Idiopathic Pulmonary Fibrosis

DEFINITION
Idiopathic pulmonary fibrosis is defined as
a specific form of chronic, progressive
fibrosing interstitial pneumonia of
unknown cause, primarily occurring in
older adults, limited to the lungs, and
associated with the histopathologic and/or
radiologic pattern of usual interstitial
pneumonia
CLINICAL PRESENTATION
1) Symptoms- are nonspecific and can be shared with
many pulmonary and cardiac diseases
 no symptoms
 exertional dyspnea
 nonproductive cough
Extrapulmonary symptoms
 Weight loss
 Low-grade fever
 Fatigue
 Arthralgias
 Myalgias
CLINICAL PRESENTATION

2) Signs
 Digital clubbing (25-50%)
 Bylateral fine basilar inspiratory crackles
 Loud P2 component of the second heart
sound, a fixed split S2 (Pulmonary
hypertension )
 Holosystolic tricuspid regurgitation murmur
 Edema of the legs
LABORATORY TESTS
Routine laboratory tests are nonspecific for the
diagnosis of idiopathic pulmonary fibrosis.
Some tests may be helpful to exclude other
causes of interstitial lung disease:
 Antinuclear antibodies or rheumatoid factor
titers: Positive results in about 30% of patients
with IPF, but the titers are generally not high.
The presence of high titers may suggest a
connective tissue disease
 C-reactive protein level
 Erythrocyte sedimentation rate
 Complete blood cell count- polycythemia (rare)

OTHER TESTS
Pulmonary function tests: Nonspecific
findings of a restrictive ventilatory
defect and reduced diffusion capacity
for carbon monoxide (DL CO) 
IMAGING TESTS
1) High-resolution computed
tomography (HRCT) scanning
 Is
Sensitive, specific, and essential
for the diagnosis of idiopathic
pulmonary fibrosis.
 Show patchy, peripheral,
High-resolution computed
tomography (HRCT)
scanning
shows increased
pulmonary attenuation
with distortion of
the pulmonary
architecture. 
2) Chest radiography
 Show peripheral reticular opacities
(netlike linear and curvilinear
densities) predominantly at the
lung bases, honeycombing (coarse
reticular pattern), and lower lobe
volume loss
Honeycombing
image
CHEST X-RAY

interstitial shadowing
of small (1- to 2-mm),
irregular opacities 
OTHER TESTS
3) Transthoracic echocardiography
 Detects pulmonary hypertension
4) Bronchoscopy
 Absence of lymphocytosis in bronchoalveolar
lavage fluid may be important for the diagnosis
(increased neutrophils [70-90% of patients] and
eosinophils [40-60% of all patients]).
 This procedure may be used to exclude
alternative diagnoses.
5)Surgical lung biopsy
(via open lung biopsy or
video-assisted
thoracoscopic surgery
[VATS])
Best sample for
distinguishing usual
interstitial pneumonia
from other idiopathic
interstitial pneumonias.
Three ports are used,
with camera in center
position of triangle.
MANAGEMENT
 The optimal medical therapy for the treatment
of idiopathic pulmonary fibrosis has yet to be
identified.
 Treatment strategies for idiopathic pulmonary
fibrosis include the assessment and
management of comorbid conditions according
to current practice guidelines, including chronic
obstructive pulmonary disease, obstructive
sleep apnea, gastroesophageal reflux disease,
and coronary artery disease.
 Encourage tobacco users to quit and offer
pharmacotherapy as needed.
TREATMENT
 Oxygen therapy in patients with
hypoxemia at rest or with exercise (partial
pressure of oxygen [PaO 2] < 55 mmHg or
an oxygen saturation by pulse oximetry
[SpO 2] < 88%). The goal is to maintain an
oxygen saturation of at least 90% at rest,
with sleep, and with exertion.
 Vaccinate
patients against influenza and
pneumococcal infection.
 Lung transplantation
 Pharmacotherapy:

