Pulmonary fibrosis
Encyclopedia
Pulmonary fibrosis is the formation or development of excess fibrous connective tissue
(fibrosis
) in the lung
s. It is also described as "scarring of the lung".
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.
. 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.
Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include:
with fibrotic tissue. The replacement of normal lung with 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.
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.
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.
, creates scar tissue. The scarring is permanent once it has developed. Slowing the progression and prevention depends on the underlying cause:
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. There are pharmacological agents in the experimental phase intended to prevent scarring. Anti-inflammatory
agents have only limited success in reducing the fibrotic progress.
Oxygen supplementation improves the quality of life and exercise capacity. Lung transplantation
may be considered for some patients.
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 anticoagulant
s.
Based on these rates, pulmonary fibrosis prevalence in the United States could range from more than 29,000 to almost 132,000, based on the population in 2000 that was 18 years or older. The actual numbers may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed while the incidence of idiopathic pulmonary fibrosis increases dramatically after the age of fifty. However, loss of pulmonary function is commonly ascribed to old age, heart disease or to more common lung diseases. Fibrosis is best known for killing Peter Benchley
in 2006.
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
(fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
) in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s. It is also described as "scarring of the lung".
Symptoms
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
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
) with exertion. Sometimes fine inspiratory crackles can be heard at the lung bases on auscultation. A chest x-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
may or may not be abnormal, but high Resolution CT
High Resolution CT
High Resolution Computed Tomography or HRCT of the lung is a medical diagnostic test used for diagnosis and assessment of Interstitial lung disease. It involves the use of special computed tomography scanning techniques to assess the lung parenchyma....
will frequently demonstrate abnormalities.
Cause
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 or other microscopic injuries to the lung. However, pulmonary fibrosis can also appear without any known cause. In this case, it is termed "idiopathic". Most idiopathic cases are diagnosed as idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis is a chronic, progressive form of lung disease characterized by fibrosis of the supporting framework of the lungs...
. This is a diagnosis of exclusion of a characteristic set of histologic/pathologic features known as usual interstitial pneumonia
Usual interstitial pneumonia
Usual interstitial pneumonia is a form of lung disease characterized by progressive scarring of both lungs. The scarring involves the supporting framework of the lung. UIP is thus classified as a form of interstitial lung disease. The term "usual" refers to the fact that UIP is the most common...
(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
Surfactant protein C
The N-terminal propeptide of surfactant protein C adopts an alpha-helical structure, with turn and extended regions. Its main function is the stabilisation of metastable surfactant protein C , since the latter can irreversibly transform from its native alpha-helical structure to beta-sheet...
(SP-C) has been found to exist in some 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 asbestosisAsbestosisAsbestosis is a chronic inflammatory and fibrotic medical condition affecting the parenchymal tissue of the lungs caused by the inhalation and retention of asbestos fibers...
, silicosisSilicosisSilicosis, also known as Potter's rot, is a form of occupational lung disease caused by inhalation of crystalline silica dust, and is marked by inflammation and scarring in forms of nodular lesions in the upper lobes of the lungs...
and exposure to certain gases. Coal miners, ship workers and sand blasters among others are at higher risk.- Hypersensitivity pneumonitisHypersensitivity pneumonitisHypersensitivity pneumonitis is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.-Pathophysiology:Hypersensitivity pneumonitis involves inhalation of an antigen...
, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products.
- Hypersensitivity pneumonitis
- Cigarette smoking can increase the risk or make the illness worse.
- Some typical connective tissue diseaseConnective tissue diseaseA connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
s such as rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, SLESystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
and sclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:... - Other diseases that involve connective tissue, such as sarcoidosisSarcoidosisSarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
and Wegener's granulomatosisWegener's granulomatosisWegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...
. - Infections
- Certain medications, e.g. amiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
, bleomycinBleomycinBleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
, busulfanBusulfanBusulfan is a cancer drug, in use since 1959.Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates...
, methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, and nitrofurantoinNitrofurantoinNitrofurantoin is an antibiotic which is marketed under the following brand names; Furadantin, Macrobid, Macrodantin, Nitrofur Mac, Nitro Macro, Nifty-SR, Martifur-MR, Martifur-100 , Urantoin, and Uvamin . It is usually used in treating urinary tract infection... - Radiation therapyRadiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
to the chest
Pathogenesis
Pulmonary fibrosis involves gradual exchange of normal lung parenchymaParenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...
with fibrotic tissue. The replacement of normal lung with scar tissue causes irreversible decrease in oxygen diffusion capacity. In addition, decreased compliance makes pulmonary fibrosis a restrictive lung disease
Restrictive lung disease
Restrictive lung diseases are a category of extrapulmonary, pleural, or parenchymal respiratory diseases that restrict lung expansion, resulting in a decreased lung volume, an increased work of breathing, and inadequate ventilation and/or oxygenation...
