Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Assistant Professor at NSU
The cause of interstitial lung disease (ILD) is often unknown and treatment with oral steroids is often ineffective.
30% of ILD cases are due to idiopathic pulmonary fibrosis (IPF). IPF is a diagnosis of exclusion.
Interstitial Lung Diseases (ILD) (click to enlarge the image).
Pathology of ILD
Mechanisms of IPF (click to enlarge the image). Image source: PLoS Medicine, Creative Commons license.
Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology and uncertain pathogenesis, and there are no effective therapies. This is a devastating disease with an average survival of less than three years from the time of diagnosis.
Blood Test for Lung Fibrosis
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. Elevation of plasma matrix metalloproteinases (MMP1 and MMP7) may help to confirm a diagnosis of IPF and probably non-specific interstitial pneumonia (NSIP), and help to distinguish these diseases from hypersensitivity pneumonitis (HP), sarcoidosis, and perhaps other fibrotic lung diseases. However, a normal individual value does not exclude these diagnoses, as there is considerable overlap between levels of these MMPs in healthy people and patients with other chronic lung diseases. However, the plasma concentrations of MMP7 may be useful in following disease progression and even in facilitating early diagnosis. Source: PLoS Medicine, Creative Commons license.
A normal CXR does not rule out ILD. HRCT scan is the preferred imaging method for diagnosis of ILD. HRCT is false-negative in 12% of biopsy-proven ILD cases.
- ground glass appearance - alveolar inflammation, alveolitis
- reticular pattern with septal thickening and honeycombing -- IPF
Biopsy can be useful in determine which patients may respond to CS. HRCT determines which patient needs lung biopsy. Biopsy can be done if there is ground glass appearance on HRCT with less than 25% reticular changes. If there are more than 25% reticular changes (more than 25% of lungs are inviolved), no biopsy is advised since CS will likely not be beneficial.
There are 4 histology patterns in ILD -- BLUD:
BIP, bronchiolitis with interstitial pneumonia
LIP, lymphocytic interstitial pneumonia
UIP, usual interstitial pneumonia, this is IPF
DIP, desquamative interstitial pneumonia
- CD8 in HP, "H" looks like "8"
- CD4 in sarcoidosis
Autoantibodies can show which ILD is due to connective tissue diseases (CTD):
- SLE (ANA, anti-DNA antibodies, Sm antigen)
- Sjögren’s syndrome (SS-A, SS-B)
- RA (rheumatoid factor, RF)
RF and ANA are increased in 30% of patients with IPF without evidence of CTD.
Differential diagnosis of ILD
A history of exposure to antigen (Ag) can help in diagnosis of hypersensitivity pneumonitis (HP):
- microbial aerosols
- contaminated humidifiers
- exotic birds
- moldy or wet hay in poorly ventilated barns
History can help in diagnosis of:
- hypersensitivity pneumonitis (HP):
- asbestosis - miners, shipbuilders, pipe fitters
- other pneumoconioses - remote exposure to fibrogenic dusts such as silica (foundry workers)
- berylliosis -- beryllium is a metal used in the ceramics, computer, and electronics industries
- drugs - nitrofurantoin, gold, methotrexate, amiodorone, or sulfonamides
Treatment of ILD
DIP and LIP can respond to CS. If biopsy shows UIP, CS are useless and supportive care is advised.
UIP, IPF has the worst prognosis.
- 66% in UIP
- 28% in DIP
Reticular pattern, more than 25% of lung involved
Resistance to CS
The algorithm is:
HRCT --> if less than 25% reticular pattern --> lung biopsy --> if DIP or LIP --> oral CS.
The investigational antifibrotic agent pirfenidone may slow progression of idiopathic pulmonary fibrosis.
Triple therapy for idiopathic pulmonary fibrosis was investigated in "hear PANTHER roar" and included N-acetylcysteine (NAC), prednisolone, and azathioprine (Thorax, 2012). Triple therapy in idiopathic pulmonary fibrosis (prednisolone/azathioprine/N-ACC) linked to excess deaths (11% vs. 1%) (ERJ, 2012).
Allergy and Immunology MKSAP, 3rd edition.
A Blood Test for Lung Fibrosis. Peter J. Barnes. PLoS Medicine, 04/2008.
ATS: Antifibrotic Slows IPF Progress. ATS: American Thoracic Society Meeting, 2009.
Occupational Lung Diseases: Slideshow. Medscape.
Sarcoidosis is a Th1/Th17 multisystem disorder, Thorax 2011.
Idiopathic pulmonary fibrosis. The Lancet, 2011.
Audio and Video
Video: Cherry Wongtrakool, MD Discusses Patterns of Restrictive Lung Disease on Spirometry. InsiderMedicine.