1. Systemic corticosteroids (eg,

prednisone)
2. Immunosuppressant agents (eg,
azathioprine, cyclophosphamide)
3. Tyrosine kinase inhibitors (eg,
nintedanib)
4. Antifibrotic agents (eg, pirfenidone)
Interstitial (Nonidiopathic)
Pulmonary Fibrosis
 Diffuse parenchymal lung diseases (DPLDs)
comprise a heterogenous group of disorders.
Clinical, physiologic, radiographic, and
pathologic presentations of patients with these
disorders are varied. However, a number of
common features justify their inclusion in a
single disease category.
 Some forms of DPLD are related to
occupational, environmental, drug, and/or
radiation exposure, as well as systemic illness
such as collagen-vascular disease
 Another category of DPLDs includes
granulomatous forms (sarcoidosis, and
hypersensitivity pneumonia (HSP)
 Very rare forms of DPLDs- pulmonary Langerhans
cell histiocytosis (PLCH) , tuberous sclerosis,
lymphangioleiomyomatosis (LAM), and
Hermansky-Pudlak syndrome.
 Some of these disorders, for example, RBILD, DIP,
and PLCH, are clearly associated with smoking.
 Some forms of DPLD, as noted above, may also be
related to occupational, environmental, drug,
radiation exposure, or systemic illness such as
collagen-vascular diseas
Pathophysiology

 acuteinjury to the pulmonary

parenchyma, leading to chronic
interstitial inflammation
 fibroblastactivation and
proliferation
 finally
progressing to the common
endpoint of pulmonary fibrosis and
tissue destruction.
 inflammation is less important in IPF,
which appears to be primarily a
disorder of fibroblast activation and
proliferation in response to some as yet
unknown triggers
 all
DPLDs manifest histologically with
disease largely within the interstitial
compartment of the lung
 alveolar
and airway architecture also
may be disrupted to varying degrees.
 mortalityrate is approximately 50%
at 5 years.
 IPFaffects men more than women
(at a ratio of 1.5:1), while LAM and
pulmonary tuberous sclerosis
exclusively affect women.
 Many of the IPF are more prevalent
in older adults than in younger
adults.
DPLDs associated with environmental
or occupational exposures include the
following:
 Pneumoconioses (a group of occupational lung
diseases related to inhalational exposures to
inorganic dusts [eg, silicosis, asbestosis, berylliosis,
coal worker's pneumoconiosis {black lung}])
 HSP caused by exposure to protein antigens (eg,
farmer's lung, pigeon-breeder's lung, hot-tub lung)
 Fibrotic lung disease due to exposure to toxic gases,
fumes, aerosols, and vapors (eg, silo-filler's disease)
 Radiation exposure (ionizing radiation, frequently
used in medical therapeutics)
DPLDs associated with
rheumatologic/connective-tissue
diseases include the following:
 Scleroderma (CREST syndrome/progressive
systemic scleroderma)
 Rheumatoid arthritis
 Mixed connective-tissue disease
 Systemic lupus erythematosus
 The pulmonary-renal syndromes (ie, Wegner or
Goodpasture disease) - Often included with this
group; however, predominant manifestation is
vasculitis rather than fibrosis
DPLDs related to drug exposure include
the following:

 Cytotoxic agents (eg, bleomycin, busulfan,

methotrexate)
 Antibiotics (eg, nitrofurantoin, sulfasalazine)
 Antiarrhythmics (eg, amiodarone, tocainide)
 Anti-inflammatory medications (eg, gold,
penicillamine)
 Illicit drugs (eg, crack cocaine, heroin)
 Sarcoidosis and other granulomatous diseases
(eg, berylliosis)
DPLDs related to other systemic illnesses
include the following:
 Hepatitis C
 Inflammatory bowel disease
 Acquired immunodeficiency syndrome

Idiopathic or rare DPLDs include the following:

 COP (idiopathic)
 PLCH (rare)
 Eosinophilic pneumonia
Inherited DPLDs include the following:
 Familial IPF or sarcoidosis
 Tuberous sclerosis
 Neurofibromatosis
 Niemann-Pick disease
 Gaucher disease
 Hermansky-Pudlak syndrome
CLINICAL DIAGNOSIS