. It is the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast, quadriplegia
Quadriplegia
Tetraplegia, also known as quadriplegia, is paralysis caused by illness or injury to a human that results in the partial or total loss of use of all their limbs and torso; paraplegia is similar but does not affect the arms...
and kyphosis
Kyphosis
Kyphosis , also called roundback or Kelso's hunchback, is a condition of over-curvature of the thoracic vertebrae...
are examples of causes of restrictive lung disease that do not necessarily involve pulmonary fibrosis.
Diagnosis
The diagnosis can be confirmed by lung biopsy. 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.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.
On spirometry
Spirometry
Spirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...
, as a restrictive lung disease, both the FEV1 (Forced Expiratory Volume in 1 Second) and FVC (Forced Vital Capacity
Vital capacity
Vital capacity is the maximum amount of air a person can expel from the lungs after a maximum inspiration. It is equal to the inspiratory reserve volume plus the tidal volume plus the expiratory reserve volume....
) are reduced so the FEV1/FVC ratio
FEV1/FVC ratio
The FEV1/FVC ratio, also called Tiffeneau index, is a calculated ratio used in the diagnosis of obstructive and restrictive lung disease.It represents the proportion of the forced vital capacity exhaled in the first second....
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 and prevention
Pulmonary fibrosis which is also called Idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis is a chronic, progressive form of lung disease characterized by fibrosis of the supporting framework of the lungs...
, creates scar tissue. The scarring is permanent once it has developed. 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. There are pharmacological agents in the experimental phase intended to prevent scarring. Anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
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 immunosuppressiveImmunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
therapy such as corticosteroids. However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, azathioprineAzathioprineAzathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, penicillaminePenicillaminePenicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...
, and cyclosporine may be used. ColchicineColchicineColchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
has also been used with limited success. There are ongoing trials with newer drugs such as IFN-γInterferon-gammaInterferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
, mycophenolate mofetilMycophenolate mofetilMycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
, and pirfenidonePirfenidonePirfenidone is a drug developed by InterMune Inc. for the treatment of idiopathic pulmonary fibrosis. In 2011 it was approved for use in Europe for idiopathic pulmonary fibrosis under the trade name Esbriet. The proposed trade name in the US is also Esbriet.In Japan it is marketed as Pirespa by...
. - Hypersensitivity pneumonitisHypersensitivity pneumonitisHypersensitivity pneumonitis is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.-Pathophysiology:Hypersensitivity pneumonitis involves inhalation of an antigen...
, 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
Lung transplantation
Lung transplantation, or pulmonary transplantation is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor...
may be considered for some patients.
Prognosis
HypoxiaHypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
caused by pulmonary fibrosis can lead to pulmonary hypertension
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
, which, in turn, can lead to heart failure of the right ventricle
Right ventricle
The right ventricle is one of four chambers in the human heart. It receives deoxygenated blood from the right atrium via the tricuspid valve, and pumps it into the pulmonary artery via the pulmonary valve and pulmonary trunk....
. This can be prevented with oxygen supplementation.
Pulmonary fibrosis may also cause increased risk for pulmonary emboli, which can be prevented by anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s.
Epidemiology
Five million people worldwide are affected by pulmonary fibrosis. A wide range of incidence and prevalence rates have been reported for pulmonary fibrosis. The rates below are per 100,000 persons, and the ranges reflect narrow and broad inclusion criteria, respectively.| Study authors | Incidence rate | Prevalence rate | Population | Years covered | |
|---|---|---|---|---|---|
| Raghu et al | |||||
| 6.8-16.3 | 14.0-42.7 | U.S. health care claims processing system | 1996-2000 | ||
| Fernandez Perez et al | |||||
| 8.8-17.4 | 27.9-63.0 | Olmstead County, MN | 1997-2005 | ||
| Coultas et al | Male | 27.5 | 30.3 | Bernalillo County, NM | 1988-1990 |
| Female | 11.5 | 14.5 |
Based on these rates, pulmonary fibrosis prevalence in the United States could range from more than 29,000 to almost 132,000, based on the population in 2000 that was 18 years or older. The actual numbers may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed while the incidence of idiopathic pulmonary fibrosis increases dramatically after the age of fifty. However, loss of pulmonary function is commonly ascribed to old age, heart disease or to more common lung diseases. Fibrosis is best known for killing Peter Benchley
Peter Benchley
Peter Bradford Benchley was an American author, best known for his novel Jaws and its subsequent film adaptation, the latter co-written by Benchley and directed by Steven Spielberg...
in 2006.