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Approach to the adult with interstitial lung disease: Diagnostic testing
Author: Talmadge E King, Jr, MD

Section Editor: Kevin R Flaherty, MD, MS
Deputy Editor: Helen Hollingsworth, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2017. | This topic last updated: Dec 04, 2015.
INTRODUCTION The diffuse parenchymal lung diseases, often collectively referred to as the
interstitial lung diseases (ILDs), are a heterogeneous group of disorders that are classified together
because of similar clinical, radiographic, physiologic, or pathologic manifestations (algorithm 1) [1-5].
The descriptive term "interstitial" reflects the pathologic appearance that the abnormality begins in the
interstitium, but the term is somewhat misleading, as most of these disorders are also associated with
extensive alteration of alveolar and airway architecture.
The initial evaluation of patients with ILD is aimed at identifying the etiology of the ILD and its severity.
The results of laboratory, radiographic, and pulmonary function tests guide the decisions about
whether to pursue bronchoalveolar lavage and/or transbronchoscopic, thoracoscopic, or open lung
biopsy.
An overview of the diagnostic testing that is helpful in the diagnosis of ILD will be presented here
(algorithm 2) [6-8]. The clinical findings that aid in the diagnosis of ILD and the individual causes of
ILD are discussed separately. (See "Approach to the adult with interstitial lung disease: Clinical
evaluation" and "Idiopathic interstitial pneumonias: Clinical manifestations and pathology" and "Clinical
manifestations and diagnosis of pulmonary sarcoidosis" and "Role of bronchoalveolar lavage in
diagnosis of interstitial lung disease" and "Pulmonary toxicity associated with systemic antineoplastic
therapy: Clinical presentation, diagnosis, and treatment".)
CAUSES OF ILD The list of causes of interstitial lung disease (ILD), also known as diffuse
parenchymal lung disease, is broad and includes those ILDs that are associated with a broad range of
diseases (table 1), exposures (table 2A-B), and drugs (table 3). ILD may also occur as an idiopathic
condition (algorithm 1). The treatment choices and prognosis vary among the different causes and
types of ILD, so ascertaining the correct diagnosis is important.
A variety of infectious processes cause interstitial opacities on chest radiograph, including fungal
pneumonias (eg, coccidioidomycosis, cryptococcosis, Pneumocystis jirovecii), atypical bacterial
pneumonias, and viral pneumonias. These infections often occur in immunocompromised hosts and
are discussed separately. (See "Approach to the immunocompromised patient with fever and
pulmonary infiltrates".)
The most common identifiable causes of ILD are exposure to occupational and environmental agents
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(table 2A-B), especially to inorganic or organic dusts, and drug-induced pulmonary toxicity (table 3).
(See "Asbestos-related pleuropulmonary disease" and "Chronic beryllium disease (berylliosis)" and
"Silicosis" and "Classification and clinical manifestations of hypersensitivity pneumonitis (extrinsic
allergic alveolitis)" and "Diagnosis of hypersensitivity pneumonitis (extrinsic allergic alveolitis)".)
ILD can potentially complicate the course of most of the rheumatic diseases (eg,
polymyositis/dermatomyositis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis
[scleroderma], mixed connective tissue disease).
Idiopathic causes of ILD include sarcoidosis, cryptogenic organizing pneumonia, acute and chronic
eosinophilic pneumonia, and the idiopathic interstitial pneumonias (algorithm 1). The idiopathic
interstitial pneumonias have been further characterized: idiopathic pulmonary fibrosis (usual interstitial
pneumonia), desquamative interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease,
acute interstitial pneumonia, and nonspecific interstitial pneumonia. (See "Idiopathic interstitial
pneumonias: Clinical manifestations and pathology".)
CLINICAL EVALUATION The initial recognition that a patient may have an interstitial lung disease
(ILD) usually follows the onset of progressive breathlessness with exertion (dyspnea), a persistent
nonproductive cough, and/or pulmonary symptoms associated with another disease, such as a
rheumatic disease. The clinical evaluation includes careful exploration of past medical history
(comorbidities, medications, irradiation), potential exposures (occupational, avocational,
environmental, infectious), and extrapulmonary evidence of a systemic illness. The clinical evaluation
of ILD is discussed separately. (See "Approach to the adult with interstitial lung disease: Clinical
evaluation".)
LABORATORY TESTS The routine laboratory evaluation of suspected interstitial lung disease
(ILD) typically includes biochemical tests to evaluate hepatic and renal function; hematologic tests with
differential blood count to check for evidence of anemia, polycythemia, leukocytosis, or eosinophilia;
and urinalysis (table 4) [1]. Depending on the clinical situation and results of hepatic function tests,
hepatitis serology and HIV testing may be appropriate.
Serologic studies Serologic studies are obtained to ensure that subclinical rheumatic disease
is not overlooked. We typically obtain anti-nuclear antibodies (ANA) and a rheumatoid factor [2].
We reserve additional testing with other serological studies, for example, antisynthetase
antibodies (eg, Jo-1), creatine kinase and aldolase, Sjgrens antibodies (SS-A, SS-B),
scleroderma antibodies (anti-topoisomerase [Scl-70]), and overlap antibodies (PM-1, also known
as PM-Scl), for patients with a clinical suspicion of rheumatic disease (table 4). However, not all
patients with positive serologic tests will develop a well-differentiated rheumatic disease [9-11].
Importantly, patients should be carefully screened for signs and symptoms of rheumatic disease,
as ILD precedes the onset of myositis in about 70 percent of patients with the anti-synthetase
syndrome, and the ANA may be negative [3]. (See "Overview of the clinical manifestations of
systemic sclerosis (scleroderma) in adults", section on 'Skin involvement' and "Interstitial lung
disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis", section on
'Clinical features'.)
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Serologic testing for hypersensitivity pneumonitis antibodies is based on patient exposure to

