Idiopathic Pulmonary Fibrosis Imaging 

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary disease of unknown etiology. It is primarily diagnosed on the basis of clinical, physiologic, and radiologic criteria. In its International Consensus statement, the American Thoracic Society defines IPF as a specific chronic interstitial pneumonia that is limited to the lung and that has the histologic appearance of usual interstitial pneumonia (UIP) on open or thoracoscopic biopsy. No specific pathognomonic clinical or pathologic findings are associated with IPF, and the diagnosis is made after other causes of interstitial lung disease are excluded.^{[1, 2, 3, 4, 5, 6, 7]} Radiologic characteristics of pulmonary fibrosis appear in the image below.

The diagnosis is confirmed with a lung biopsy, but the histology shows striking variation from one region to the next (ie, the disease is characterized by histologic temporal and spatial heterogeneity). It is not unusual to find areas of normal lung next to areas with severe thickening of alveolar walls. Therefore, findings on bronchoscopic or percutaneous lung biopsy are difficult to interpret. Open lung biopsy and video-assisted thoracoscopic lung biopsy are the preferred methods.

IPF usually affects patients 50-70 years of age. Most series report a male preponderance, with a male-to-female ratio of 2:1. Clinical features consist of progressive exertional dyspnea; the presence of interstitial infiltrates, as evidenced on chest radiographs; and physiologic evidence of restriction and impaired gas exchange on pulmonary function testing.

Patients are generally treated with corticosteroids, other immunosuppressants, or both.

The prognosis of patients with IPF is poor; most patients die of respiratory failure. The mean survival is approximately 4 years.

Preferred examination

The diagnosis of IPF is made on the basis of the patient's history, clinical findings, pulmonary physiology, and imaging results. The diagnosis is one of exclusion. Nonidiopathic causes must be excluded first because of the important therapeutic implications. After nonidiopathic causes are excluded, further investigation of patients with IPF typically reveals radiographic abnormalities and restrictive lung physiology with decreased diffusion capacity.^{[8, 9, 10]}

Plain chest radiography is usually the first investigation performed for patients with suspected interstitial lung disease. However, the findings on conventional radiography are highly nonspecific.

High-resolution computed tomography (HRCT) scanning defines the underlying lung parenchymal abnormalities better than does plain radiography.

Studies have shown that HRCT may obviate surgical lung biopsy in some patients. Raghu et al compared the diagnostic accuracy of clinical evaluation in combination with HRCT with the accuracy of histology of surgical lung-biopsy samples.^[11] Clinical assessment in conjunction with careful review of HRCT scans was 60% sensitive and 97% specific for IPF. However, although HRCT may obviate the need for tissue diagnosis in 60% of patients, surgical lung biopsy is still needed in 40%.

For diagnoses other than IPF, a combination of clinical assessment and HRCT is neither sensitive nor specific enough to be relied on without surgical biopsy. Open lung biopsy remains the criterion standard. In immunocompetent patients, the benefit is relatively low because corticosteroid therapy is frequently administered after biopsy. In immunocompromised patients, approaches to therapy change substantially after tissue confirmation, but the mortality rate is high. Therefore, open biopsy should be performed only in patients in whom the diagnosis is likely to change therapy and in patients who have a reasonable prognosis.

Radionuclide scanning with gallium-67 may depict interstitial fibrosis and may show changes early. This feature may be of therapeutic benefit, but the changes are nonspecific and do not obviate the need for lung biopsy.

The radiographic pattern differs with the stage of the disease. Early in the disease, the most common radiographic changes are an interstitial shadowing of small (1- to 2-mm), irregular opacities, which are seen in about three fourths of patients. Less common are small, round opacities, which are seen in one fifth of patients. This finding is generally known as reticulonodular opacities. Septal lines are occasionally observed. The distribution is predominantly basal. (See the image below.)

Peripheral accentuation is also a common feature, but it is more easily appreciated on CT scans than on plain chest radiographs.

The pattern is usually symmetrical. Another common pattern is hazy, ground-glass opacification, which is either diffuse or patchy. Volume loss and a raised diaphragm are seen in up to 60% of patients. This may be accompanied by basal discoid atelectasis.

