Changes in airway responsiveness following mantle radiotherapy for Hodgkin's disease

Study objectives: To investigate whether mantle radiotherapy (MRT) for the lung, through its proinflammatory effects, can induce an increase in airway responsiveness. Design: Follow-up of the changes in lung function and methacholine responsi veness in patients 1, 6, 12, and 24 months after they underwent MRT. Patients: Thirteen nonasthmatic patients with bulky Hodgkin's lymphoma who were scheduled for MRT. Measurements and results: Chest radiographs, lung function tests, methachol ine thresholds of the bronchi (the provocative dose of methacholine causing a 10% fall in FEV1 [PD10] and central airway (the provocative dose of meth acholine causing a 25% fall in the maximal mid-inspiratory flow [PD25MIF50] ), and the provocative dose of methacholine causing five or more coughs (PD cough) were serially assessed. One month after patients underwent MRT, ther e were significant decreases in PD10 [mean +/- SEM], 2,583 +/- 414 mu g to 1,512 +/- 422 mu g, respectively; p < 0.05), PD25MIF50 (mean 2,898 +/- 372 mu g to 1,340 +/- 356 mu g, respectively; p < 0.05), and PDcough (mean 3,12 7 +/- 415 mu g to 1,751 +/- 447 mu g; p < 0.05), which were independent of the decrease in FEV1 and reversed within 6 months in all patients but three . Six months after undergoing MRT, four patients showed radiation-induced l ung injury (RX) on chest radiographs, which subsequently evolved into fibro sis. These patients had greater decreases in vital capacity, FEV1, MIF50, a nd methacholine thresholds than those without RI, and this persisted up to 2 years after they had undergone MRT. One year after the patients underwent MRT, a close relationship was found overall between the change in FEV1 and those in both PD10 (r = 0.733; p = 0.004) and PD25MIF50 (r = 0.712; p = 0. 006). Conclusions: MRT triggers an early transient increase in airway responsiven ess, which reverses spontaneously. In patients with RI, the persistence of airway dysfunction long after undergoing MRT may depend on airway remodelin g from radiation fibrosis.