We report a fatal case of acute interstitial pneumonitis in a patient treated with carmustine (BCNU) for a brain tumor.

We report a fatal case of acute interstitial pneumonitis in a patient treated with carmustine (BCNU) for a brain tumor. Bronchoalveolar lavage (BAL) revealed lymphocyte alveolitis with a reasonable CD4/CD8 ratio (0.36), consistent with an immunoallergic phenomenon, rather than the greatest in quantity often evoked toxic hypothesis.

Bischloroethylnitrosourea (BCNU [carmustine]) is a chemotherapeutic agent used to treat various signs of tumors, cerebral in particular. The first pulmonary adverse termination related to this drug was reported in 1976[1] and several cases of pulmonary fibrosis secondary to BCNU treatment have since been reported and published. A toxic mechanism has generally been evok We report a case of acute pulmonary fibrosis in a 23-year-old patient with cerebral stalk tumor treated with BCNU and vincristine, the origin of which appears to be linked to an immunoallergic mechanism, considering the characteristics of bronchoalveolar lavage (BAL).

CASE REPORT

A 21-year-old man was hospitalized in July 1986 for headache, diplopia, and balance disorders. Cranial comput tomographic scan and encephalic magnetic resonance imaging revealed a lesion of the cerebral stock so localized and extended as to obviate surgical biopsy. Radiotherapy (54 Gy forward the tumor site) was performed in September 1986 followed from noticeable clinical recovery. The evolution of balance disorders in September 1988 l to another encephalic magnetic resonance imaging that confirmed relapse. Monthly treatment with 100 mg BCNU forward day 1 and day 2 and 1 mg vincristine upon day 3 and day 4 was initiated in October 1988 Five courses were thus implemented until January 1989 (BCNU cumulative doses: 1 g) when rapidly aggravating dyspnea and cough l to suspension of the sixth course and transfer of the patient to the department of pneumology

At the time of admission, the patient had no febrile affection and was very asthenic. He weighed 55 kg (8 kg missing in 4 months). He was not cyanotic when at stillness but became dyspneic after the slightest effort. The lung examination revealed bilateral basilar inspiratory crackles. Findings from physical examination were otherwise normal take exception the known neurologic disorder. Chest radiograph revealed a diffuse interstitial proces (Fig 1) Arterial kindred gases substantiated hypoxemia at security with no hypercapnia ([PaO.sub.2], 66 mm Hg; [PaCO.sub.2], 34 mm Hg; pH 747) Otherwise, biologic workup revealed the following: hemoglobin=11.5 g/dl; leukocytes=5700/cu mm; polymorphonuclear neutrophils=67 percent; eosinophils=6 percent; lymphocytes=18 percent; fibrin=3.55 g/L; Na=142 mmol/L; urea=13.5 mmol/L; creatinine=101 [mu]mol/L; protein total=6.6 g/dl; AST=43 U/L (N [les than] 50); ALT=41 U/L (N [les than] 50); alkaline phosphatase=209 UI/L (N [les than] 111); lactate deshydrogenase=750 U/L (N [les than] 420) Pulmonary function experiments revealed a severe restrictive pattern: vital capacity 890 ml (17 percent of theoretical values), total lung capacity 1980 ml (30 percent of theoretical values), with [FEVsub1]/VC 63 percent Fiberoptic bronchoscopy was macroscopically normal. Histologic, bacteriologic, virologic, or parasitologic analysis of all bronchial samplings were negative. All the viral and bacterial posterity investigations (HIV, syncytial respiratory virus, herpes virus, Chlamydia, Mycoplasma, Legionella) as well as the usual precipitins (bird fancier's lung farmer's lung) prov negative. Bronchoalveolar lavage performed with 200 ml physiological serum yielded 475000 lonely dwellings per milliliter, including 24 percent lymphocyte 73 percent macrophages, and 1 percent polymorphonuclear small rooms The CD4/CD8 ratio of lymphocyte subset was 036

Despite steroid therapy at the initial dose of 1 mg/kg/day for 11 days, then by the agency of intravenous bolus doses of 240 mg methylprednisolone for 3 days, the condition evolv to gradual worsening of respiratory failure which provok death forward March 18, 1989.

DISCUSSION

According to near authors, pneumonitis secondary to BCNU treatment involves up to 20 percent of treated patients.[2] It can present itself in an acute or subacute form in the course or after the completion of treatment.[2-4] The course is chiefly often fatal despite BCNU suspension and steroid treatment, as reported herein.[3,4] O'Driscoll et al[5] lately reported a series of 17 patients with brain tumor treated with BCNU Four died from pulmonary fibrosis 8 to 13 years after treatment, and those who survived not past nor future with restrictive respiratory syndrome, principally often symptomatic. In these patients, BAL does not reveal any excessive lymphocytosis.

A toxic mechanism has frequently been evoked at the origin of pulmonary fibrosis, based in succession several points. An animal archetype was developed in rats from subcutaneous injection of BCNU[6] who exhibited pulmonary fibrosis with granulomatosis. The reduc activity of glutathione that was observ may sensitize pulmonary tissue to oxidants.[7] Pulmonary disease is mainly observ with high-dose treatments (in exces of 1500 mg/[msup2]; 50 percent of cases), whereas its affair is exceptional with doses below 500 mg/[msup2][23] Pathology specimens simply reveal fibrosis, with no inflammatory infiltrates.[1,3] Corticosteroids appear to have no efficiency on the course of disease.[3,4] Gaetani et al[8] studied 40 patients treated with BCNU for glioma in whom sequential pulmonary function ordeals revealed a steady decrease in DCO for all patients.[8] Lastly, Aronin et al[2] reported high incidence of side validitys in patients with a history of respiratory disorders (42 percent v 10 percent)

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