June 2013

Dr Paul Johannesma and Professor Piet Postmus, and Paula

Dr Paul Johannesma is a Medical Resident currently undertaking his PhD research in the laboratory of Dr Pieter Postmus, Professor of pulmonary diseases at VU Medical Center in the Netherlands. Here they discuss their work characterising the pulmonary symptoms of BHD.

1. How did you get interested in BHD research?

Dr Johannesma: I started  with research during medical school at the department of Respiratory Medicine. The topic of the research was primary pneumothorax and different treatment options. Prof. Postmus introduced me to the BHD working group in the VU University Hospital. I was immediately interested in the variability in the phenotype of this syndrome and mainly interested in the pulmonary cysts and pneumothorax in BHDS. After graduating as a medical doctor, I started my PhD under supervision of Prof. Postmus and Dr. Menko. The main topics of my PhD are the clinical implications of pneumothorax and lung cysts in BHD.

Prof. Postmus: Through my colleague from the department of clinical genetics, and my previous research on pneumothorax.

2. What are you currently working on?

Dr Johannesma: Currently we’re working on several projects. We expect to publish in a couple of months an updated overview of 56 families (200 FLCN mutation carriers) including analysis of other benign and malign tumours in these pathogenic FLCN mutation carriers. We’ll show statistical analysis regarding whether BHD patients have an increased risk in developing other tumours (e.g. colorectal carcinomas) than RCC. Next to that, we are finishing our pilot study about the prevalence of FLCN mutation carriers in apparently spontaneous pneumothorax patients. Interesting results will be published in this paper. Further we do research on the occurrence and development of pulmonary cysts and the optimal treatment of pneumothorax in BHD patients. During the BHD Symposium in Paris last month, patients had a lot of questions about this topic. We hope to give more answers on that next year.

Prof. Postmus: “BHD for the pulmonologist”: how to find it? What is the natural course? What is the optimal treatment of pneumothorax?

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

Dr Johannesma: In the Netherlands we try to cluster all the FLCN mutation carriers in our center. Next to that we have a collaboration on BHD research with the research group of Prof. van Steensel (Maastricht University Medical Center, The Netherlands). A complete database of worldwide BHD patients with an overview of all clinical and molecular aspects in these patients would really help to understand the occurrence of clinical variability in BHD patients. It would be great to find a genotype/ phenotype correlation in BHD patients, to optimize the current treatment in pneumothorax and renal cancer. Next to that, I think it’s very important that clinicians know more about the occurrence of the Birt-Hogg-Dubé syndrome and recognize (at an early stage) the clinical presentation of this syndrome. I’m convinced that the Birt-Hogg-Dubé syndrome is under diagnosed worldwide.

Prof. Postmus: Improving guidelines on pneumothorax.

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

Dr Johannesma: I think that overall the increasing knowledge worldwide of the function of folliculin and the variability in clinical aspects are a great development. We also see an increasing collaboration between different research centers wordwide, which we encourage. Next to that we see an international increasing interest in the research field for the pulmonary features in the Birt-Hogg-Dubé syndrome.

Prof. Postmus: Detection by chest CT.

5. Do you have a favourite research paper?

Dr Johannesma: Not one in particular. The scientific papers by the research groups of Laura Schmidt, Linehan and Zbar were very crucial for understanding BHD. Further the excellent overview paper Menko et al.. 2009. And of course the papers about pulmonary features in BHD by Gupta et al., 2013, the papers by Mitsuko Furuya (Furuya and Nakatani, 2013 and Furuya et al., 2012) and  Medvetz et al., 2012 contribute to a better understanding of the pulmonary phenotype in BHD.

6. What are your short/long term goals?

Dr Johannesma: Our short term goals are, as I already mentioned earlier, to publish an overview of the 200 FLCN mutation carriers in the Netherlands and to publish our really interesting results about the prevalence of BHD in apparently spontaneous pneumothorax patients.

My long term goal is to finish my PhD and start my residency in thoracic surgery and continue my research on pulmonary features in the BHD syndrome.

Prof. Postmus: If a pneumothorax patient is seen by a pulmonologist he or she should be aware that this patient might have an inherited disorder with potential fatal consequences through renal cancer.

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

Dr Johannesma: I think we’ll have a much greater understanding in the precise molecular mechanism of FLCN for better understanding the development of pneumothorax, lung cysts, fibrofolliculomas and especially renal cell cancer. Hopefully we will have in 10 years some druggable targets on RCC. Next to that I hope we can differentiate in the next 10 years the BHD patients among the general spontaneous pneumothorax patients and renal cancer patients when presenting with clinical symptoms. I hope we find a genotype/phenotype correlation in FLCN mutation carriers. And last but not least, more worldwide awareness of the BHD syndrome among medical doctors.

