International study furthers understanding of development, clinical features, diagnosis and management of LAM (Lymphangioleiomyomatosis)

LAM – rare, slowly progressive, low grade, metastasising lung disease in women

 

(Sat 28th August @ 0900 hrs) A manuscript published today in Lancet Respiratory Medicine HERE, led at the Department of Respiratory Medicine in St Vincent’s University Hospital (SVUH) and UCD School of Medicine, has summarised the diagnostic criteria for women with compatible, cystic lung disease on CT scan to confirm a diagnosis of Lymphangioleiomyomatosis (LAM), without requiring lung biopsy. These include the presence of Tuberous Sclerosis Complex (TSC), elevated Serum Vascular Endothelial Growth Factor D, renal angiomyolipoma, lymphangioleiomyoma or chylous effusions.

The review which was also conducted in Respiratory Medicine Units associated with the University of Cincinnati and University of Nottingham, further summarised that trials of mechanistic target of Rapamycin Inhibitors have shown efficacy in stabilising lung function for most patients with LAM. These trials have been done in tandem with the development of the key diagnostic and prognostic biomarker; Vascular Endothelial Growth Factor D, which shows evidence of a uterine source of LAM cells and in tandem with the development of LAM clinical practice guidelines, when the patient is best managed with a personalised treatment and monitoring plan.

LAM is a rare, slowly progressive, systemic disease associated with cystic lung destruction, abdominal tumours and chylous fluid accumulations (causing ascites) due to the infiltration of neoplastic LAM cells. It almost exclusively affects women and presents during the reproductive years. The source of the cells is largely unknown, but it is believed they reach the lung via the lymphatic system or blood stream. The most common presenting manifestations of LAM are progressive dyspnoea (often ten years after symptom onset) on exertion and spontaneous pneumothorax, especially in women in their fourth or fifth decade of life. But disease manifestations and rate of progression of LAM are highly variable.

In addition, the Review confirmed that; 

  • PFTs are useful for determining the severity of pulmonary dysfunction and for guiding LAM therapy
  • A chronic or acute pneumothorax is occasionally discovered as in incidental finding in asymptomatic patients
  • The decision to proceed to biopsy should be jointly made by the physician and the patient and considered only when minimally invasive measures have been unsuccessful and the benefit of a diagnosis exceeds the risk
  • Early in the disease course, the chest radiograph is often normal or might show features of a subtle increase in interstitial markings or a pleural effusion
  • As LAM progresses, reticular or nodular opacities, pleural thickening, lymphadenopathy or hyperinflation can appear

Speaking about the Review, Dr Cormac McCarthy, Consultant Respiratory Physician, SVUH, Associate Professor of Medicine, UCD, and Lead Author in this Lancet Respiratory Medicine publication said ‘Rapid advances in understanding and managing LAM can be attributed in part to the foresight of patients who have partnered with us, facilitating research and clinical trials. Close interactions between investigators and patients with LAM in scientific meetings, grassroots fundraising to support pilot studies and distribution of expertise across multiple centres have been key to this significant progress, as shared in this Review.”

“Future research goals include generating cell and animal models of LAM that more accurately explain the human disease, understanding the role of the immune system in LAM pathogenesis and therapy and further defining how mTORC1 activation promotes cell growth and metastasis” continued Dr McCarthy.

The LAM Clinic and Rare Lung Disease Clinic at SVUH cares for almost 40 women with LAM and provides clinical and supportive care, access to clinical trials, and conducts original research in LAM, including diagnostic studies with novel imaging approaches, translation studies in exosomes and innate immune cells. While the prevalence of LAM is reported at 3-8 women per million women, 38 women in SVUH have been identified, which translates as a minimum of 14.5 women per million women, indicating that this condition remains underdiagnosed. This Lancet Respiratory Medicine publication should aid clinicians in identifying and considering this important condition.

Research, science and a commitment to enquiry and discovery inform every aspect of UCD School of Medicine’s mission. The School has a wide and dynamic research portfolio extending from in silico bioinformatics, molecular laboratory investigations of disease to clinical research evaluating new therapeutic strategies. 100 investigators associated with the School generate approximately €15 million in annual research income and have grants under management worth over €85 million. They also generate over 1,500 publications per year. Undergraduate students are always encouraged to immerse themselves in structured medical research throughout their studies. This approach is consistent with our desire to shape not just world-class healthcare professionals but also scientific innovators who will advance the boundaries of medical understanding and contribute to the development of new approaches to treatment and care to benefit patients. Please see https://www.ucd.ie/medicine/research/

 

ENDS

 

References 

LANCET RESPIRATORY MEDICINE 27th August 2021 LAM; Pathogenesis, Clinical Features, Diagnosis and Management

DOI:https://doi.org/10.1016/S2213-2600(21)00228-9