potential antigens. (See "Diagnosis of hypersensitivity pneumonitis (extrinsic allergic alveolitis)",
section on 'Serum precipitins'.)
Further evaluation of positive ANA For patients with a positive ANA, we usually obtain
anti-double-stranded DNA and anti-extractable nuclear antigen antibodies (anti-Sm,
anti-ribonucleoprotein) to further evaluate for systemic lupus erythematosus and mixed
connective tissue disease. (See "Measurement and clinical significance of antinuclear antibodies"
and "Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP".)
ILD and pulmonary hemorrhage For patients presenting with pulmonary hemorrhage, we
typically test for antiglomerular basement membrane antibodies, antineutrophil cytoplasmic
antibodies (ANCA), antinuclear antibodies (ANA), antiphospholipid antibodies, and
antistreptococcal antibodies. (See "The diffuse alveolar hemorrhage syndromes", section on
'Clues to a specific etiology'.)
Tests that are unlikely to be helpful diagnostically We generally do not find it helpful
diagnostically to obtain a C-reactive protein level or a sedimentation rate, as these are entirely
nonspecific. Hypergammaglobulinemia is commonly observed in patients with ILD, but is also
nondiagnostic. (See "Acute phase reactants".)
Serum angiotensin converting enzyme (ACE) levels are generally not helpful in the initial
evaluation of ILD, because of the low sensitivity and specificity of the test for sarcoidosis. (See
"Clinical manifestations and diagnosis of pulmonary sarcoidosis", section on 'Serum markers'.)
Biomarkers for research use A number of serum markers suggestive of ILD have been
identified, including surfactant protein A and B (SP-A, SP-B), monocyte chemoattractant protein-1
(MCP-1), and Kerbs von Lungren (KL)-6, a circulating, high-molecular weight glycoprotein
expressed by type II pneumocytes [4,6,7,12,13]. In one report, the receiver operating
characteristics of these four markers were evaluated in a mixed population of patients with
idiopathic ILD, collagen vascular disease-associated ILD, and controls with and without
pulmonary disease [6]. KL-6 was associated with the highest sensitivity, specificity, and diagnostic
accuracy for the presence of ILD (94, 96, and 94 percent, respectively). The clinical role of these
serum markers in the diagnosis of ILD is unclear and these tests are generally not commercially
available.
In the future, the KL-6 assay may help to identify and monitor ILD in patients with rheumatoid
arthritis and other rheumatic diseases. (See "Interstitial lung disease in rheumatoid arthritis".)
IMAGING
Chest radiography The most common radiographic abnormality on routine chest radiograph is a
reticular pattern (image 1); however, nodular (image 2) or mixed patterns (alveolar filling and
increased interstitial markings) are not unusual (table 5A-C) [8]. Although the chest radiograph is
useful in suggesting the presence of interstitial lung disease (ILD), the correlation between the
radiographic pattern and the stage of disease (clinical or histopathologic) is generally poor. Only the
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radiographic finding of honeycombing (small cystic spaces) correlates with pathologic findings and,
when present, portends a poor prognosis.
In the evaluation of ILD, it is important to review all previous chest films to assess the rate of change
in disease activity.
The chest radiograph is normal in as many as 10 percent of patients with some forms of ILD,
particularly those with hypersensitivity pneumonitis. Thus, a complete evaluation should be
undertaken even if a symptomatic patient has a normal chest radiograph or an asymptomatic patient
has radiographic evidence of ILD. Failure to adequately evaluate such individuals may lead to disease
progression that is irreversible by the time the patient seeks additional medical attention. The
radiologic patterns and disease distributions associated with specific ILDs are discussed separately.
(See "Evaluation of diffuse lung disease by conventional chest radiography".)
Computed tomography High resolution computed tomography (HRCT) should be obtained in

almost all patients with diffuse pulmonary parenchymal disease. We typically obtain both supine and
prone images to avoid confusing dependent atelectasis with interstitial opacities. Comparing
inspiratory and expiratory views is helpful when bronchiolitis is suspected. (See "High resolution
computed tomography of the lungs" and "Bronchiolitis in adults", section on 'Chest imaging'.)
HRCT provides greater diagnostic accuracy than the plain chest radiograph, but several series have
reported inconsistency among observers in the accuracy of differentiating between the ILDs [14-16]. In
addition, it is difficult to extrapolate from the diagnostic accuracy in carefully controlled series to that in
routine clinical practice because of variability in radiologic experience and scanning protocols.
Nonetheless, certain HRCT findings help to narrow the differential diagnosis of ILD. The correlations
between the various HRCT patterns and likely diagnoses are shown in the table (table 6A-B) [8,17-20]
(see "High resolution computed tomography of the lungs"). As examples:
Bilateral symmetric hilar adenopathy and upper lung zone reticular opacities suggest sarcoidosis
or another granulomatous disease.
Pleural plaques with linear calcification in association with a basilar predominance of reticular
opacities suggest asbestosis. (See "Asbestos-related pleuropulmonary disease".)
Centrilobular nodules that spare the subpleural region are seen in hypersensitivity pneumonitis,
sarcoidosis, Langerhans cell histiocytosis and also respiratory, follicular, and cellular bronchiolitis.
Irregular cysts associated with nodules in the upper and middle lung zones suggest pulmonary
Langerhans cell histiocytosis. (See "Pulmonary Langerhans cell histiocytosis".)
Basal and peripheral reticular opacities, traction bronchiectasis, and honeycombing (clustered
airspaces 3 to 10 mm in diameter) in a subpleural location are the classic features associated
with a histopathologic pattern of usual interstitial pneumonitis (UIP) (algorithm 1) [21,22]. While
ground glass opacities may be present, they are less extensive than reticular opacities. A UIP
pattern is seen in idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, and
ILD-associated with rheumatoid arthritis.
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In an asymptomatic patient, diffuse, calcified, nodular, interstitial opacities may reflect healed
varicella-zoster pneumonia [23].
Other imaging Other types of chest imaging, such as (18)F-2-deoxy-2-fluoro-D-glucose (FDG)

positron emission tomography (PET) and gallium-67 scans, are rarely useful in the evaluation of ILD.
FDG-PET scanning We do not typically obtain FDG-PET scans in the evaluation of ILD, as
the findings are nonspecific. In a series of 35 patients with pulmonary lymphangitic
carcinomatosis, diffuse uptake of FDG was noted in 30 patients and focal uptake in four [24].
However, FDG-PET positivity does not differentiate malignant from benign ILD, as FDG uptake
can also be seen in sarcoidosis and pulmonary Langerhans cell histiocytosis. (See "Clinical
manifestations and diagnosis of pulmonary sarcoidosis", section on 'FDG-PET scan' and
"Pulmonary Langerhans cell histiocytosis", section on 'Fluorodeoxyglucose-PET scan'.)
Gallium-67 lung scanning Gallium-67 lung scanning is rarely used as a means of evaluating
patients with ILD. Gallium-67 scanning may have a limited role in the identification of the
lambda-panda sign in patients with sarcoidosis. (See "Clinical manifestations and diagnosis of
pulmonary sarcoidosis", section on 'Other radiotracer scanning'.)
PULMONARY FUNCTION TESTING Complete lung function testing (spirometry, lung volumes,
diffusing capacity) and resting and exercise pulse oximetry are obtained in virtually all patients with
suspected interstitial lung disease (ILD) [1,25,26]. Measurement of lung function is most helpful for
assessing the severity of lung involvement and the pattern, whether obstructive, restrictive, or mixed.
The pattern is useful in narrowing the number of possible diagnoses.
Arterial blood gases are often obtained to corroborate results of pulse oximetry. (See "Overview of
pulmonary function testing in adults" and "Office spirometry".)
Spirometry and lung volumes Most of the interstitial disorders have a restrictive defect with
reductions in total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV)
[27,28]. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) are
decreased, but usually the changes are in proportion to the decreased lung volumes; thus, the
FEV1/FVC ratio is usually normal or increased (figure 1). The reductions in lung volumes become
more pronounced as lung stiffness increases with disease progression (figure 2). (See "Overview of
pulmonary function testing in adults", section on 'Restrictive ventilatory defect'.)
In contrast, an interstitial pattern on chest radiograph accompanied by obstructive airflow limitation (ie,
a reduced FEV1/FVC ratio) on lung function testing is suggestive of any of the following processes:
Sarcoidosis
Lymphangioleiomyomatosis
Hypersensitivity pneumonitis
Pulmonary Langerhans cell histiocytosis
Tuberous sclerosis and pulmonary lymphangioleiomyomatosis
Combined chronic obstructive pulmonary disease (COPD) and ILD
Constrictive bronchiolitis
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Diffusing capacity A reduction in the diffusing capacity (DLCO) is a common, but nonspecific
finding in ILD. The decrease in DLCO is due, in part, to effacement of the alveolar capillary units but
more importantly to the extent of mismatching of ventilation and perfusion of the alveoli. In some ILDs,
particularly sarcoidosis, there can be considerable reduction in lung volumes and/or severe
hypoxemia but normal or only slightly reduced DLCO. (See "Diffusing capacity for carbon monoxide".)
Moderate to severe reduction of DLCO in the presence of normal lung volumes in a patient with ILD
suggests one of the following:
Combined emphysema and ILD

