Efficacy of hormonal suppression in a patient with chyluria due to lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting almost exclusively young women, characterised by abnormal proliferation of atypical smooth muscle cells. We describe a young woman presenting with chyluria secondary to the presence of a large retroperitoneal lymphangioleiomyoma. Immunohistochemical analysis revealed HMB45-negative LAM cells (HMB45 staining is absent only in rare cases) expressing low levels of estrogen receptors. Estrogen suppressive treatment with triptoreline, a synthetic analogue of Gn-RH, resulted in dramatic reduction of the retroperitoneal mass size. The role of estrogens in the pathogenesis of LAM remains poorly understood, and hormonal therapy is still debated, but this case suggests that at least in some LAM patients, possibly those with HMB45-negative disease and estrogen receptor expression, hormonal therapy may be effective in controlling the disease process.

Efficacy of hormonal manipulation in lymphangioleiomyomatosis. A 20-year-experience in 36 patients.

RATIONALE: Lymphangioleiomyomatosis (LAM) is a rare disease of unknown aetiology which mainly affects women of reproductive age. A growing body of evidence suggests a relation between the disease and estrogenic hormones. In particular, pregnancy and use of estrogens favour the progression of the disease, which is in turn slowed down by menopause. These observations suggested already in the past a treatment strategy based on hormonal manipulation: discontinuation of estrogens containing medications, avoiding pregnancy, inhibition of estrogens activity and induction of menopause. OBJECTIVES: In the present study, conducted on a relatively large population for a rare disease, we sought to show the hormonal manipulation's positive effects for the survival rate. METHODS: 36 women suffering from LAM were evaluated between January 1985 and March 2005. All our patients were treated with hormonal therapy, following different schemes. The response to the treatment was evaluated in all patients with arterial blood sampling, lung function tests (total body plethysmography, DLCO), measurement of the hormones in the blood, chest and abdomen CT scan. MEASUREMENTS AND MAIN RESULTS: The survival rate since the clinical onset was 97% at the 5 year timepoint, 90% at 10 years, and 71% at 25 years. Previous studies, conducted before the introduction of the hormonal treatment showed a survival rate of 20% at 10 years. CONCLUSIONS: Our results highlight the role of the hormonal manipulation as a mainstay in the treatment of LAM, with the capability of reducing mortality and improving the quality of life as well.

Rapid growth and regression of intracranial meningiomas in lymphangioleiomyomatosis: case report.

BACKGROUND: Lymphangioleiomyomatosis is a progressive interstitial lung disease that affects young women. It has been suggested that estrogens play a role in its evolution, and progesterone therapy is often provided in these cases. CASE DESCRIPTION: We present a case of a postmenopausal woman with LAM treated with progesterone; subsequently, rapid growth of multiple intracranial meningiomas was observed. One prominent lesion was excised, and 3 other lesions regressed spontaneously over 2 years. CONCLUSIONS: This is a rare case of a non-pregnancy-related regression of meningiomas in a woman affected by LAM. The significance of this association and the hormonal treatment of the disease are discussed.

Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex.

RATIONALE: The three previously reported cases of conclusively documented pulmonary lymphangioleiomyomatosis (LAM) in men were associated with definite or probable tuberous sclerosis complex (TSC). OBJECTIVES: To describe an unequivocal case of pulmonary LAM occurring in a man with no clinical or genotypic evidence of TSC. METHODS: At high-resolution computed tomography, a 37-year-old phenotypically and karyotypically normal man with left pneumothorax and massive pulmonary collapse had widespread thin-walled cysts throughout both lungs. Histological diagnosis of LAM was performed on biopsy material, and immunohistochemically confirmed with the HMB-45 monoclonal antibody. MEASUREMENTS AND MAIN RESULTS: Remarkably, the HMB-45-positive cells lining the cysts also showed strong reactivity for estrogen and progesterone receptor proteins. TSC was clinically excluded, and TSC1 and TSC2 germline mutations were not detected at DNA analysis. CONCLUSIONS: This article indicates that occurrence of LAM may be possible in a chromosomally normal man unaffected by TSC. On diagnostic grounds, the possibility of LAM should be borne in mind when diffuse cystic lung disease occurs in a man, even in the absence of signs of TSC.

