The first aim of the study is to determine whether combined lung diffusing capacities of nitric oxide (TLNO) and of carbon monoxide (TLCO) are accurate in the followup of patients receiving either methotrexate (MTX) or bleomycin (BLM). The second objective is to determine whether TLCO, TLNO, KCO, and TLCO/VI% (inspiratory volume expressed as percentage of predicted value) correlate better with the diffusing capacity of the membrane (Dm) and/or capillary lung volume (Vc). TLNO and TLCO were measured in three groups: 22 “normal” subjects (N group), 17 patients receiving MTX, and 12 patients treated with BLM. TLCO, TLNO, Dm, and Vc were much lower in the MTX and BLM groups compared to those of the N one. The ratio TLNO/TLCO was higher in the BLM group compared to that of the N group and compared to that of the MTX group. KCO correlated neither with Dc nor with Vc, whereas TLCO/VI% correlated significantly with both Dm and Vc. Combined measurement of TLCO and TLNO seems to be useful in the followup of patients receiving agents inducing lung toxicity and gives a good idea of the alveolar membrane and the capillary volume. 1. Introduction Methotrexate (MTX), a folic acid antagonist, is widely used for the treatment of many autoimmune diseases such as rheumatoid arthritis (RA), psoriasis, or lupus erythematous (LE). This agent acts as a folic acid antagonist and is known to be an effective anti-inflammatory agent. However, it is also known for its pulmonary toxicity which is independent of the dose delivered [1–7]. MTX-induced pulmonary toxicity is an unpredictable, unusual, and mostly reversible event. Nevertheless, it is a serious adverse effect, since it may be fatal, particularly in patients with psoriatic arthritis [1]. Its incidence ranges from 1% to 5% [2, 3], and its prognosis is usually favorable [4]. Bleomycin (BLM) is another agent known for its pulmonary toxicity [8–13]. This cytotoxic agent is successfully used in the treatment of several malignancies such as germ cell tumors, lymphomas, and some squamous cell carcinomas. The most frequent adverse effects of BLM are interstitial pneumonitis (ILD), followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in around 46% of patients treated with a BLM-based chemotherapy. This lung toxicity usually appears during treatment [13] but can also appear up to 10 years after the incriminated treatment. Mulder et al. studied a cohort of childhood cancer survivor who received a BLM-based chemotherapy. After a followup of 18 years, 44% of patients presented with a pulmonary function impairment including
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