Combined ILD and pulmonary vascular disease
Pulmonary lymphangioleiomyomatosis
Pulmonary vascular disease, and thus a reduction in DLCO, can develop in patients with ILD as a
consequence of hypoxemic vasoconstriction, thromboembolic disease complicating the ILD, or a
disease with both ILD and pulmonary hypertension, such as scleroderma.
In general, the severity of the DLCO reduction does not correlate well with disease prognosis, unless
the DLCO is less than 35 percent of predicted [29]. Longitudinal changes in DLCO have been used to
assess disease progression or regression. Due to difficulties with reproducibility in measuring DLCO,
a change of 15 percent is needed to identify a true change in disease severity [1].
Gas exchange at rest and on exertion Resting arterial blood gases may be normal in early ILD or
may reveal hypoxemia (secondary to mismatching of ventilation to perfusion) and respiratory
alkalosis. Carbon dioxide retention is rare and usually a manifestation of end-stage disease. (See
"Arterial blood gases".)
Normal values for resting arterial partial pressure of oxygen (PaO2) or pulse O2 saturation do not rule
out significant hypoxemia during exercise or sleep. Thus, it is important to perform exercise testing
with serial measurement of arterial blood gases or pulse oximetry (figure 3). Exercise testing may take
the form of a cardiopulmonary exercise test, a six-minute walk test (6MWT), or informal ambulatory
oximetry including a stair climb to replicate the patient's usual daily activity. (See "Overview of
pulmonary function testing in adults", section on 'Pulse oxygen saturation'.)
Cardiopulmonary exercise testing In a cardiopulmonary exercise test, arterial oxygen

desaturation, a failure to decrease dead space appropriately with exercise (ie, a high dead space
[VD]/tidal volume [VT] ratio), and an excessive increase in respiratory rate with a lower than
expected recruitment of tidal volume provide useful information regarding physiologic
abnormalities and the extent of disease. Full cardiopulmonary exercise testing is not necessary
for every patient with ILD. However, when the significance of symptoms or radiographic
abnormalities is unclear, a normal maximal cardiopulmonary exercise test effectively excludes
significant ILD [1]. (See "Exercise physiology" and "Oxygenation and mechanisms of
hypoxemia".)
Serial assessment of pulse oxygen saturation Serial assessment of resting and exercise gas
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exchange is one of the methods used to follow ILD activity and responsiveness to treatment,
especially in idiopathic pulmonary fibrosis (IPF). As an example, the results of a 6MWT have
correlated with prognosis in several studies of IPF [30-33]. Pulse oximetry desaturation to 88
percent or below during the 6MWT is associated with a median survival of 3.21 years compared
with a median survival of 6.63 years in those who did not desaturate below 89 percent [31]. The
distance walked during the 6MWT is a reproducible measure and correlates with the maximal
oxygen consumption (VO2 max) obtained during a maximal exercise test [33]. Among patients
with idiopathic pulmonary fibrosis, a heart rate recovery of less than 13 beats per minute by one
minute after completion of a 6MWT is associated with a median survival of 1.96 years, compared
with 3.2 years in patients with a faster heart rate recovery [34].
CARDIAC EVALUATION It is prudent to assess cardiac function during the initial evaluation of
interstitial lung disease (ILD), as heart failure is in the differential diagnosis of ILD. An
electrocardiogram is typically obtained to evaluate for evidence of pulmonary hypertension or
concurrent cardiac disease. If heart failure or pulmonary hypertension is suspected, a serum brain
natriuretic peptide or N-terminal-proBNP level is measured. (See "Approach to the patient with
dyspnea", section on 'Cardiovascular' and "Approach to the patient with dyspnea", section on 'Initial
testing in chronic dyspnea'.)
There are no clear guidelines on when to obtain a transthoracic echocardiogram in a patient with ILD.
A reasonable approach is to perform echocardiography in patients with an abnormal
electrocardiogram, suspected heart failure, rapid onset of radiographic findings, or a moderate to
severe reduction in diffusing capacity (DLCO). A low DLCO may suggest concomitant pulmonary
hypertension. The presence of an abnormal heart rate recovery one minute after a 6MWT has also
been associated with an increased likelihood of underlying pulmonary hypertension [35]. If it has not
been performed previously, echocardiography is typically performed before obtaining a surgical lung
biopsy to exclude occult heart failure. (See 'Diffusing capacity' above and "Clinical features and
diagnosis of pulmonary hypertension in adults", section on 'Echocardiography' and "Tests to evaluate
left ventricular systolic function".)
Assessment for concomitant pulmonary hypertension is important because the presence of pulmonary
hypertension may be a clue to the underlying ILD etiology (eg, systemic sclerosis, mixed connective
tissue disease) or severity. In addition, among patients with idiopathic pulmonary fibrosis (IPF),
pulmonary hypertension is associated with increased disease severity and decreased survival.
Doppler echocardiography has been shown to have a sensitivity as high as 88 percent for the
diagnosis of pulmonary hypertension, but the correlation between Doppler echocardiogram-derived
pulmonary artery systolic pressure (PASP) and right heart catheterization-derived PASP is lower in
right-heart predominant disease [36,37]. Right heart catheterization may be appropriate in patients
with a normal echocardiogram but a high clinical suspicion for pulmonary hypertension (eg, dyspnea
or oxygen desaturation out of proportion to the degree of parenchymal lung disease). (See
"Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension):
Treatment and prognosis".)
ROLE OF BRONCHOALVEOLAR LAVAGE Bronchoalveolar lavage (BAL) is performed during