Pleural disease is not typical of IPF. Its presence should raise the possibility of other conditions, such as asbestosis, rheumatoid pulmonary disease, or systemic lupus. Pneumothorax, pneumomediastinum, or both have been reported in a few patients; these conditions have been associated with bullae in the lung parenchyma.

With progression of alveolitis to fibrosis, the initial fine lines become coarse, and small (2-mm) cysts appear. These cysts coalesce and increase to 5-7 mm in diameter; they appear as ring opacities within the honeycomb lung. As fibrosis worsens, the honeycombing becomes coarser with larger honeycomb cysts, and further volume loss occurs. In advanced stages, there is radiographic evidence of pulmonary arterial hypertension.

Degree of confidence

The radiographic findings are not correlated with the stage of the disease, the histology, the respiratory symptoms, the respiratory function tests, or the prognosis.

In the majority of patients with IPF, the chest radiograph is abnormal at presentation; previous radiographs often will have shown reticular shadowing, even before symptom development.^[12] Chest radiography is frequently the first investigation employed for patients with IPF; physiologic testing and HRCT scanning follow.

False positives/negatives

For symptomatic patients in whom the diffusion capacity is abnormal, results of chest radiography may be normal. For other patients, the radiographic appearances are abnormal before clinical symptoms appear. Results of HRCT scanning are abnormal for most patients with IPF.

For patients with IPF, HRCT scan findings may be used to predict outcomes and to guide the treatment, because the findings are well correlated with the histologic pattern of IPF (see the images below). On HRCT, end-stage lung disease is characterized by honeycombing without ground-glass attenuation in typical distribution; with such findings on HRCT, the diagnosis may be made with confidence. This spares patients the risk of invasive diagnostic processes, such as a lung biopsy. In the active stage, scans demonstrate ground-glass attenuations. The active stage of the disease, which is characterized by active alveolitis, is potentially reversible and potentially amenable to treatment, unlike end-stage disease, which is irreversible.^{[13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]}

On HRCT, IPF is commonly characterized by patchy and predominantly peripheral, subpleural, and bibasilar reticular opacities. The distribution is predominantly posterior. It is often associated with traction bronchiectasis and subpleural honeycombing.

Ground-glass attenuations are relatively uncommon; they usually progress to the more common reticular attenuations and honeycombing. HRCT scans have been reported to show honeycombing in 90% of patients with IPF.

When a trained observer interprets HRCT, the accuracy of a diagnosis of IPF or cryptogenic fibrosing alveolitis (CFA) appears to be about 90%. Such a confident diagnosis is made in about two thirds of patients with histologic UIP.

In cases of suspected IPF in which lung HRCT shows more than 30% ground-glass attenuation, consideration should be given to other diagnoses; alternative diagnoses include desquamative interstitial pneumonitis, idiopathic bronchiolitis obliterans organizing pneumonia, respiratory bronchiolitis–associated interstitial lung disease, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia.

Degree of confidence

The accuracy of the diagnosis of IPF is significantly increased with HRCT, as compared with chest radiography. When a trained observer performs HRCT, the accuracy of the diagnosis is reported to be about 90%.^[25]

False positives/negatives

One third of all cases of IPF are missed on HRCT; a confident diagnosis of IPF is made in about two thirds of cases.^[25]

Nuclear medicine currently has little, if any, role in the management of IPF.

In cases of IPF, perfusion lung scintigraphy shows nonspecific, subsegmental mismatched perfusion defects. These are not correlated with clinical severity.

Gallium-67 imaging has not proven to be of value in cases of established IPF.^[26]

Technetium-99m diethylenetriamine penta-acetic acid (DTPA) is cleared more rapidly when capillary permeability is increased than when it is not, and the findings may provide an index of lung inflammation.^[27] Fluorodeoxyglucose (FDG) positron-emission tomography (PET) may show FDG accumulation in the lung bases; such findings correlate with the honeycomb fibrosis seen on high-resolution HRCT.^{[28, 29, 30, 31, 32]}