Pulmonary Fibrosis

Pulmonary fibrosis is the formation or development of excess fibrous connective tissue (fibrosis) in the lungs. It can be described as "scarring of the lung".

Pathogenesis

Pulmonary fibrosis involves gradual replacement of normal lung parenchyma with fibrotic tissue. Thickening of scar tissue causes irreversible decrease in oxygen diffusion capacity. In addition, decreased compliance makes pulmonary fibrosis a restrictive lung disease. It is the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast, quadriplegia and kyphosis are examples of causes of restrictive lung disease that do not necessarily involve pulmonary fibrosis.

Etiology

Pulmonary fibrosis may be a secondary effect of other diseases, most of them being classified as interstitial lung diseases, e.g. autoimmune disorders, viral infections or other microscopic injuries to the lung. However, it may also appear without any known cause, then termed "idiopathic". Most of the idiopathic cases can be diagnosed as idiopathic pulmonary fibrosis, a diagnosis of exclusion, yet having a characteristic set of histologic/pathologic features known as usual interstitial pneumonia (UIP). In either case, there is a growing body of evidence which points to a genetic predisposition. For example, a mutation in Surfactant protein C (SP-C) has been found to exist in families with a history of pulmonary fibrosis.

Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include:

• Inhalation of environmental and occupational pollutants, such as in asbestosis, silicosis and exposure to certain gases. Coal miners, ship workers and sand blasters among others are at higher risk.
• Hypersensitivity pneumonitis, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products.
• Cigarette smoking can increase the risk or make the illness worse.
• Some typical connective tissue diseases such as rheumatoid arthritis, SLE and scleroderma
• Other diseases that involve connective tissue, such as sarcoidosis and Wegener's granulomatosis.
• Infections
• Certain medications, e.g. nitrofurantoin
• Radiation therapy to the chest

Symptoms and diagnosis

Symptoms of pulmonary fibrosis are mainly:

• Shortness of breath, particularly with exertion
• Chronic dry, hacking coughing
• Fatigue and weakness
• Chest discomfort
• Loss of appetite and rapid weight loss

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. Sometimes crackles can be heard in the chest with stetoscope. A chest x-ray may or may not be abnormal, but high Resolution CT will frequently demonstrate abnormalities.

The diagnosis can be confirmed by lung biopsy. An open surgical biopsy, meaning that the chest wall is surgically opened under general anesthesia to remove a portion of lung tissue, may be necessary to obtain enough tissue to make an accurate diagnosis. The removed tissue is examined histopathologically by microscopy to confirm the presence of fibrosis.

Misdiagnosis is common because the origin and development of the disease is not completely understood. There is varying terminology and lack of standard diagnostic criteria and this complicates the gathering of accurate information about pulmonary fibrosis.

On spirometry, as a restrictive lung disease, both the FEV1 (Forced Expiratory Volume in 1 Second) and FVC (Forced Vital Capacity) are reduced so the FEV1/FVC ratio is normal or even increased in contrast to obstructive lung disease where this ratio is reduced. The values for residual volume and total lung capacity are generally decreased in restrictive lung disease[7].

Prevalence

Five million people worldwide are affected by pulmonary fibrosis. In the United States there are over 500,000 patients with pulmonary fibrosis. The actual numbers may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed.

Treatment and prevention

Scarring is permanent once it has developed. Slowing in the progression and prevention depends on the underlying cause:

• For idiopathic pulmonary fibrosis (IPF) there is currently no effective treatment or cure. There are pharmacological agents in the experimental phase intended to prevent scarring. Anti-inflammatory agents have only limited success in reducing the fibrotic progress.
• Some of the other types of fibrosis, such as nonspecific interstitial pneumonitis (NSIP), may respond to immunosuppressive therapy such as such as corticosteroids. However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, penicillamine, and cyclosporine may be used. Colchicine has also been used with limited success. There are ongoing trials with newer drugs such as IFN-γ, mycophenolate mofetil, and pirfenidone.
• Hypersensitivity pneumonitis is prevented from becoming aggravated by avoiding contact with the causative material.
• Oxygen supplementation improves the quality of life and exercise capacity. Lung transplantation may be considered for some patients.

Complications

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to heart failure of the right ventricle. This can be prevented with oxygen supplementation.

Pulmonary fibrosis may also cause increased risk for pulmonary emboli, which can be prevented by anticoagulants.