Medication Summary
Medications are best used for specific diagnoses. Corticosteroids, cytotoxic agents, and immunosuppressive agents have been used with varying success.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and can modify the body's immune response.
Prednisone (Sterapred)
Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, it may decrease inflammation. It is an oral corticosteroid with relatively less mineralocorticoid activity. Therapy is best prescribed in consultation with a pulmonary disease specialist.
Cytotoxic agents
Class Summary
These agents inhibit cell growth and proliferation.
Cyclophosphamide (Cytoxan, Neosar)
Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, its mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells of the immune system. It is a possible steroid-sparing medication.
Azathioprine (Imuran)
Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting the synthesis of DNA, RNA, and proteins. These effects may decrease the proliferation of immune cells and result in lower autoimmune activity. It is a possible steroid-sparing medication.
Anti-inflammatory agents
Class Summary
These agents reduce inflammation by inhibiting key steps of the immune system.
Colchicine
Colchicine decreases leukocyte motility and phagocytosis observed in inflammatory responses.
Pulmonary, Tyrosine Kinase Inhibitors
Class Summary
These agents target numerous intracellular pathways to reduce the fibrosis process by interrupting cell signaling pathways.
Nintedanib (Ofev)
Nintedanib is a tyrosine kinase inhibitor that targets growth factors that have been shown to potentially be involved in pulmonary fibrosis (eg, vascular endothelial growth factor receptor [VEGFR], fibroblast growth factor receptor [FGFR], platelet derived growth factor receptor [PDGF]).
Pirfenidone (Esbriet)
Pirfenidone is an inhibitor of transforming growth factor-beta (TGF-β), and it also inhibits the synthesis of tumor necrosis factor-alpha (TNF-α).
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Approximately half of the patients with idiopathic pulmonary fibrosis develop clubbing. Clubbing is commonly seen in patients with asbestosis.
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Lung volume is plotted against transpulmonary pressure. Compliance is the change in volume for a given change in pressure. A patient with emphysema has a higher lung compliance compared with a patient with no lung disease, while a patient with restrictive lung disease has a reduction in compliance.
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Idealized flow volume curves for normal, obstructive, and restrictive lungs.
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The expiratory flow volume curves of 2 patients are depicted graphically. A is a patient with restrictive lung disease (idiopathic pulmonary fibrosis), low forced vital capacity (FVC), but an increased ratio of forced expiratory volume in 1 second (FEV1) to FVC because of increased elastic recoil. B is a patient with chronic obstructive lung disease whose FEV1/FVC ratio is low but whose lung volumes are increased.
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Pulmonary function test results from a patient with restrictive lung disease.
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Gross pathology of small and firm lungs due to restrictive lung disease from advanced pulmonary fibrosis.
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Intrinsic lung disease may progress to extensive fibrosis, regardless of etiology. This is described as honeycomb lung.
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End-stage sarcoidosis.
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Usual interstitial pneumonitis (left).
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Usual interstitial pneumonitis (right).
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Histopathology of a case of idiopathic pulmonary fibrosis. Alveolitis with fibroblast proliferation and collagen deposition is present.
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In usual interstitial pneumonitis or idiopathic pulmonary fibrosis, subpleural and paraseptal inflammation is present, with an appearance of temporal heterogeneity. Patchy scarring of the lung parenchyma and normal, or nearly normal, alveoli interspersed between fibrotic areas are the hallmarks of this disease. Additionally, the lung architecture is completely destroyed.
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Characteristic features of usual interstitial pneumonitis as described in the image below.
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Cryptogenic organizing pneumonia (also called proliferative bronchiolitis) is often patchy and peribronchiolar. The proliferation of granulation tissue within small airways and alveolar ducts is excessive and is associated with chronic inflammation of surrounding alveoli.
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Cryptogenic organizing pneumonia, as described in the image below, showing a close-up view of fibrogranulation tissue in terminal airspaces.
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Granulomatous lung diseases are marked by granulomas characterized by the accumulation of T lymphocytes, macrophages, and epithelioid cells. These may progress to pulmonary fibrosis. This low-power image shows well-formed granuloma along the airway.
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Multiple well-formed noncaseating granulomas secondary to sarcoidosis.
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Sarcoid granulomas.
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High-power view of sarcoid granuloma shows giant cells.
