Sorry if this question is of the "out there" type. If an asthmatic recipient receives a lung transplant from a non-asthmatic donor, would the recipient asthma be "cured"? I've read about the reciprocal phenomenon -- one gets asthma if the donor was an asthmatic.
I am guessing compared living a lung transplant, severe asthma may seem like a walk in the woods.
No cause asthma is autoimmune so body attacking itself. And a lung transplant is not going to change that.
Emma, this old 2005 paper appears to suggest the opposite:
Bilateral lung transplantation for severe persistent and difficult asthma
Hubert R Wirtz, Claus Kroegel, Paul Caffier, Hartmut Bittner
PMID: 16210150 DOI: 10.1016/j.healun.2005.01.015
Abstract
Although asthma is listed as an indication for lung transplantation, only 2 cases have been reported to date. Here, we describe a 42-year-old woman with progressive, severe, persistent bronchial asthma resistant to high-dose oral steroids and adjuvant immunosuppressive therapy. Because conventional and experimental therapeutic strategies failed, the patient was listed for bilateral lung transplantation and received a transplant shortly thereafter. At 12 months after transplantation, her lung function parameters are normal and an asthma attack has not occurred since.
This suggests that one of the asthmatics in question was non-eos and non-allergic asthma as they were non steroid responsive. I cannot access the article to read it properly, and the abstract does not clearly state it.
As even now they don’t know what drives this type of asthma, so it may be created in the lungs rather than externally.
Equally this paper was in 2005. Testing and treatment has changed a lot since then. Or she may have been wrong diagnosed cause different testing is now available etc, and more (rarer) respiratory conditions have been diagnosed.
Medication wise, back then Xolair was the only MAB, and whilst not suitable for the above patient (as she’s non-allergic) there have been new asthma meds that have been released since then. Other treatments have also come out such as bronchial thermoplasty.
Or it may even be the immunosuppressive drugs that you have to take for transplant is what stopped the issues. Most asthmatics have over reactive immune systems (as prev stated) so depressing it would help, however there’s a reason most of us aren’t on methotrexate (a drug that CAN be given for asthma now…).
I also find the fact that even 16 years later, there has been no follow up article, no article on the other participant and seemingly no other patients to have received transplant (as something this rare, most docs who want to publish), suggests that either since then things have been unsuccessful OR they just haven’t occurred again, which suggests that for the majority the risk would outweigh the benefit, and it may be that it’s the drugs, not the transplant that is the solution, or that less invasive intervention is now enough to help patients in this situation.
>Or it may even be the immunosuppressive drugs that you have to take for transplant >is what stopped the issues.
I agree with this.
I think the reason for no follow-up is that treating millions of asthmatics with lung transplants would be not sustainable. Like the designer drug they gave to Trump for his covid would not be accessible to 99.9% of people.
My consultant has explained that my phenotype starts in the bone marrow so a change of lungs wouldn't result in a cure. The symptoms may be contained in the lungs, but the biological blue touch paper starts elsewhere in the body, depending on your asthma type.
I would say, the magic bullet will be gene therapy, but it's early days and I doubt I'll see this as mainstream treatment in my lifetime. asthma.org.uk/about/media/n...
For the gene therapy, they would need to know the genes involved in each specific case. These genes likely will be responsible for other functions as well, so it won't be a clear single-gene mutation like sickle-cell anemia etc.
This is a good article, explaining the work done to date and the hurdles to progress. cell.com/molecular-therapy-...
There has been a hiatus in gene therapy after the famous lethal case with adenovirus. Since, then, there was progress made with Zg-finger nucleases, AFAIK. CRISPR still has off-target issues which are poorly understood. Maybe countries with more lax regulations will get it done first and we can do gene-therapy tourism.
What about the infamous parasitic worm therapy? There was a trial in the UK, from what I heard
asthma.org.uk/about/media/n...
I don't know the latest on gene therapy for asthma, though I would note the paper Poobah cited is from 2003, so may not reflect more recent research and understanding about asthma pathophysiology and genetics.
I know they've certainly made progress on gene therapy recently for some devastating diseases caused by mutations in single genes (such as spinal muscular atrophy (SMA) or metachromatic leukodystrophy (MLD)). I worked on creating scientific materials about these a few years ago, and I know they were extremely aware of the problems with earlier gene therapies and looked at ways to address that as well as monitoring for the issue during treatment. So far it doesn't seem to have been an issue again, and at least one gene therapy has been approved for use for SMA and MLD. Of course these are very different from asthma in multiple ways, but I wanted to add that gene therapy as a whole, at least for monogenic disorders, has been moving ahead since Jesse Gelsinger died in 1999.
To me, as a layman, the more research into asthma and gene therapy, the more variables seem to come into play, making it ever more complicated/impossible to develop a universal therapy. Precision medicine for asthma, in terms of gene therapy, seems to be as futuristic now as it was when I was a kid. But I have a huge appreciation for those who continue their research and for those who fund it, whether it's for asthma or other debilitating diseases.
Yes - I actually think progress in asthma will come from understanding that the term describes a fairly wide range of underlying biological mechanisms, instead of trying to reduce it to one 'asthma'. This does seem to be the direction that precision medicine is going in for asthma. (Slowly. With sometimes a disturbing lack of appreciation for reality, and a pressing need for more real-world evidence.)
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