flexible bronchoscopy to obtain samples of cells and fluid from the distal airways and alveoli [38]. The
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lavage fluid is sent for cell counts; cultures for mycobacterial, viral, and fungal pathogens; and
cytologic analysis (table 7 and table 8 and table 9 and table 10). BAL is particularly useful in the
evaluation of patients with interstitial lung disease (ILD) that is associated with hemoptysis, is acute or
rapidly progressive, or is likely caused by one of the following diseases: sarcoidosis, hypersensitivity
pneumonitis, pulmonary Langerhans histiocytosis, or infection. (See "Role of bronchoalveolar lavage
in diagnosis of interstitial lung disease".)
Virtually all patients presenting with hemoptysis and radiographic ILD should promptly undergo BAL
with sequential lavages to confirm an alveolar source of bleeding and identify any infectious etiologies.
(See "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease", section on
'Hemorrhagic BAL' and "The diffuse alveolar hemorrhage syndromes".)
The majority of patients with an acute onset of ILD will undergo BAL to evaluate for acute eosinophilic
pneumonia, alveolar hemorrhage, malignancy, and opportunistic or atypical infection, which can often
be diagnosed on the basis of BAL findings (table 7). (See "Role of bronchoalveolar lavage in
diagnosis of interstitial lung disease", section on 'Eosinophilic BAL' and "Role of bronchoalveolar
lavage in diagnosis of interstitial lung disease", section on 'Hemorrhagic BAL' and "Approach to the
immunocompromised patient with fever and pulmonary infiltrates", section on 'Invasive procedures'.)
For patients with a subacute or chronic presentation of ILD, BAL is often performed when sarcoidosis,
hypersensitivity pneumonitis, pulmonary Langerhans cell histiocytosis (PLCH), or infection are
suspected based on the radiographic pattern (eg, upper lobe predominance of reticular opacities, hilar
lymphadenopathy, irregular cystic airspaces), history of exposure (eg, bird keeping, farming), or
concomitant clinical findings (eg, hemoptysis, renal insufficiency). In these patients, the results of BAL
analysis may be used to narrow the differential diagnostic possibilities between various types of ILD,
but tissue confirmation is usually required (table 11 and table 10). When PLCH is suspected, a sample
of BAL fluid should be examined for Langerhans cells, which are CD-1a positive; a finding of more
than 5 percent CD-1a positive cells is strongly suggestive of PLCH. (See "Role of bronchoalveolar
lavage in diagnosis of interstitial lung disease", section on 'Lymphocytic BAL' and "Pulmonary
Langerhans cell histiocytosis", section on 'Bronchoalveolar lavage' and "Clinical manifestations and
diagnosis of pulmonary sarcoidosis", section on 'Bronchoscopy'.)
BAL is less likely to be helpful in patients with a radiographic pattern suggestive of idiopathic
pulmonary fibrosis (IPF) [21,39,40]. In the evaluation of patients with suspected IPF, the main role of
BAL is to exclude chronic hypersensitivity pneumonitis. A BAL lymphocytosis >40 percent is
suggestive of chronic hypersensitivity pneumonitis [40]. We do not typically perform BAL in patients
with typical HRCT findings for IPF and have no identifiable exposure to agents that cause
hypersensitivity pneumonitis based upon a thorough discussion of potential environmental and
occupational exposures.
BAL does not have an established role in the assessment of ILD progression or response to therapy.
ROLE OF LUNG BIOPSY When the results of the above evaluation do not allow the clinician to
make a confident diagnosis of a given type or stage of interstitial lung disease (ILD), lung biopsy with
multidisciplinary interpretation of the results may be necessary [1,41]. The decision to pursue lung
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biopsy must be made on a case-by-case basis, weighing the morbidity of the procedure, the likely
diagnoses, the toxicity of therapy, and the values and preferences of the patient. (See "Role of lung
biopsy in the diagnosis of interstitial lung disease", section on 'Overview' and "Interpretation of lung
biopsy results in interstitial lung disease", section on 'Clinician - pathologist interaction'.)
Indications We typically obtain a lung biopsy in patients with atypical or progressive symptoms
and signs (fever, weight loss, hemoptysis, signs of vasculitis), atypical radiographic features,
unexplained extrapulmonary manifestations, rapid clinical deterioration, or sudden change in
radiographic appearance.
Occasionally, the noninvasive evaluation will yield conflicting findings, which may require a lung
biopsy for clarification. As an example, a cardiopulmonary exercise test may indicate that ILD is
the most likely cause of a patient's symptoms and signs, while their high resolution computed
tomography (HRCT) shows only minimal interstitial changes. In this situation, a lung biopsy may
be indicated to confirm that an ILD, rather than another process, is the cause of the patient's
clinical findings, thus enabling appropriate treatment.
Lung biopsy may also be indicated to exclude neoplastic and infectious processes. As an
example, sarcoidosis can sometimes have a similar HRCT appearance to lymphangitic
carcinomatosis or hypersensitivity pneumonitis (table 6A-B). Or, a patient with rheumatoid arthritis
might develop ILD due to the underlying disease, drugs used in treatment, or tuberculosis.
Patients with minimal symptoms, signs, physiologic impairment, and radiographic abnormalities
may prefer close observation over several months with interval repetition of pulmonary function
tests and HRCT, rather than proceeding immediately to lung biopsy. Other patients prefer to
undergo a lung biopsy sooner to obtain a definitive diagnosis, rather than watchful waiting.
Selection of procedure Lung biopsy may be obtained by flexible bronchoscopy, video-assisted

thoracoscopic (VATS) biopsy, or lung biopsy via thoracotomy. These techniques and the reasons
to choose one over another are discussed separately. (See "Role of lung biopsy in the diagnosis
of interstitial lung disease", section on 'Specimen collection'.)
Transbronchial lung biopsy (TBLB) often in combination with bronchoalveolar lavage (BAL;
although not at the same site) may be preferred over VATS or thoracotomy as the initial step
when sarcoidosis, hypersensitivity pneumonitis, lymphangitic carcinomatosis, eosinophilic
pneumonia, alveolar proteinosis, or infection appears likely. For most other types of ILD, surgical
biopsy via VATS or thoracotomy is preferred over TBLB due to the small size of TBLB samples,
which are insufficient for diagnosis of the idiopathic interstitial pneumonias.
For patients with mediastinal adenopathy and a suspicion of sarcoidosis, endobronchial

ultrasound guided transbronchial needle aspiration (EBUS-TBNA) may be the preferred route. An
alternate approach in these patients is to obtain a BAL and, during the same procedure, an
endobronchial biopsy of any abnormal areas of mucosa. (See "Clinical manifestations and
diagnosis of pulmonary sarcoidosis", section on 'Endoscopic ultrasound guided needle
aspiration'.)
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Multidisciplinary evaluation of biopsy results The histopathologic pattern found on the lung
biopsy specimen is evaluated in combination with the clinical information to determine the
diagnosis. The histopathologic patterns of common interstitial lung diseases are described
separately. (See "Idiopathic interstitial pneumonias: Clinical manifestations and pathology" and
"Interpretation of lung biopsy results in interstitial lung disease", section on 'Interpretation of
histopathologic patterns'.)
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Basics topics (see "Patient education: Idiopathic pulmonary fibrosis (The Basics)" and "Patient
education: Interstitial lung disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
Diffuse parenchymal lung diseases, often collectively referred to as interstitial lung diseases
(ILDs), are a heterogeneous group of disorders that are classified together because of similar
clinical, radiographic, physiologic, or pathologic manifestations (algorithm 1). (See 'Introduction'
above.)
The differential diagnosis of diffuse parenchymal lung diseases includes a broad range of
diseases, from those that are associated with a long list of known causes (table 2A-B) and
associations (table 1) to those that are idiopathic (algorithm 1). (See 'Causes of ILD' above.)
The treatment choices and prognosis vary among the different causes and types of ILD, so
ascertaining the correct diagnosis is important. An algorithm for evaluating a patient with ILD is
provided in the figure (algorithm 2). (See 'Causes of ILD' above.)
The routine laboratory evaluation is often nonspecific, but should include biochemical tests to
evaluate hepatic and renal function; hematologic tests with differential blood count to check for
evidence of anemia, polycythemia, leukocytosis, or eosinophilia; urinalysis; and creatine kinase
for myositis (table 4). Additional serologic testing is often obtained, based on the results of the
clinical findings. (See 'Laboratory tests' above.)
High resolution computed tomography (HRCT) is obtained in almost all patients with diffuse
pulmonary parenchymal disease. We typically obtain both supine and prone images to avoid
confusing dependent atelectasis with interstitial opacities. Expiratory views are helpful when a
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condition associated with air-trapping (ie, bronchiolitis) is suspected. (See 'Imaging' above and
"High resolution computed tomography of the lungs".)
Certain HRCT findings help to narrow the differential diagnosis of ILD. The correlations between
the various HRCT patterns and likely diagnoses are shown in the table (table 6A-B). (See
'Imaging' above and "High resolution computed tomography of the lungs".)
An electrocardiogram is typically obtained to evaluate for evidence of pulmonary hypertension or

