eMedicine Specialties > Pulmonology > Interstitial Lung Diseases
Pulmonary Fibrosis, Idiopathic: Differential Diagnoses & Workup
Updated: Jun 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Chronic aspiration pneumonia
Collagen-vascular diseases
Granulomatosis (sarcoidosis, histoplasmosis)
Lung cancer (especially bronchoalveolar carcinoma)
Radiation pneumonitis
Recurrent intra-alveolar hemorrhage
Recurrent pulmonary edema
Workup
Laboratory Studies
Blood test results are not specific for idiopathic pulmonary fibrosis (IPF); however, some abnormal values can be related to the pathophysiology of idiopathic pulmonary fibrosis. Normal hemoglobin and leukocyte values are found in persons with idiopathic pulmonary fibrosis; however, an elevated hemoglobin value may reflect chronic hypoxemia secondary to idiopathic pulmonary fibrosis. The erythrocyte sedimentation rate is elevated in 50% of patients. Serologic test results (eg, antinuclear antibodies, rheumatoid factor, circulating immune complexes) are nonspecific; however, high titers should raise the possibility of connective-tissue disorders.
Imaging Studies
Chest radiography
Radiographic findings are not specific for idiopathic pulmonary fibrosis. At the time of diagnosis of idiopathic pulmonary fibrosis, almost all patients have abnormal chest radiography findings. Bilateral diffuse reticular or reticulonodular infiltrates are observed, predominately at the periphery and the bases.
Chest radiograph of a patient with idiopathic pulmonary fibrosis showing bilateral lower-lobe reticular opacities (red circles).
HRCT scanning
A typical pattern on HRCT scans that correlates with histologic UIP is characterized by reticular opacities, traction bronchiectasis, honeycombing, and architectural distortion with basal and peripheral distribution. Ground-glass opacity, if present, is less extensive than the reticular abnormality.
The term reticular opacities refers to the fine network of lines that sometimes include interlobular thickening or intralobular lines. Honeycombing is recognized by the presence of one or more rows of clustered cysts (<5 mm in diameter), which are almost always subpleural. Reticular opacities and honeycombing (seen on HRCT scans) correlate histologically with fibrosis and honeycombing, respectively. See Media Files 2-3 below.
The presence of pleural effusions, hilar adenopathy, and localized parenchymal densities are unlikely, and these findings suggest a different disease. Other entities that can have similar HRCT scan findings include nonspecific interstitial pneumonia and chronic hypersensitivity pneumonitis.11 See Media File 4 and Table 2 below.
HRCT scanning has improved the ability to make a definitive diagnosis (in 50-90% of cases, depending on the experience of the observer) without performing a biopsy in patients with idiopathic pulmonary fibrosis.12 The higher extent of honeycombing found on HRCT scans is an independent predictor of mortality.13 Patients with typical idiopathic pulmonary fibrosis changes on HRCT scans have a worse prognosis than patients with atypical idiopathic pulmonary fibrosis findings (but biopsy-proven diagnosis).14
Classic honeycombing (red circle) in a patient with a diagnosis of idiopathic pulmonary fibrosis
Patient with a diagnosis of usual interstitial pneumonia. Note the reticular opacities (red circle) distributed in both lung bases, with minimal ground-glass opacities (blue circles).
Table 2. Radiologic Characteristics Seen on HRCT Scans of Different Types of Pneumonitis
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Table
| | Usual Interstitial Pneumonia | Nonspecific Interstitial Pneumonitis | Hypersensitivity Pneumonitis |
Hallmark Findings | Honeycombing and reticular opacities | Ground-glass and reticular opacities | Nodules and mosaic attenuation |
Other findings | Ground-glass opacities typically absent | Honeycombing typically absent (except in fibrotic nonspecific interstitial pneumonitis) | Ground-glass and reticular opacities |
Location | Lower-lobe predominance (subpleural) | Peribronchovascular predominance | Throughout the lungs |
| | Usual Interstitial Pneumonia | Nonspecific Interstitial Pneumonitis | Hypersensitivity Pneumonitis |
Hallmark Findings | Honeycombing and reticular opacities | Ground-glass and reticular opacities | Nodules and mosaic attenuation |
Other findings | Ground-glass opacities typically absent | Honeycombing typically absent (except in fibrotic nonspecific interstitial pneumonitis) | Ground-glass and reticular opacities |
Location | Lower-lobe predominance (subpleural) | Peribronchovascular predominance | Throughout the lungs |
Patient with nonspecific interstitial pneumonitis. Note the predominance of ground-glass opacities (blue circle) and some reticular lines (red arrow).
Other Tests
The typical finding is a restrictive ventilatory defect with a reduced diffusing capacity; however, these findings are nonspecific and should be used in conjunction with clinical, radiographic, and histologic information to ensure an accurate diagnosis.
