Today (June 30th) is World Pneumothorax Day. We are coming together to raise awareness of the inherited (familial) causes of collapsed lungs. Around 1 in 10 lung collapses have a genetic cause. Early and accurate diagnosis of the cause of familial pneumothorax is important. There are many different conditions associated with collapsed lungs. They often have other symptoms that need to be managed.
Birt-Hogg-Dubé Syndrome (BHD) is the most common genetic cause of collapsed lungs, where a diagnosis can be made. BHD is associated with mutations in the gene folliculin (FLCN). BHD can cause:
- Skin bumps called fibrofolliculomas
- Lung cysts and collapsed lungs
- Kidney cancer
Another condition associated with collapsed lungs is lymphangioleiomyomatosis (LAM). LAM is a rare condition caused by mutations in the tuberous sclerosis genes. It affects the lungs, kidneys and lymphatic system. The most common symptom of LAM is shortening of breath that gets worse over time. LAM almost exclusively occurs in women.
As BHD and LAM can have similar symptoms, the two can commonly be confused. We spoke to Professor Nishant Gupta to find out more about LAM and BHD. Professor Gupta is Director of the Interstitial Lung Diseases Center, University of Cincinnati.
What are the main similarities and differences between BHD and LAM?
Both BHD and LAM can present with air-filled pockets in the lungs called cysts. These cysts are prone to rupture frequently leading to lung collapse (pneumothorax). While both BHD and LAM can have kidney symptoms, the type of symptoms differ. People with BHD tend to have multiple different types of kidney tumours. However, people with LAM tend to have benign (non-cancerous) fatty tumours called angiomyolipomas.
The lung disease in LAM can progress over time while the lung disease in BHD generally doesn’t tend to be severe or progressive. Patients with BHD can also have (benign) skin tumours (fibrofolliculomas). Skin tumours are typically not seen in patients with LAM unless LAM is associated with the inheritable syndrome called Tuberous Sclerosis Complex (TSC).
How is each condition diagnosed and why are some people misdiagnosed?
The fact that both diseases can cause lung cysts and present with lung collapses often leads to misdiagnosis. Critical review of the chest CT scan is very important and can often provide clues to distinguish between BHD and LAM. For instance, cysts in LAM tend to be round, uniform, and present in all areas of the lung. In contrast, cysts in BHD tend to be oval and have varying sizes. They are more commonly seen at the bottom of the lungs often close to the lung linings (pleura) and blood vessels.
Personal and/or family history of skin bumps, collapsed lungs, and kidney tumours can also provide a clue towards underlying BHD. The diagnosis of BHD can be strongly suggested by confirming the skin lesions are fibrofolliculomas. This can be confirmed with genetic testing. Lung biopsy is not helpful to diagnose BHD.
The diagnosis of LAM can be established based on one or more of these features in a patient with compatible chest CT scan:
- presence of underlying TSC
- renal angiomyolipomas
- elevated blood values of a protein called vascular endothelial growth factor-D (VEGF-D)
- lymphatic involvement such as chylous (milky) fluid collections (e.g. in the chest cavity).
One or more of these features are present in approximately 7 in 10 people with LAM. In the remaining people, a lung biopsy may be needed to confirm the diagnosis of LAM.
How is each condition managed?
From a lung standpoint, both diseases predispose people to the development of collapsed lungs. Individuals who have one lung collapse have a very high chance of having repeat episodes. It is recommended that people with LAM and BHD undergo procedures such as pleurodesis following the first lung collapse. This can help to reduce the risk of future lung collapses. Beyond the risk of collapsed lungs, the lung disease in BHD generally is not severe or progressive. It doesn’t normally need any specific treatment. In contrast, the lung disease in LAM can be progressive and may require treatment with a drug called sirolimus. This has been shown to stabilize lung function decline and improve quality of life in LAM.
What should a person do if they think they may have BHD or LAM?
People with suspected BHD or LAM should see a physician who is familiar with these disorders. Detailed history, physical examination and critical review of the chest CT scan can often provide a good idea of the likely answer. It is important to note that there are other conditions that can cause lung cysts beyond BHD and LAM. Some of these may be diagnosed based on family history and blood work (for example, autoimmune diseases such as Sjögren’s). There is a worldwide network of lung physicians interested in rare lung diseases such as BHD and LAM. They can help patients navigate through the right diagnosis and management pathway:
What is the focus of your research?
My research is focused on rare cystic lung diseases such as LAM and BHD including:
- Improving the understanding of the natural history of disease progression.
- Devising novel ways to monitor disease progression.
- Exploring new biomarkers and treatment options.
- Helping answer questions that are relevant to the daily lives of patients living with these conditions.
What do you hope for the future of BHD and LAM?
My long-term hope for both diseases is the development of a cure. My short-term hope is for us to be able to reduce the time it takes for some patients to get diagnosed. It is also important to establish the diagnosis in a non-invasive manner as much as possible. I hope we can devise blood-based biomarkers that can help distinguish between these diseases. In LAM, this would remove the need for invasive procedures such as lung biopsies. Improved means of pleurodesis and other management strategies is another aspect that needs to be improved. This would reduce the burden of lung collapses in both sets of patients.
There are lots of common themes that are relevant to both conditions. I hope our scientific and patient communities can work together to accelerate the progress in both LAM and BHD.
The BHD Foundation sincerely thanks Professor Gupta for taking part in this interview and sharing his expertise on LAM and BHD. The LAM Foundation have many great resources to help people diagnosed with LAM.