in the spotlight: 
With Jacob Greene

By Andrea Eisenman

Age: 24

Home: Edmonds, WA

Current Location: San Francisco, CA

Readers, it is my pleasure to introduce Jacob Greene, who recently joined our board as a director. You may have seen his photo in recent issues because he has received the Higher Education scholarship, not once but twice. He won initially as an undergraduate and the second time while pursuing a medical degree at the University of California San Francisco (UCSF). Jacob became a director in spring 2023 and is active on several other CF boards. As you will see when you read his interview, he is highly motivated to keep himself healthy and become a caring physician due to his personal experience as someone with a lifelong illness. Since starting Trikafta in 2019, his health has improved immeasurably and he is able to tackle more effortlessly all that lies ahead for a bright future. This propels him to make things better for others once he is an anesthesiologist. He hopes to ease his patients’ fears and anxieties and possibly contribute to making lives better for those in need of medical assistance, as recent medical innovations, such as modulators, have done for him. Please welcome our latest star. Spotlight, please!

Where did you attend school for your undergraduate degree?

I attended Stanford University from 2017-2021 and I hold a Bachelor of Science with honors in Biology.

When were you diagnosed?

I was diagnosed at birth after an ultrasound revealed that I had meconium ileus.

Was your sister also tested at birth due to your diagnosis? Where is she now?

Since my family had no history of CF, my parents did not know they were carriers until I was born. My sister was diagnosed with CF via amniocentesis before being born. My sister recently graduated from the University of Washington and now works in San Diego, CA, at Bristol Myers Squibb as a research associate.

How was it growing up with a sibling with CF?

Both my sister and I are homozygotes for F508del. Growing up before Trikafta, we were fortunate to be relatively healthy. As a kid, I was chronically colonized with Pseudomonas, while my sister frequently cultured Staphylococcus aureus and Aspergillus. Despite us living together, we seldom cultured the same bacteria. Now, both my sister and I are on Trikafta. Neither of us has needed any IV antibiotics since starting Trikafta in 2019. I have not cultured any bacteria since starting Trikafta.

Where are you studying medicine?

I am a medical student at the University of California San Francisco (UCSF) School of Medicine. UCSF does not have an undergraduate college, so many people outside of the Bay Area have not heard of UCSF. However, UCSF is the major academic medical provider for San Francisco. UCSF also operates the San Francisco Veterans Affairs Hospital and San Francisco General Hospital.

How is medical school so far? What is the most challenging?

I just finished my first year of medical school and am starting my second year. So far, it has been great! I have learned a ton and am excited to care for patients full-time starting in January of 2024! I think the most challenging part of medical school is how different it is from high school and college. After the one-and-a-half years of pre-clinical curriculum, we are learning to care for patients in the hospital full-time for the remaining two-and-a-half years. Thus, the types of accommodations needed for this clinical curriculum differ from classroom learning. For example, my academic accommodation is that, when I am around patients in the hospital, I wear an N95 mask. Thankfully UCSF, has been incredibly accommodating of this. Additionally, since my CF center is also at UCSF, it makes getting to my doctor appointments very easy.

What made you choose UCSF?

There are several reasons why I chose UCSF. My girlfriend, who is a genetic counseling student, matched at UCSF for genetic counseling school. When she matched, that largely sealed the deal. But additionally, UCSF was the most financially affordable option for me. I also was a patient at UCSF when I lived in the Bay Area from kindergarten through half of third grade. My first memories as a CF patient were from UCSF. I remember my first in-patient hospitalization, which was at the UCSF Parnassus campus. So UCSF holds some sentimental memories for me, too.

How do you balance your needs versus your work and time for your relationship?

Ultimately, everything is about priorities. I prioritize my relationship and taking care of my health because, at the end of the day, I can learn and, eventually, care for patients only if I am caring for myself. If I am sick, then I can’t effectively learn or treat patients.

Do you exercise regularly?

Yup! I run a couple of miles three times per week.

Did you always want to be a doctor?

