Pulmonary fibrosis

Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include
shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include
pulmonary hypertension, respiratory failure, pneumothorax, and lung cancer.

Causes include environmental pollution, certain medications, connective tissue diseases, infections, and
interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF), an interstitial lung disease of unknown
cause, is most common. Diagnosis may be based on symptoms, medical imaging, lung biopsy, and lung
function tests.

There is no known cure. Treatment is directed towards efforts to improve symptoms and may include
oxygen therapy and pulmonary rehabilitation. Certain medications may be used to try to slow the
worsening of scarring.[4] Lung transplantation may occasionally be an option. At least 5 million people
are affected globally.[5] Life expectancy is generally less than five years.

Symptoms of pulmonary fibrosis are mainly

Shortness of breath, particularly with exertion

Chronic dry, hacking coughing

Fatigue and weakness

Chest discomfort including chest pain

Loss of appetite and rapid weight loss

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion.
Sometimes fine inspiratory crackles can be heard at the lung bases on auscultation. A chest X-ray may or
may not be abnormal, but high-resolution CT will frequently demonstrate abnormalities.[3]

Cause

Further information: Interstitial lung disease

Pulmonary fibrosis may be a secondary effect of other diseases. Most of these are classified as interstitial
lung diseases. Examples include autoimmune disorders, viral infections and bacterial infection like
tuberculosis which may cause fibrotic changes in both lung's upper or lower lobes and other microscopic
injuries to the lung. However, pulmonary fibrosis can also appear without any known cause. In this case,
it is termed "idiopathic".[7] Most idiopathic cases are diagnosed as idiopathic pulmonary fibrosis. This is
a diagnosis of exclusion of 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 in a subset of patients. For example, a mutation in surfactant protein C (SP-C) has been
found to exist in some families with a history of pulmonary fibrosis.[8] Autosomal dominant mutations in
the TERC or TERT genes, which encode telomerase, have been identified in about 15 percent of
pulmonary fibrosis patients.[9]

Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include:[3][8]

Inhalation of environmental and occupational pollutants, such as metals[10] in asbestosis, silicosis and
exposure to certain gases. Coal miners, ship workers and sand blasters among others are at higher risk.[7]

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.[7]

Some typical connective tissue diseases[7] such as rheumatoid arthritis, ankylosing spondylitis SLE and
scleroderma

Other diseases that involve connective tissue, such as sarcoidosis and granulomatosis with polyangiitis.

Infections

Certain medications, e.g. amiodarone, bleomycin (pingyangmycin), busulfan, methotrexate,[7]

Radiation therapy to the chest

Pathogenesis

Further information: Fibrosis

Pulmonary fibrosis involves gradual exchange of normal lung parenchyma with fibrotic tissue. The
replacement of normal lung with scar tissue causes irreversible decrease in oxygen diffusion capacity, and
the resulting stiffness or decreased compliance makes pulmonary fibrosis a restrictive lung disease.[13]
Pulmonary fibrosis is perpetuated by aberrant wound healing, rather than chronic inflammation.[14] It is
the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast,
quadriplegia[15] and kyphosis[16] are examples of causes of restrictive lung disease that do not
necessarily involve pulmonary fibrosis.

Diagnosis

HRCT of lung showing extensive fibrosis possibly from usual interstitial pneumonitis. There is also a
large emphysematous bulla.
The diagnosis can be confirmed by lung biopsy.[3] A videoscopic assisted thoracoscopic wedge biopsy
(VATS) under general anesthesia may be necessary to obtain enough tissue to make an accurate
diagnosis. This kind of biopsy involves placement of several tubes through the chest wall, one of which is
used to cut off a piece of lung to send for evaluation. The removed tissue is examined histopathologically
by microscopy to confirm the presence and pattern of fibrosis as well as presence of other features that
may indicate a specific cause e.g. specific types of mineral dust or possible response to therapy e.g. a
pattern of so-called non-specific interstitial fibrosis.[3]

Misdiagnosis is common because, while overall pulmonary fibrosis is not rare, each individual type of
pulmonary fibrosis is uncommon and the evaluation of patients with these diseases is complex and
requires a multidisciplinary approach. Terminology has been standardized but difficulties still exist in
their application. Even experts may disagree with the classification of some cases.[17]

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.

Treatment

Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed.[3] Slowing the
progression and prevention depends on the underlying cause:

Treatment options for idiopathic pulmonary fibrosis are very limited. Though research trials are ongoing,
there is no evidence that any medications can significantly help this condition. Lung transplantation is the
only therapeutic option available in severe cases. Since some types of lung fibrosis can respond to
corticosteroids (such as prednisone) and/or other medications that suppress the body's immune system,
these types of drugs are sometimes prescribed in an attempt to slow the processes that lead to fibrosis.

The immune system is felt to play a central role in the development of many forms of pulmonary fibrosis.
The goal of treatment with immune suppressive agents such as corticosteroids is to decrease lung
inflammation and subsequent scarring. Responses to treatment are variable. Those whose conditions
improve with immune suppressive treatment probably do not have idiopathic pulmonary fibrosis, for
idiopathic pulmonary fibrosis has no significant treatment or cure.

Two pharmacological agents intended to prevent scarring in mild idiopathic fibrosis are pirfenidone,
which reduced reductions in the 1-year rate of decline in FVC. Pirfenidone also reduced the decline in
distances on the 6-minute walk test, but had no effect on respiratory symptoms.[19] The second agent is
nintedanib, which acts as antifibrotic, mediated through the inhibition of a variety of tyrosine kinase
receptors (including platelet-derived growth factor, fibroblast growth factor, and vascular endothelial
growth factor). A randomized clinical trial showed it reduced lung-function decline and acute
exacerbations.

Anti-inflammatory agents have only limited success in reducing the fibrotic process. Some of the other
types of fibrosis, such as non-specific interstitial pneumonia, may respond to immunosuppressive therapy
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.[3] There are ongoing
trials with newer drugs such as IFN-γ and mycophenolate mofetil.

Hypersensitivity pneumonitis, a less severe form of pulmonary fibrosis, 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.[22]

Prognosis

Lung with end-stage pulmonary fibrosis at autopsy

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to
heart failure of the right ventricle. Hypoxia can be prevented with oxygen supplementation.[3]

Pulmonary fibrosis may also result in an increased risk for pulmonary emboli, which can be prevented by
anticoagulants.[3]