Respiratory medicine
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Respiratory medicine · Jul 2010
Lymphangioleiomyomatosis (LAM): molecular insights lead to targeted therapies.
LAM is a rare lung disease, found primarily in women of childbearing age, characterized by cystic lung destruction and abdominal tumors (e.g., renal angiomyolipoma, lymphangioleiomyoma). The disease results from proliferation of a neoplastic cell, termed the LAM cell, which has mutations in either of the tuberous sclerosis complex (TSC) 1 or TSC2 genes. Molecular phenotyping of LAM patients resulted in the identification of therapeutic targets for drug trials. ⋯ The metastatic properties of LAM cells offer additional potential for targets. Thus, insights into the molecular and biological properties of LAM cells and molecular phenotyping of patients with LAM have led to clinical trials of targeted therapies. Funded by the Intramural Research Program, NIH/NHLBI.
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Respiratory medicine · Jul 2010
Therapeutic options for systemic sclerosis related interstitial lung diseases.
Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) mainly encountered in patients with diffuse disease. Unlike idiopathic interstitial pneumonias (IIP), SSc associated ILD corresponds to non-specific interstitial pneumonia (NSIP) in most cases, whereas usual interstitial pneumonia (UIP) is encountered less frequently. This explains the better prognosis of SSc associated ILD compared to IIP. ⋯ Anti-fibrosing treatments have failed to demonstrate any benefit and cyclophosphamide, which has been used in the treatment of this condition for about 15 years, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. Since none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD, and since only a minority of SSc patients develop severe ILD, further studies should focus on the subgroup of SSc patients with worsening ILD. A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily but this remains to be confirmed.
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The diagnosis of idiopathic pulmonary fibrosis (IPF) currently requires an integrated clinical-radiological-pathological approach in which the histology plays a different role from in the past. The first reason for this change is that non-invasive diagnostic procedures, particularly pulmonary function tests and high resolution computed tomography, have become increasingly competitive with biopsy in providing prognostic information. The other reason is a better appreciation of the limitations of histology: sampling error and interobserver variation. In this review we analyze the reasons for this change of perspective, provide an update on the practical role of histology in the diagnosis of IPF and discuss some of its complications.