Download inerstitial lung disease

INERSTITIAL LUNG DISEASE
Dr. M. SOFI MD; FRCP (London);
FRCPEdin; FRCSEdin
Interstitial lung disease: Clinical evaluation
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.
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
Interstitial lung disorders: major categories
• Idiopathic interstitial pneumonia
• Idiopathic pulmonary fibrosis
(IPF)
• Non-specific interstitial
pneumonia (NSIP)
• Cryptogenic organizing
pneumonia (COP)
• Respiratory bronchiolitis
interstitial lung disease (RBILD
• Desquamative interstitial
pneumonia (DIP)
• Acute interstitial pneumonia (AIP)
• Connective tissue diseaseassociated interstitial lung disease
(CTD-ILD)
• Sarcoidosis
• Lymphoid interstitial
pneumonia (LIP)
• Hypersensitivity pneumonitis
• Iatrogenic pneumonitis/fibrosis
(drug-induced ILD, radiation
injury)
• Eosinophilic ILD (e.g.
eosinophilic pneumonia)
• Occupational lung disease
• Inherited disorders (e.g. familial
pulmonary fibrosis, HermanskyPudlak syndrome)
• Primary disorders (e.g. pulmonary
Langerhans cell histiocytosis)
CLINICAL PRESENTATION —
Patients with ILD come to clinical
attention for the following ways:
• Symptoms of progressive
breathlessness with exertion
(dyspnea) or a persistent
nonproductive cough.
• Pulmonary symptoms associated
with another disease, such as a
connective tissue disease
• History of occupational
exposure (eg, asbestosis, silicosis)
• An abnormal chest imaging study
• Lung function abnormalities on
simple office spirometry,
particularly a restrictive ventilatory
pattern (ie, reduced total lung
capacity and forced vital capacity)
• HISTORY — Careful
documentation of the PMH is
important in the initial assessment
because the cause of the illness is
often recognized from the
patient's history.
• Age and gender — Some of the
ILDs are more common in certain
age groups or have a male or
female predominance. IPF, also
called cryptogenic fibrosing
alveolitis are over age 50.
• Lymphangioleiomyomatosis and
pulmonary involvement in
tuberous sclerosis occur
exclusively in premenopausal
women
• ILD associated with rheumatoid
arthritis is more common in men.
Onset of symptoms: The acute
eosinophilic pneumonia,
cryptogenic organizing
pneumonia, connective tissue
associated ILD) often share
features with atypical infectious
pneumonias, such as the rapid
onset of symptoms, diffuse
radiographic opacities, and fever
• ILDs with a chronic or indolent
presentation (eg, idiopathic
pulmonary fibrosis, sarcoidosis,
pneumoconioses) need to be
differentiated from each other and
from diseases such as chronic
obstructive pulmonary disease and
heart failure.
• Some ILDs, such as
hypersensitivity pneumonitis and
sarcoidosis, may have an acute,
subacute, or chronic presentation
• Past medical history — Any
history of connective tissue
disease, inflammatory bowel
disease, or malignancy might be a
clue to an associated ILD
• A number of medications have
also been associated with ILD,
notably amiodarone.
• Allergic rhinitis and asthma may
implicate chronic eosinophilic
pneumonia
• Nasal polyposis and asthma may
suggest eosinophilic
granulomatosis with polyangiitis
(EGPA, Churg-Strauss).
• An immunocompromised state
due to an underlying disease or
immunomodulatory therapy may
suggest an infectious cause of ILD.
Smoking history — Some diseases
occur largely among current or
former smokers (eg, pulmonary
Langerhans cell histiocytosis,
desquamative interstitial
pneumonitis, respiratory
bronchiolitis-interstitial lung
disease, and idiopathic pulmonary
fibrosis) or among never or former
smokers (sarcoidosis and
hypersensitivity pneumonitis).
Family history — The family history
is occasionally helpful, as several
familial associations have been
identified. However, different
types of ILD (eg, idiopathic
pulmonary fibrosis and
nonspecific interstitial
pneumonitis) may occur within a
single family
• An autosomal dominant pattern of
inheritance has been reported for
idiopathic pulmonary fibrosis
(IPF), tuberous sclerosis, and
neurofibromatosis
• Prior medication use and
irradiation — A detailed history
of all medications taken and any
exposure to therapeutic irradiation
is needed to exclude the possibility
of drug-induced or radiationinduced lung disease
• Occupational/environmental
exposures : In hypersensitivity
pneumonitis (extrinsic allergic
alveolitis), the development of
respiratory symptoms, fever, chills,
and an abnormal chest radiograph
are often temporally related to the
workplace (farmer's lung) or to a
hobby (pigeon breeder's disease).