Initially, my inspiration to be a physician was due to my experience as a CF patient. From birth until the age of 20, I consumed over 250,000 pills, spent 10,000 hours doing medical therapies, received over a dozen rounds of inpatient intravenous (IV) antibiotics, and was operated on more than ten times. Before Trikafta, this was a pretty typical representation of life with CF. These experiences as a patient have inspired me to be a doctor. Since starting Trikafta, my FEV1 has completely stabilized, I have not needed any IV antibiotics, and my treatment regimen has pretty much been eliminated. I want to be a physician to give the gift of medicine to others. Furthermore, I believe my first-hand experiences as a patient will inform my clinical practice. There are not many people with CF who are physicians, so I hope combining my experiences as a patient with my ongoing medical training will help me be the best physician I can be.

How were your undergraduate studies? How was your health through those four years?

I was hospitalized every 12 to 18 months for CF infections during college and, despite my FEV1 being in the 80s, my health was getting worse. Then, in December 2019, I started modulators. Amazingly, there was no longer a need for IV antibiotics. I still occasionally use the if I have a cold, but my daily treatment regimen is very minimal. I have not cultured Pseudomonas since starting modulators.

Do you know the area of concentration you will go into after medical school? If so, why?

I am pursuing a residency in anesthesiology, although one does not apply for residency until the fourth year of med school. I like the physiology, pharmacology, and hands-on nature of the specialty. Patients are often nervous going into surgery, as I have been when I was a patient. Anesthesiologists can help alleviate some of that anxiety. I vividly remember my anesthesiologists and wanting to provide the excellent care I have received motivates me to pursue this specialty. I also am very interested in the sub-specialties that branch off anesthesiology—critical care medicine, pain medicine, neuroanesthesia, or pediatric anesthesia.

You received the Lauren Melissa Kelly Higher Education Scholarship from USACFA. Tell us about that.

Yes, twice. Once as an undergrad and once in med school. Medical students graduate with an average of $200,000 in student loans, so the scholarships I have received go to offset my student loan burden.

Do your friends and classmates know you have CF? Do your professors know?

I am very open about my CF. I take enzymes publicly. My professors know about my CF because the disability office shares that information with them. One unexpected benefit of being so open about my disease is I have been invited to give talks at school about CF. Every year, I give a lecture about life with CF at a class taught at Stanford University (my alma mater). Now, I lead a Q&A session with the UCSF Genetic Counseling students about CF.

Who or what are sources of support for you in times you need it?

My family and friends are my main source of support.

Now that you are on Trikafta, what is most important for you to keep doing treatment-wise to stay healthy?

For me, besides taking Trikafta and pancreatic enzymes, regular exercise is most important. I am not particularly nervous about starting my clinical years of med school.

Do you have advice for others who have CF who may consider medical school?

The first thing I would say is that representation is very important! There are not many physicians who have cystic fibrosis. We (CF patients) have valuable insight into what it is like to be a patient. And with medications like Trikafta, now is as good a time as ever to pursue a career as a physician. I would also advise those with CF (or any other chronic illness) starting medical school to connect with more senior medical students at their school to get their advice on how to do well academically. I also would recommend plugging in with the school’s disability office if any accommodations are needed. Medical education is very different from primary school/high school/college.

Did you have a mentor or someone who influenced you to be who you are today?

Yup, I have had many mentors. In high school, I had a few teachers who really inspired me to pursue my intellectual interests in STEM. In college, Dr. Michelle Monje and Dr. Erin Gibson inspired and cultivated my interests in medicine and biomedical research. Now, in medical school, Dr. Denise Chang, Dr. Jonathan Pan, and Dr. Ban Tsui are inspiring me to explore the field of anesthesiology and research within that field. And since I was a kid, my CF physicians have demonstrated to me what it means to be a great physician.

If you would like to be interviewed for “In The Spotlight,” please contact either Xan Nowakowski or Andrea Eisenman. Their contact information is on page 2.

What Nonsense!

