Airways distinctly different in asthma-COPD overlap: Tasmanian study


By Mardi Chapman

1 Sep 2022

Patients with asthma-COPD overlap (ACO) show distinct airway changes compared to people with asthma or COPD alone, raising hopes for more targeted therapy for the under-recognised condition, Australian researcher say.

Their study compared remodelling changes in 90 large airway endobronchial biopsies obtained from the Tasmanian Respiratory and Newcastle biobanks. Donors were adults with confirmed ACO, asthma only, COPD only, healthy volunteers, and smokers with normal lung function.

The study found a significantly thicker epithelium (p=0.0263) and higher epithelial cell numbers in ACO samples compared to healthy controls.

Goblet cell numbers in ACO were also significantly higher than in healthy controls (p=0.0028) and COPD patients who were ex-smokers (COPD-ES).

“Furthermore, we demonstrate an increase in percent goblet cells in ACO, which constituted 3.5% of their total epithelial cell population compared to 2.4%, 1.2%, and 0.4% in asthma, COPD-current smokers and COPD-ES, respectively.”

The study, published in Lung Cellular and Molecular Physiology, also found changes in the reticular basement membrane (RBM), and the lamina propria (LP) and smooth muscle area.

In patients with ACO, RBM (11.95 [8.5-16.95] μm) was significantly thicker than healthy controls (6.74 [2.81-14.37] μm, p=0.0002), tended to be thicker than in asthma patients, COPD-ES and smokers with normal lung function, and was thinner than in COPD-current smokers.

There were also more RBM cells in the ACO RBM compared to other groups, except for people with asthma who had higher cellularity.

LP cells per mm2 were highest in asthma patients and other pathological groups, while cellularity in COPD-current smokers and smokers with normal lung function was the lowest.

“The present finding of a high number of total LP cells in asthma could reflect the disease pathology, and to date, studies have shown the increased cellularity and abundance of inflammatory cells such as eosinophils and mast cells in the asthmatic airway,” the researchers said.

They noted a significantly reduced smooth muscle area in ACO (0.061 [0.035-0.116]) as compared to asthma (0.133 [0.086-0.322], p=0.001) and COPD-current smokers (0.131 [0.079-0.191], p=0.0290).

These findings were consistent with other evidence that increased smooth muscle thickness is one of the characteristic features of airway remodelling in both asthma and COPD.

The researchers, led by the Respiratory Translational Research Group from the University of Tasmania, concluded there was an urgent need to further characterise the ACO phenotype pathologically.

“We believe that our work provides valuable histopathological evidence on the airway wall changes in patients with ACO, which will help clinicians in informed decision-making for diagnostic purposes and better patient management by reducing airway remodelling and subsequently the disease severity with appropriate therapeutic interventions.”

Structural changes

Speaking to the limbic, senior investigator Dr Sukhwinder Singh Sohal said theirs was the first study to comprehensively look at structural changes in asthma-COPD overlap.

“And what we found was that we do see airway remodelling or these structural changes in asthmatics as well as in COPD patients. But in someone who has asthma COPD overlap, then we see that these structural changes are actually more severe compared to asthma or COPD alone.”

He said the findings would eventually lead to better targeted therapies for ACO.

Dr Sohal said previous work in COPD had described a process of epithelial to mesenchymal transition (EMT) which may also be occurring in ACO.

“And what happens in that is epithelial cells gain a mesenchymal phenotype and they become myofibroblasts or fibroblasts. And those are the cells which actively secrete matrix proteins which we believe causes small airway fibrosis…”

“So it does appear to me that that process of EMT which leads to fibrosis is active in asthma COPD overlap patients, and that is the next piece of work which we’re doing that is currently being analysed in the lab.”

He said if EMT is shown to be active in patients with asthma COPD overlap, there may be an opportunity for treatment with antifibrotic agents.

The study was funded by the Clifford Craig Foundation, Launceston General Hospital.

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