ILD covers a wide range of pathological conditions that
lead to progressive lung destruction and scarring.
Interstitial lung disease (ILD)
has long presented a vexing (and often baffling) picture to
patients and their clinicians. In the strictest sense, ILD may
be a misnomer, since this condition affects not only the
interstitium, but also the alveolar space and, at times, the
airways. The pulmonary interstitium is, in effect, the space
between the air-space epithelium and the endothelial cells
lining the vasculature.1 Consequently, diffuse
parenchymal lung disease (DPLD) may be a more appropriate
term.2 ILD continues to be the commonly recognized
name, however, and it is a convenient blanket term for a wide
range of pathological conditions leading to progressive lung
destruction and scarring.
The umbrella term ILD covers more than 200 discrete
conditions associated with the cause of the disease. The
specific causal agents create an immune reaction, generating
the formation of fibrous nodules. As the disease progresses,
fibrous tissue increasingly replaces elastic lung tissue. Loss
of lung function is signaled by dyspnea, wheezing, coughing,
and difficulty in expectorating.
The disease can be the result of almost any kind of lung
insult. Its causes include inhaling organic or inorganic dusts
such as asbestos, silica, heavy metals, and hay; inhaling
toxic gases such as ammonia, chlorine, sulfuric acid, and
hydrochloric acid; reacting to drugs such as amiodarone,
narcotics, salicylates, terbutaline, oxygen, and paraquat; and
metabolic disorders such as cystic fibrosis and lipoidoses.
Causative respiratory infections can be bacterial (Legionella
species); viral (cytomegalovirus, influenza, respiratory
syncytial virus, and HIV); or fungal (Pneumocystis carinii).
Interstitial lung diseases can be the result of a wide array
of additional causes, including rheumatoid arthritis,
sarcoidosis, renal failure, hepatitis, congestive heart
failure, and recurrent aspiration. Many ILDs have been given
descriptive names associated with the occupation or activity
responsible for the patientís exposure to a causative agent
and the resulting pneumoconiosis. These names include black
lung, farmerís lung, hot-tub lung, bird-fancierís disease, and
The blanket term provides an expedient means of describing
conditions that present similar clinical pictures. The
causative agent is identified in fewer than 20% to 30% of
patients with ILD.3 The cases of unknown cause have
sometimes been classified as idiopathic pulmonary fibrosis
(IPF), which is one of several idiopathic interstitial
pneumonias, and is now recognized as a distinct clinical
disorder.4 Adding to the potential confusion is a
history of inconsistency in naming the conditions (and, in
some cases, diametrically opposed opinions on how to manage
them best). The terms DPLD, ILD, pulmonary fibrosis, and IPF
continue to be used to describe the same condition.
Multidisciplinary Consensus Classification of the Idiopathic
Interstitial Pneumonias. Am J Respir Crit Care Med.
Copyright American Thoracic Society.
Reprinted with permission.
It may be useful to think of IPF as a distinct type of
idiopathic interstitial pneumonia, which is, in turn, a subset
of ILD. In 2001, a joint commission5 of the
American Thoracic Society and the European Respiratory Society
approved a multidisciplinary consensus for the classification
of the idiopathic interstitial pneumonias in an effort to
bring order to a potentially chaotic set of conditions (see
figure). Conditions categorized as falling under the umbrella
of idiopathic interstitial pneumonia are IPF, nonspecific
interstitial pneumonia, acute interstitial pneumonia,
cryptogenic organizing pneumonia, respiratory bronchiolitis,
desquamative interstitial pneumonia, and lymphoid interstitial
Various conditions have long been categorized in
conflicting ways, but the international consensus
statement5 offers a guideline for organizing
current understanding of these diseases in a consistent way.
It clarifies the terminology, definitions, and descriptions
used in clinical practice. Most important for optimal
respiratory care of these patients is an understanding of the
elements that the conditions within ILD/DPLD have in
By the time ILD
patients seek medical attention, they can present with a wide
range of symptoms, from mild dyspnea to severe incapacitation.
Dyspnea, especially with exercise, is often the first clue.
Fevers, chills, and night sweats may also manifest themselves.
A careful, detailed patient history focusing on work, home
life, environmental exposures, hobbies, medications, and
family history is often a critical element in identifying the
cause of ILD. Success or failure here can be a matter of life
or death for the patient. Identifying and eliminating the
causative agent (when possible) is central to successful
treatment. Once the cause has been identified, treatment plans
and outcomes still vary significantly, but where there is no
identifiable causative agent (as in idiopathic pulmonary
fibrosis), the prognosis may be very poor.
Chest radiographs will typically reveal diffuse
interstitial infiltrates; this hazy increase in lung density
is often referred to as a ground-glass appearance.
Lung-function studies reveal decreased diffusing capacity of
the lung for carbon monoxide resulting from the fibrosis
associated with lung scarring. Likewise, a reduced forced
vital capacity is expected, indicating a restrictive
The use of high-resolution CT is an important advance in
the diagnosis and staging of ILD. Sections of 1 mm to 2 mm are
imaged to detect two distinct patterns of disease: a
ground-glass increase in attenuation and a reticular pattern.
The ground-glass appearance is associated with a histologic
cellular appearance of that area of the lung; the reticular
pattern is found in patients whose subsequent lung biopsies
confirm fibrosis. High-resolution CT is significantly more
sensitive and specific than chest radiography for the
diagnosis of ILD and for the assessment of both the extent and
the severity of the disease.3,6
Further investigation often includes bronchoscopy. A
bronchoalveolar lavage (BAL) test floods a segment of the lung
with approximately 60 mL to 100 mL of saline, which is then
pulled, via suction, into a sterile specimen trap for
diagnostic cytology and histology. These studies may identify
the antagonist causing the inflammatory process, in addition
to excluding other possible diagnoses (such as lung cancer).
