Early detection of asthma and COPD, disease mechanisms and precision medicine were the focus of the European Respiratory Journal’s stand-out research papers in airways disease over the last year, ERS 2023 delegates heard.
Two of the papers, which were selected by Professor Mona Bafadhel, Consultant Respiratory Physician and Chair of Respiratory Medicine at King’s College London, could pave the way for faster diagnosis of COPD and asthma, as well as help better differentiate between the two diseases.
“We know in terms of asthma and COPD, spirometry is the gold standard for diagnosis, but many of us have come to understand that there are significant limitations with regard to its use,” Prof Bafadhel told delegates.
Identifying COPD and asthma would lead to earlier and better treatments for patients and allow clinicians to consider altering the disease trajectory, she said.
Overall, Prof. Bafadhel applauded the number of papers on asthma and COPD published in the ERJ and noted that there were far more publications on the former condition.
“So for all COPD scientists…I think it’s really important that we continue to drive what we want to do in terms of understanding COPD,” she stressed.
Questions that improve disease detection in clinical practice
The first paper presented to delegates centred on deriving and validating a new questionnaire designed to help clinicians better detect undiagnosed asthma and COPD.
The research, led by epidemiologist Chau Huynh, The Ottawa Hospital Research Institute, University of Ottawa, Canada, included adults with respiratory symptoms but no diagnosis of asthma or COPD, who underwent pre and post bronchodilator spirometry to confirm the presence of either disease.
The team subsequently identified 13 predictive questions that could be used as part of a screening or case-finding process, gathering information on factors such as work history, wheeze symptoms, and smoking exposure.
The Undiagnosed COPD and Asthma Population questionnaire (UCAP-Q) was linked to a web-based risk probability calculator for each disease.
Overall, this had a sensitivity of 92% for asthma and 97% for COPD in the derivation cohort and 93% and 92%, respectively, in the validation cohort. Respective specificity was 17% and 19%.
“The UCAP questionnaire is very easy to follow [and is] potentially a very good tool for us to use,” Prof Bafadhel told delegates.
“The authors demonstrated that we could apply this tool in clinical practice [to] identify these patients, and [then] follow on by doing a confirmatory test with spirometry”.
Derivation and Validation of the UCAP-Q Case-finding Questionnaire to Detect Undiagnosed Asthma and COPD (link here)
Differentiating between asthma and COPD on CT scans
The second paper determined a subset of features on CT imaging that could differentiate between asthma and COPD using machine learning.
The study, led by Dr Amir Moslemi, Department of Physics, Ryerson University, Toronto, Canada, was based on 95 COPD and asthma patients from Heidelberg University Hospital.
The team identified a subset of 10 CT parameters for classification of asthma and COPD with moderate-high accuracy of up to 80%.
“This is probably quite important because it allows us to consider standardisation of our CT parameters when we’re looking for patients who might have asthma or COPD,” Prof Bafadhel said.
Differentiating COPD and Asthma using Quantitative CT Imaging and Machine Learning (link here)
Ciliogenesis and identifying new targets
With regard to understanding the mechanisms of airways disease, Prof. Bafadhel highlighted research exploring the relationship between ciliogenesis and COPD.
“This is an exciting area because we’ve learned a lot in terms of what happens in terms of modelling of the airway and how this could really persist and perhaps be the cause of damage, and how we could think about mechanisms and potential treatment targets in the future,” she noted.
The authors, led by Emilie Luczka-Majérus, the University of Reims Champagne-Ardenne (URCA), Reims, France, set out to determine whether bronchial epithelial remodelling is characterised by cilia function, as well as investigate the differentiation of bronchial epithelium.
They studied the small airways of nine COPD patients and seven patients without COPD and found a clear reduction in cilia in the COPD group. Primary cilia cells were also reduced in those with COPD.
Also, when looking at gene expression, they found downregulation of the genes regulating ciliogenesis, “implying that this might be a mechanism that we need to explore in more detail, particularly in patients with COPD,” Prof Bafadhel noted.
The authors said the alterations they observed “could impact the mucociliary clearance with a potential involvement in the initiation of remodelling mechanisms in airway epithelium and/or the development of emphysema”.
Prof. Bafadhel said the paper “adds to the literature of further potential new targeted therapeutics in patients with airways disease, particularly patients with COPD”.
Ciliogenesis is intrinsically altered in COPD small airways (link here)
Airway smooth muscle area and steroid response
Moving on to precision treatment, researchers looked at whether airway smooth muscle cell area might be able to predict steroid responsiveness in patients with COPD receiving triple therapy.
For this paper, led by Dr Daiana Stolz, Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland, the authors split participants with COPD into two groups depending on whether their airway smooth muscle area was high (more than 20% of biopsy) or low.
During a run-in period, all participants were taking triple inhaled therapy, after which they were subsequently randomised to receive triple therapy or a dual bronchodilator.
Results showed that patients with a high airway smooth muscle cell area taking triple therapy had a greater response to treatment, as demonstrated by the FEV1 range, compared to those taking a dual bronchodilator and those in the low airway smooth muscle cell area group.
“What was really interesting about the paper and in need of further exploration was that the time to next exacerbation, which was one of the secondary endpoints, did not seem to be different between the groups whether they had a high or low airway smooth muscle area, and whether they were on the triple inhaled therapy or not,” Professor Bafadhel said.
“There seemed to be a suggestion potentially that for the low airway smooth muscle area, there might have been an extension in the time to the next exacerbation or first exacerbation with the triple inhaled therapy compared to the dual bronchodilator therapy.
“I think this suggests that there are clearly different mechanisms from what we see in terms of FEV one response versus these exacerbation events,” she added.
Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial (link here)