Symptoms
• Dyspnea – SOB, dyspnea, is a
common complaint. Grading the
level of dyspnea is useful as a
method to gauge the severity of
the disease
• Spontaneous pneumothorax is a
characteristic that may occur in
pulmonary Langerhans cell
histiocytosis, tuberous sclerosis,
lymphangioleiomyomatosis, and
neurofibromatosis
• Cough – A dry cough is common
and bothersome in sarcoidosis,
bronchiolitis obliterans with or
without organizing pneumonia,
respiratory bronchiolitis,
pulmonary Langerhans cell
histiocytosis, hypersensitivity
pneumonitis, lipoid pneumonia,
and lymphangitic carcinomatosis.
• Hemoptysis – may occur in the
diffuse alveolar hemorrhage
syndromes, tuberous sclerosis,
lymphangioleiomyomatosis,
pulmonary veno-occlusive disease,
and granulomatous vasculitides.
• Diffuse alveolar bleeding may
be present without hemoptysis;
the clinical manifestations in such
patients may be dyspnea and an
iron deficiency anemia.
• Wheezing – is an uncommon
manifestation of ILD. It has been
described in cases of lymphangitic
carcinomatosis, chronic
eosinophilic pneumonia, EGPA,
and respiratory bronchiolitis
• Chest pain – uncommon in most
ILDs. Described in RA; SLE and
MCTD
Physical examination of patients with ILD is usually nonspecific
• Lung examination — The lung
examination is frequently
abnormal in ILD, but the findings
are generally nonspecific. Crackles
or "velcro rales" are present on
chest examination in most forms
of ILD
• Scattered late inspiratory highpitched rhonchi, so-called
inspiratory squeaks, are frequently
heard on chest examination in
patients with bronchiolitis, but
may also be heard in patients with
traction bronchiectasis due to
pulmonary fibrosis.
• Clubbing — is common in some
pulmonary disorders (idiopathic
pulmonary fibrosis, asbestosis)
and rare in others (sarcoidosis,
hypersensitivity pneumonitis.
• Cardiac examination — Usually
normal except in more advanced
stages of pulmonary fibrosis, when
findings are cor pulmonale & PHT
• Pulmonary hypertension may also
be a primary manifestation of some
CTD disorders (progressive systemic
sclerosis).
• Cor pulmonale are rare in ILD.
When present, is advanced disease.
• Extrapulmonary findings of
systemic disease : alopecia,
angiofibromas, cutaneous
sarcoidosis, Gottron's papules,
heliotrope rash, joint inflammation,
"mechanics" hands, muscle
weakness, nasal obstruction,
peripheral neuropathy, and
sclerodactyly
Age at onset of presentation in different interstitial lung diseases
Idiopathic pulmonary fibrosis (IPF) has an older age distribution than
either pulmonary Langerhans cell histiocytosis (LCH) or sarcoidosis.
LABORATORY TESTS —
• CBC with differential blood
count to check for evidence
of anemia, polycythemia,
leukocytosis, or eosinophilia
• Liver function tests: ALT,
SGPT, AST, SGOT
• Tests for possible rheumatic
disease
– Antinuclear antibody
(ANA)
– Rheumatoid factor (RF)
• Hepatitis serology
• HIV testing may be
appropriate.
