Glycopyrronium inhalation, bronchodilator reversibility assessment, and defining asthma: A new paradigm

The understanding of asthma by humanity seems an ever-evolving process. The existing practice of identifying the disease is based on FEV1 reversibility (≥200 ml and 12%) to salbutamol inhalation, essentially with exclusion of alternate diagnosis.[1] Once the quantitative bronchodilator reversibility with salbutamol (a β2-agonist) is a determinant for defining asthma, then it should ideally apply to the other class of bronchodilators as the anti-muscarinic agents (AMAs) too. Until recently, reversibility with any AMA remained a less-discussed issue possibly for the unsuitable pharmacokinetic properties of available agents. The GOLD, however, has mentioned recently "AMA reversibility" for diagnosing COPD without any discussion and mentioning of the agent used for the purpose.[2] Of late, AMA reversibility assessment is possible with inhalation of glycopyrronium, a relatively rapid onset and long-acting AMA.[3] Such reversibility testing with glycopyrronium is done after performing the salbutamol reversibility and is found feasible and acceptable.[4,5] The agent can impart reversibility in COPD, which is often equal to or more than that produced by salbutamol.[5] The sequence of use (salbutamol- glycopyrronium) or (glycopyrronium-salbutamol) has been found to have little difference.[5] We have extended the use of glycopyrronium reversibility to our patients of obstructive airway disease (unqualified: who were not identified as asthma or COPD) with no other concomitant respiratory (tuberculosis, malignancy, pneumonia, ILD) or any significant systemic disease. The focus was on eliciting the reversibility potential of both salbutamol and glycopyrronium independently to identify the frequency of asthma-defining FEV1 reversibility (≥200 ml and 12%) with both. The result shows that both salbutamol and glycopyrronium can lead to the critical asthma defining reversibility independently in 28.80% (n = 142) and 9.33% (n = 46), respectively, out of 493 subjects [see Table 1]. Except for a male predominance for the glycopyrronium-sensitive subjects, the two groups were found similar demographically (age, BMI). The baseline spirometry parameters were also similar between the two groups, except the FEV1 reversibility, which was significantly higher in the salbutamol-sensitive group (351.9 ± 129.5 vs. 301.3 ± 101.5 ml; P = 0.0104) [see Table 1]. Here, the 9.33% of subjects with "asthma-equivalent" reversible airway disease could have remained undiagnosed had the reversibility exercise with glycopyrronium were not done. A question similar to this may ensue for combined glycopyrronium and salbutamol reversibility amounting to ≥200 ml plus 12%.Table 1: Total number of subjects of OAD study subjected to both salbutamol and glycopyrronium reversibility tests: 493The revelation brings us to questions as a) whether we shall include the glycopyrronium reversible obstructive airway disease and recognize them as asthma based on the reversibility criterion or b) make and maintain a fresh OAD group as glycopyrronium reversible disease. It may compel us to altogether reconsider the classification system of OAD afresh based on reversibility (as reversible and non-reversible/poorly reversible disease) to both the two categories of bronchodilators [salbutamol (β2 agonist) and glycopyrronium (anti-muscarinic agent)]. The issue demands the attention of the experts and a serious discussion as the knowledge has enormous potential for application in the treatment of OAD. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.