Quantification of smoking-related airway remodelling in COPD using a novel fast-response capnometer (ID 502)
TidalSense Limited
Abstract
Aim
Airway remodelling due to cumulative tobacco smoking and its association with airflow limitation severity in COPD is difficult to characterise using non-specific methods such as spirometry. To evaluate the relationship between smoking history and features of small to medium-sized airway obstruction in participants with COPD with fast-response capnometry using TidalSense’s N-Tidal™ device.
Methods
305 COPD GOLD stage 3/4 participants were included from three longitudinal observational studies conducted in the UK: COPD Breathing Record Study (CBRS); CBRS 2; and the Cardiorespiratory Diagnostic Study (CARES). Tobacco smoking data was collected at baseline; capnography data was collected twice daily for up to 6 weeks. CO2 features from the expiratory upstroke and plateau phases known to correlate with the degree of airways obstruction in COPD were compared to participants’ smoking histories.
Results
Higher smoking pack-years was associated with greater curvature in the alpha-angle region, which may relate to structural airway remodelling of smaller airways. The alpha-angle feature of obstruction demonstrated a positive non-linear correlation with pack years, indicating that a greater degree of airways obstruction is associated with increased cumulative exposure to smoking.
Alpha-angle features showed a significantly altered CO2 waveform geometry beyond 40 pack years, suggesting this level of smoking history may represent a threshold beyond which demonstrable airway remodelling is highly likely. Of participants with over 40 pack years, 96% had an FEV1/FVC <0.7, further supporting this hypothesis.
Figure 1: (A) Regression plot of CO2 alpha-angle feature vs. pack years. (B) Average CO2 waveforms across subjects with <15 pack years, 15-40 pack years and >40 pack years smoking history.
Conclusion
CO2 waveform features of airway obstruction demonstrate a dose-response relationship with cumulative smoking history. N-Tidal may be able to directly probe airway remodelling as a result of smoking, potentially enabling early identification of physiological changes undetectable by spirometry.
Funding: The studies which provided the data for this report were funded by NIHR (i4i grant), Innovate UK, and Pfizer OpenAir. The authors had sole responsibility for the study design, data collection, data analysis, data interpretation and report writing. The CBRS study was supported by SBRI Healthcare, the CBRS2 study was supported by Pfizer OpenAir and the CARES study was supported by Innovate UK through two grants (Grant Reference Numbers: 133879 and 74355).
Conflicts of interest: LT, CD, ABS, JCC, HB, RHL, GL, AXP are currently employed, or were employed/funded at the time of the research, by TidalSense Limited. GH and HFA are funded by the National Institute for Health Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative at Oxford Health NHS Foundation Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
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