The new finding of this study is that VEAL observed in a small proportion of patients with negative MCT at our facility was not interpreted nor reported to the referring healthcare providers. Conceivably, these spirometric data could indicate the presence of alternative disorders associated with laryngeal hyperresponsiveness that should then be pursued and treated accordingly [6,7,8,9,10,11]. Hence, we propose that FEF50/FIF50 recorded during MCT should be interpreted and reported to the referring healthcare providers and its clinical implications addressed as indicated.

Kelso et al. [3] showed that in fourteen of seventy-six consecutive patients with negative MCT (18%) FIF50 decreased by 20 to 35% from baseline suggesting the presence of VEAL. However, baseline and post-MCT FEF50/FIF50 data were not reported. Moreover, criteria for a positive inspiratory challenge during MCT of ≥ 20% fall in FIF50 from baseline chosen by these authors have not been published so far [1, 2].

To the best of our knowledge, VEAL reported in our patients with OSA and a negative MCT has not been previously described in the literature. To that end, Lin et al. [12] found positive MCT in four of sixteen patients with OSA but did not report FEF50/FIF50 data in those with negative MCT. Whether patients with OSA and VEAL observed during negative MCTs represent a distinct phenotype of upper airway dysfunction in this disorder remains to be determined. To that end, obesity, a distinct feature in patients with OSA, is associated with tidal flow limitation due to reduced functional residual capacity and expiratory reserve volume [13]. Conceivably, this phenomenon could result in higher nebulized methacholine dose delivered to the upper airway of obese patients leading to local, non-selective muscarinic receptor activation and VEAL. Further studies are warranted to support or refute this hypothesis.

Several limitations of this study are notable. It was a small, retrospective, single site study comprised predominantly of white obese males. Hence, generalizability of our observations is limited. Therefore, we propose that a larger, prospective, multi-site study should be conducted to determine the prevalence of VEAL in patients with negative MCT and to unravel upper airway disorders associated with this phenomenon.

In summary, we found that VEAL is observed in some patients with a negative MCT. This phenomenon should be interpreted and reported to the referring healthcare providers and its clinical implications addressed as indicated.