PULMONARY TOXICITY OF DRUGS AND THORACIC IRRADIATION IN CHILDREN

The pathology of drug-induced pulmonary toxicity in children is poorly understood and probably under-estimated, in the absence of any prospe ctive studies evaluating in a systematic fashion the side effect of me dication on the respiratory apparatus. The pulmonary toxicity of thora cic irradiation has markedly receded with move restricted indications for this sort of treatment. Three clinical patterns are most commonly encountered in drug induced lung disease in children: interstitial lun g disease, hypersensitivity lung disease and non-cardiogenic pulmonary oedema. The diagnosis isa diagnosis of exclusion and rests on a group of clinical arguments and also on the progress of the disease. Bronch o-alveolar lavage rules out infectious disease. Respiratory function t ests show non-specific anomalies. A lung biopsy may be indicated. The mechanism of the pulmonary toxicity are associated with disequilibrium of the oxidant/antioxidant and protease/antiprotease system as well a s disturbance of the immune response or alteration of the pulmonary ma trix by disease of the collagen system. Increased toxicity may be seen in children because of a very significant cumulative dose. The cytoto xic drugs which are most often implicated in causing this are bleomyci n, methotrexate, cyclophosphamide and busulfan. Other drugs which are responsible for toxic lung disease are nitrofurantoin, sulfasalazine, D-penicillamine, betalactams, Diphenylhydantoin and carbamazepine. Acu te posh-radiation lung disease is rare. Post-radiation fibrosis is fou nd six months after irradiation and hinders thoraco-pulmonary growth i n the child. It is important to assess lung function in all children b efore any chemotherapy or thoracic irradiation. Cytotoxic drugs are th e most common cause of toxic lung disease. This iatrogenic disease req uires a multi-discipline approach to ensure the quality of care for th ese children.