586
U N I T 6
Respiratory Function
Interstitial Lung Diseases
The diffuse interstitial lung diseases, also called
diffuse
parenchymal lung diseases
, are a diverse group of lung
disorders that produce similar inflammatory and fibrotic
changes in the interstitium or interalveolar septa of the
lung. Because the interstitial lung diseases result in a stiff
and noncompliant lung, they are commonly classified as
restrictive lung disorders
.
In contrast to the obstructive lung diseases, which
primarily involve the airways of the lung, the intersti-
tial lung disorders exert their effects on the collagen and
elastic connective tissue found in the delicate interstitium
of the alveolar walls.
10,15,54–56
Many of these diseases also
involve the airways, arteries, and veins. The clinical
hallmark of these widespread lung changes is dimin-
ished lung compliance, which presents as restrictive
lung disease. The lungs are stiff and difficult to inflate.
More pressure is needed to expand the lungs, which in
turn necessitates more effort in breathing. Damage to
alveolar epithelium and interstitial vasculature produces
impaired gas exchange and hypoxemia. With progres-
sion, persons develop respiratory failure, often in associ-
ation with pulmonary hypertension and cor pulmonale.
The interstitial lung diseases may be acute or insidi-
ous in onset; they may be rapidly progressive, slowly
progressive, or static in their course. Over 100 distinct
entities of interstitial lung diseases have been recog-
nized including hypersensitivity pneumonitis (discussed
in Chapter 16); lung diseases caused by medications
(e.g., the cancer drug bleomycin and the antiarrhythmic
drug amiodarone) and radiation therapy; the occupa-
tional lung diseases, including the pneumoconioses that
are caused by the inhalation of inorganic dusts such as
silica, coal dust, and asbestos; immunologic lung disor-
ders, such as those that accompany rheumatoid arthri-
tis and scleroderma; and granulomatous diseases such
as sarcoidosis.
15,58
Examples of interstitial lung diseases
and their causes are listed in Chart 23-1. The discussion
in this chapter focuses on idiopathic pulmonary fibro-
sis and sarcoidosis, two of the most common interstitial
lung diseases seen in the clinical setting.
55
Pathogenesis
Current theory suggests that most interstitial lung dis-
eases, regardless of their cause, have a common patho-
genesis.
15
It is thought that these disorders are initiated
by some type of injury to the alveolar epithelium, fol-
lowed by an inflammatory process that involves the
alveoli and interstitium of the lung. If the injury is mild
and self-limited, resolution with restoration of normal
lung structures follows. However, with persistence
of the injurious agent, an accumulation of inflamma-
tory and immune cells causes continued damage to
lung tissue and replacement of normally functioning
lung tissue with fibrous scar tissue. Alveolar macro-
phages secrete a host of fibrogenic factors, including
fibroblast growth factor, transforming growth factor-
β
(TGF-
β
), and platelet-derived growth factor, which can
attract fibroblasts as well as stimulate their prolifera-
tion. Alveolar cells also appear to play a role in the
process. Destruction of type I alveolar cells is often
accompanied by proliferation of type II alveolar cells
(see Chapter 21). These cells secrete chemotactic fac-
tors that attract additional macrophages, growth fac-
tors, and cytokines such as TGF-
β
that contribute to
fibrotic changes.
Clinical Features
In general, the interstitial lung diseases are character-
ized by clinical changes consistent with restrictive rather
than obstructive changes in the lung. Persons with
■■
Cystic fibrosis (CF) is an autosomal recessive
genetic disorder manifested by chronic lung
disease, pancreatic exocrine deficiency, and
elevation of sodium chloride in the sweat.
The defect causes exocrine gland secretions
to become exceedingly viscid, and promotes
colonization of the respiratory tract with
P. aeruginosa and other organisms such as
S. aureus. Accumulation of viscid mucus in the
bronchi, impaired mucociliary function, and
infection contribute to the development of chronic
lung disease and a decreased life expectancy.
SUMMARY CONCEPTS
(continued)
CHART 23-1
Causes of Interstitial Lung Disease*
Occupational and Environmental Inhalants
Pneumoconioses (coal miner’s pneumoconiosis,
silicosis, asbestosis)
Hypersensitivity pneumonitis (farmer’s lung, bird
breeder’s lung)
Talcosis (talc inhalation in injection drug users)
Smoking related
Drugs andTherapeutic Agents
Cancer drugs (e.g., bleomycin, busulfan,
cyclophosphamide, methotrexate)
Antiarrhythmic drugs (amiodarone)
Ionizing radiation (i.e., radiation therapy)
Granulomatous Disorders
Sarcoidosis
Immunologic Disorders
Systemic lupus erythematosus
Rheumatoid arthritis
Scleroderma
Unknown Causes
Idiopathic pulmonary fibrosis
*This list is not intended to be inclusive.
