revisiting bronchiectasis

A couple of days ago I had a minor operation on what the specialist (pulmonologist) described as a partially collapsed lung, which sounded rather serious. It certainly impressed others when I mentioned it. I was diagnosed with bronchiectasis more than a decade ago, and I wrote about it at the time, but I can’t be bothered looking it up so I’ll start again.

Bronchiectasis is – at least I thought it was – a kind of damage to the walls of the many tiny airways in the lungs. Those airways become loose and distended, creating cul-de-sacs which collect bacteria. Think of it as a kind of bend in a creek which collects stagnant, smelly water. Not flushing properly. So the affected part of the lung carries a high bacterial load which means a lot of sputum is produced and the victim tends to have a lot of bacterial infections. I also cough a lot, especially in the mornings.

But – and this I think is new to me – bronchiectasis is also an auto-immune disease – and there’s apparently an effective treatment in the offing. I had an interview with the pulmonologist a few days before my op, and he told me he’d just come back from a conference in Tokyo, as you do, at which this treatment was touted. He didn’t go into detail, so I looked it up.

Pulmonary macrophages, neutrophils and Brinsupri, the trademark name for brensocatib, the first ever FDA approved treatment (in August 2025) for non-cystic fibrosis bronchiectasis (NCFBE)…

A PubMed article published in September has this to say in its abstract:

Bronchiectasis is a chronic airway disease marked by irreversible bronchial dilation, persistent cough, and recurrent infections. Its pathogenesis is explained by the “vicious cycle hypothesis,” which involves impaired mucociliary clearance, neutrophil activation, and tissue damage from neutrophil serine proteinases (NSPs). In August 2025, the FDA approved Brensocatib, a selective dipeptidyl peptidase-1 (DPP-1) inhibitor, as the first disease-modifying therapy for bronchiectasis. By blocking NSP activation, Brensocatib reduces inflammation and exacerbation. WILLOW and ASPEN trials demonstrated significant improvements in exacerbation rates, lung function decline, and exacerbation-free survival, establishing a novel therapeutic paradigm for this previously undertreated condition.

So bronchiectasis is an auto-immune disease, in which the over-active production of neutrophils, the most common type of white blood cells, causes ‘unnecessary’ inflammation – or more specifically, the overproduction of NSPs by those neutrophils.

So how to write about this without getting too technical and confusing myself? So there’s clearly a type of bronchiectasis associated with cystic fibrosis, which I’m tempted to explore, but maybe another time. For the rest I’ll obviously be relying on professional sources, referenced below. My type of bronchiectasis is characterised by ‘permanent airway damage, mucus build-up, and frequent chest infections’. This new medication ‘targets one of the causes of inflammation in bronchiectasis, rather than just treating the symptoms’. It inhibits DPP1 (dipeptidyl peptidase 1), an enzyme, or protein, which activates these NSPs – sometimes too much. Over-activity damages lung tissue. So the blocking of this enzyme reduces the inflammation and the damage.

So an obviously interesting question for me is – why do some people get this over-active response by the DPP1 enzymes? Well, here’s what AINL (artificial intelligence never lies) says on this very topic:

An “over-active response” by Dipeptidyl Peptidase 1 (DPP1) enzymes is not typically a result of the enzyme itself being overactive, but rather a reflection of underlying
chronic inflammatory diseases that lead to excessive neutrophil activity and the release of mature, active DPP1. The enzyme itself is often present in high amounts in the sputum and airways of affected patients, correlating with disease severity.

So I think what this is saying is that it’s not that the enzymes themselves are being over-active, but that the neutrophils are producing/secreting too many of the buggers. Which takes us back a step to the neutrophils, and the same question – why do some neutrophils, or the neutrophils of some individuals, produce more DPP1 than others? Did I have an underlying chronic inflammatory disease that I didn’t know about? I didn’t have this problem in my youth, as far as I’m aware.

To put the matter in its most basic terms, why do some people ‘get’ bronchiectasis, seemingly out of the blue, while others, presumably the vast majority, don’t? A basic question indeed, with no answers – but then the same question can be asked about ME/CFS and many other diseases or conditions. I have a theory, or should that be a hypothesis, or a hunch (funny word), or just a guess, based on getting as sick as I’ve ever been, by far, in the late eighties or early nineties, due to food poisoning. Now food poisoning obviously affects the digestive rather than the respiratory system, but… err… we still have much to learn…?

I was living in a granny flat at the time, in College Park, not far from Adelaide University, where I was a student, and when I’d sufficiently recovered I dragged myself to the university doctor. I was barely able to articulate anything, and was surprised when she sent me off to the hospital down the road for some blood tests. I took me a while to realise she suspected I had AIDS. Them were the days….

So it seems to me – and I don’t really trust myself on this – that this body-blow of an illness (at its worst I didn’t even have the energy to go to the toilet) might’ve thrown my whole system, and not just my digestive system, out of whack, to use a technical term. Our bodily systems, such as our immune system, seem to get more complex the more we analyse them. A while back I wrote a few pieces on immunology, having discovered the immunology podcast, but I soon realised it was just too complex for my ageing brain to encompass. In any case, I’ve divided my life into the pre- and post-food-poisoning eras, and am half-convinced, I keep trying to convince myself, that I didn’t have any of these bronchial problems in the pre- era.

So there you go, it’s the everything-is-connected to-everything-else hypothesis, which I reckon to be irrefutable….

References

https://pubmed.ncbi.nlm.nih.gov/41180673/

Brensocatib: Is this breakthrough a Game-Changer for Bronchiectasis?

https://emedicine.medscape.com/article/296961-treatment#aw2aab6b6b1aa?form=fpf

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Written by stewart henderson

December 8, 2025 at 6:04 pm

Posted in bronchiectasis, digestive system, immune system, immunology

a bonobo humanity?