Interstitial Lung Disease- Prager

Question 1

Definition of interstitial lung disease

Answer 1

A diverse group of lung infiltrations that
cause disruption of the alveolar structures
and have in common clinical, radiographic
and physiologic consequences

Restrictive disease but can have additional obstructive disease, especially in smoking

Question 2

Pathology of ILD

Answer 2

In ILD, the alveolar wall becomes
anatomically altered by a variety of
inflammatory cells, hyperplastic alveolar
epithelial lining cells, proliferating
fibroblasts, myofibroblasts, disordered
collagen deposition, and smooth muscle
proliferation

Question 3

What are the classifications of diffuse parenchymal lung disease?

Answer 3

2 basic categories: DPLD of Known Etiology (autoimmune collagen vascular disease, drugs, environmental/pneumoconioses) and unknown (Idiopathic interstitial pneumonia, Granulomatous DPLD-more like known cause because associated with sarcoidosis and hypersensitivity pneumonitis, other forms).

Question 4

How does idiopathic interstitial pneumonia contrast with scarring from other pneumonias?

Answer 4

In TB and other pneumonias get scarring that is stable and localized. In IIPs fibrosis is a progressive and diffuse process. Unknown etiology but assume inhalation of organic or inorganic substance plays a role. Chain of inflammation and fibrosis.

Question 5

Important types of idiopathic interstitial pneumonia

Answer 5

Idiopathic pulmonary fibrosis/Usual Interstitial Pneumonia (IPF/UIP)-Not inflammatory process, mortality almost as high as lung cancer, slow decline with acute exacerbations, heterogenous normal long and fibrosis and honeycomb

Nonspecific Interstitial Pneumonia (NISP)-higher survival, treated with antiinflammatories

Question 6

Major diagnostic criteria of IPF

Answer 6

 Exclusion of other known causes of ILD such as
certain drug toxicities, environmental exposures, and
connective tissue diseases
 Abnormal pulmonary function studies that include
evidence of restriction (reduced VC, often with an
increased FEV1/FVC ratio) and impaired gas
exchange [increased P(A–a)O2, decreased PaO2 with
rest or exercise or decreased DLCO-HALLMARK]
 Bibasilar reticular abnormalities with minimal ground
glass opacities on HRCT scans
 Per the discretion of the clinician: transbronchial lung
biopsy or BAL showing no features to support an
alternative diagnosis

Biopsy a bad idea because need a big enough sample to sample heterogeneity and in advanced cases of ground glass opacities would cause further injury

Question 7

Clinical features of IPF

Answer 7

 Age >50 yr
 Insidious onset of otherwise unexplained
cough and dyspnea on exertion
 Physical activity limited; quality of life
decreased
 Bibasilar, inspiratory crackles, rales (dry or
Velcro-type in quality)
 Median survival 2.5-3.5 years after
diagnosis

 Symptoms
 Dyspnea with exertion (eventually at rest)
 Non productive cough
 History
 Occupational exposure
 Drug history
 Review of systems (joints, skin, etc.)

 Tachypnea
 Dry cough
 Basal inspiratory velcro rales (crackles)
 Cyanosis—late stage
 Clubbing—some cases

Question 8

Hypotheses for pathogenesis of IPF

Answer 8

 Noninflammatory (multiple hit) hypothesis:
fibrosis results from epithelial injury and
abnormal wound healing in the absence of
chronic inflammation, growth factor mediated, including (myo)fibroblast proliferation and ECM deposition for progressive fibrosis and lack of architecture

 Vascular remodeling: chemokine imbalance causes increased angiogenesis, aberrant vascular
remodeling supports fibrosis, and may contribute
to increased shunt and hypoxemia (V/Q mismatch)

Still under investigation

Question 9

What sort of occupational exposure leads to ILD?

Drugs?

Answer 9

• Inorganic dusts (pneumoconioses)

 Silicosis, asbestosis, berylliosis, talcosis, coal
miner’s lung (black lung)

• Organic dusts

 Pigeon breeder’s lung
 Bagassosis (sugar cane)
 Farmer’s lung (silage)
 Air humidifier lung

 Antibiotics (Nitrofurantoin, cephalosporins)
 Antiarrhythmics (Amiodarone)
 Chemotherapeutic agents (Bleomycin, methotrexate, busulfan)

Question 10

What is Sarcoidosis?

Answer 10

One of Collagen Vascular Related causes of ILD

 Inflammatory disease characterized by
non-caseating granulomas in many organs
 Immune-mediated disease
 T-helper cells reduced in blood but
increased in granulomas
 Thoracic lymph nodes most often involved,
but lungs, liver, spleen, marrow, heart,
skin, muscle, as well-interstitium

 65-70% of patients recover spontaneously
 20% have permanent loss of lung function
 5-10% die of progressive pulmonary
fibrosis and cor pulmonale
 Corticosteroids/antiinflammatories may be of benefit in
patients with progressive disease
 Chest film: hilar adenopathy +/- interstitial
disease

Question 11

Physiomechanics of ILD

Answer 11

Decreased compliance (stiff lungs), decreased lung volume (low FVC) but pulmonary restriction and preservation of flow rates (FEV1 low-normal because fibrosis stabilizes airways, normal-high FEV1/FVC), low tidal volumes, tachypnea, exercise induced arterial hypoxemia (normal at rest because dependent on cardiac output, less time in pulmonary capillary), elevated A-a gradient, low TLC, low RV, low FRC

Decreased DLCO

Question 12

Imaging in ILD

Answer 12

CXR: Diffuse abnormalities

 Increased interstitial shadows
 Linear
 Finely nodular
 Small lung volumes
 Honeycombing

Count ribs to determine height of diaphragm: use inhale to get lowest level, if low-obstructive disease

CT scan:

 Detection of disease in patients with
normal X rays
 Staging of disease
 Ground glass infiltrates: hazy, active inflammation, often reversible component of disease
 Linear fibrotic changes—irreversible changes, scarring

Early stage is more at the base and edges.

Traction bronchiectasis: shouldn’t normally be seeing bronchi in periphery, scar tissue is pulling it out
 Monitoring disease progression/response
to therapy

Question 13

Lung Biopsy in ILD

Answer 13

• Transbronchial biopsy via bronchoscope

 Least invasive, but provides small, inadequate
pieces of tissue.
 Useful in diagnosis of cancer and
granulomatous diseases, and for culture

Not useful because may not get true sample, not homogeneous

• VATS (video-assisted thoracoscopic) lung biopsy

 More invasive but small incisions; safe;
provides much larger specimens; very helpful

Question 14

Treatment of ILD

Answer 14

Corticosteroids for NSIP but not for IPF

 Mycophenolate (Cellcept): antiinflammatory, may be used as
steroid sparing agent
 Azathioprine (Imuran) may be used as
steroid sparing agent

New: Tyrosine kinases inhibit fibroblast proliferation

Lung transplant (last resort, poor survival, shortage)