Returnings V: Just Keep Going
No matter what happens, never give up.
1.
The May 18, 2025, New England Journal of Medicine published the first results from the FIBRONEER-IPF study, which examined Nerandomilast, an orally administered antifibrotic and immunomodulatory agent, as a potential therapy for Idiopathic Pulmonary Fibrosis (IPF). At the minimum, it’s encouraging to read about new treatment options for such a challenging disease, since there has been very little to celebrate in the last ten years since the approval of Ofev (nintedanib) and Pirespa (pirfenidone).
Early on, in my own IPF journey, I was prescribed Ofev by my local pulmonologist. She warned me about the potential side effects, which were mostly digestive (nausea, diarrhea), and I did begin a course of treatment. Fortunately, I did not have any side effects. Unfortunately, I did not have any therapeutic effects either. Not particularly surprising, since these drugs were shown to have slight to moderate effects at best.
Nerandomilast seems to have performed significantly better; however, as one reviewer said, it produced ‘less of a home run and more of a single.’ One area in which it showed significant results was the preservation of Forced Vital Capacity (FVC), the total volume of air a person can forcibly exhale in one breath after taking the deepest possible inhalation. Patients on the drug experienced less decline in FVC compared to placebo. However, there was no improvement in exacerbation, hospitalization, or mortality endpoints.
Still, after years of fibrosis failures, it’s a real step forward.
Just not a leap.
The drug works by inhibiting the phosphodiesterase 4 (PDE4) enzyme family, which breaks down cyclic adenosine monophosphate (cAMP), a molecule involved in regulating inflammation and immune responses in cells.
By inhibiting PDE4, Nerandomilast increases cAMP levels, reducing inflammation and modulates immune activity in tissues like the lungs. This makes them useful for treating inflammatory lung diseases.
Cyclic adenosine monophosphate (cAMP) is a critical internal messenger in cells that regulates various physiological processes, including inflammation, metabolism, and immune function. Certain natural products can increase cAMP levels by stimulating adenylate cyclase (which synthesizes cAMP from ATP) or inhibiting phosphodiesterase from degrading cAMP. These include:
Forskolin, derived from the roots of the Ayurvedic Coleus forskohlii plant. Forskolin directly activates adenylate cyclase, leading to increased cAMP production
Resveratrol: Found in red grapes, berries, and peanuts, resveratrol inhibits PDE, preventing cAMP degradation and thereby increasing intracellular cAMP levels
Caffeine is also a well-known inhibitor of PDE, which is a large part of its energizing qualities
Another interesting bit of news arrived on the post-transplant front in the form of an upcoming study to see if a skin test may have the potential to predict lung rejection. The study subjects will receive a skin patch from the forearm of the organ donor, which will be transplanted onto the undersurface of the patient’s forearm at the same time as the lung transplant. Skin seems to reject earlier than other organs and is easily visible at all times. Doctors can then treat the rejection as soon as a rash appears, to try to prevent the lungs from also rejecting.
Lots of movement in the area of fibrosis research, although not necessarily due to pulmonary concerns. Fibrosis contributes to almost all forms of chronic disease, and more people will die from its long-term consequences than from any other chronic disease.
To quote my first pulmonologist, ‘It’s a pity that you didn’t get this ten years from now.’
2.
As for myself, each day begins with a feeling of intense gratitude. Grateful for this new chance at life. Grateful for my family and the support they so selflessly give me. Grateful for the hundreds of notes of love and support, many from people I’ve never met face-to-face.
Now, at eight weeks post-transplant, I’m able to do most things for myself, like dressing and showering. I can get around the house on my feet okay, although I don’t have the ability to exert myself in a sustained manner to any great degree. I do exercise almost daily, on two machines, one called a NuStep and another a typical treadmill.
Some of my missing mojo can be traced to a rather difficult time the transplant team has had trying to get the levels of Prograf (tacrolimus) to a tight therapeutic window. Two recent blood levels were way high, and that is not a good drug to have high levels of. At the best of times, you get shakes and some tiredness. With these high levels, I felt that there were two of me, connected by strings, one alongside the other. Fortunately, the team over at Brigham was on top of things, and the levels are now where they are supposed to be.
My spirometry numbers could be better, but the crisis I wrote about in the previous entry definitely set things back a bit. We continue to travel to Boston weekly for my ‘Freshy Transplanted’ clinic visits, which include an X-ray, pulmonary function tests, and a meeting with the nurse practitioner.
Everyone seems happy enough with the current state of affairs, and constantly reassure me that for where I am, I’m doing well. ‘The X-rays show ‘small lung volume’, but that is likely due to an unfilled area of lung (atelectasis) at the bottom. They tell me it will eventually fill up, and the numbers will rise.
As my somewhat ascerbic nurse practitioner likes to put it, ‘Look, you’re home in Connecticut two months after transplant. I have patients who had their transplants four months ago, and they’re still in the hospital.’
Still, there appears to be a definite dichotomy at work here. As I am a single-lung transplant, the other diseased lung (known as the ‘native lung’ but called ‘Yuki’ by me) just hangs out there with the new lung, whom I have named ‘Eddy’. They say Yuki will just do its thing for a while and then just kinda shivel up, and eventually Eddy will do all the work.
The problem is, Yuki is a mess, with a lot of issues, and one of them is that he likes to make me cough. A lot. This cough was ever present in my pre-transplant IPF days, and it took a while for it to occur to me that this was not in Eddy, the new lung. And since the transplant team ceaselessly encourages you to ‘cough and walk,’ you just accept it as fact.
However, a recent CT scan showed just how bad Yuki is. The current wisdom is that I just have to put up with things until he decides to turn out the lights, and at that point, the cough will go away. In the meantime, I can get by with Mucinex (guaifenesin, a mucous thinner), mullein tea, and a cough suppressant. Martha also pounds on my side and chest with these suction cup things, which is very helpful.
3.
One could probably count the number of people who have had a completely problem-free post-transplant existence. They are seen to be inevitable.
However, most are navigable, solvable, and the body, if given the space and time, can almost always be counted on to heal and regenerate in the aftermath.
I recently saw a short clip on YouTube of Sir Anthony Hopkins being interviewed on American late-night television. The host asked him, now at this point in his life and career, if he had any insights to share that is something we might have overlooked.
‘Just keep going. Never give up’ was his immediate answer.
A rubric perhaps easier done than said.