• Sicca features or
– positive anti-extractable
nuclear antigen (ENA)
– anti-RO (SS-A)
– anti-La (SS-B)
– anti-ribonucleoprotein
(RNP)
– serum protein
electrophoresis
• Coagulation studies
– anti-glomerular
basement membrane
(GBM) antibodies
– antiphospholipid
antibodies,
• Urinalysis
LABORATORY TESTS —
• Laboratory tests in selected
patients with ILD:
• Additional possible tests for
rheumatic disease*
– Anti-cyclic citrullinated
peptide (Anti-CCP)
– Creatine kinase (CK),
aldolase
– Anti-Jo-1 antibody
– Anti-neutrophil
cytoplasmic antibody
(ANCA)
– Anti-topoisomerase (Scl70) antibody, anti-PM-1
(PM-Scl) antibody
– Anti-double stranded
(ds) DNA antibodies
• Serum celiac panel
– serum IgA endomysial
– tissue transglutaminase
antibodies in patients
who may have idiopathic
pulmonary hemosiderosis
Chest radiography —
• The most common
radiographic abnormality
on routine chest radiograph
is a reticular pattern
• Nodular or mixed patterns
(alveolar filling and
increased interstitial
markings) are not unusual
• Radiographic finding of
honeycombing (small cystic
spaces) correlates with
pathologic findings
• The CXR is normal in 10% of
patients with some forms of
ILD, particularly those with
hypersensitivity
pneumonitis
• An electrocardiogram is
obtained to evaluate for
evidence of pulmonary
hypertension or concurrent
cardiac disease.
Computed tomography
• High resolution
computed tomography
(HRCT) should be obtained
in almost all patients with
diffuse pulmonary
parenchymal disease.
• Obtain both supine and
prone images to avoid
confusing dependent
atelectasis with interstitial
opacities.
• HRCT provides greater
diagnostic accuracy than the
plain chest radiograph
• 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.
Frontal chest radiograph
demonstrating bilateral
reticular and nodular
interstitial infiltrates with
upper zone predominance.
High-resolution chest CT scan
of patient with bilateral
reticular and nodular
interstitial infiltrates with
upper zone predominance.
Normal chest radiograph
Postero-anterior view of a
normal chest radiograph.
Nodular and Reticular opacities
Bilateral nodular and reticular
shadows of interstitial lung
disease.
PULMONARY FUNCTION TESTING:
Spirometry and lung
volumes — Most of the
ILDs have a restrictive
defect with reductions
TLC, FRC, RV
• 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
• Pulmonary
Lymphangioleiomyomatosis
• Hypersensitivity
pneumonitis
• Pulmonary Langerhans cell
histiocytosis
• Tuberous sclerosis
• Combined chronic
obstructive pulmonary
disease (COPD) and ILD
• Constrictive bronchiolitis
PULMONARY FUNCTION TESTING:
Diffusing capacity — A
reduction in the diffusing
capacity (DLCO) is a
common, but nonspecific
finding in ILD. The decrease
in DLCO is due to
effacement of the alveolar
capillary units but more
importantly to the extent of
mismatching of ventilation
and perfusion of the alveoli.
• 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 Langerhans cell
histiocytosis
• Pulmonary
lymphangioleiomyomatosis
PULMONARY FUNCTION TESTING:
Gas exchange at rest and on
exertion —
• Resting ABG 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.
Bronchoalveolar lavage:
• The 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
• In everyone presenting with
hemoptysis and
radiographic ILD, BAL is
performed promptly to
confirm an alveolar source of
bleeding and identify
infectious etiologies, if present
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.
The decision to pursue lung biopsy must be made on a caseby-case basis, weighing the morbidity of the procedure, the
likely diagnoses, the toxicity of therapy, and the values and
preferences of the patient
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.
Or, a patient with rheumatoid arthritis might develop ILD due
to the underlying disease, drugs used in treatment, or
tuberculosis.
Treatment: Significant interstitial lung disease (ILD)
predicts poor outcome.
• The clinical benefits of
immunosuppressive therapy
appear to be modest and
associated with substantial
toxicity
• The goal of treating ILD is
to reduce alveolar and
interstitial injury and
inflammation, in the hope
that progression of
interstitial fibrosis will be
retarded.
• For patients who have
respiratory symptoms,
abnormal and/or declining
pulmonary function,
initiating treatment with
cyclophosphamide plus
low dose glucocorticoids
(equivalent of ≤10 mg/day of
prednisolone.
Treatment:
• Cyclophosphamide can be
administered as a monthly
intravenous dose (our
preference) or as a daily oral
dose (eg, ≤2 mg/kg)
prednisolone.
• After a 12 month course of
cyclophosphamide, patients
are commonly transitioned
to maintenance therapy
with mycophenolate,
mofetil (eg, 1.5 to 3 g daily,
usually in two divided
doses).
• Patients whose disease is
refractory to the above
measures may be candidates
for rituximab
• Selected SSc patients who
have severe ILD that is
unresponsive to therapy
may be referred for lung
transplantation.