Stratified medicine on the horizon for bronchiectasis as focus shifts to inflammation: ERS 2022

An era of personalised medicine is on the horizon for bronchiectasis, driven by a growing understanding of the interplay between the microbiome and inflammation that underpins disease activity, delegates heard at ERS 2022.

According to Professor James Chalmers, a Professor and Consultant Respiratory Physician at the School of Medicine, University of Dundee, the mindset on bronchiectasis needs to change to give more consideration to its inflammatory component, so that “the goal becomes not to treat infection, but how to control activity of the disease and its manifestations, such as exacerbations”.

“We’re moving towards an era of stratified medicine in bronchiectasis where we think about the type of inflammation our patients have and we think about bronchiectasis as an inflammatory disease, because when you think about it as an inflammatory disease it changes the way you think about how to manage your patients,” he said.

That’s not to say that inflammation is more important than infection as a driver of bronchiectasis; “My message is that inflammation and infection are two sides of the same coin, they are something that we really need to think about together”, he advised clinicians.

“Bacteria drive inflammation but inflammation may also drive infection. And that’s the principle of the vicious vortex, these relationships are not unidirectional. It’s the chicken and the egg,” he said.

As Prof Chalmers noted, while antibiotics are the current mainstay treatment of bronchiectasis, they don’t cure the disease. “We all have patients that are on long-term antibiotics but they continue to experience exacerbations and they continue to experience severe symptoms”.

Also, RCTs have shown that inhaled antibiotics have a rather modest effect on symptoms, reducing exacerbations by 15%-20%, “which means that there’s ongoing burden of disease that is not entirely explained by ongoing infection”.

In addition, host response to pathogens is not uniform; pathogens can induce various different inflammatory responses in bronchiectasis patients – including neutrophilic and Type 2 – the individual extent of which will determine the clinical phenotype of the patient, and in future potentially shape an optimal treatment pathway.

“So what we’re really leaning towards here is the idea that patients with bronchiectasis are not a homogeneous group with infection with X,Y,Z needing treatment with X,Y,Z, we are leading towards personalised medicine and the idea that patients with bronchiectasis actually have inflammatory endotypes”, Prof Chalmers told delegates.

This was demonstrated in one clinical trial (Huang et al, AJRCCM), in which researchers looked at integrated analyses of the microbiome and inflammatory pathways in people with COPD, bronchiectasis and the associated exacerbations, and discovered 5 endotypes with different microbiome profiles and different inflammatory profiles that translated into different clinical presentations, potentially requiring different treatments.

“So patients with an intensely infected airway with marked neutrophil degranulation might respond well to an antibiotic or to an anti-inflammatory strategy, while patients who have a relatively normal microbiome but eosinophilic inflammation may respond better to an anti-inflammatory strategy and may not require antibiotics, and then patients with type 2 inflammation, who tend to have a more normal microbiome, may require a different treatment such as inhaled corticosteroids,” he said.

“I think inflammation explains a lot of the heterogeneity [we see in bronchiectasis patients] and I think it will help us to understand how to move forward to resolve that heterogeneity to give patients better treatments”.

Going forward, clinicians need to embrace personalised medicine and think of bronchiectasis as an “inflammatory problem that we can tackle”, Prof Chalmers concluded.

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