By Andrea Eisenman

Once I had my lung transplant in 2000, I stopped going to a CF clinic. The transplant center advised me that they were now my main pulmonologists and medical providers. If I needed to see other specialists, they would recommend them to me at NY Presbyterian—a one-stop shopping experience. It was working great until my enzymes stopped aiding the digestion of food. At that time, I was taking Pancrease capsules. All of a sudden, about eight to ten years after transplant, my digestion deteriorated. And, due to that, I had stomach aches, diarrhea, and frequency of running to the bathroom. This all became untenable for an active lifestyle, so I asked the transplant center to help me with my enzymes. They recommended I see my old CF center with my pediatric pulmonologist. But my previous pulmonologist and his team had moved to the Children’s Hospital at NY Presbyterian. I now had to see the adult CF care team at NY Presbyterian. I made an appointment; they recommended I start using Creon caps, and things vastly improved in my gut. During my follow-up visit with them, the CF doctor asked if had any other issues. I did: I had heard about the new modulators that had been developed and seemed quite successful for many people whom I knew and read about. I guess for some, taking these new drugs was transformational.

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I asked the CF center if they could test for my mutations because, the last time I was tested via sweat test, there were only about 14 known mutations for CF at that point, which was possibly around the 1990s. I was not positive for any of them. So I embarked on finding out my mutations in the hope that, if my lungs started failing, I would have a back-up of taking these miracle medications. This time it was a saliva test for my CF markers, and they tested for over 2,000 known mutations. I was then called about the results, which were puzzling to me. I was homozygous for a nonsense mutation called W1282X. It is common among Ashkenazi Jews. 

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I didn’t know what my mutations meant at first. But I later found out that W1282X was a nonsense mutation and meant I could not benefit or even try the new Vertex drugs that were potentiators first and now modulators (Trikafta). I was a bit crushed emotionally. At that time, I was not experiencing anything major with my transplanted lungs. It was 16 years before I was put on IV antibiotics for an exacerbation. I was fortunate. That soon changed as IV antibiotics became more frequent, usually at least once or twice a year due to my recurrent sinus infections, which then infected my lungs. I had sinus surgery almost every three to four years to keep my sinuses clear. I then started hearing that those on corrector medications (at the time it was Kalydeco) were experiencing an improvement in their sinuses, even if they had lung transplants. I was truly jealous then. But I had to just keep doing what I had to do. I didn’t obsess about being left out. I was still doing relatively well with a decent lung function in the 70s.

Then my health status changed abruptly in 2017 when I was diagnosed with a form of lymphoma called Post-Transplant Lymphoproliferative Disease (PTLD). I was angry at getting cancer after living what I considered a “healthy” lifestyle of exercise, mindfulness practices, and eating decently. And while the treatment for PTLD was not horrible, it did involve IV infusions of Rituxan that made my lungs feel inflamed for one to two days afterward and made me short of breath. This occurred initially when I was on weekly doses of the treatment. As my treatments were more spread out—monthly at first and eventually as little as once every three months—they were not so obviously affecting my breathing. Then, PTLD returned after two years of remission. This time I was in a clinical trial receiving T-cell therapy that took donor T-cells from those with the Epstein Barr virus (EBV), which is the catalyst for this type of lymphoma. These infusions made my body mount an attack on the EBV in my own cells. 

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After this therapy went on for eight months, it did not rid me completely of lesions. But because they were localized in my right axilla, I was advised to complete a month-long treatment of radiation. This involved daily visits for 28 days receiving radiation directed at my armpit, and hence, I was warned that part of my right lung may be affected by inflammation and scar tissue. Thankfully I am still in remission for PTLD. But it has only been a year. My EBV is watched monthly for elevated numbers. A consistent rise in numbers could indicate that the lymphoma lesions have returned. I get a PET scan twice a year to get a definitive measurement that cancer is either still in remission or recurring again. After all of these treatments, I noticed my lung function was slowly sliding into the 50s, where it remains today. I also have more shortness of breath.

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Due to my declining lung function, my doctor tried putting me on massive doses of steroids starting with 800 mg of solumedrol IV for three days, then tapering to 60 mg of oral prednisone. Every three days I tapered down 10 mgs to finally get back to my normal 5mg dose. The high doses of steroids didn’t make a difference in my breathing; they made me crazy in my own skin and increased my blood sugars astronomically. My doctor said that there was one more treatment to try, but it involved a hospitalization and a bronchoscopy first to rule out infection, acute rejection, or fungus. Once my lungs were free of anything harmful, I would be admitted to the hospital for five days to receive antibodies to halt the progression of the decline of my lungs. But this treatment would also wipe my immune system, so I could not be around people or in areas with others I didn’t know, like a movie theater or indoor venues (good bye, Broadway shows!). This was considered one of the only treatments left for me to take safely.