concurrent cardiac disease. If heart failure is suspected, a serum brain natriuretic peptide (BNP)
level is measured. An echocardiogram is also obtained when there is suspicion for heart failure or
pulmonary hypertension. (See 'Cardiac evaluation' above.)
Complete lung function testing (spirometry, lung volumes, diffusing capacity) and exercise pulse
oximetry are obtained in all patients with suspected ILD. Resting room air arterial blood gases are
often obtained to corroborate findings of pulse oximetry. (See 'Pulmonary function testing' above.)
In virtually everyone presenting with hemoptysis and radiographic ILD, BAL is performed promptly
to confirm an alveolar source of bleeding and identify infectious etiologies, if present. The majority
of patients with an acute onset of ILD will also undergo bronchoalveolar lavage (BAL) to evaluate
for alveolar hemorrhage, malignancy, and opportunistic or atypical infection. (See 'Role of
bronchoalveolar lavage' above and "Role of bronchoalveolar lavage in diagnosis of interstitial lung
disease".)
In patients with a more chronic presentation, the BAL is less helpful, as the findings are typically
nonspecific. However, when sarcoidosis, hypersensitivity pneumonitis, pulmonary Langerhans
histiocytosis, or infection are suspected based on the radiographic pattern, history of exposure, or
concomitant clinical findings, BAL may help to narrow the differential diagnosis. (See 'Role of
bronchoalveolar lavage' above and "Role of bronchoalveolar lavage in diagnosis of interstitial lung
disease".)
When it is not possible to make a confident diagnosis or to stage the disease after an initial
noninvasive evaluation, lung biopsy with careful examination of lung tissue may be necessary.
This decision is made on a case-by-case basis, weighing the morbidity of the procedure, the likely
diagnoses, the toxicity of therapy, and the values and preferences of the patient. (See 'Role of
lung biopsy' above and "Role of lung biopsy in the diagnosis of interstitial lung disease".)
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Topic 4358 Version 10.0
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GRAPHICS
Diffuse parenchymal lung diseases
Diffuse parenchymal lung diseases consist of disorders of known causes

(rheumatic disease, environmental or drug related) as well as disorders of
unknown cause. The latter include idiopathic interstitial pneumonias,
granulomatous lung disorders (eg, sarcoidosis), and other forms of interstitial
lung disease including lymphangioleiomyomatosis, pulmonary Langerhans cell
histiocytosis/histiocytosis X, and eosinophilic pneumonia. The interstitial
pneumonias are further categorized as chronic fibrosing, acute or subacute
fibrosing, or smoking related. Lymphoid interstitial pneumonia is typically
associated with other disease processes, such as rheumatic disease or
immunosuppression; idiopathic lymphoid interstitial pneumonia is rare.
DPLD: diffuse parenchymal lung disease; IIP: idiopathic interstitial pneumonia; LAM:
lymphangioleiomyomatosis; PLCH: pulmonary Langerhans cell
histiocytosis/histiocytosis X.
Graphic 77345 Version 10.0
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Interstitial lung disease
PFT: pulmonary function tests; HRCT: high resolution computed tomography; ILD:
interstitial lung disease; BAL: bronchoalveolar lavage; UIP: usual interstitial pneumonia;
IPF: idiopathic pulmonary fibrosis; NSIP: nonspecific interstitial pneumonia; OP: organizing
pneumonia; PLCH: pulmonary Langerhans cell histiocytosis; TBB: transbronchial lung
biopsy.
* Serology as indicated by clinical findings: rheumatoid factor, anti-cyclic citrulinated
peptide, antinuclear antibody, antisynthetase antibodies, creatine kinase, aldolase,
Sjgren's antibodies and scleroderma antibodies.
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Classic HRCT features of UIP:

1. Reticular opacities in basal and peripheral distribution.
2. Traction bronchiectasis.
3. Honeycombing (clustered airspaces 3 to 10 mm diameter) in subpleural location.
4. Ground glass opacities may be present but are less extensive than reticular
opacities.
Adapted from: Raghu G. Am J Respir Crit Care Med 1995; 151:909.
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Partial list of primary diseases associated with interstitial lung disease
Sarcoidosis
Vasculitides
Granulomatosis with polyangiitis (Wegener's)
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
Hemorrhagic syndromes
Anti-glomerular basement membrane antibody (Goodpasture's) disease
Idiopathic pulmonary hemosiderosis
Pulmonary Langerhans cell histiocytosis (eosinophilic granuloma)
Chronic gastric aspiration
Amyloidosis
Neurofibromatosis
Lymphangitic carcinomatosis
Chronic pulmonary edema
Chronic uremia
Respiratory bronchiolitis
Alveolar proteinosis
Gaucher's disease
Niemann-Pick disease
Hermansky-Pudlak syndrome
Pulmonary veno-occlusive disease
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Occupational and environmental exposures associated with interstitial lung

disease
Inhaled inorganic dust
Silicates
Silica ("silicosis")
Asbestos ("asbestosis")
Talc (hydrated Mg silicates; "talcosis")
Kaolin or "china clay" (hydrated aluminum silicate)
Diatomaceous earth (Fuller's earth, aluminum silicate with Fe and Mg)
Nepheline (hard rock containing mixed silicates)
Aluminum silicates (sericite, sillimanite, zeolite)
Portland cement
Mica (principally K and Mg aluminum silicates)
Beryllium ("berylliosis")
Carbon
Coal dust ("coal worker's pneumoconiosis")
Graphite ("carbon pneumoconiosis")
Metals
Tin ("stannosis")
Aluminum
Powdered aluminum
Bauxite (aluminum oxide)
Hard metal dusts
Cadmium
Titanium oxide
Tungsten
Hafnium
Niobium
Cobalt
Vanadium carbides
Iron ("siderosis", "arc welder's lung") Barium (powder of baryte or BaSO4; "baritosis")
Antimony (oxides and alloys)
Hematite (mixed dusts of iron oxide, silica and silicates; "siderosilicosis")
Mixed dusts of silver and iron oxide ("argyrosiderosis")
CuSO4 neutralized with hydrated lime (Bordeaux mixture; "vineyard sprayer's lung")
Rare earths (cerium, scandium, yttrium, lanthanum)
Adapted from Crystal, RG. Interstitial lung disease. In: Wyngaarden, JB, Smith, LH, Jr, Bennett, JC, (Eds), Cecil
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Textbook of Medicine, 19th ed, WB Saunders Co, Philadelphia, 1992.
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Occupational and environmental exposures associated with interstitial lung

