Interstitial Lung Disease
Other names: Diffuse parenchymal lung disease (DPLD), Alveolitis, Cryptogenic fibrosing alveolitis (CFA), Idiopathic pulmonary pneumonitis (IPP)
Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), refers to a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues.
The term ILD is used to distinguish these diseases from obstructive airways diseases.
Most types of ILD involve fibrosis, but this is not essential. The term “pulmonary fibrosis” is no longer considered a synonym. Idiopathic pulmonary fibrosis is one form of “interstitial lung disease”.
Interstitial lung disease actually describes a group of disorders, most of which cause progressive scarring of lung tissue. This eventually affects the ability to breathe and get enough oxygen into the bloodstream. Beyond this, the disorders vary greatly.
Most cases of interstitial lung disease develop gradually, but some come on suddenly. Doctors can pinpoint why some cases of interstitial lung disease occur, but many have no known cause.
In all cases, once lung scarring occurs, it’s generally irreversible. Medications occasionally can slow the damage of interstitial lung disease, but many people never regain full use of their lungs. Researchers hope that newer drugs, many still experimental, may eventually prove more effective in treating interstitial lung disease.
Signs and Symptoms
Signs and symptoms of the wide variety of disorders classified as interstitial lung disease may include:
- A feeling of breathlessness (dyspnea), especially during or after physical activity
- A dry cough
- Chest pain
- Abnormal enlargement of the base of the fingernails or fingernails that curve over the tops of the fingertips (clubbing)
Breathlessness and a dry cough are often the primary signs and symptoms. Because these problems are vague and tend to develop gradually — often long after the irreversible lung damage — some may assume that they are due to aging, asthma, being overweight or out of shape, smoking, or the lingering effects of an upper respiratory infection.
Symptoms tend to become progressively worse. Eventually the patient may notice they’re getting out of breath during routine activities — getting dressed, talking on the phone, even eating. At this point, breathing problems become impossible to ignore.
Other symptoms include:
- Blue color of the lips, skin, or fingernails due to low blood oxygen levels (cyanosis)
- Decreased tolerance for activity
- Rapid breathing
- Shortness of breath at rest or while active
List of Conditions
- Acute Interstitial Pneumonia (AIP or Hamman-Rich Syndrome)
- Connective Tissue-related ILD
- Myositis-related ILD
- Rheumatoid arthritis-related ILD
- Scleroderma-related ILD
- Sjogren’s syndrome-related ILD
- Systemic Lupus Erythematosis-related ILD
- Undifferentiated Connective Tissue Disease-related ILD
- Cryptogenic Organizing Pneumonia (COP)
- Desquamative Interstitial Pneumonia (DIP)
- Diffuse Alveolar Hemorrhage (DAH)
- Drug-related ILD
- Eosinophilic Pneumonia
- Familial Pulmonary Fibrosis
- Hypersensitivity Pneumonitis
- Idiopathic Pulmonary Fibrosis (IPF)
- Langerhan’s Cell Histiocytosis (aka Eosinophilic granuloma or Histiocytosis X)
- Lymphangioleiomyomatosis (LAM)
- Lymphocytic Interstitial Pneumonia (LIP)
- Non-specific Interstitial Pneumonia (NSIP)
- Pulmonary Alveolar Proteinosis (PAP)
- Radiation fibrosis
- Respiratory Bronchiolitis-related ILD (RB-ILD)
- Wegener’s granulomatosis and other vasculitidies
Because interstitial lung disease has a wide range of causes, determining the reason for an initial injury to lung tissue can be difficult. Some of the many possible contributing factors include:
Occupational and environmental factors. Long-term exposure to a number of toxins or pollutants can lead to serious lung damage. Workers who routinely inhale silica dust, asbestos fibers or hard metal dust are especially at risk of serious lung disease. So are people exposed to certain chemical fumes and ammonia or chlorine gases.
But chronic exposure to a wide range of substances, many of them organic, also can damage the lungs. Among these are grain, sugar cane, and dust from bird and animal droppings. Other substances, such as moldy hay, can be a problem when they cause a hypersensitivity reaction in the lungs (hypersensitivity pneumonitis). Even bacterial or fungal overgrowth in poorly maintained humidifiers and hot tubs can cause lung damage.
Infections. These include viral infections such as cytomegalovirus, a particular problem for those who have a weakened immune system; some bacterial infections, including pneumonia; fungal infections such as histoplasmosis; and parasitic infections.