The presence of emphysema further impairs physiologic function in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Emphysema, especially in the upper lobes, is frequently observed in association with idiopathic pulmonary fibrosis (IPF). However, the combination of emphysema plus IPF has received little attention. OBJECTIVE: To investigate the additional functional impairment from emphysema in IPF patients. METHODS: Twenty-one patients (mean age 66 y, 20 men) (Group I) who had both IPF (mean 35% of total lung volume) and emphysema (mean 14% of total lung volume) were compared to a group of 21 subjects who had IPF but no emphysema (Group II). The groups were matched for (among other criteria) the total extent of disease. Pulmonary function tests, Medical Research Council dyspnea score, 6-min walk test, and radiographic extents of both IPF and emphysema were obtained for each patient. The Composite Physiologic Index was calculated. In the total population (n = 42), the independent contributions of IPF and emphysema to several physiologic variables were investigated by using stepwise multiple regression analysis. RESULTS: Despite the limited extent of emphysema, Groups I and II had similar physiologic impairment. Only residual volume and total lung capacity were significantly higher in Group I. According to stepwise multiple regression analysis, the extent of IPF and either the presence or the extent of emphysema in the total population were independent and significant predictors of dyspnea score, 6-min walk test, P(aO2), forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), FEV1/FVC, the diffusing capacity of the lung for carbon monoxide, carbon monoxide diffusing capacity adjusted for alveolar volume (gas-transfer coefficient), and residual volume. The Composite Physiologic Index was closely related to the extent of IPF (r = 0.65, p < 0.0001) and to the dyspnea score (rho = 0.59, p < 0.0001). CONCLUSIONS: In former smokers with IPF, the presence and the extent of emphysema have a profound influence on physiologic function in terms of both further impairment and confounding effects.

Functional predictors of exertional dyspnea, 6-min walking distance and HRCT fibrosis score in idiopathic pulmonary fibrosis.

BACKGROUND: Exertional dyspnea and exercise incapacity are the most prominent and disabling symptoms and the main contributors to health-related quality of life in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: There are no comprehensive studies on pulmonary function tests (PFTs), dyspnea, exercise capacity and radiographic scores in IPF. We therefore sought to investigate the functional variables that can predict dyspnea, exercise capacity and disease extent in IPF. METHODS: Thirty-four patients with IPF according to the ATS/ERS criteria underwent PFTs, Medical Research Council (MRC) dyspnea scoring, 6-min walking distance (6-MWD) and radiographic evaluation of fibrosis (HRCT score). RESULTS: The 6-MWD (% pred.) was more impaired than PFTs. Residual volume (RV) showed the best correlation with the extent of fibrosis (r = -0.67, p = 0.0001) and, together with the alveolar-arterial gradient for O(2) [DeltaP(A - a)O(2)], was an independent predictor of disease extent (R(2) = 0.44). PFTs showed significant though weak correlations with MRC score and 6-MWD. According to the regression analysis, DL(CO) and the HRCT fibrosis score were independent predictors of dyspnea, though they explained only 28% of the overall variance. FEV(1) and DeltaP(A - a)O(2) were independent predictors of 6-MWD (R(2) = 0.31). CONCLUSIONS: PFTs and lung volumes in particular are closely related to the HRCT score, a measure of the extent of IPF. The correlation of dyspnea score and 6-MWD to PFTs is limited, due to the complexity of mechanisms leading to exercise limitation in IPF. Therefore dyspnea and exercise performance are largely independent indices and should be followed together with PFTs and HRCT score in order to better assess the status and progress of IPF patients.