Obstructive ventilatory defect is unusual and, if present, should raise the possibility of a different diagnosis. The most common abnormality found in patients with idiopathic pulmonary fibrosis is a decreased diffusing capacity. Diffusing capacity also correlates with the extent of disease as indicated on HRCT scans. Different studies have shown that a decreased baseline diffusing capacity is associated with high mortality in patients with idiopathic pulmonary fibrosis.16
Serial forced vital capacity and diffusing capacity measurements provide valuable information in determining disease progression and response to therapy. Oxygen desaturation during exercise of less than 88% at baseline over the course of short-term follow-up identifies patients at particularly high risk of mortality.17
Bronchoalveolar lavage
Bronchoalveolar lavage is not required for diagnosis; however, findings help exclude other diseases such as infection, alveolar proteinosis, eosinophilic pneumonia, and malignancy. Most patients with idiopathic pulmonary fibrosis have an increase in macrophages, polymorphonuclear cells, and cytokines, with a paucity of lymphocytes. An increased neutrophil percentage could be a predictor of early mortality in patients with idiopathic pulmonary fibrosis.18
Echocardiography
Patients with severe and advanced idiopathic pulmonary fibrosis show signs of pulmonary hypertension on echocardiograms (pulmonary artery systolic pressure >30 mm Hg at rest with dilated right-sided chambers).
Procedures
Bronchoscopy with transbronchial biopsy and bronchoalveolar lavage can help to exclude some forms of diffuse interstitial disease. However, this procedure is often of limited value to diagnose idiopathic pulmonary fibrosis because tissue samples may be inadequate.
Surgical lung biopsy (open lung biopsy or video-assisted thoracoscopic lung biopsy) is much more sensitive to show histologic findings related to idiopathic pulmonary fibrosis. Surgical lung biopsy is not required in all patients with suspected idiopathic pulmonary fibrosis, such as those with a highly suggestive clinical presentation and typical findings after HRCT scanning. If the clinical features are inconsistent with idiopathic pulmonary fibrosis or if atypical HRCT scan features are present, consider performing a surgical lung biopsy.
According to the 2000 ATS/ERS international consensus statement, a correct clinical diagnosis (in the absence of surgical lung biopsy findings) of idiopathic pulmonary fibrosis must include all of the major criteria and at least 3 of the 4 minor criteria.
- Major criteria
- Exclusion of other known causes of intersitial lung diseases (eg, drug toxicities, environmental exposures, connective-tissue diseases)
- Abnormal pulmonary function study results that include evidence of restriction (reduced vital capacity often with an increased ratio of forced expiratory volume in 1 second to forced vital capacity) and impaired gas exchange
- Bibasilar reticular abnormalities with minimal ground-glass opacities on HRCT scan images
- Transbronchial lung biopsy or bronchoalveolar lavage findings showing no features to support an alternative diagnosis
- Minor criteria
- Patient older than 50 years
- Insidious onset of otherwise unexplained dyspnea upon exertion
- Duration of illness longer than 3 months
- Bibasilar, inspiratory crackles
Histologic Findings
Lung biopsy of patients with idiopathic pulmonary fibrosis shows a histologic pattern of UIP characterized by a heterogeneous, variegated appearance with alternating areas of normal lung, interstitial inflammation, fibrosis, and honeycomb change (patchwork appearance).
Fibroblast foci (ie, the combination of fibroblasts and myofibroblasts arranged in a linear fashion within pale-staining matrix) are not specific for UIP, but they are an important diagnostic criterion that is associated with poor survival in patients with idiopathic pulmonary fibrosis.
Honeycomb change is defined as cystic, dilated bronchioles (containing mucous and leukocytes) lined by columnar respiratory epithelium in scarred, fibrotic lung tissue.
Fibrotic scars (dense eosinophilic collagen without associated honeycomb change) are also characteristic for UIP.
UIP is not specific for idiopathic pulmonary fibrosis and can also be seen in patients with other underlying conditions or etiologies such as autoimmune diseases.
During the period of accelerated idiopathic pulmonary fibrosis, lung biopsy typically shows a combination of UIP with superimposed diffuse alveolar damage, characterized by fibroblast proliferation of the alveoli septa, hyperplasia of type 2 pneumocytes, and hyaline membrane remnants.
Patchwork distribution of abnormalities in a classic example of usual interstitial pneumonitis (low-magnification photomicrograph; hematoxylin and eosin stain; original magnification, X4). Courtesy of Chad Stone, MD.
More on Pulmonary Fibrosis, Idiopathic |
| Overview: Pulmonary Fibrosis, Idiopathic |
 Differential Diagnoses & Workup: Pulmonary Fibrosis, Idiopathic |
| Treatment & Medication: Pulmonary Fibrosis, Idiopathic |
| Follow-up: Pulmonary Fibrosis, Idiopathic |
| Multimedia: Pulmonary Fibrosis, Idiopathic |
| References |
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References
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Further Reading
Keywords
IPF, cryptogenic fibrosing alveolitis, usual interstitial pneumonitis, UIP, interstitial disease, intersitial lung disease, desquamative interstitial pneumonitis, DIP, cor pulmonale, pneumothorax, thromboembolism disease, thromboembolic disease, chronic fibrosing alveolitis, fibrosing alveolitis, Hamman-Rich syndrome, collagen-vascular disease, collagen vascular disease, alveolar injuries, alveolar injury, inflammation of the lung parenchyma, fibrosis of the lung parenchyma, Ebstein-Barr virus, chronic aspiration secondary to gastroesophageal reflux