Radiation. Some people who receive radiation therapy for lung cancer or breast cancer show signs of lung damage long after they finish radiation treatment. The severity of the damage may depend on how much the lung is exposed to radiation, the total amount of radiation receive, whether chemotherapy is also used, and whether there is an underlying lung disease.
Drugs. Some drugs can damage the tissue that lines the lungs. Those most likely to cause lung problems include chemotherapy drugs, medications used to treat heart arrhythmias and other cardiovascular problems, certain psychiatric medications, and some antibiotics.
Other medical conditions. Interstitial lung disease can occur with other disorders. Often, those conditions that don’t directly attack the lungs, but instead affect tissue processes throughout the body. Among these are lupus, scleroderma, rheumatoid arthritis, dermatomyositis, polymyositis, Sjogren’s syndrome and sarcoidosis. Some researchers think that gastroesophageal reflux disease (GERD) — in which the lungs chronically intake a small volume of gastric contents — can result in pulmonary fibrosis.
Unknown causes. Although doctors can determine why some people develop interstitial lung disease, in many cases the cause isn’t known. Disorders without a known cause are grouped together under the label idiopathic pulmonary fibrosis or idiopathic interstitial lung disease. Although the idiopathic diseases have certain features in common, each also has unique characteristics.
Usual interstitial pneumonitis, also called idiopathic pulmonary fibrosis, is the most common of the idiopathic interstitial lung diseases. Because usual interstitial pneumonitis develops in patches, some areas of the lungs are normal, others are inflamed and still others are marked by scar tissue. The disease affects more men than women and usually develops in people over age 50.
Identifying and determining the cause of interstitial lung disease can be extremely challenging. An unusually large number of disorders fall into this broad category. What’s more, the distinction between interstitial lung disorders with identifiable causes and those with no known cause isn’t always clear.
In addition, the signs and symptoms of a wide range of medical conditions — among them chronic obstructive pulmonary disease (COPD), heart failure and asthma — can mimic interstitial lung disease, and doctors must rule these out before making a definitive diagnosis.
To help cut through the confusion and rule out other possible illnesses, the doctor is likely to begin with a detailed medical history and physical exam. Once certain conditions have been ruled out, the doctor will recommend tests such as:
Chest X-ray. Although this is often the first test given in cases of suspected lung problems, a chest X-ray isn’t as effective as a computerized tomography (CT) scan in diagnosing interstitial lung disease. It can, however, help eliminate conditions that cause signs and symptoms similar to those of interstitial lung disease, including emphysema and a collapsed lobe of one of the lungs.
High-resolution computerized tomography (HRCT) scan. Whereas a traditional chest X-ray produces two-dimensional images of the lungs, a CT scan uses an X-ray-sensing unit and a large computer to create cross-sectional images that are far more detailed. An HRCT scan goes even further, showing lung tissue in great detail and providing more information than conventional CT scans do.
Pulmonary function tests (PFTs). These noninvasive tests check how well the lungs function. For the test, the patient is usually asked to blow into a simple instrument called a spirometer, which measures how much air the lungs can hold and how much air flows out of the lungs. As scarring becomes worse, the patient may only be able to take less air in and blow less out. Some pulmonary function tests also measure the amount of gas exchanged across the membrane between the alveoli and capillary blood vessels.
Exercise tests. Because symptoms of interstitial lung disease are worse when the patient is active, the doctor may assess the patient’s lung function while they exercise, usually on a stationary bike or treadmill. Although specific tests vary, the blood pressure and blood oxygen levels are usually monitored as the difficulty of the exercise increases.
Bronchoscopy (transbronchial biopsy). In many cases, interstitial lung disease can be definitively diagnosed only by examining a small amount of lung tissue (biopsy). In a transbronchial biopsy, the doctor passes a flexible, fiber-optic tube (bronchoscope) through the patient’s mouth, into the lungs, and removes one or more tissue samples, each about the size of the head of a pin. These are then examined in a laboratory. Bronchoscopy is performed on an outpatient basis using local anesthesia.
Bronchoalveolar lavage. In this procedure, the doctor injects salt water (saline) through a bronchoscope into a section of the lung and then immediately suctions it out. The withdrawn solution contains cells from the air sacs. Although bronchoalveolar lavage samples a larger area of the lung than other procedures do, it may not provide enough information to diagnose a specific interstitial lung disease. Instead, doctors often use it to check the progress of a lung disorder or to help determine the best treatment.