Symptoms - may be chronic, insidious, and

slowly progressive or may be subacute or
may be acute, with a fulminant,
progressive, remitting, or resolving course.
 Dyspnea is the most frequent symptom
 Chronic cough
 Wheezing
 Hemoptysis
 Chest pain
Signs
Digital clubbing
Central cyanosis (hypoxemia and arterial
oxygen desaturation are present).
Fine end-inspiratory pulmonary rales are
a common finding and may be difficult to
distinguish from those auscultated in
patients with congestive heart failure.
Wheezes may be heard and reflect airway
involvement
 A right-sided gallop (S 3), an accentuated
second heart sound (P 2) with fixed or paradoxic
splitting, and a right ventricular lift may be
present and indicate cor pulmonale.
 Generalized lymphadenopathy often occurs with
sarcoidosis.
 Cutaneous and articular findings are associated
with rheumatologic disease.
 Gastrointestinal manifestations occur with
inflammatory bowel disease.
Laboratory Studies
 Routine blood analysis and serum chemistries
are nonspecific.
 Serologic testing for rheumatologic disease or
vasculitis (eg, antinuclear antibodies,
rheumatoid factor, erythrocyte sedimentation
rate, C-reactive protein, anticitrulline antibody,
antineutrophil cytoplasmic antibodies,
antiglomerular basement membrane)
 ACE testing is not very specific or sensitive but
may offer a confirmatory clue to the diagnosis of
sarcoidosis.
Imaging Studies
Chest X-Ray
 Reticular and/or nodular opacities are the
hallmark 
 Honeycombing is a late finding and
correlates with severe histopathologic
findings. 
 Findingsmay be normal in 10% of
patients with histologically proven
disease.
Diffuse reticular opaci
the shadows at
the lung base
and the diffuse
ground-glass
appearance.
 symmetric hilar adenopathy in sarcoidosis
 IPF, asbestosis, and connective-tissue disease–related
changes are most often basilar and peripheral in
distribution.
 Radiation fibrosis is restricted to the previous radiation
port but also may have upper lung zone predominance, as
may sarcoidosis, PLCH, HSP, pneumoconioses, and drug-
related DPLD due to gold or nitrofurantoin therapy.
 Some patterns of abnormality, such as reverse congestive
heart failure or a bat-wing pattern, are described with
eosinophilic pneumonia.
High-resolution chest computed tomography
(CT) scanning is more sensitive than chest radiography
and may reveal characteristic, if not diagnostic, findings.
 Linear reticular opacities are the most common
findings.
 A ground-glass pattern is less common.
 Airspace consolidation in eosinophilic pneumonia and
COP.
 The presence of nodules in HSP, granulomatous
disease (eg, sarcoidosis), PLCH, and RBILD.
 Large cystic spaces in PLCH and LAM.
 Honeycombing is indicative of end-stage disease and
carries a poor prognosis
Other Tests
Pulmonary function testing may demonstrate:
 reduced lung volumes with testing of total
lung capacity, forced expiratory volume in 1
second, and forced vital capacity.
 Diffusing capacity for carbon monoxide
(DLCO) is generally reduced.
 Static pulmonary compliance is reduced.
 An obstructive defect may be present in
patients with coexistent chronic obstructive
pulmonary disease, sarcoidosis, LAM, and
tuberous sclerosis.
Arterial blood gas analysis often reveals an
increased alveolar-arterial partial pressure
of oxygen gradient and a reduced partial
pressure of oxygen (Oxygen desaturation
is common, Pulmonary exercise testing
may demonstrate decreased exercise
capacity with exercise-limiting
impairments in ventilation and gas
exchange)
 Bronchiolar lavage is useful in evaluating
the possibility of infection or malignancy or
for eosinophilic pneumonia. 
 Transbronchial and endobronchial lung
biopsies may be diagnostic, particularly for
sarcoidosis or lymphangitic spread of
carcinoma but frequently are not useful for
other diagnoses.
 Open or thoracoscopic lung biopsy to
establish a definitive diagnosis. Currently,
video-assisted thoracoscopic lung biopsy is
the preferred method.
TREATMENT
 corticosteroids (eg, prednisone)
 cytotoxic
agents (eg,
cyclophosphamide, azathioprine,
methotrexate)
 Other immunosuppressive or
antifibrotic agents such as
colchicine, cyclosporine, and D-
penicillamine may have a role in
specific cases.
 Interferon-gamma-1b, pirfenidone, and N-
acetylcysteine have been studied for the
treatment of IPF.
 recombinant TNF-alpha antagonists and
tyrosine kinase inhibitors, are currently
under investigation
 More recently, lung transplantation has
become a treatment option for selected
patients with advanced disease
refractory to medical therapy