Neutrophils, Apoptosis, and Why This Matters in Bronchiectasis

“Recent research has revealed that… neutrophils are not normal in bronchiectasis. I mean, they are fundamentally different. They have delayed apoptosis compared to the normal host…”
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Dr. Pamela McShane

A pop-a-what?Let’s talk about apoptosis.

Yes, it is one of those words that sounds like what it actually is. But before we get there, we need to talk about those ever-discussed immune cells called neutrophils.
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What are neutrophils supposed to do? Neutrophils are white blood cells that act as the body’s first responders. Their role is to rush to infection sites and kill bacteria quickly and aggressively.
Just as importantly, once their job is done, neutrophils are supposed to die off promptly through a tightly regulated, natural process called apoptosis. This allows inflammation to resolve and tissues to heal.
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In a healthy immune system, this entire cycle is fast and well-controlled, typically completed within a few days.
Neutrophils themselves are not harmful. In fact, they are essential for fighting infection. The problem arises when their activity is not properly regulated.

What goes wrong in bronchiectasis?

In bronchiectasis, neutrophils are fundamentally altered. They do not behave the way they should.
Instead:

• They release excessive and destructive enzymes
• They delay apoptosis, meaning they do not die when they should

When neutrophils remain active for too long, they continue releasing proteases such as neutrophil elastase, along with inflammatory signaling molecules. This ongoing activity damages airway walls and interferes with normal mucus clearance.
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Neutrophils are meant to be short-term emergency responders. Their weapons are powerful by design, but they are intended to be used briefly. In bronchiectasis, however, these cells linger and continue firing within already vulnerable airways.

Why delayed apoptosis causes harm

When neutrophils fail to undergo apoptosis:

• Airway tissue is repeatedly injured
• Chronic inflammation persists
• Cilia, the tiny hair-like structures that help clear mucus, are damaged
• The airways become more vulnerable to infection

Neutrophil enzymes do not distinguish between bacteria and lung tissue. They attack whatever is in front of them. When these cells do not shut down as they should, the result is a prolonged inflammatory assault that drives airway damage.
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The degree of delayed apoptosis and neutrophil-driven inflammation can vary from person to person, which helps explain why bronchiectasis severity and progression differ so widely among individuals.

A newer approach: calming neutrophils, not eliminating them

It has been about five months since some people started Brinsupri™, and early feedback is beginning to emerge. Many who choose to share their experiences publicly report benefits such as less breathlessness and more energy. Everyone’s experience is different, but these early observations are encouraging.

So how does Brinsupri (brensocatib) work?

Brinsupri does not stop the body from making neutrophils. The immune system still sends these cells into the lungs as usual.
What Brinsupri appears to do is make neutrophils less damaging. This reflects a reduction in harmful neutrophil-driven inflammation rather than elimination of neutrophils or suppression of the immune system.

With Brinsupri, neutrophils remain present but tend to be less aggressive, cause less irritation and injury, and trigger less ongoing inflammation.

In simple terms, Brinsupri helps calm neutrophils down.
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It does not kill them.
It does not force them to die sooner.
It helps reduce the ongoing lung tissue damage they can cause once they reach the lungs.

These therapies are intended to limit inflammatory injury and may help slow disease progression, but they do not reverse existing structural airway damage.
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Deciding when or whether to consider treatment

Some people are choosing to wait to see how others respond to the new medication. This can be a reasonable and thoughtful approach.

However, if your lung function is declining or you are experiencing frequent exacerbations, the ongoing damage also needs to be considered. Each exacerbation can leave lasting effects on the airways and influence long-term outcomes.

At your next medical visit, consider asking your clinician about Brinsupri and whether it might be an option for you. There are also similar therapies currently in clinical trials that may become available where you live.

Understanding the biology behind bronchiectasis empowers patients to have more informed, collaborative conversations with their care teams.
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