Inflammatory activity is still present in the advanced stages of idiopathic pulmonary fibrosis.

OBJECTIVE: The role of active inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. A gallium-67 citrate (Ga(67) scan) is a sensitive indicator of inflammatory activity. The aim of this study was to assess the Ga(67) uptake and other markers of inflammation at different stages of IPF and to investigate its prognostic role. METHODOLOGY: Twenty-two patients (aged 66 +/- 11 years, 18 males) with IPF were monitored for a period of 6-20 months (mean 13 months). At presentation (T0), high resolution CT (HRCT) scans showed reticular opacities and traction bronchiectasis with bi-basilar and peripheral distribution in all cases. At both T0 and follow-up (T1), we measured pulmonary function (PaO(2), FVC, DLco), overall radiographic extent of fibrosis (HRCT visual score), Ga(67) uptake, serum concentrations of lactate dehydrogenase (LDH) and C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: All parameters showed a significant deterioration during the T0-T1 interval, though the increase in Ga(67) uptake and serum markers was not significant. Patients with Ga(67) uptake indices graded as normal or mildly increased (group I), and graded as considerably or severely increased (group II) at presentation, were compared. There was no significant difference with respect to lung function or HRCT score between the two groups at T1. Ga(67) uptake, LDH, CRP and ESR at presentation did not correlate significantly with the interval change in pulmonary function and disease extent. CONCLUSIONS: Our findings indicate that inflammatory activity in the advanced stage of IPF is still relevant, although a Ga(67) scan is not predictive of the clinical course.

Bullous emphysema versus diffuse emphysema: a functional and radiologic comparison.

The contribution of bullous emphysema (BE) to the functional impairment of patients with concomitant diffuse emphysema (DE) and the confounding effects of BE on functional measurements were investigated. Twenty-nine patients (Group I), with BE and DE were compared with a group of patients without BE matched, among other criteria, for radiographic extent of DE (Group II). Group I showed significantly lower PaO2, FEV1 and DLCO values and higher MRC score than Group II. In Group I the radiographic extent of BE and the extent of DE did not predict the functional impairment. The FEV1/FVC ratio in the subgroup with BE extent > 25% of total lung volume was higher than in subgroups with BE extent > 20% and 15%, respectively. In the same subgroups the correlation between DE and DLCO increased with the extent of BE. We conclude that BE contributes to the functional impairment of patients with concomitant DE. The confounding functional effect of bullae depends on BE extent: relatively milder obstruction can be observed with severe BE, whereas moderate BE causes modest deterioration of diffusing capacity, explaining the lack of functional-radiologic correlations in Group I. Therefore the computed tomographic scan is very useful in the work-up of BE with DE associated.

Does technetium-99m diethylenetriaminepentaacetate clearance predict the clinical course of idiopathic pulmonary fibrosis?

Clearance of inhaled technetium-99m diethylenetriaminepentaacetate (99mTc-DTPA) is a potential indicator of disease activity and progression in idiopathic pulmonary fibrosis (IPF). The objective of the present study was to evaluate the prognostic value of 99mTc-DTPA scans in IPF. A total of 22 patients (18 males), aged 33 to 80 years with IPF were followed for six to 20 months (mean 13 months). At diagnosis, high resolution computed tomography (HRCT) scans showed a honeycomb pattern with bibasilar reticular opacities in all cases. At T0 (diagnosis) and T1 (follow-up), each patient had pulmonary function tests (forced vital capacity, diffusing capacity of the lung for carbon monoxide and partial arterial O2 pressure), extension of fibrosis evaluated by HRCT visual score and 99mTc-DTPA lung clearance. Results at T0 and T1 were compared, taking into account the whole population and patients with relatively fast and slow 99mTc-DTPA wash-out. 99mTc-DTPA clearance did not show any significant correlation with functional tests or HRCT score. These findings indicate that clearance of inhaled 99mTc-DTPA is not of value in following the progress of IPF.