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Chapter 10 Interstitial Lung Disease PDF
Chapter 10 Interstitial Lung Disease PDF
The lungs of patients with interstitial disease show varying degrees of fibrosis
and inflammation. Fibrosis is characterized by an increased amount and
abnormal structure of the connective tissue; inflammation is characterized by
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Men Women
Interstitial lung disease diagnosis (per 100,000) (per 100,000)
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(defined by its presence in two or more first-degree relatives), the onset of fibro-
sis appears to be earlier. Both incidence and mortality of interstitial disease
increase with age (2,3).
IPF has been reported to occur throughout the world in many different racial
and ethnic groups. Studies in the United States have suggested that Cauca-
sians are more likely to be diagnosed with IPF and have higher mortality rates
from IPF than African Americans (3,4). It is unclear if these findings are due to
real differences in racial characteristics or to an under-diagnosis of this condition
in minority populations.
The causes of interstitial lung disease can be classified into one of the fol-
lowing four categories: 1) diseases associated with a condition that affects other
parts of the body (for example, autoimmune or collagen vascular disease),
2) diseases associated with a specific exposure to an agent known to damage
the lungs (for example, medications such as bleomycin, occupational exposures
such as asbestos, tobacco smoke, or agents in the environment that cause an
immune reaction called hypersensitivity pneumonitis), 3) diseases associated
with known genetic abnormalities (for example, Hermansky–Pudlak syndrome),
and 4) idiopathic diseases (diseases of an unknown cause). The most common
interstitial lung diseases are idiopathic (5).
Two recent studies found that both the number of new cases diagnosed per
year and the mortality rates for idiopathic pulmonary fibrosis are rising in the
United States (3,6). Investigators from the United Kingdom have reported simi-
lar trends: from 1990 to 2003, the incidence of this disease more than doubled (7).
Of even greater concern, mortality rates from idiopathic pulmonary fibrosis are
expected to increase because there is no established treatment that prolongs
life for patients with these diseases (3).
Persons with exposure to environmental hazards (for example, asbestos)
have a higher incidence of interstitial lung disease, although less is known about
most of the other forms of interstitial disease. Although not all patients who
develop IPF have a history of cigarette smoking, smoking has been associated
with the development of disease. Exposure to metal and wood dusts has also
been associated with an increased likelihood of developing IPF. Although data
are limited, other possible risk factors include exposure to certain prescription
drugs and chronic gastroesophageal reflux disease. Genetics play a role in the
development of the familial cases of IPF. About 8 percent of familial cases can
be attributed to a single set of genes (8).
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CASE STUDY
Comment
As in this case, IPF typically develops insidiously, with a gradual onset of
shortness of breath and a nonproductive cough. The symptoms often
progress to become debilitating and all consuming. Although not necessary
in this patient, a tissue biopsy is often needed to reach a conclusive
diagnosis. Interstitial diseases are generally difficult to treat because
established fibrosis causes permanent structural changes of the lungs.
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When the cause of the disease is known, the injurious agent should be avoided.
For example, with hypersensitivity pneumonitis, one should avoid dust and mold.
With idiopathic disorders, because the cause is unknown, there is no known way
to prevent them. However, a number of possible risk factors for disease have
been reported, and abstaining from cigarette smoking and treating gastroesoph-
ageal reflux disease are recommended.
As it has been long thought that inflammation precedes fibrosis, therapeutic
regimens for interstitial lung disease have included corticosteroids (for example,
prednisone) and immunosuppressive agents (for example, azathioprine and
cyclophosphamide). These drugs are helpful in cases of connective tissue–
related lung disease and certain other interstitial lung diseases. In patients with
severe fibrosis, treatments targeting inflammation, however, have not been
shown to improve survival or quality of life. One study did find that patients with
IPF treated with high-dose N-acetyl cysteine, an antioxidant, in addition to a
standard regimen of corticosteroids and azathioprine had better lung function
compared to those on the standard regimen alone (9). Other drugs are being
studied.
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Interstitial lung disease is killing more Americans each year. Former Utah Governor Olene Smith Hulton Archive/Getty Images
Walker (top left) is living with the disease. Others, unfortunately, have died of the disease, including
folk singer and human rights advocate Odetta, writer Peter Benchley (bottom left) and actors
Marlon Brando and James Doohan.
arkers. To date, trials testing new drugs for the treatment of interstitial lung
m
disease have not been successful or have slowed the progression of disease
only modestly, but it is hoped as more is learned about the cells and molecules
that are altered in these conditions, the better the chance for success. Both
academic centers and pharmaceutical companies are conducting clinical trials
to test the safety and effectiveness of several drugs. The National Heart, Lung,
and Blood Institute’s clinical research network (IPFnet) conducts therapeutic tri-
als in the United States. Recently, stem cells have been considered for therapy,
but more needs to be learned before these and other potential therapeutic strat-
egies can be used.
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References
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10. Trulock EP, Christie JD, Edwards LB, Boucek MM, Aurora P, Taylor DO, Dobbels F, Rahmel
AO, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplanta-
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1998–2007. Am J Transplant 2009;9:942–958.
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