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The antibodies were given at the end of May this year. They remain in the body for three months. I am now about three months post treatment. I am again feeling short of breath and know my options are limited. There is still hope for the remaining 10% who are unable to take current modulators—new inhaled options like gene therapy and mRNA particles inhaled into people’s lungs to correct the gating process for chloride and sodium. But, unfortunately, those with solid organ transplants will not be able to join clinical trials due to the risk of inflammatory response, cancer, or possible rejection. If shown to be effective for those in the trials, however, I may be eligible sooner than expected if the results are demonstrated to be beneficial and safe. I am still excited that new treatments like these and gene editing may yet be treatments for us all to benefit from systemically, not just via inhalation. It seems researchers and CF care centers are working valiantly to find new ways to get our CFTR to function correctly, specifically for those in the remaining 10% population.

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Even after receiving the antibodies, my lung function was not expected to drastically increase. Just not reduce further. So far, that is the case. I am holding at around 50% with some shortness of breath on exertion. If my lung function starts to slide further down, getting another lung transplant might be my only option to staying alive. This option may not be available to me due to having cancer (that is activated by having a suppressed immune system, which allows EBV to thrive). In order to be considered for another lung transplant at NY Presbyterian, I would have to be in remission for another two years, three total. Otherwise, I would have to search elsewhere and relocate to another center and city where I might be considered as a viable candidate with only one year in remission. 

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It can be frustrating to continue to feel left out of benefitting from all that is being done to cure 100% of the CF population. I do not obsess about this but rather go about my day to day while staying on top of my care and being openminded about new research as well as just continuing to enjoy life through my spouse, friendships, good food, sports, and my dogs. All of them feed my soul and keep me going so I can spend more quality time with them all. I remain hopeful and positive that, eventually, I may live to see CF cured. What a day that will be! 

Andrea Eisenman is 58 and has CF. She recently realized that her initials are AGED: Andrea Gail Eisenman Downey (her husband’s surname)! She lives in New York, NY, with her husband Steve and dogs, Willie, Roscoe, and Trixie. Andrea is the Executive Editor for USACFA. She enjoys cooking new recipes, playing pickle ball, biking, tennis when possible, and staying active as her health allows. Her contact information is on page 2.

Late Diagnosis And
In The 10%

I was diagnosed with cystic fibrosis (CF) at the age of 19. It came after one of my siblings did genetic testing in preparation for IVF. As a young child, I spent time in the hospital on three separate occasions for my lungs and even spent time on home oxygen when I was four. I frequently had a cough that felt embarrassing, especially for a shy girl on testing days at school. 

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I didn’t know very much about CF when I went in for the sweat test and definitely had no clue what it would mean to have a diagnosis. After my sweat test results came back positive, I went to my first CF clinic appointment. I was expecting it to be a normal, quick doctor appointment and was ill prepared for five hours of talking to clinicians, doing tests, and learning about this disease. During that appointment, they collected blood to complete genetic testing, which later came back with two Class 1 mutations. I didn’t think much about the results at the time. 

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Starting on CF meds was incredible. I remember after my first dose of pulmozyme, I was walking with friends to a campus event and I kept coughing up huge chunks of mucus. It was amazing the difference the breathing treatments made for me. It was both gross and remarkable to see how much would come out of my lungs during breathing treatments. The changes were drastic for me and these symptoms that had been my normal eased for me. 

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In 2019, I started a masters in social work program. It was my lifelong dream to become a therapist and I was thriving. At the beginning of 2020, I had a lung exacerbation that took me out of school and my internship for a couple weeks. On my second day back in school, my state shut down for COVID-19. Life changed drastically and suddenly CF took a front seat. I had my first pancreatitis attack later that year, resulting in a month-long stay in the hospital and four months with a nasojejunal tube because of persistent pain and inability to tolerate food. I first became involved with the CF community during this time. 

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I got to learn about Trikafta and other modulators by hearing firsthand accounts as friends and acquaintances started it. I remember bringing it up to my doctor and her telling me about what Class 1 mutations meant and that it was highly unlikely any modulator would work on me due to my genetics. I have always felt like my CF is unique but typically it felt like mine was unique in terms of not being that scary disease other people have because of my late diagnosis. Also, the recent bout of pancreatitis felt like the bigger issue, whereas it seemed like others with CF struggled with their lungs more than anything. This was the first time that being unique was considered a bad thing. 

