C h a p t e r 2 3
Disorders of Ventilation and Gas Exchange
587
interstitial lung diseases have dyspnea, tachypnea, and
eventual cyanosis, without evidence of wheezing or
signs of airway obstruction. Usually, there is an insid-
ious onset of breathlessness that initially occurs dur-
ing exercise and may progress to the point at which
the person is totally incapacitated. Typically, the per-
son breathes with a tachypneic pattern of breathing,
in which the respiratory rate is increased and the tidal
volume is decreased. This pattern of breathing serves to
maintain minute volume yet reduces the work of breath-
ing because it takes less work to move air through the
airways at an increased rate than it does to stretch a stiff
lung to accommodate a larger tidal volume. A nonpro-
ductive cough may develop, particularly with continued
exposure to the inhaled irritant. Clubbing of the fingers
and toes may develop.
Lung volumes, including vital capacity and total
lung capacity, are reduced in interstitial lung disease. In
contrast to COPD, in which expiratory flow rates are
reduced, the FEV
1.0
usually is preserved, even though
the ratio of FEV
1.0
to FVC may increase. Although rest-
ing arterial blood gases usually are normal early in the
course of the disease, arterial PO
2
levels may fall during
exercise. In persons with advanced disease, hypoxemia
often is present, even at rest. In the late stages of the
disease, hypercapnia and respiratory acidosis develop.
The impaired diffusion of gases is thought to be caused
by alterations in the alveolar–capillary membrane as
well as an increase in shunt resulting from unventilated
regions of the lung.
The diagnosis of interstitial lung disease requires
a careful personal and family history, with particular
emphasis on exposure to environmental, occupational,
and other injurious agents.
55,56
Chest radiographs may
be used as an initial diagnostic method, and to follow
the progress of the disease. A biopsy specimen for his-
tologic study and culture may be obtained by surgi-
cal incision, bronchoscopy, or bronchoalveolar lavage,
in which fluid is instilled into the alveoli through
a bronchoscope and then removed by suction for
laboratory study.
The treatment goals for persons with interstitial lung
disease focus on identifying and removing the injurious
agent, suppressing the inflammatory response (typically
with corticosteroids), preventing progression of the dis-
ease, and providing supportive therapy for persons with
advanced disease. Many of the supportive treatment
measures, such as oxygen therapy and measures to pre-
vent infection, are similar to those discussed for persons
with COPD.
Idiopathic Pulmonary Fibrosis
The most common diagnosis among persons with
interstitial lung disease is idiopathic pulmonary fibro-
sis. The disease is characterized by diffuse interstitial
fibrosis, which in severe cases results in severe hypox-
emia and cyanosis. As the name implies, the cause
of the disorder is unknown. Men are affected more
commonly than women and approximately two thirds
of persons are older than 60 years of age at the time of
presentation.
A number of conditions and risk factors are associ-
ated with the disease.
15,56
Cigarette smoking increases
the risk, as do certain occupations such as farming,
hairdressing, stonecutting, and metal cutting. Although
viruses have not been clearly implicated in the patho-
genesis of idiopathic pulmonary fibrosis, several viral
proteins and antibodies to viruses are associated with
the disease. In addition, some people may have a genetic
predisposition to the disease.
The disease is characterized by patchy interstitial
fibrosis that causes collapse of alveolar walls and forma-
tion of cystic spaces lined by hyperplastic type II alveolar
cells or bronchial epithelium. Secondary hypertensive
changes due to intimal fibrosis and medial thickening of
the pulmonary arteries are often present.
Idiopathopathic pulmonary fibrosis usually presents
insidiously, with gradual onset of a nonproductive cough
and progressive dyspnea. Cyanosis, cor pulmonale,
and peripheral edema may present late in the disease.
Diagnosis is confirmed by surgical biopsy. Unfortunately,
the progress of the disease is relentless despite current
methods of treatment. The mean survival after diagnosis
is 3 to 5 years.
Sarcoidosis
Sarcoidosis is a multisystem disorder in which granulo-
mas are found in many tissues and organs, particularly
the lung.
15,16,57,58
The disorder predominantly affects
adults younger than 40 years of age, although it can
occur in older persons. The incidence is highest among
North American blacks and northern European whites;
and women are affected more frequently than men.
The cause of sarcoidosis remains unclear. It is
thought that the disorder may result from exposure of
genetically predisposed persons to specific environmen-
tal agents. Defective human leukocyte antigen (HLA)
genes located in the major histocompatibility complex
may be linked to disease susceptibility and progno-
sis. Multiple lines of evidence suggest that the inciting
agent triggers an immune response that depends on host
susceptibility.
The immune response is characterized by chronic
inflammation, monocyte recruitment, and granuloma
formation in which multinucleated giant cells are fre-
quently seen. These granulomas do not show evi-
dence of necrosis or caseation. The inflammation often
involves the alveoli (alveolitis). It is composed largely of
macrophages and lymphocytes, with the latter thought
to be of particular importance in the pathogenesis of
the disease.
Sarcoidosis has variable manifestations and an
unpredictable course of progression in which any organ
system can be affected. The three systems that most
commonly manifest symptoms are the lungs, eyes, and
skin. Persons with sarcoidosis frequently seek health
care either as a result of abnormalities detected on an
incidental chest film or because of insidious onset of
