will the chronic inflammation eventually develop into interstitial fibrosis.
Smoking isn’t just associated with obstructive diseases (chronic bronchitis and emphysema), but restrictive ones as well.
Desquamative interstitial pneumonia (DIP) is characterized by macrophages containing brown pigment, and inflamed alveolar septa. The fibrosis is usually mild and doesn’t cause severe pulmonary dysfunction.
Pulmonary langerhans cell histiocytosis is a systemic disease that can affect the lung, causing restrictive disease.
Eosinophilic diseases
A number of diseases are characterised by infiltration and activation of eosinophils due to increased alveolar IL-5 (which activates eosinophils). They generally have immunological origin.
Acute eosinophilic pneumonia is characterised by rapid onset of fever, dyspnoea, hypoxia and diffuse pulmonary infiltrate.
Secondary eosinophilia, due to asthma or drug allergies for example, can cause pneumonitis.
Idiopathic chronic eosinophilic pneumonia is characterised by lymphocytes and eosinophils in the alveolar septa and alveolar spaces.