Prof. Postmus: More of the natural course of the lung abnormalities will be discovered, possible relations between genotype and phenotype and risk assessment based on that.

8. What’s your favourite book/film/music?

Dr Johannesma: Book – The House of God, by Samuel Shem. I think this book is highly recommended for physicians (in training). I actually enjoy a wide range of music, so no favourite.

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

Dr Johannesma: I always wanted to become a medical doctor. And since I started medical school, I was impressed by the beauty of anatomy and surgery. My goal is to start as a surgeon in training after my PhD. So I’m still on the right track for that I think.

Prof. Postmus: An excellent clinician.

10. Where do you see yourself in 10 years?

Dr Johannesma: Working as a thoracic surgeon, combined with scientific research in the pulmonary research field.

Prof. Postmus: A retired and relaxed husband and grandfather.

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

Dr Johannesma: Use all the opportunities you get in an optimal way.

Prof. Postmus: Do well and don’t look back.

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

Dr Johannesma: Not especially. But the enthusiasm of my supervisor Dr. Menko (clinical geneticist) in BHD research and the knowledge and clinical experience in pulmonary research of my supervisor Prof. Postmus (pulmonologist) are a great example for me. I’m really pleased to work with them on BHD at the moment.

Prof. Postmus: Yes my mentor in oncology, Prof. Dirk Sleijfer.


BHD Personal Story: Paula is from the USA and was diagnosed with BHD in 2008.

1. When and how were you first diagnosed?

I was diagnosed in 2008 by Dermatologist, Catherine Colorado in Brandon, Florida. After many years of struggling with my skin issues, no one could ever tell me why I had these bumps that would not go away.  All Dermatologists that I see previous, would always try to sell me their products that would never work.

2. What symptoms prompted the BHD diagnosis?

In 1992 my symptoms started when I experienced my first pneumothorax at age 19.

3. What impact did the diagnosis have on you?

I have always been self conscious of my skin, but always came to live with it, because nothing I tried ever worked.

4. Have you explained BHD to family members?

Yes, in fact, my immediate family (mother and father) would not get tested to see who was the one carrying the gene.  But a few years after I was diagnosed, I met a blood cousin from my mother’s side of the family, and his skin had the fibrofolliculomas worse than I had, but no other symptoms.  My mother’s brother also has lung issue like I have had, and experienced two Thoracotomies.  No one has ever diagnosed anyone other than myself.

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

None as of right now.  I am hoping that my son doesn’t have this.

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

The BHD forum is the only place that I am aware of to get information.

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

Be persistent and patient.  I was diagnosed when I was 37 and started having the problems when I was 19 years old. No one could ever tell me why my lungs just collapse at any given time.

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

I took my son to a genetic counsellor.  I couldn’t afford to have him tested.  The testing for this disorder was going to cost our family 6000.00.

9. What are your current symptoms?

I am currently doing well.  I have some periodic pain, and to be safe it always takes me to the ER because of what I have been through.

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

My last surgery was in 2009.  Since 1992, I have had so many pneumothoraces that I have honestly lost count.  From 1992 to 95, I was free, then in 1995, my right lung collapsed again.  They performed a Laparoscopic Thoracoscopy on me at that time.  I was free again until 2002 when my right lung collapsed again. They tried to insert a chest tube and that didn’t work so they attempted the Thoracoscopy again, and that didn’t work. They then performed a full Thoracotomy on my right lung.  That lasted two months and it collapsed again in February 2003, where another full Thoracotomy was performed.  In 2008, my left lung collapsed, and went through both Thoracoscopy and a full Thoracotomy, because the Thoracoscopy didn’t work.

11. How did you find a doctor?

Through the hospitals that I had surgery in.

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

I haven’t really had any problems with either the healthcare system or any professionals in the field.  I have always been well taken care of through my treatments.

13. What are your thoughts for the future?

I am fearful that I am going to experience the kidney cancer.  I am not able to be tested until I start having problems because my insurance will not cover kidney scans unless there has been an official diagnosis of a problem with the kidneys.

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

Just be patient. It’s not easy.  I have had these problems for many years, and I try to stay as active and stress free as possible.  If I do get stressed, I always end up in the hospital with bullae on my lungs, and then I am in fear that I will be having a collapsed lung.