Video-assisted thoracoscopic surgery. When less invasive tests don’t yield a specific diagnosis, a thoracic surgeon may perform a surgical lung biopsy. In this procedure, a flexible tube with a camera (endoscope) is inserted through a small incision between the ribs, allowing the surgeon to view the lungs on a video monitor. Surgical instruments are then inserted through another incision, and the surgeon removes thumbnail-sized tissue samples from two or three sites in the lungs.
Most ILDs share a common pathophysiologic feature, namely, structural remodeling of the distal airspaces, leading to impaired gas exchange. In general, this remodeling has been believed to be the sequela of persistent inflammation; however, more recently, the paradigm has shifted away from inflammation to one of tissue injury with aberrant wound healing resulting in collagenous fibrosis. Until recently, most research in this field has been based on adult histopathology and data from animal models.
Wound healing and fibrosis are complex pathophysiologic processes that involve numerous cell types and cellular processes, such as adhesion; migration; proliferation; apoptosis; and a vast array of soluble mediators, extracellular matrix (ECM) molecules, and signaling intermediates.
Many types of ILD follow some type of injury to the distal airspaces, such as adenoviral infection or exposure to organic dust, resulting in damage to the epithelial or endothelial layers and the associated basement membrane. In an animal model of lung fibrosis using bleomycin, as well as in models of surfactant-dysfunction mutations (SDMs), apoptosis of the alveolar epithelium was demonstrated to be a key inciting event.
Fibroblasts, which are normally present in the attenuated interstitial spaces between alveoli and surrounding distal airways, play a key role in lung remodeling, which is characterized by proliferation and excessive elaboration of matrix molecules such as collagen. Fibroblasts also affect remodeling through production of proteases, protease inhibitors, cytokines, and chemokines. Recent data indicate alternate origins of fibroblasts, such as circulating precursors known as fibrocytes, which hone in on injured tissues, and transdifferentiation of other cells, such as epithelial-mesenchymal transition (EMT).
Inflammation is present in many types of ILD, and many forms of ILD are triggered by inflammatory events, such as infection or hypersensitivity. Neutrophils and lymphocytes are prominent in bronchoalveolar lavage (BAL) samples in many types of ILD. In DIP, the airspaces are filled with cells that were once believed to be desquamated epithelium but which are, in fact, activated macrophages. The mediators released by inflammatory cells, particularly IL-1 and transforming growth factor (TGF)-beta, are potent activators of fibroblast-mediated remodeling. Almost every type of inflammatory cell, including eosinophils and mast cells, have been described in various types of ILD and can interact with fibroblasts and other parenchymal cells. However, lung inflammation does not necessarily result in fibrotic remodeling, and fibrosis can occur in the absence of inflammation; therefore, inflammation has a prominent, but not a central, role in lung remodeling and fibrosis.
A large number of other pathophysiologic events are increasingly recognized as having clinically significant effects on lung remodeling. Markers of angiogenesis have been prominent in several animal models of ILD and substantially affect outcomes. The ECM is a complex, biologically active structure that signals cells either by direct means or by means of its soluble breakdown products and that binds, sequesters, and presents growth factors and other mediators to cells. The ECM is altered in ILDs, and alterations in the ECM may also have a causative role.
Resolution of fibrotic remodeling involves a complex series of orderly steps, including matrix breakdown and restructuring, reepithelialization, and apoptosis of fibroblasts and inflammatory cells.
Fibrotic remodeling is responsible for most of the morbidity and mortality associated with ILD. Remodeling of distal airspaces results in hypoxemia. Persistent hypoxemia results in pulmonary hypertension and vascular remodeling, leading to cor pulmonale. The increased work of breathing associated with reduced compliance results in increased energy expenditure, which, combined with the effects of inflammatory mediators, can result in cachexia. Portions of the lung may be replaced by fibrotic septae between dilated airspaces, the so-called honeycomb changes of endstage interstitial disease. Although the events described above are necessary for repair of the injured lung, excessive activation or failure of resolution of any of these pathways can result in disabling fibrosis.
The treatment depends on the cause of the disease. Most often, anti-inflammatory drugs, such as corticosteroids or immunosuppressing drugs, are prescribed.
If there is no specific treatment for the condition, therapy is aimed at making the person more comfortable and supporting lung function. Those with low blood oxygen levels will receive oxygen. Lung rehabilitation can help people with advanced ILD.
Chances of recovery or the disease getting worse depend on the cause, and how severe the disease was when it was first diagnosed.
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