Lymphangioleiomyomatosis (LAM) is a slowly progressive lung disease that is associated with mutations in tuberous sclerosis complex genes, infiltration of the pulmonary parenchyma and lymphatics with neoplastic smooth muscle cells, extensive tissue remodeling and architectural distortion of the lung, and tumors of the chest and abdomen, including lymphangiomyomas and angiomyolipomas. LAM occurs in women in the general population and in patients of both genders with tuberous sclerosis. Overt clinical manifestations of LAM occur almost exclusively in females, however, and include progressive dyspnea on exertion, recurrent pneumothorax, and chylous effusions. The molecular basis of LAM has been extensively characterized over the past decade, resulting in the development of a targeted therapy. This article reviews emerging approaches to the diagnosis and treatment of LAM.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that targets women during their reproductive years. A confident diagnosis can often be based on clinical grounds, but diagnostic certainty requires pathological analysis. Although surgical lung biopsy is considered the gold standard for obtaining tissue in patients with diffuse lung disease, it is also associated with higher morbidity and mortality than alternative, less invasive techniques. The objective of our study was to examine the utility of transbronchial biopsy in the diagnosis of LAM. We conducted two online surveys of over 1,000 LAM patients registered with the LAM Foundation who were accessible by email. Transbronchial biopsy specimens were subsequently collected and reviewed by an expert pathologist to validate the diagnosis. We found that transbronchial biopsy has a yield of approximately 60% in patients with LAM. We conclude that transbronchial biopsy may be a safe and effective method for establishing the diagnosis of LAM, obviating the need for surgical lung biopsy in more than half of LAM patients.

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseasesTo the Editor:The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt-Hogg-Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs.The utility of HRCT in the diagnosis of LAM and differentiation from other DCLDs is not completely defined. According to the European Respiratory Society (ERS) guidelines, characteristic HRCT features along with a compatible clinical history are sufficient to confidently diagnose LAM, without the need for a tissue biopsy [3]. However, previously reported accuracy rates for diagnosing LAM based on HRCT findings may not be sufficient in an era when interventions with substantial risks are becoming available. Two prior studies have reported accuracy rates of 72-84% in diagnosing LAM based on imaging characteristics alone [4,5]. The aim of our study was to determine the diagnostic accuracy of HRCT evaluation by radiologists and pulmonologists, at various levels of expertise, in patients with DCLDs presenting to referral centres.We retrospectively obtained HRCTs from 89 patients referred to LAM Foundation Clinics at the University of Cincinnati (Cincinnati, OH, USA), Mayo Clinic Rochester ( Rochester, MN, USA) and National Kinki-Chou Hospital (Osaka, Japan) for further evaluation of DCLDs. All scans were non-contrast HRCTs and only thin section (1-3 mm) images were employed in the analysis. Patient 1196 identifiers were removed and the digital image files and a DICOM viewer (Santesoft, Athens, Greece), with full scrolling and magnification capabilities, were distributed to all reviewers. When necessary, abdominal cuts of the HRCT were removed to ensure that pathognomonic abdominal features, such as the presence of angiomyolipomas, would not influence the interpretation. The scans were analysed by three expert thoracic radiologists, and 12 pulmonary physicians with varying levels of expertise, subclassified as DCLD expert pulmonologists (n=5), general pulmonologists (n=4) and pulmonary fellows (n=3).Observers were asked to record the most likely diagnosis and degree of confidence (confident or not confident). Observers were blind to all clinical or pathological data. Images used for analysis were exclusively derived from patients with definite diagnoses established by biopsy, genetic testing or professional society guidelines. The results were used to calculate sensitivity and sp...

Objectives: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan. Study Design: A cross-sectional descriptive survey was conducted among representative samples. Results: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of parliament (MPs) were included in the survey. The groups showed considerable difference in their attitudes towards different aspects of the issue. A large proportion (88.5%) agreed to the idea of genetic diagnostic screening, especially the parents of thalassemic patients. Premarital carrier screening was favored by 77% of the respondents. Prenatal screening was most favored by the parents of thalassemic children (94.4%). Likewise, a majority of parents of thalassemic children were in favor of abortion in case of an affected fetus. Genetic self-screening was also favored most by the parents of thalassemic patients (78.2%). Only 24% of the doctors favored making genetic screening mandatory, whereas 63% of the parents agreed to the idea. Conclusion: Attitudes regarding genetic diagnosis are markedly different among various societal groups in Pakistan. The parents of the affected children strongly favor genetic screening as does the medical community, though not as strongly as the parents. The legislative groups, particularly the MPs, are reserved in their support. Genetic diagnosis can help decrease the disease burden in the future. However, it raises a number of ethical issues, which need to be addressed. It is important to educate the population about potential benefits as well as ethical dilemmas involved so that the general public is able to make the right decisions for themselves and their families.

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