September 2015

Nishant Gupta and Maria

Gupta photo
BHD Researcher Interview: Nishant Gupta is a pulmonologist with an interest in BHD and other rare cystic lung diseases. His research focuses on ways to aims to raise awareness of BHD and to increase diagnosis rates in pneumothorax patients.

1. How did you get interested in BHD research?

On rounds during my fellowship training my mentor, Dr Frank McCormack, gave me a case history on a patient and asked me to come up with the diagnosis. After some literature searches I found that the correct answer was BHD. That was the first time I had heard about BHD!

As I read more about BHD I found this disease to be fascinating. I already had an interest in rare lung diseases, especially cystic lung diseases and was working on a project in LAM (another related cystic lung disease). As I read more, and especially after getting a chance to write a review article on the pulmonary manifestations of BHD, I knew this was an area where I wanted to continue further work.

2. What are you currently working on?

I am currently working on developing a decision-analytic model to see if chest CT screening at the time of presentation with a pneumothorax will be cost-effective and lead to earlier recognition of BHD.

3. What would help current research (equipment, technique etc.)?

I think having a contact registry of worldwide BHD patients will help grow the field of research in BHD. This will provide the required sample size to the investigators in order to answer some of the commonly asked and clinically relevant questions related to BHD.

4. What recent developments in the field have interested you most?

Recent work in the Henske and Krymskaya labs looking at the role of FLCN inactivation and it’s impact on AMPK and mTORC pathways is interesting and has led to improved understanding of the pathogenesis of lung cyst formation in BHD.

5. Do you have a favourite research paper?

Not one in particular. I refer to the paper by Toro et al., 2007 (AJRCCM) quite a bit. In addition I like the review article by Menko et al., 2009 (Lancet Oncology). Some of the recent work by Johannesma et al. focusing more on the pulmonary aspects of BHD is really interesting.

6. What are your short/long-term goals?

My goals include continuing to improve as a clinician and provide the best possible care to my patients. In my research career, I would like to grow further and be able to spearhead multicentre collaborative studies and help grow the science in the field of BHD and other rare lung diseases.

7. How do you see the field developing in the next ten years?

There are a few things that I think are critical in development of field in BHD in the next few years including improved understanding of the molecular mechanisms leading to cyst formation. Development of biomarkers, which can predict renal cancers, will also be immensely helpful. Hopefully in the coming few years, with improved understanding of disease pathogenesis, we can start thinking about clinical trials for targeted therapeutic agents, especially for renal cell carcinomas.

Light-hearted questions:

8. What is your favourite book /  film/ music

Movies – The Shawshank Redemption, My Cousin Vinny, Pulp Fiction.

Books –The House of God, Catch 22, Sherlock Holmes.

9. What did you want to be when you were younger?

Lots of things, from a locomotive driver to an engineer, but nothing even closely related to the field of medicine! And of course, that’s what I ended up doing. I still wonder how that happened!

10. Where do you see yourself in 10 years?

I see myself improving as a physician scientist and continuing to work towards answering some of the common clinical questions facing patients with rare lung disorders. I also look forward to watching my currently 18-month-old son grow and continue to provide us with what seems like a new adventure everyday!

11. What’s the best advice you’ve ever been given?

It’s all about doing the little things right, and doing them on a consistent basis.

12. Do you have a scientific hero, dead or alive?

I would have to say it’s my mentor, Dr Frank McCormack. I admire and respect the amount of work he has done for patients with LAM and other rare lung diseases. The amount and range of tasks he is able to accomplish is truly amazing.

BHD Personal Story: Maria is from Brazil and was diagnosed with BHD in 2015.

1. When and how did you first get diagnosed?

On December 23rd 2014, as I was going about my last Christmas errands, I felt a slight pain in my back, as if I had pulled a muscle, which then irradiated to my chest. Soon after I started feeling like I couldn´t breathe properly. Then breathing itself started to hurt, and I soon realized something was quite wrong. So I went to the ER, and a few hours later was diagnosed as having had a pneumothorax on my right lung. As soon as the doctor said that word, I remembered my father – who passed away in 1999 – telling me about the time he had one, as he was climbing a ladder to get a book that was very high on his bookcase. The first person I called after hearing about the pneumothorax was my godfather, who was a close friend of my father and also happens to be a doctor. He said my father had in fact had multiple pneumothoraces. That information stayed on my mind. The chest CT scan that confirmed the pneumothorax also showed that I had multiple lung cysts.

So, on the day I had the pneumothorax, a thoracic surgeon placed a drain on my chest and I was admitted to hospital. At first it looked like my lung was healing well, but after seven days with the drain, an x-ray showed that the pneumothorax was still there, so I had to undergo VATS. The surgeon performed pleurodesis and removed the part of my lung that seemed to be “leaking” air. They also took a sample of tissue so that a biopsy could be performed. The biopsy eliminated the possibility of LAM, which was suspected because of the multiple lung cysts, and another test ruled out alpha1 anti-trypsin deficiency.

Meanwhile, I was intrigued by the fact that my father had had many spontaneous pneumothoraces and started researching possible genetic causes. That’s how I came across BHD syndrome. I don’t know anyone in my family with kidney cancer, but I read about some cases of families where only the lungs were affected – and I did have a couple of white “bumps” appear in my face in the years before, which I thought might be fibrofolliculomas. At first, I think my doctors were a bit sceptical, but fortunately, instead of telling me I was crazy, my pulmonologist referred me to a dermatologist who biopsied one of the bumps, and it was indeed a fibrofolliculoma. So that sort of confirmed it for us. Subsequently, a genetic test confirmed that I indeed have BHD.

