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Adult Cystic Fibrosis
I carry a CF variance S895N, very common in Taiwanese, or specifically for Asian. Asian do not carry the most common CF mutation Caucasian carry and the symptoms are quite different ( usually without digestive symptoms or just BE or sinus infection) so CF is very much underdiagnosed in Asia. Though my sweat tests ( twice) is negative, I believe this mutation causes me bronchiectasis. I had frequent newborn pneumonia. My parents told me I had Otitis media twice before school age. I am now diagnosed as mild bronchiectasis/ MAC. I wonder how likely a mutation carrier will develop another CF mutation and become a CF patient. By research, I know currently there is no medication to treat this mutation.
I will see a CF director in NYU to understand this mutation next month. If anyone can recommend a great doctor in CF, that will be appreciated.
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The variant G895N in the CFTR gene is generally considered a non-pathogenic polymorphism or a variant of varying clinical consequences (VVCC), and it is not typically classified as a primary pathogenic (CF-causing) mutation by major databases like CFTR2.
Sorry if the above post appeared to veer into "adult CF' territory. It was meant to refer to the potential benefit of using CFTR modulators (Trikafta et al) in people with BE who carry a CF mutation. It's not that unusual to carry the mutation, and most people go through life without knowing it, but it does appear to increase the risk of problems such as BE, pancreatitis, et al.
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1 Reaction@tw508 I appreciate your information. Here is what I searched for. My mother also died of lung cancer at age of 77. My grandfather got TB when he served in the army. I will get into more research in CF and related mutation. I believe it will benefit most of the patients in MAC/BE forum too.
Trikafta (elexacaftor/tezacaftor/ivacaftor) is a revolutionary triple-combination medicine for Cystic Fibrosis (CF), targeting specific genetic mutations like F508del, and works as a CFTR modulator to help the protein function better, treating CF in patients 2+ years with responsive mutations, but requires liver monitoring due to risks of serious liver damage, with S895N being a specific but less common CF mutation often responsive to this therapy.
What Trikafta Does
Mechanism: It's a CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator that corrects the faulty CFTR protein, helping it move to the cell surface and function correctly, improving mucus clearance.
Components: Contains elexacaftor, tezacaftor (correctors), and ivacaftor (potentiator).
Responsiveness: Trikafta is indicated for patients with at least one F508del mutation or other mutations, that are responsive to the drug based on clinical data.
Key Considerations
Liver Issues: A major warning is potential serious liver damage or failure, requiring regular blood tests.
Dosage: Taken orally, usually twice daily, with fat-containing food.
Eligibility: For CF patients aged 2 and older with at least one F508del or another responsive mutation.
As a CF mutation carrier, without formal diagnosis of CF, it may be hard to get into any clinical trial or receive modulator treatment. But I almost am certain that a CFTR mutation makes us more susceptible to BE and other lung disease than people without this mutation. We may also develop another mutation when we age. Will see a CF director next month to better understand the disease and symptoms.
@tw508 Thanks so much for your information. I wonder whether the modulator be effective life long or they will be effective for 12 months and then patients have to change to another modulator? My mother got lung cancer, and the target therapy works on her for only 12 months. After 12 months, the effect is diminishing. Will the modulator be the same?
Some therapies (antibiotics, eg) select for resistant bacterial or tumor populations. That is not true of the CFTR modulators Trikafta or Alyftrek, which work by helping the mutant chloride channel protein fold, getting it to the surface of the cell, and increasing the amount of time the channel stays open. There's no apparent theoretical advantage to the host cell to keep the modulator from entering the cell where it is needed.
That's not to say the modulators prevent all pulmonary exacerbations (PE) long term - they don't. But PE are greatly reduced. It is quite likely that the bacteria colonizing the lung adapt to the changing conditions resulting from a vastly different extracellular environment post-modulator treatment and can flare up, often in response to viral insults. However, data do show that the bacterial burden in the CF lung (the only population studied to date) remains orders of magnitude lower even after several years of effective modulator treatment.
I hope that helps.
@tw508 Thanks for your info! I will also check with the CF director. By research, Asian CF patients do have a milder form of CF due to different mutation. They even do not have a positive sweat test result or only show as BE. My sweat test is 11/12. I think there is no modulator available for my mutation as it is so rare/not a significant indicator. However it is such a significant finding to me. Thank you!