disease
Inhaled organic dusts
(hypersensitivity pneumonitis) (Partial list)
Thermophilic fungi (ie, Macropolyspora faeni, Thermactinomyces vulgaris, T. sacchari)
Farmer's lung
Grain handler's lung
Humidifier or air conditioner lung
Bacteria (ie, Bacillus subtilis, B. cereus)
Humidifier lung
True fungi (ie, Aspergillus, Cryptostroma corticale, Aureobasidium pullulans, Penicillium species)
Animal proteins (eg, bird fancier's disease)
Inhaled agents other than inorganic or organic dusts
Chemical sources
Synthetic - fiber lung (Orlon, polyesters, nylon, acrylic)
Bakelite worker's lung
Vinyl chloride, polyvinyl chloride powder
Gases
Oxygen
Oxides of nitrogen
Sulfur dioxide
Chlorine gas
Methyl isocyanate
Fumes
Oxides of zinc, copper, manganese, cadmium, iron, magnesium, nickel, brass, selenium, tin, and antimony
Diphenylmethane diisocyanate
Trimellitic anhydride toxicity
Vapors
Hydrocarbons
Thermosetting resins (rubber tire workers)
Toluene diisocyanate (TDI - asthmatic reactions prominent)
Mercury
Aerosols
Oils
Fats
Pyrethrum (a natural insecticide)
Adapted from Crystal, RG. Interstitial lung disease. In: Wyngaarden, JB, Smith, LH, Jr, Bennett, JC, (Eds), Cecil
Textbook of Medicine, 19th ed, WB Saunders Co, Philadelphia, 1992.
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Examples of drugs and biologics that can cause interstitial lung disease
Antibiotics Drug-induced systemic lupus

erythematosus
Ethambutol
Minocycline Hydantoins
Nitrofurantoin, acute and chronic Hydralazine
Isoniazid
Anti-inflammatory agents
Penicillamine
Abatacept
Procainamide
Azathioprine*
Illicit drugs
Cyclophosphamide*
Gold Cocaine
Interleukin-1 blockers (anakinra) Heroin
Leflunomide Methadone
Methotrexate* Propoxyphene
Nonsteroidal antiinflammatory agents Talc
Penicillamine Miscellaneous
Rituximab (anti-CD20 monoclonal antibody) Bacille Calmette-Guerin (BCG)
Sulfasalazine Bromocriptine
Thalidomide* Drugs inducing pulmonary infiltrates and

eosinophilia
Tocilizumab
L-tryptophan
Tumor-necrosis factor-alpha blockers
Oxygen
Anti-arrhythmic agents
Radiation
Amiodarone
Statins
Tocainide
Antineoplastic agents
Alkylating agents
Busulfan
Chlorambucil
Cyclophosphamide*
Melphalan
Procarbazine
Antibiotics
Bleomycin sulfate
Mitomycin C
Antimetabolites
Azathioprine*
Cytosine arabinoside
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Methotrexate*
Nitrosoureas
BCNU (carmustine)
CCNU (lomustine)
Methyl-CCNU (semustine)
Other
Alpha interferon
Docetaxel
Etoposide (VP-16)
Gefitinib
Nilutamide
Paclitaxel
Temsirolimus
Thalidomide*
* Drugs that are used as both antineoplastic and anti-inflammatory agents.
Adapted from: Rosenow EC III, Martin WJ II. Drug-induced interstitial lung disease. In: Interstitial Lung Disease,
Schwarz MI, King TE Jr, (Eds), Mosby Year Book, St. Louis, 1993, p.255-270.
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Laboratory testing in the evaluation of interstitial lung disease
Laboratory tests to order in the majority of patients with interstitial lung

disease
Complete blood count and differential
Urinalysis
Alkaline phosphatase
Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT)
Blood urea nitrogen (BUN)
Creatinine
Tests for possible rheumatic disease
Antinuclear antibody (ANA)

Rheumatoid factor (RF)
Laboratory tests to order in selected patients with interstitial lung disease
Additional possible tests for systemic rheumatic disease*
Anti-cyclic citrullinated peptide (Anti-CCP)

Creatine kinase (CK), aldolase
Anti-Jo-1 antibody
Anti-neutrophil cytoplasmic antibody (ANCA)
Anti-topoisomerase (Scl-70) antibody, anti-PM-1 (PM-Scl) antibody
Anti-double stranded (ds) DNA antibodies
Sicca features or positive anti-extractable nuclear antigen (ENA): Check anti-RO (SS-A), anti-La (SS-B),
anti-ribonucleoprotein (RNP), serum protein electrophoresis, serum IgG4
Sclerodactyly, prominent GERD: Check anti-centromere, anti-topoisomerase I (anti-Scl-70)
Mechanics hands: Antisynthetase antibodies (in addition to anti-Jo-1)
Suspicion of heart failure or pulmonary hypertension: Brain natriuretic peptide (BNP) or N-terminal
proBNP (NT-proBNP)
Anemia and/or hemoptysis: Coagulation studies, anti-glomerular basement membrane (GBM) antibodies,
antiphospholipid antibodies, serum IgA endomysial or tissue transglutaminase antibodies in patients who
may have idiopathic pulmonary hemosiderosis
Mediastinal lymphadenopathy: serum protein electrophoresis
Beryllium exposure: Peripheral blood beryllium lymphocyte proliferation test
Risk factors for HIV: HIV test
Testing for hypersensitivity pneumonitis antibodies based on patient exposures
Laboratory tests that are unlikely to be helpful in the diagnosis of interstitial

lung disease
Angiotensin converting enzyme (ACE)
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
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GERD: gastroesophageal reflux disease; IgA: immunoglobulin A; IgG4: immunoglobulin G4.

* Additional tests are obtained when rheumatic disease is suspected based on clinical features, positive
antinuclear antibody (ANA) test, positive rheumatoid factor (RF), or presence of pleural disease on chest imaging.
These tests are nonspecific. Occasionally, patients will have elevated values for ESR or CRP that are twice
normal in the setting of an idiopathic interstitial pneumonia (IIP). So, these tests may be obtained to assess for
undifferentiated rheumatic disease in a patient with IIP.
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Reticular opacities
Standard International Labor Office film for small irregular s opacities, less than
1.5 mm in diameter (reticular opacities).
Courtesy of Paul Stark, MD.
Normal chest radiograph
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Posteroanterior view of a normal chest radiograph.
Courtesy of Carol M Black, MD.
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Small, rounded nodules
Standard ILO film for small rounded opacities, 3 to 10 mm in diameter.
ILO: International Labour Organization.
Courtesy of Paul Stark, MD.
Normal chest radiograph
Posteroanterior view of a normal chest radiograph.
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Courtesy of Carol M Black, MD.
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Helpful radiographic patterns in the differential diagnosis of interstitial lung

disease
Normal* Reticular or linear opacities
Hypersensitivity pneumonitis (common in population Peripheral lung zone predominance

studies, rare in isolated chronic cases)
Bronchiolitis obliterans with organizing
Sarcoidosis pneumonia
Connective tissue disease Eosinophilic pneumonia
Bronchiolitis obliterans Upper zone predominance

IPF (especially early "cellular" stage) Granulomatous disease
Asbestosis Sarcoidosis
Lymphangioleiomyomatosis Pulmonary Langerhans cell histiocytosis
Chronic hypersensitivity pneumonitis

