Change in phase 3 slope of exhaled CO2 in response to β2 agonist inhalation is associated with asthma control in children

Background: Airway hyper-reactivity, inflammation and remodelling contribute to inhomogeneity of ventilation-perfusion ratio (V/Q) in asthma. Short-term variations in V/Q can cause changes in expired capnographic indices. Objectives: to measure acute changes in the phase 3 slope of the exhaled volumetric capnogram after β2-agonist inhalation (ΔSv3), for comparison with airway response based on FEV1 (ΔFEV1), and asthma control. Subjects and Methods: After ethical approval and informed consent, 72 children aged 6.0 – 17.7 y, followed up for asthma underwent spirometry and exhaled capnography before and after β2-agonist inhalation through a spacer, using a side-stream rapid infrared analyser. Asthma control was assessed using the GINA questionnaire. Results: Children with positive reversibility tests (defined as ΔFEV1>12%) had a significantly higher ΔSv3 (m±SE: 87.4±41.4) vs. negative tests (31.3±14.0%, p=0.001). Uncontrolled asthma was associated with a significantly larger ΔSv3 (103.4±64.0%, n=7) compared to partly controlled (52.0±26.1, n=24; p=0.009) and controlled asthma (30.8±16.3, n=41; p=0.003). Neither Bohr dead space nor ΔFEV1 were different between asthma control groups. Conclusions: mean ΔSv3 was significantly larger in children with positive response to β2-agonist, and in uncontrolled asthmatics, albeit with some variability. To our knowledge these are the first data on exhaled CO 2 phase 3 volumetric slope change in asthma control. The positive β2-agonist-induced change in ΔSv3 could be due to increased ventilation of inhomogeneous peripheral lung units, and merits further evaluation as a potential phenotypic biomarker in asthma.