2. What symptoms prompted the BHD diagnosis?

The history of pneumothorax in the family, my own spontaneous pneumothorax, the CT scan showing multiple cysts in my lungs and the skin biopsy, positive for fibrofolliculoma. I also have what looks like simple cysts in my kidneys.

3. What impact did the diagnosis have on you?

It was not really surprising, as I myself was the first to suspect I had it. To be honest, it was a bit of a relief, as I prefer having a plausible explanation for what happened to me than wondering forever what might have caused it (and whether it would happen again), and also because it definitely ruled out LAM. Furthermore, it means that I will be regularly screened for kidney cancer.

So, knowing that I have BHD was not bad. But that does not mean that having BHD has made me happy. The risk of early-onset kidney cancer did change my perspective about life in a way, especially since I have two kids. And the risk of having another pneumothorax if I take an airplane has made me a bit sad, as travelling is one my favourite things in life.

Also, I was never one to worry much about my health, but the whole unexpected pneumothorax experience and subsequent diagnosis has made me quite insecure about it, and it’s been a bit of a challenge to know when I should be concerned and when I shouldn´t. I’ve experienced some breathlessness since the surgery and was quite worried in the first few times that I might be experiencing another pneumothorax. Luckily, my pulmonologist is very patient and reassuring, and now I think I´ve learned how to live with the occasional shortness of breath.

Even though I know my life is not in immediate threat from BHD, experiencing a pneumothorax was quite scary. I was also very fearful of the risks associated with lung surgery. But thinking you are going to die but not actually dying can be one of the best things to happen to you, as you change your perspective on life AND have time to act upon it. So I feel lucky in that way too.

4. Have you explained BHD to family members?


5. What implications do you think it has had on your family?

I had my pneumothorax on the day before Christmas Eve, and I sort of ruined our holiday travel plans (summer holidays are in December, January and February in Brazil). Also, I couldn’t really do much in the first few weeks after surgery, couldn’t lift my kids etc. But things are back to normal now.

The diagnosis itself has not really affected them negatively yet. Actually, it might have even had some positive consequences, as, after being diagnosed, spending more time with my kids has become one of my priorities, and I am less inclined to be concerned about petty issues such as whether their room is messy or they’ve eaten too much ice-cream this week :)

6. Where did you go for more information on BHD syndrome?

In the beginning of my research, I looked at Wikipedia and some medical websites, but after finding the BHD Foundation website, it has become my main source of information.

7. Do you have advice for people who are looking for a diagnosis?

Do read about BHD, as most doctors have never heard of it, and, if you do think you might have it, insist on getting tested. I think there is a tendency among doctors to dismiss the possibility of rare diseases, maybe precisely because they are rare and they have never seen a patient with it.

8. If you have children, has BHD affected you as a parent? E.g. telling your children, starting a family, genetic counselling.

I have two kids, a 7-year-old girl and a 4-year-old boy. As with everything else, one does hope they have only inherited one’s “good” traits… But I do want to get them tested. I haven’t really withheld much information from them. They do know what a pneumothorax is, they’ve visited me in hospital etc. I haven’t told them specifically about the kidney cancer risk, because for now it’s only a risk, and I would prefer if they did not have to worry about it unnecessarily.

9. What are your current symptoms?

I have lung cysts, a few fibrofolliculomas on my face and some kidney cysts.

10. What treatment are you having, and have you had?

In terms of my lungs, I had pleurodesis through VATS after having the pneumothorax, and I am have my pulmonary function regularly tested. As for my kidneys, I’ve seen a renal oncologist and we’ve made a plan to get regular MRIs. Additionaly my dermatologist is “testing” hyfrecation and laser on a few of my fibrofolliculomas, in case they multiply and I want to get them removed.

11. How did you find a doctor?

When I had the pneumothorax, my godfather, who is a gastroenterologist, put me in touch with my pulmonologist, who then referred me to the thoracic surgeon and renal oncologist. And my current dermatologist is an old friend of mine.

12. What has been your experience of the healthcare system and healthcare professionals?

In terms of the doctors, my experience could hardly have been any better. I’ve found that, even though they did not have much information about BHD to begin with, they were all were very interested in learning more about it and making sure I was getting tested and treated in the best possible way.

As for the healthcare system, I am really lucky to be able to afford (even if just barely) good quality private healthcare insurance, so that gives me access to excellent hospitals and labs. Still, it does not cover everything, so I had to pay for a great part of my expenses relating to my time in hospital, doctor’s visits etc., which means I am actually in debt now…

13. What are your thoughts for the future?

As I said before, this whole experience has made me think about life in a different light. I am 39, and until last year, even though I knew it, and I did not really feel that life was a finite experience. Now I do hope to make the most of it in the time I have left, whatever that may be!

And I hope that all these wonderful scientists and doctors working on BHD shed a light on the mechanisms that govern kidney cancer, so that we can have effective treatment – or maybe even a cure – for it.

14. What advice would you give to someone who has just been diagnosed with BHD?

Read all you can about it (the BHD Foundation website is an excellent resource), inform your doctors about it, and consider that even though there are some really annoying things associated with BHD, knowing that you have it means that you can manage these things much better than if you didn’t know, especially the kidney cancer issue.