Airspace opacities
Chronic infectious diseases (eg,
Pulmonary hemorrhage tuberculosis, histoplasmosis)
Chronic or acute eosinophilic pneumonia Pneumoconiosis
Bronchiolitis obliterans with organizing pneumonia Silicosis
Alveolar proteinosis Berylliosis
Coal miners' pneumoconiosis
Hard metal disease
Miscellaneous
Rheumatoid arthritis (necrobiotic nodular

form)
Ankylosing spondylitis
Radiation fibrosis
Drug-induced (amiodarone, gold)
Lower zone predominance
Idiopathic pulmonary fibrosis
Rheumatoid arthritis (associated with

usual interstitial pneumonia)
Asbestosis
* The HRCT scan is abnormal in most of these cases.
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disease
End-stage or honeycomb lung Associated with pneumothorax
Upper zone predominance Pulmonary Langerhans cell histiocytosis
Sarcoidosis Lymphangioleiomyomatosis
Pulmonary Langerhans cell histiocytosis Tuberous sclerosis
Chronic hypersensitivity pneumonitis Pleural involvement

Lymphangioleiomyomatosis Asbestosis
Lower zone predominance Connective tissue disorders
Idiopathic pulmonary fibrosis Systemic lupus erythematosus
Rheumatoid arthritis (associated with usual interstitial Rheumatoid arthritis

pneumonia) Scleroderma
Asbestosis Mixed connective tissue disease
Increased lung volumes Lymphangitic carcinomatosis
Lymphangioleiomyomatosis Lymphangioleiomyomatosis (chylous

effusion)
Tuberous sclerosis
Drug-induced (nitrofurantoin)
Sarcoidosis (stage 3)
Sarcoidosis (lymphocytic effusion)
Pulmonary Langerhans cell histiocytosis (chronic, with cyst
formation) Radiation pneumonitis (chronic with
mediastinal lymphatic obstruction)
Neurofibromatosis
Hilar or mediastinal
lymphadenopathy
Reticular or nodular infiltration, increased
Sarcoidosis
lung volumes and bullous changes
Lymphoma
Kaposi's sarcoma
Tuberous sclerosis
Methotrexate-induced lung disease
Neurofibromatosis
Lymphangitic carcinomatosis
Chronic sarcoidosis
Berylliosis
Amyloidosis
Chronic hypersensitivity pneumonia
Gaucher's disease
Endstage pulmonary involvement in microscopic
polyangiitis Acute disseminated histoplasmosis
Intravenous drug abuse (Ritalin) Acute disseminated coccidioidomycosis
Eggshell calcification of lymph

nodes
Silicosis
Sarcoidosis
Radiation
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32 de 44 19-06-17 16:55

disease
Associated with Kerley B lines Fleeting or migratory infiltrates
Lymphangitic carcinomatosis Bronchiolitis obliterans with organizing

pneumonia (idiopathic or radiation-induced)
Chronic left ventricular failure
Simple pulmonary eosinophilia (Loffler's
Mitral valve disease
syndrome)
Lymphoma
Hypersensitivity to drugs
Parasitic infections
Amyloidosis
Fungus-induced, especially allergic
Miliary pattern bronchopulmonary aspergillosis
Sarcoidosis Subcutaneous calcinosis

Silicosis Scleroderma (CREST)
Hypersensitivity pneumonitis Dermatopolymyositis
Bronchiolitis obliterans
Infectious granulomatous disease (tuberculosis,

histoplasmosis, coccidioidomycosis)
Metastatic malignant disease
Renal cell carcinoma
Adenocarcinoma of breast
Malignant melanoma
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HRCT patterns in interstitial lung disease
Normal
Sarcoidosis
Bronchiolitis obliterans
Asbestosis
Distribution of disease within the lung
Peripheral lung zone
Asbestosis
Connective tissue disease
Cryptogenic organizing pneumonia
Eosinophilic pneumonia
Central disease (bronchovascular thickening)
Sarcoidosis
Lymphangitic carcinoma
Upper zone predominance
Granulomatous disease
Sarcoidosis
Pulmonary histiocytosis X (eosinophilic granuloma)
Chronic infectious diseases (eg, tuberculosis, histoplasmosis)
Pneumoconiosis
Silicosis
Berylliosis
Coal miners' pneumoconiosis
Lower zone predominance
Rheumatoid arthritis (associated with usual interstitial pneumonia)
Asbestosis
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HRCT patterns in interstitial lung disease
Airspace opacities
Haze or ground glass attenuation
Desquamative interstitial pneumonia
Respiratory bronchiolitis-associated interstitial lung disease
Drug toxicity
Pulmonary hemorrhage
Lung consolidation
Chronic or acute eosinophilic pneumonia
Cryptogenic organizing pneumonia (bronchiolitis obliterans with organizing pneumonia)
Aspiration (lipoid pneumonia)
Alveolar carcinoma
Lymphoma
Alveolar proteinosis
Reticular opacities
Asbestosis
Nodules
Respiratory bronchiolitis-associated interstitial lung disease
Sarcoidosis
Pulmonary langerhans cell histiocytosis
Silicosis
Coal workers' pneumoconiosis
Metastatic cancer
Isolated lung cysts
Pulmonary langerhans cell histiocytosis
Chronic Pneumocystis carnii (P. jirovecii) pneumonia
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Maximal expiratory flow volume (MEFV curve) in

idiopathic pulmonary fibrosis
A: shown are the MEFV curves at presentation in a 42-year old nonsmoking man
with a normal chest roentgenogram and lung biopsy-proven idiopathic
pulmonary fibrosis. The FEV1 and FVC values are low relative to the predicted
values, but the FEV1 to FVC ratio is increased. However, at any given lung
volume, the flow rates are higher than expected because of elevated driving
pressure due to an increased elastic recoil. B: shows the MEFV curve for a
patient with chronic obstructive lung disease. The FEV1 and FVC values are low
relative to the predicted values, and the lung volumes are increased.
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Relationship of the static deflation volume and pressure

in a patient with idiopathic pulmonary fibrosis
The lung volume (as a percent of predicted TLC) is plotted against the static
transpulmonary pressure (cmH2O) for a patient with ILD. In general, the
compliance, maximum static transpulmonary pressure, and the coefficient of
retraction (the maximum transpulmonary pressure to TLC) tend to correlate
with the extent of parenchymal lung involvement observed on lung biopsy.
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Exercise testing
Exercise test in a woman who presented for evaluation of dyspnea on running

and a dry cough of 18 months duration. She did not smoke or have a history of
lung disease. The chest x-ray and lung function tests were normal. Her resting
room air arterial blood gases (elevation 5000 feet) revealed PO2: 78; PCO2: 34;
pH: 7.43; Sat: 94 percent; AaO2: 3.8. The patient performed an exercise test
on a cycle ergometer. The work rate was increased 10 watts per minute to her
symptom limited maximum. Blood was sampled every minute from an
indwelling catheter. Her resting and exercise ECG was normal. The patient
achieved 94 watts (65 percent of predicted workload). The PO2 decreased,
AaO2 increased, and minute ventilation (Ve) increased systematically with
increasing work rate (shown as the percent of predicted maximal VO2). The
study was stopped because of mild shortness of breath and leg fatigue. Lung
biopsy revealed UIP.
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Diagnostic features of bronchoalveolar lavage in interstitial lung disease
Disease category Examples Findings in BAL fluid
Malignancy Lymphangitic carcinomatosis Malignant cells
Bronchioloalveolar cell carcinoma Malignant cells
Pulmonary lymphoma Malignant cells
Diseases due to inhaled Lipoid pneumonia Fat globules in macrophages

