High levels of exhaled nitric oxide (NO) and NO synthase III expression inlesional smooth muscle in lymphangioleiomyomatosis

Smooth-muscle proliferation is the hallmark of lymphangioleiomyomatosis (LA M). Although little is known about the pathogenesis of LAM, nitric oxide (N O) is a key regulator of smooth-muscle proliferation. NO is linked to the p athogenesis of other lung diseases such as asthma, in part by the finding o f higher-than-normal levels of exhaled NO. If NO were involved in the abnor mal smooth-muscle proliferation in LAM, we reasoned that exhaled NO from in dividuals with LAM would also differ from that of healthy control subjects. To evaluate this hypothesis, we studied exhaled NO in individuals with LAM in comparison with healthy and asthmatic women using a chemiluminescent NO analyzer. Women with LAM had higher exhaled NO than did healthy women but lower than asthmatic women (NO [parts per billion] median (25 to 75%): LAM 8 [7 to 15] [n = 28], control 6 [5 to 8] [n = 27], asthma 14 [8 to 25] [n = 22]; Kruskal-Wallis P < 0.001). Immunohistochemical studies on formalin-fi xed, paraffin-embedded sections of surgical and autopsy material from lungs of individuals with LAM showed diffuse NO synthase III (NOSIII) expression in the lesional smooth muscle of LAM similar to that in the vascular endot helium, NOSIII expression was limited to the vascular endothelium and bronc hial smooth muscle in healthy control lungs. The increased NO and the prese nce of NOSIII expression in lesional smooth muscle warrants further study i nto the potential role for NO in the pathogenesis of LAM.