BAL testingís sensitivity may be more than 90%, with nearly
100% specificity for P. carinii infections, in
particular.7,8 A transbronchial biopsy using
forceps is the accepted standard for differentiating between
other possible causes of ILD. If questions remain following a
transbronchial biopsy, the gold standard for diagnosis is a
surgical (open) lung biopsy, although the associated risks
make it a less attractive first choice. For IPF,
transbronchial biopsy is not usually diagnostic, and surgical
lung biopsy is ultimately required.3
Diagnosis is often a dynamic process that is amended as
additional pieces of the puzzle become available. The final
diagnosis should be rendered only after the pulmonologist,
radiologist, and pathologist have reviewed all the data
obtained from the patient.5
Once healthy lung tissue has
been destroyed by scarring, it cannot be repaired. Left
untreated, many ILDs will continue to progress, with lung
function deteriorating rapidly. Oxygen therapy may be required
as the condition progresses and respiratory insufficiency
increases. In these cases, frank discussions with the patient
and family about the initiation of ventilator support should
be undertaken. Lung transplantation may offer hope for select
individuals with advanced disease who meet transplantation
The most important element in the successful treatment of
ILD is eliminating the causative agent after it has been
identified; this drives the often exhaustive search for a
cause of the disease. If no agent is found, therapy can be
directed toward suppression of inflammatory and cellular
immune responses.3 Because an ongoing inflammatory
process is a central element in some ILDs, corticosteroids may
be of benefit.
There is considerable debate about the value of
corticosteroids in treating IPF, which is, arguably, one of
the most troublesome members of the ILD family. Its mortality
rate is approximately 50% at 5 years.3 Treatment
options are extremely limited (and recommendations are
conflicting). One author,9 for example, claims that
inflammatory mechanisms are a minor component of the
pathogenesis of IPF, so anti-inflammatory drugs have little or
no effect. Meanwhile, another author10 defends the
practice, arguing that inflammatory mechanisms are not a minor
Immunosuppressive or cytotoxic agents may be considered for
patients for whom corticosteroids appear to have failed.
Supportive care, including influenza immunization,
bronchodilators, supplemental oxygen, and pulmonary
rehabilitation programs, can help the patient live with lungs
that have been permanently damaged by ILD. Unfortunately,
clinicians often face patientsí therapy using drugs and
treatment plans that may have serious side effects, or may
withhold treatment until the condition has progressed to a
point at which there is little choice remaining. Improvements
in lung function are uncommon, and prevention of further
deterioration is often the most optimistic outcome that can be
ILD represents a large family of lung disorders. That
family continues to grow as clinicians and researchers learn
more about the diverse causes of ILD. Some members of the
family are much more sinister than others, and outcomes are
closely related to the clinicianís ability to identify and
eliminate the antagonist that instigated the condition.
John A. Wolfe, RRT, CPFT, is a contributing writer for
RT and a member of RTís editorial advisory
1. Schlenker EH.
Cardiopulmonary anatomy and physiology. In: Hess DR, MacIntyre
NR, Mishoe SC, Galvin WF, Adams A, Saposnick AB, eds.
Respiratory Care: Principles and Practices. Philadelphia: WB
2. Huaringa AJ, Leyva FJ. Diffuse
parenchymal lung disease: a practical approach. The Internet
Journal of Pulmonary Medicine.TM Available at: http://www.ispub.com/.
Accessed January 6, 2005.
3. Ghio AJ. Interstitial lung
disease. In: Hess DR, MacIntyre NR, Mishoe SC, Galvin WF,
Adams A, Saposnick AB, eds. Respiratory Care: Principles and
Practices. Philadelphia: WB Saunders; 2002:955-967.
American Thoracic Society. Idiopathic pulmonary fibrosis:
diagnosis and treatment. International consensus statement.
American Thoracic Society (ATS) and the European Respiratory
Society. Am J Respir Crit Care Med. 2000;161(2 Pt
5. American Thoracic Society/European
Respiratory Society. International multidisciplinary
consensus: classification of the idiopathic interstitial
pneumonias. Am J Respir Crit Care Med. 2002;
6. Muller NL. Clinical value of high
resolution CT in chronic diffuse lung disease. Am J
7. Carter C, Stone MK.
Respiratory microbiology, infection, and infection control.
In: Hess DR, MacIntyre NR, Mishoe SC, Galvin WF, Adams A,
Saposnick AB, eds. Respiratory Care: Principles and Practices.
Philadelphia: WB Saunders; 2002:255-276.
8. Paradis IL,
Grgurich WF, Dummer JS, Dekker A, Dauber JH. Rapid detection
of cytomegalovirus pneumonia from lung lavage cells. Am Rev
Respir Dis. 1988;138(3):697-702.
9. Gauldie J. Pro:
Inflammatory mechanisms are a minor component of the
pathogenesis of idiopathic pulmonary fibrosis. Am J Respir
Crit Care Med. 2002;165(9):1206-1207.
10. Strieter RM. Con:
Inflammatory mechanisms are not a minor component of the
pathogenesis of idiopathic pulmonary fibrosis. Am J Respir
Crit Care Med. 2002; 165:1206-1207.