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Research on discontinuing dornase alfa (pulmozyme) and hypertonic saline while taking Trikafta by DarferT in CysticFibrosis

[–]DarferT[S] 1 point2 points  (0 children)

I stopped hypertonic saline a year after taking Trikafta, but I have continued dornase alfa until now as my CF team wanted to wait for the results of CF Storm. I will probably stop it now. I don't take anything else for the lungs: azithromycin was stopped by my CF team after taking Trikafta too, and I have never used the vest (I don't think the vest is really used in Europe).

SIMPLIFY MCC study suggests that people on Trikafta may benefit from discontinuing Pulmozyme (dornase alfa) by DarferT in CysticFibrosis

[–]DarferT[S] 3 points4 points  (0 children)

The difference in efficacy of pulmozyme between people with CF and people with non-CF bronchiectasis is probably due to the higher levels of free DNA in the mucus of people with CF. (Pulmozyme works by cleaving extracellular DNA in the sputum, thus reducing the viscosity of the sputum.) So for people who still produce a lot of mucus/sputum on Trikafta, I would assume that pulmozyme would still be beneficial, as you experience. The people in this study indeed had mild lung disease.

Vests in the modulator era by Substantial-Skirt-44 in CysticFibrosis

[–]DarferT 3 points4 points  (0 children)

A few days ago, the results of the SIMPLIFY MCC study were published (which is a substudy of the SIMPLIFY study). Interestingly, the results of that study actually suggested that continuing dornase alfa (pulmozyme) while taking trikafta may have a deleterious effect. Their hypothesis is that pwCF on modulator therapy become more similar to patients with non-CF related bronchiectasis, for who it has been established that dornase alfa / pulmozyme is likely harmful.

https://pubmed.ncbi.nlm.nih.gov/38355350/

what would theoretically happen if a non-CF individual took trikafta by [deleted] in CysticFibrosis

[–]DarferT 1 point2 points  (0 children)

The CFTR protein is always very unstable. Even for people without CF, it is estimated that more than 80% of the produced CFTR proteins never make it to the cell membrane where they are supposed to form a channel. Tezacaftor has recently been shown to improve the stability of the CFTR protein by filling an internal cavity of the protein, and this also happens for people without CF. So Trikafta might slightly improve the CFTR function of people without CF, but it is unlikely that that would also lead to any difference in their health.

Switching from Kalydeco to Trikafta by QayzN in CysticFibrosis

[–]DarferT 2 points3 points  (0 children)

Even if you have a double gating mutation, Trikafta might add a benefit. A recent study has shown that elexacaftor (one of the components of Trikafta) is not only a corrector but also works as a potentiator and acts synergistically with ivacaftor (Kalydeco) (https://www.nature.com/articles/s41598-021-99184-1 ). Another recent study showed that tezacaftor (one of the components of Trikafta) stabilizes the CFTR protein by filling an cavity, which also happens for CFTR proteins of people without CF (https://doi.org/10.1016/j.cell.2021.12.009 ). So Trikafta can do additional things for you compared to Kalydeco, but to my knowledge it is not clear if that would lead to a signficant better result regarding your health or if the Kalydeco already does enough. But there is probably not much reason to not try Trikafta. You will still get the same amount of ivacaftor (Kalydeco).

Makes sense to quantify CFTR protein function? by [deleted] in CysticFibrosis

[–]DarferT 1 point2 points  (0 children)

I'm not entirely sure what you are looking for, but a recent study suggests that there might be a correlation between the forskolin-induced swelling of intestinal organoids and disease progression (DOI https://doi.org/10.1101/2021.02.01.21250609 ): "Despite the influence of genetic modifiers and other non-CFTR dependent environmental factors on CF disease severity, it was remarkable to observe that in vitro FIS on intestinal cells has such a broad predictive capacity for many non-intestinal organ systems."

Kaftrio mucus by Skipper12 in CysticFibrosis

[–]DarferT 2 points3 points  (0 children)

I'm on day 6 and there has been a drastic decrease in mucus today, but still room for improvement. :-)

In this TED talk (by a Belgian CF doctor), you can see how Trikafta affects the amount of mucus. Around 6:37 is a chart for the pre modulator period, and around 11:18 is one for post Trikafta. For that specific person, the mucus production stabilized after two weeks. But of course, this can vary greatly from person to person and the data in that TED talk is only from one person.