From a research planning perspective, our study findings have generated some hypotheses and related considerations that could be evaluated in future clinical trials. One hypothesis is that the combination of variables that we observed to change in our study (i.e., FEV 1 , FVC, FEV 1 / FVC, arterial carbon dioxide, breathing rate, heart rate, pack years, and oxygen saturation) could represent a new definition for a 'severe' exacerbation event. Most definitions in the literature, including the recent ATS/ERS definition, do not indicate any assessment of (patho)physiological variables as signs of an exacerbation. They simply regard the exacerbation as a worsening of the normal day-to-day symptoms and/or an adjustment in medical management [17] . A definition that encompasses a clear set of objective measures would be useful to medical practitioners who predominantly rely on clinical judgement or past experiences for diagnosing an exacerbation and its severity as well as for assessing treatment effect.