C h a p t e r 2 3
Disorders of Ventilation and Gas Exchange
585
to collect the sweat followed by chemical analysis of
its chloride content, remains the standard approach to
diagnosis. Newborns with CF have elevated blood levels
of immunoreactive trypsinogen, presumably because of
secretory obstruction in the pancreas. A variety of
new-
born screening
tests are in place to identify infants with
cystic fibrosis, most of which consist of a combination
of immunoreactive trypsinogen and limited DNA analy-
sis. These tests can be done on blood spots collected for
routine newborn screening tests.
Treatment measures are directed toward early and
aggressive measures to slow progression of secondary
organ dysfunction and sequelae such as chronic lung
infection and pancreatic insufficiency.
51
They include the
use of antibiotics to prevent and manage infections, the
use of chest physical therapy (chest percussion and pos-
tural drainage) and mucolytic agents to prevent airway
obstruction, and nutritional therapy including pancre-
atic enzyme replacement. Routine laboratory evaluations
are key to assessing pulmonary function and response to
therapeutic interventions. These studies include radio-
logic examinations, pulmonary function testing, and
microbiologic cultures of respiratory secretions.
Appropriate antibiotic therapy directed against bacte-
rial pathogens isolated from the respiratory tract is an
essential component in the management of CF lung dis-
ease. Antibiotics are initially used to prevent colonization
with
P. aeruginosa;
they are used as maintenance therapy
once the airways are colonized with
P. aeruginosa
and
other organisms such as
S. aureus;
and they are adminis-
tered as aggressive treatment during acute exacerbations
of pulmonary symptoms caused by infections.
51
To avoid
adverse effects and to obtain high airway concentrations,
the inhalation route is often used as an option for home
delivery of these agents, with other routes of delivery
being used during periods of progressive symptoms.
The abnormal viscosity of airway secretions is attrib-
uted largely to the presence of polymorphonuclear white
blood cells and their degradation products. A purified
recombinant human deoxyribonuclease (rhDNase),
an enzyme that breaks down these products, has been
developed.
54
Clinical trials have shown that the drug,
which is administered by inhalation, can decrease pul-
monary symptoms and reduce the frequency of respi-
ratory exacerbations. Although many persons benefit
from the therapy, the drug is costly, and recommenda-
tions for its use are evolving.
Up to 90% of patients with CF have complete loss
of exocrine pancreatic function and inadequate diges-
tion of fats and proteins. They require supplemental
vitamins and minerals and enteric-coated, pH-sensitive
pancreatic enzyme supplements. At one time, a low-fat,
high-protein, high-calorie diet was recommended. With
the advent of improved pancreatic enzyme products,
however, normal amounts of fat in the diet are usually
tolerated and preferred.
Progress of the disease is variable. Improved medi-
cal management has led to longer survival.
49,51,52
Today,
many people with the disease can expect to live into
their 40s and beyond. Lung transplantation is being used
as a treatment for persons with end-stage lung disease.
The last 10 years have seen promising results from
research into the management of cystic fibrosis using small
molecules called
cystic fibrosis transmembrane regulator
protein (CFTR) modulators
designed to increase the time
the CFTR channels in the cell surface remain open.
53
SUMMARY CONCEPTS
■■
Obstructive airway disorders due to bronchial
smooth muscle hyperreactivity or changes in
bronchial wall structure, injury to the mucosal
lining of the airways, or excess respiratory tract
secretions are characterized by limitation in
movement of atmospheric air into and out of the
gas exchange portion of the lung.
■■
Bronchial asthma is a chronic disorder of the
airways that causes reversible episodes of airway
obstruction due to bronchial smooth muscle
hyperreactivity and airway inflammation. Extrinsic
(or atopic) asthma is a type I hypersensitivity
reaction triggered by an allergen; whereas
intrinsic asthma is triggered by respiratory tract
infections, exercise, drugs and chemicals, air-
borne pollutants, and gastroesophageal reflux.
■■
An asthmatic episode is characterized by two
types of responses—acute and late phase.The
acute-phase response results in immediate
bronchoconstriction on exposure to an inhaled
antigen and usually subsides within 90 minutes.
The late-phase response develops 4 to 8 hours
after exposure to an asthmatic trigger; and
involves inflammation and increased airway
responsiveness that prolong the attack and cause
a vicious cycle of exacerbations.
■■
Chronic obstructive pulmonary disease (COPD)
encompasses two types of obstructive airway
disease: emphysema, with enlargement of
air spaces and destruction of lung tissue, and
chronic obstructive bronchitis, with increased
mucus production, obstruction of small airways,
and a chronic productive cough. Persons with
COPD often have overlapping features of both
emphysema and chronic bronchitis, and both
are manifested by eventual mismatching of
ventilation and perfusion. As the conditions
advance, signs of respiratory distress and
impaired gas exchange become evident, with
development of hypercapnia and hypoxemia.
■■
Bronchiectasis is an uncommon form of COPD
that is characterized by an abnormal dilation of
the large bronchi associated with infection and
destruction of the bronchial walls.
(continued)