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For me, starting on CF-specific treatments made a huge difference for my lung health. I went from an almost constant cough to being able to sit through classes without coughing and I had a significant reduction in both bronchitis and pneumonia episodes. While they are not the same as modulators, the experience was similar to what I’ve heard others describe with the modulators. There are a lot of exciting studies being done currently and a community that I know is fighting for every single one of us. I don’t think it will be long before more advances are made. This is a community that knows how to fight, advocate, support, and beat the odds. I’ve watched it happen before and I see the progress happening in real time.   

Camille Richards is 27 years old and has CF. She lives in Woodscross, UT. She is a practicing therapist specializing in helping individuals with OCD and anxiety-related disorders. In her free time, she enjoys art, cooking, and maintaining her role of favorite aunt to her 32 nieces and nephews. 

Notes From My
Trikafta Journal

Bending away from my concerns about the cost, I listened to the excitement in our community about the triple-combo modulator and Dr. Francis Collins’s presentation at NACFC and asked about starting Trikafta. My F508Del mutation let me into the growing circle of those eligible for CFTR modulators. After a few short weeks, I had insurance approval, copay support, and a patient support specialist at Vertex. On December 2nd, the pharmacist and case manager from the specialty pharmacy called me to discuss dosing and potential side effects: dizziness, headache, diarrhea, and elevated liver enzymes. It was very fast coordination.  

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In the dark December days of 2019, I started Trikafta. 

Preparing to share my experience with you, I’m reminded of the early, not-so-easy days with the magic pills.

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• 1st week: sputum!, runny nose, headache, nausea, sad, teary, agitated.

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Okay, I might be agitated from being told “you definitely need oxygen” while picking up results of overnight oximetry testing at the respiratory care company. As the nurse explained the results and consequences of low oxygen, I see another person’s name and a different doctor at the top of the page. 

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• 2nd week: headache, bloating, exhaustion/fatigue, hunger.

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• 3rd week: body changes, gurgling, burping, sadness, dry eyes, my new pants don’t fit, stool changes.

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• 4th week: dry, scratchy eyes, disrupted sleep, extreme sadness.

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Deep into January I am sleepless and sad. Our nurse coordinator hears my discouragement, uncommon alongside the joyous response to Trikafta. We tried alternate dosing: taking the two orange morning (happy) pills in the evening and the blue evening (sleepy) pill in the morning. It didn’t help.  

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My patient support specialist calls frequently and I continue to tell him about my side effects. Hoping my experience would get better, I opened a second box of Trikafta.

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• 5th week: sad, revved up in p.m., busy, another day—not so sad.

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• 6th week: constipation, night sweats, no sleep :(.

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In February, I wondered how to tease out the mood of the cold, dark, snowy/icy winter with my sad mood.

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Meanwhile, I had more testing for cardiac concerns with medication changes. The repeat overnight oximetry results were good, so I let go of the worries I carried about transitioning to supplemental oxygen.

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• 7th week: sleepy/tired, no sleep :(, bowel movements at 4a.m., feeling flu-like, still tired, sleepless after 1a.m., headache.

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• 8th week: no sleep, visual aura without headache.

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• 9th week: sad, TIRED, sleepless, revved up at bedtime, yeasty.

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After weeks of reporting my increasing sadness, agitation, sleeplessness, and frustration, we decided to d/c Trikafta, waiting until my next clinic visit to check FEV1 and sweat chloride. There is good news: my FEV1 was up by 15 points, the highest since my diagnosis, and my sweat chloride dropped to 49/53 from my baseline of 120. My liver function was fine. Still, I wanted to leap off the Trikafta bandwagon. The psychologist at our CF Center gave me the quality-of-life questionnaire, which confirmed depression. I wonder if others are also struggling.

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• 10th week: stopped Trikafta

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• Two days later: GOOD SLEEP! 