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A patient who developed restrictive lung disease had findings of cryptogenic organizing pneumonia on an open lung biopsy specimen.
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A patient who developed restrictive lung disease had findings of cryptogenic organizing pneumonia on an open lung biopsy specimen. The biopsy sample shows intraluminal buds of granulation tissue.
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Lymphocytic interstitial pneumonitis, for which the prominent finding is a lymphoid infiltrate that involves both the interstitium and alveolar spaces.
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Usual interstitial pneumonitis honeycombing.
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Chest radiograph of a 67-year-old man diagnosed with idiopathic pulmonary fibrosis, based on open lung biopsy findings. Extensive bilateral reticulonodular opacities are seen in both lower lobes.
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High-resolution CT scan of the same patient in the image below demonstrates peripheral honeycombing and several areas of ground-glass attenuation. Ground-glass opacification may correlate with active alveolitis and a favorable response to therapy.
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A CT scan image from a 59-year-old woman shows advanced pulmonary fibrosis. Extensive honeycombing and traction bronchiectasis are present.
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Restrictive lung disease may occur in stage II and stage III sarcoidosis. In this image, mediastinal lymphadenopathy is shown secondary to stage II disease.
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Sarcoidosis on CT scan shows nodules in midlung zones. These nodules are predominantly along the bronchovascular bundles and in a subpleural location.
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Restrictive lung disease secondary to sarcoidosis.
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A chest radiograph of stage III sarcoidosis. This stage refers to pulmonary infiltrates without evidence of mediastinal lymphadenopathy.
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Chest radiograph from a 39-year-old woman with severe kyphoscoliosis who developed hypercapnic respiratory failure. Spirometry findings showed a severe restrictive lung disease, with a forced expiratory volume in one second of 0.4 L/s and a forced vital capacity of 0.5 L.
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The flow volume curve of a patient with lung fibrosis.
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Likely case of idiopathic pulmonary fibrosis, which should be treated with prednisone.
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Pressure volume curve comparing lungs with emphysema, lungs with restrictive disease, and normal lungs.
Tables
Causes |
Examples |
Diagnosis |
PFT Findings |
Pleural |
Trapped lung, pleural scarring, large pleural effusions, chronic empyema, asbestosis |
Radiography, CT scanning, pleural manometry, pleural biopsy |
Low RVa, low TLC, low FVC |
Alveolar |
Edema, hemorrhage |
Radiography, CT scanning, physical examination |
Increased DLCOb in hemorrhage (Intrapulmonary hemoglobin absorbs the carbon monoxide, thus increasing the DLCO reading.) |
Interstitial |
Interstitial lung disease including IPFc, NSIPd, COPe |
Radiography, CT scanning, physical examination, echo often shows pulmonary hypertension |
Low RV, low FVC, low TLC, decreased DLCO, poor lung compliance |
Neuromuscular |
Myasthenia gravis, ALSf, myopathy |
Physical examination, EMGsg, serology |
Low RV, low TLC, low NIFh, low MMVi |
Thoracic/extrathoracic |
Obesity, kyphoscoliosis, ascites |
Physical examination |
Low ERVj and FRC in obesity, low VCk, TLC, FRCl in kyphoscoliosis |
aResidual volume. bDiffusion capacity of the lungs for carbon monoxide. cIdiopathic pulmonary fibrosis. dNonspecific interstitial pneumonitis. eCryptogenic organizing pneumonia. fAmyotrophic lateral sclerosis. gElectromyography. hNegative inspiratory force. iMaximal voluntary ventilation. jExpiratory reserve volume. kVital capacity. lFunctional residual capacity. |
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Features |
AIP |
UIP |
NSIP |
COP |
Pathologic |
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Temporal appearance |
Uniform |
Heterogeneous |
Uniform |
Uniform |
Interstitial inflammation |
Scant |
Scant |
Usually prominent |
Variable |
Collagen fibrosis |
No |
Patchy |
Variable, diffuse |
No |
Fibroblast proliferation |
Diffuse, interstitial |
Patchy (fibroblast foci) |
Occasional |
Patchy, airspace |
COP areas |
Rare |
No |
Rare |
-- |
Honeycomb changes |
Rare |
Yes |
Rare |
No |
Hyaline membranes |
Yes, often focal |
No |
No |
No |
