concern about infection (because host defenses may be impaired by the drug or the underlying malignancy), dissemination of the malignancy through the lung, bleeding into the lung, and, in patients who have received radiation therapy, toxic effects from irradiation. When the diagnosis is not clear, a diagnostic procedure such as a lung biopsy or BAL often is performed, primarily to rule out an infectious process. If atypical epithelial cells but no infectious agents are found, a drug-induced process is suspected.

For patients who are believed to have drug-related diffuse parenchymal lung disease, the drug ideally should be discontinued. Corticosteroids may be administered, but, as with their use in other diffuse parenchymal diseases, the results are variable.

Radiation-induced lung disease

Parenchymal lung disease is a potential complication of radiation therapy for tumors within or in close proximity to the thorax, particularly lymphoma (Hodgkin lymphoma) and carcinoma of the breast or lung. The incidence of clinically apparent injury is increased with higher radiation dose, a larger radiation field, and the use of concomitant chemotherapy. The risk is highest in lung cancer (5%–25%), followed by mediastinal lymphoma (5%–10%) and breast cancer (1%–5%). However, radiographic changes in the absence of symptoms are seen even more frequently, in 20% to 70% of exposed patients.

Radiation-induced pulmonary disease is generally divided into two phases: early pneumonitis and late fibrosis. The acute phase of radiation pneumonitis typically develops 1 to 3 months after completion of a course of therapy and depends on the total dose and the volume of lung irradiated. The later stage of radiation fibrosis may directly follow earlier radiation-induced pneumonitis, may occur after a symptomfree latent interval, or occasionally may develop without any prior clinical evidence of acute pneumonitis. Fibrosis, when it occurs, does so generally 6 to 12 months after radiation therapy has been completed.

Radiation-induced lung disease includes an early period of radiation pneumonitis and a later period of radiation fibrosis.

Radiation-induced lung injury results from a combination of direct injury to normal pulmonary cells and induction of fibrotic pathways. Early injury to pulmonary capillary endothelial cells leads to increased permeability. Damage to type I and type II cells ensues, leading to production of cytokines and recruitment of inflammatory cells. In the period preceding chronic fibrosis, an alveolitis develops and the body’s attempt at injury repair leads to development of fibrotic changes. The possibility of hypersensitivity also playing a role in the pathogenesis of the alveolitis has been suggested by the finding of increased lymphocytes in the BAL fluid of the nonirradiated lung in patients with radiation-induced pneumonitis.

Early pathologic changes include swelling of endothelial cells, interstitial edema, mononuclear cell infiltrates, and atypical hyperplastic epithelial cells. Subsequent changes during the fibrotic stage consist of progressive fibrosis (indistinguishable from pulmonary fibrosis from other causes) and sclerosis of small vessels, with obliteration of a major portion of the capillary bed in the involved area.

Clinically, patients may have fever with the acute pneumonitis in conjunction with respiratory symptoms, and distinguishing radiation pneumonitis from an atypical pneumonia is often difficult. On chest radiograph, the acute pneumonitis is often characterized by an infiltrate that conforms in shape and location to the region of lung irradiated. Chest CT scanning may be particularly useful, both because it may detect subtle abnormalities earlier than can be seen on chest radiograph and because the crosssectional views more readily show the correspondence of the radiographic abnormalities to the radiation

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Hypersensitivity pneumonitis

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Drug-induced parenchymal lung disease

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