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The patient support specialist made a routine check-in call. He sounded surprised that I’d decided to stop. Surprised? I’d told him about my side effects. A reminder call from the pharmacy led to a talk with the pharmacist. I shared why I had stopped taking Trikafta. He’d heard similar experiences from others and would report the adverse effects. I felt heard. 

Our COVID times began. Are the experiences of depression and anxiety from Trikafta or from the fear, uncertainty, and isolation of the pandemic?

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2021 was a hard year. I was in the hospital in January, February, and August-September for a total of eight weeks. I almost missed my daughter’s wedding. My lung function declined and new cardiac issues arose. I cultured MAC. In September I left the hospital with a pacemaker and a high-risk cardiac med. As we prepared for discharge, my doctor and I decided to try Trikafta again. He suggested I start with half doses. Another one of our CF doctors gave me information about Trikafta “slow start” with titrated dosing. My next first box of Trikafta was delivered to me in the hospital. Everyone was eager to put it in my hands. Feeling apprehensive, I waited and waited to open it as it had been so hard before.

Trikafta, Take Two: October 2021 Through April 2022

I started half doses on October 20th. I experienced new symptoms: urgent and voluminous bowel movements (a/k/a “the purge”), dizziness, and night sweats. I was feeling “revved up.” My gut was not happy. Sadness crept in along with fatigue. I became weary. We tried the lower doses with the “slow start,” then just the orange “not so happy for me” pills. Everything exacerbated no matter the dose. I continued with a very low dose while experiencing a mix of new and old symptoms: heartburn, exhaustion, bloating, headaches, early a.m. bowel movements (who poops in the middle of the night?), a “buzzy” feeling in my chest then my lips, abdominal pain. I felt a cloud of sadness on my shoulders. My legs are weak, my massage therapist tells me I’m losing muscle tone.

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I dream that I am locked in a room that has an elevator, holding a key that doesn’t work.

There were so many voices coming my way, encouraging me to persevere. The CF Team: “We want you to get to full strength.” And some CF friends: “Keep going, it will get better.” It seemed that everyone was thriving on Trikafta. 

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Clinic visits in February and April once again show benefits from Trikafta. The psychologist gives me the questionnaire and the results show that I am severely depressed. I believe it. My doctor wants to try an SSRI yet most are contraindicated with my high-risk cardiac med. Wellbutrin is okay so I start taking it. Alas, insomnia sets in on top of sleeplessness, increased sadness, and buzziness. One night I feel like I am a rocket ship taking off. After a weekend call with one of our CF doctors I stop Trikafta again. I also stop Wellbutrin. 

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The CF team wants to help me stay on Trikafta and suggests I work with a therapist to help me cope with side effects and a psychiatrist to find mental health meds that I can take and tolerate. I’m happy for a break. Two weeks later I pass through clinic on my way to the hospital with a CF exacerbation and a significant blockage. My FEV1 has dropped and doesn’t improve; it’s hard to get a good blow with spirometry. I culture MAC again. In June, we talk about treating the NTM and my doctor tells me the nurse coordinator is in the conference room searching for a modulator I can take. I’m not interested. By July, my exhaustion has lifted and my FEV1 is headed back to baseline. We stopped talking about NTM treatment and CFTR modulators and I start asking about clinical research studies. Ah, ha! There is a silver lining. We who are not eligible for or cannot tolerate CFTR modulators are needed for exciting studies in which those taking modulators are excluded. 

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I still have questions:

• How many others eligible for modulator therapy are experiencing side effects like mine?

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• Are my gut issues related to Trikafta?

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• What complementary therapies can help people experiencing mental health side effects and who wish to continue taking Trikafta?

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We now appreciate that Trikafta is not a miracle drug for everyone who is eligible to take it. To learn more about our experience, the CFF is interviewing patients who are not benefiting from modulator therapy. An important article has just been published in Current Opinion in Pulmonary Medicine: Neuropsychiatric adverse effects from CFTR modulators deserve a serious research effort. THANK YOU to authors VanElzakker, Tillman, Yonker, Ratai, and Georgiopoulos for this valuable discussion and call for research. A link to the article was shared online with this comment: It’s not you, you aren’t alone, your experience is valid. 

Laura Mentch lives in Bozeman, Montana, and is the USACFA historian. She is grateful for the partnership with her CF team and for all the researchers who continue to search for new ways to help us.