WordNet

development of excess fibrous connective tissue in an organ

PrepTutorEJDIC

線維症(線維性結合線維が増殖し過ぎる症状)
肺の;肺を冒す

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/12 17:57:38」(JST)

wiki en

A chest X-ray demonstrating pulmonary fibrosis. By history, the pulmonary fibrosis is thought to be due to amiodarone.

Pulmonary fibrosis is the formation or development of excess fibrous connective tissue (fibrosis) in the lungs. It is also described as "scarring of the lung".^[1]

Symptoms

Symptoms of pulmonary fibrosis are mainly:

Shortness of breath, particularly with exertion^[1]
Chronic dry, hacking coughing^[1]
Fatigue and weakness^[1]
Chest discomfort^[1]
Loss of appetite and rapid weight loss^[1]

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion.^[2] Sometimes fine inspiratory crackles can be heard at the lung bases on auscultation.^[2] A chest x-ray may or may not be abnormal, but high Resolution CT will frequently demonstrate abnormalities.^[2]

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 or other microscopic injuries to the lung.^[1] However, pulmonary fibrosis can also appear without any known cause. In this case, it is termed "idiopathic".^[3] 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.^[1]

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

Inhalation of environmental and occupational pollutants,^[1] such as in asbestosis,^[2] silicosis^[2] and exposure to certain gases.^[2] Coal miners, ship workers and sand blasters among others are at higher risk.^[3]
- Hypersensitivity pneumonitis, most often resulting from inhaling dust contaminated with bacterial, fungal, or animal products.^[2]
Cigarette smoking^[1] can increase the risk or make the illness worse.^[3]
Some typical connective tissue diseases^[3] such as rheumatoid arthritis,^[1]^[2] SLE^[1]^[2] and scleroderma^[1]
Other diseases that involve connective tissue, such as sarcoidosis^[1]^[2] and Wegener's granulomatosis.^[2]
Infections^[2]
Certain medications, e.g. amiodarone, bleomycin (pingyangmycin), busulfan, methotrexate, and ^[1]^[3] nitrofurantoin^[4]
Radiation therapy to the chest^[1]^[2]

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.^[1] 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^[5] and kyphosis^[6] 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.^[2] 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 .^[2] 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.^[2]

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.^[1] Terminology has been standardized but difficulties still exist in their application.^[1] 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.^[7]

Treatment and prevention

Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed.^[2] Slowing the progression and prevention depends on the underlying cause:

Treatment options for idiopathic pulmonary fibrosis are very limited.^[2] 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.^[2] There are pharmacological agents in the experimental phase intended to prevent scarring.^[1] Anti-inflammatory agents have only limited success in reducing the fibrotic progress.^[1]

Some of the other types of fibrosis, such as nonspecific interstitial pneumonitis (NSIP), may respond to immunosuppressive therapy such as corticosteroids.^[2] However, only a minority of patients respond to corticosteroids alone, so additional immunosuppressants, such as cyclophosphamide, azathioprine, methotrexate, penicillamine, and cyclosporine may be used.^[2] Colchicine has also been used with limited success.^[2] There are ongoing trials with newer drugs such as IFN-γ, mycophenolate mofetil, and pirfenidone.
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.^[1] Lung transplantation may be considered for some patients.^[1]

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. This can be prevented with oxygen supplementation.^[2]

Pulmonary fibrosis may also cause increased risk for pulmonary emboli, which can be prevented by anticoagulants.^[2]

Epidemiology

Five million people worldwide are affected by pulmonary fibrosis.^[1] 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. ^[8]	--	6.8-16.3	14.0-42.7	U.S. health care claims processing system	1996–2000
Fernandez Perez et al. ^[9]	--	8.8-17.4	27.9-63.0	Olmstead County, MN	1997–2005
Coultas et al. ^[10]	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.^[1] 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.^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z Pulmonary Fibrosis Foundation > What is Pulmonary Fibrosis? Last updated October 19, 2009
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x MedicineNet.com > Pulmonary Fibrosis Retrieved on Feb 26, 2010
^ ^a ^b ^c ^d ^e MedlinePlus > Pulmonary Fibrosis Date last updated: 09 February 2010
^ Goemaere NN, Grijm K, van Hal PT, den Bakker MA (2008). "Nitrofurantoin-induced pulmonary fibrosis: a case report". J Med Case Reports 2: 169. doi:10.1186/1752-1947-2-169. PMC 2408600. PMID 18495029.
^ Walker J, Cooney M, Norton S (August 1989). "Improved pulmonary function in chronic quadriplegics after pulmonary therapy and arm ergometry". Paraplegia 27 (4): 278–83. PMID 2780083.
^ eMedicine Specialties > Pulmonology > Interstitial Lung Diseases > Restrictive Lung Disease Author: Lalit K Kanaparthi, MD, Klaus-Dieter Lessnau, MD, Sat Sharma, MD. Updated: Jul 27, 2009
^ "www.spirXpert.com".
^ Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and Prevalence of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2006;174:810-6.
^ Fernandez Perez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, Bartholmai BJ, Yi ES, Ryu JH. Incidence, Prevalence, and Clinical Course of Idiopathic Pulmonary Fibrosis: A Population-Based Study. Chest. Jan 2010;137:129-37.
^ Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The Epidemiology of Interstitial Lung Diseases. Am J Respir Crit Care Med. Oct 1994;150(4):967-72. cited by Michaelson JE, Aguayo SM, Roman J. Idiopathic Pulmonary Fibrosis: A Practical Approach for Diagnosis and Management. Chest. Sept 2000;118:788-94.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 特発性肺線維症の治療 treatment of idiopathic pulmonary fibrosis
2. 特発性肺線維症の病因 pathogenesis of idiopathic pulmonary fibrosis
3. 間質性肺疾患を有する成人に対するアプローチ：臨床的評価 approach to the adult with interstitial lung disease clinical evaluation
4. 間質性肺疾患を有する成人に対するアプローチ：診断的検査 approach to the adult with interstitial lung disease diagnostic testing
5. 鎌状赤血球症の肺合併症の概要 overview of the pulmonary complications of sickle cell disease

English Journal

A truncated analogue of CCL2 mediates anti-fibrotic effects on murine fibroblasts independently of CCR2.

Kalderén C, Forsgren M, Karlström U, Stefansson K, Svensson R, Berglund MM, Palm G, Selander M, Sundbom M, Nilsson J, Sjögren A, Zachrisson K, Gelius SS.SourceSwedish Orphan Biovitrum AB, Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Biochemical pharmacology.Biochem Pharmacol.2012 Mar 1;83(5):644-52. Epub 2011 Dec 9.
The truncated [1+9-76] CCL2 analogue, also known as 7ND, has been described in numerous reports as an anti-inflammatory and anti-fibrotic agent in a wide spectrum of animal models, e.g. models of cardiovascular disease, graft versus host disease and bleomycin-induced pulmonary fibrosis. 7ND has been
PMID 22177985

Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.

Barnes J, Mayes MD.SourceHouston Medical School, University of Texas, Houston, Texas, USA.
Current opinion in rheumatology.Curr Opin Rheumatol.2012 Mar;24(2):165-170.
PURPOSE OF REVIEW: To identify the recent data regarding prevalence, incidence, survival, and risk factors for systemic sclerosis (SSc) and to compare these data to previously published findings.RECENT FINDINGS: SSc disease occurrence data are now available for Argentina, Taiwan, and India and conti
PMID 22269658