Table 1.

Definitions of pulmonary toxicity.

National Institutes of Health, 1993 (1)

I. Evidence of widespread alveolar injury. Criteria include: a. Multilobar infiltrates on routine chest radiographics or CT scans. b. Symptoms and signs of pneumonia, e.g., cough, dyspnea, rales. c. Evidence of abnormal pulmonary physiology. i. Increased alveolar to arterial oxygen gradient ii. New or increased restrictive pulmonary function test abnormality II. Absence of active lower respiratory tract infection. Appropriate evaluation includes: a. BAL negative for significant bacterial pathogens and/or lack of improvement with broad-spectrum antibiotics. b. BAL negative for pathogenic nonbacterial microorganisms. i. Routine bacterial viral and fungal cultures. ii. Shell-vial CMV culture iii. Cytology for CMV inclusions, fungi, and PCP iv. Detection methods for RSV, para-influenza virus, and other organisms (e.g., fluorescent antibiotics or culture) c. Transbronchial biopsy if condition of the patient permits. d. Ideally, a second confirmatory negative test for infection is done. This is usually performed 2 to 14 days after the initial negative BAL and may consist of a second BAL or open lung biopsy.

American Thoracic Society (2)

I. Evidence of widespread alveolar injury. a. Multilobar infiltrates on routine chest radiographics or CT scans. b. Symptoms and signs of pneumonia, e.g., cough, dyspnea, rales. c. Evidence of abnormal pulmonary physiology. i. Increased alveolar to arterial oxygen difference ii. New or increased restrictive pulmonary function test abnormality II. Absence of active lower respiratory tract infection. Appropriate evaluation includes: a. BAL negative for significant bacterial pathogens including acid-fast bacilli, Nocardia, and Legionella species b. BAL negative for pathogenic nonbacterial microorganisms. i. Routine bacterial viral and fungal cultures. ii. Shell-vial for CMV and respiratory RSV iii. Cytology for CMV inclusions, fungi, and PCP iv. Direct fluorescence staining with antibodies against CMV, RSV, HSV, VZV, influenza virus, parainfluenza virus, adenovirus, and other organisms c. Other organisms/tests to also consider: i. Polymerase chain reaction for human metapneumovirus, rhinovirus, coronavirus, and HHV6 ii. Polymerase chain reaction for Chlamydia, Mycoplasma, and Aspergillus species iii. Serum galactomannan ELISA for Aspergillus d. Transbronchial biopsy if condition of the patient permits. III. Absence of cardiac dysfunction, acute renal failure, or iatrogenic fluid overload as etiology for pulmonary dysfunction