(exogenous) material (oil-red-O-stain)
Multinucleated giant cells
Asbestosis Ferruginous bodies
Silicosis Dust particles seen by polarized

microscopy
Berylliosis Positive lymphocyte

transformation test to beryllium
salts
Inflammatory Diffuse alveolar hemorrhage Large numbers of erythrocytes
Hemosiderin-laden macrophages
(iron stain)
Sequential lavages progressively

more hemorrhagic
Chronic eosinophilic pneumonia Eosinophils 40 percent
Idiopathic acute eosinophilic Eosinophils 25 percent

pneumonia
Pulmonary alveolar proteinosis Lipoproteinaceous material

(periodic acid-Schiff stain)
Pulmonary Langerhans cell Monoclonal antibody (T6) positive

histiocytosis (Histiocytosis X) histiocytes
CD1 positive Langerhans cells >5

percent
Birbeck granules in lavaged

macrophages (seen by electron
microscopy)
BAL: bronchoalveolar lavage.
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Interstitial lung disease associated with BAL eosinophilia
High count (25 percent)
Chronic eosinophilic pneumonia (40 percent)
Churg Strauss syndrome with active pneumonitis
Idiopathic acute eosinophilic pneumonia (25 percent)
Tropical pulmonary eosinophilia (40 to 70 percent)
Mild to moderate counts (<25 percent)
Drug-induced pneumonitis
Fungal pneumonia
Idiopathic pulmonary fibrosis (<10 percent)
Pulmonary Langerhans cell histiocytosis (Histiocytosis X)
Sarcoidosis
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Interstitial lung disease associated with BAL neutrophilia
Idiopathic pulmonary fibrosis (15 to 40 percent)
Cryptogenic organizing pneumonia (40 to 70 percent)
Inorganic dust diseases
Asbestosis
Silicosis
Cigarette smoking (<10 percent)
Pulmonary Langerhans cell histiocytosis (Histiocytosis X)
Hypersensitivity pneumonitis (acute)
Sarcoidosis (advanced)
41 de 44 19-06-17 16:55
CD4:CD8 T lymphocyte ratios in diseases presenting with lymphocytic

alveolitis
CD4 : CD8 raised CD4 : CD8 normal CD4 : CD8 lowered
Sarcoidosis Tuberculosis Hypersensitivity pneumonitis
Berylliosis Lymphangioleiomyomatosis Silicosis
Asbestosis Drug induced
Crohn's disease BOOP
Rheumatoid arthritis HIV infection
Redrawn from Poulter LW, Rossi GA, Bjermer L, et al, Eur Respir Rev 1992; 2:75.
42 de 44 19-06-17 16:55
Interstitial lung disease associated with BAL lymphocytosis
Hypersensitivity pneumonitis (60 to 80 percent)
Sarcoidosis (Acute - 40 to 60 percent)
Idiopathic pulmonary fibrosis (15 to 30 percent)
Berylliosis
Granite workers
Amiodarone pneumonitis
Lymphoma/Pseudolymphoma
Pulmonary Langerhans cell histiocytosis (Early)
43 de 44 19-06-17 16:55
Contributor Disclosures
Talmadge E King, Jr, MD Nothing to disclose Kevin R Flaherty, MD, MS Grant/Research/Clinical
Trial Support: Boehringer Ingelheim [IPF (Nintedanib)]; Roche/Genentech [IPF (Pirfenidone)]; Bristol
Myers Squibb [IPF]; Aerent [IPF]. Consultant/Advisory Boards: Boehringer Ingelheim [IPF
(Nintedanib)]; Genetech [IPF (Pirfenidone)]; Gilead [IPF]; Roche [IPF (Pirfenidone)]; Veracyte [IPF];
Biogen [IPF]; Aeolus [IPF]; Pharmakea [IPF]; Fibrogen [IPF]. Helen Hollingsworth, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
these are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
44 de 44 19-06-17 16:55

Approach To The Adult With Interstitial Lung Disease Diagnostic Testing UpToDate

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Approach to the adult with interstitial lung disease: Diagnostic te... https://www.uptodate.com/contents/approach-to-the-adult-with-...

Official reprint from UpToDate

Approach to the adult with interstitial lung disease: Diagnostic testing

Author: Talmadge E King, Jr, MD

Serologic testing for hypersensitivity pneumonitis antibodies is based on patient exposure to

Computed tomography High resolution computed tomography (HRCT) should be obtained in

Other imaging Other types of chest imaging, such as (18)F-2-deoxy-2-fluoro-D-glucose (FDG)

Combined emphysema and ILD

Cardiopulmonary exercise testing In a cardiopulmonary exercise test, arterial oxygen

ROLE OF BRONCHOALVEOLAR LAVAGE Bronchoalveolar lavage (BAL) is performed during

Selection of procedure Lung biopsy may be obtained by flexible bronchoscopy, video-assisted

For patients with mediastinal adenopathy and a suspicion of sarcoidosis, endobronchial

SUMMARY AND RECOMMENDATIONS

An electrocardiogram is typically obtained to evaluate for evidence of pulmonary hypertension or

Use of UpToDate is subject to the Subscription and License Agreement.

interstitial pneumonia: analysis of CT appearance in 92 patients. Radiology 2006; 241:258.

Echocardiography 2015; 32:10.

Topic 4358 Version 10.0

Diffuse parenchymal lung diseases

Diffuse parenchymal lung diseases consist of disorders of known causes

Graphic 77345 Version 10.0

Interstitial lung disease

Classic HRCT features of UIP:

Adapted from: Raghu G. Am J Respir Crit Care Med 1995; 151:909.

Graphic 69044 Version 4.0

Partial list of primary diseases associated with interstitial lung disease

Granulomatosis with polyangiitis (Wegener's)

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Anti-glomerular basement membrane antibody (Goodpasture's) disease

Idiopathic pulmonary hemosiderosis

Pulmonary Langerhans cell histiocytosis (eosinophilic granuloma)

Chronic gastric aspiration

Chronic pulmonary edema

Pulmonary veno-occlusive disease

Graphic 64034 Version 4.0

Occupational and environmental exposures associated with interstitial lung

Inhaled inorganic dust

Talc (hydrated Mg silicates; "talcosis")

Kaolin or "china clay" (hydrated aluminum silicate)

Diatomaceous earth (Fuller's earth, aluminum silicate with Fe and Mg)

Nepheline (hard rock containing mixed silicates)

Aluminum silicates (sericite, sillimanite, zeolite)

Mica (principally K and Mg aluminum silicates)

Coal dust ("coal worker's pneumoconiosis")

Graphite ("carbon pneumoconiosis")

Bauxite (aluminum oxide)

Hard metal dusts

Antimony (oxides and alloys)

Hematite (mixed dusts of iron oxide, silica and silicates; "siderosilicosis")

Mixed dusts of silver and iron oxide ("argyrosiderosis")

Rare earths (cerium, scandium, yttrium, lanthanum)

Textbook of Medicine, 19th ed, WB Saunders Co, Philadelphia, 1992.

Graphic 80757 Version 1.0

Occupational and environmental exposures associated with interstitial lung

Inhaled organic dusts

(hypersensitivity pneumonitis) (Partial list)

Thermophilic fungi (ie, Macropolyspora faeni, Thermactinomyces vulgaris, T. sacchari)

Grain handler's lung

Humidifier or air conditioner lung

Bacteria (ie, Bacillus subtilis, B. cereus)

Animal proteins (eg, bird fancier's disease)

Inhaled agents other than inorganic or organic dusts

Synthetic - fiber lung (Orlon, polyesters, nylon, acrylic)