Involvement of peripheral airways during methacholine-induced bronchoconstriction after lung transplantation

Previous studies have shown that the presence of nonspecific bronchial hype rreactivity (NSBHR) in transplanted subjects is associated with the develop ment of bronchiolitis obliterans, which suggests that NSBHR in these subjec ts may involve the peripheral airways. We investigated this question by stu dying the effects of methacholine on the distribution of ventilation using single-breath washouts in 15 heart-lung transplant recipients; 17 nontransp lanted subjects with NSBHR were studied for comparison. All subjects had no rmal baseline lung function, and seven transplanted subjects displayed NSBH R. Methacholine induced a similar decline in FEV1 and specific airway condu ctance in the two groups. In contrast, whereas methacholine produced simila r increases in the slope of the alveolar plateau for SF6 (SSF6) and He (SHe ) in the nontransplanted subjects, it always produced greater increases in SHe than SSF6 in the transplanted subjects. This suggests that in the latte r, methacholine-induced bronchoconstriction made the distribution of ventil ation more heterogeneous in peripheral airways. This involvement of small a irways may help in understanding why assessing bronchial reactivity in tran splanted subjects provides information on the presence of a pathologic proc ess affecting the bronchioles, and hence on the risk of progression to bron chiolitis obliterans.