Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study.

Background: Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. Methods: This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Results: Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Conclusion: Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). METHODS: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-ß expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. RESULTS: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. CONCLUSION: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).

Tele-Intensive Care Unit Program in Brazil: Implementation and Expansion.

In this scientific report, we aimed to describe the implementation and expansion of a Tele-Intensive Care Unit (Tele-ICU) program in Brazil, highlighting the pillars of success, improvements, and perspectives. Tele-ICU program emerged during the COVID-19 pandemic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), focusing on clinical case discussions and training of health practitioners in public hospitals of the state of São Paulo in Brazil, to support health care professionals for treating COVID-19 patients. The success of implementing this initiative endorsed the project expansion to other five hospitals from different macroregions of the country, leading to the Tele-ICU-Brazil. These projects assisted 40 hospitals, allowing more than 11,500 teleinterconsultations (exchange of medical information between health care professionals using a licensed online platform) and training more than 14,800 health care professionals, reducing mortality and length of hospitalized patients. A segment in telehealth for the obstetrics health care was implemented after detecting these were a susceptible group of patients to COVID-19 severity. As a perspective, this segment will be expanded to 27 hospitals in the country. The Tele-ICU projects reported here were the largest digital health ICU programs ever established in Brazilian National Health System until know. Their results were unprecedented and proved to be crucial for supporting health care professionals nationwide during the COVID-19 pandemic and guide future initiatives in digital health in Brazil's National Health System.

Desaturation-Distance Ratio During Submaximal and Maximal Exercise Tests and Its Association With Lung Function Parameters in Patients With Lymphangioleiomyomatosis.

Background: The desaturation-distance ratio (DDR), the ratio of the desaturation area to the distance walked, is a promising, reliable, and simple physiologic tool for functional evaluation in subjects with interstitial lung diseases. Lymphangioleiomyomatosis (LAM) is a rare neoplastic condition frequently associated with exercise impairment. However, DDR has rarely been evaluated in patients with LAM. Objectives: To assess DDR during maximal and submaximal exercises and evaluate whether DDR can be predicted using lung function parameters. Methods: A cross-sectional study was conducted in a cohort of women with LAM. The 6-min walking test (6MWT) and the incremental shuttle walking test (ISWT) were performed, and DDR was obtained from both tests. The functional parameters were assessed at rest using spirometry and body plethysmography. The pulmonary function variables predictive of DDR were also assessed. Results: Forty patients were included in this study. The mean age was 46 ± 10 years. Airway obstruction, reduced DLCO, and air trapping were found in 60, 57, and 15% of patients, respectively. The distance walked and the DDR for the 6MWT and ISWT were, respectively, 517 ± 65 and 443 ± 127 m; and 6.6 (3.8-10.9) and 8.3 (6.2-12.7). FEV1 (airway obstruction) and reduced DLCO and RV/TLC (air trapping) were independent variables predictive of DDR during exercises field tests [DDR6MWT = 18.66-(0.06 × FEV1%pred)-(0.10 × DLCO%pred) + (1.54 × air trapping), R adjust 2 = 0.43] and maximal [DDRISWT = 18.84-(0.09 × FEV1%pred)-(0.05 × DLCO%pred) + (3.10 × air trapping), R adjust 2 = 0.33]. Conclusion: Our results demonstrated that DDR is a useful tool for functional evaluation during maximal and submaximal exercises in patients with LAM, and it can be predicted using airway obstruction, reduced DLCO, and air trapping.

An Unusual Combination of Diffuse Pulmonary Cysts and a Nodule / Una combinación infrecuente de quistes pulmonares difusos y un nódulo

No disponible

Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center.

INTRODUCTION: Serum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement. METHODS: We conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels. RESULTS: One hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404-1588) versus 162 (117-232) pg/mL, respectively (p < 0.001). Patients with tuberous sclerosis complex-LAM, TSC-LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641-2732) vs. 772 (370-1383), p = 0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r = - 0.26, p = 0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800 pg/mL (35% vs. 13%, p = 0.02). CONCLUSIONS: In LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.

Experience of Lung Transplantation in Patients with Lymphangioleiomyomatosis at a Brazilian Reference Centre.

INTRODUCTION: Lung transplantation (LT) is the standard of care for patients with advanced lung diseases, including lymphangioleiomyomatosis (LAM). LAM accounts for only 1% of all LTs performed in the international registry. As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited. METHODS: We conducted a retrospective review of all LAM patients who underwent LT at our centre between 2003 and 2016. Pre- and post-transplant data were assessed. RESULTS: Eleven women with LAM underwent LT, representing 3.3% of all procedures. Ten (91%) patients underwent double-LT. The mean age at diagnosis was 39 ± 6 years and the mean FEV1 before LT was 28 ± 14%. Only one patient underwent pleurodesis for recurrent pneumothorax. Pulmonary hypertension was confirmed in 3 (27%) patients. Four (36%) patients received sirolimus preoperatively; three of them received it until the day of LT, and there was no occurrence of bronchial anastomotic dehiscence after the procedure. Four patients (36%) received mTOR inhibitors post-transplant. The median follow-up from LT was 44 months. There were 3 deaths (27%) during the study and survival probabilities at 1, 3, and 5 years after LT were, 90, 90, and 77%, respectively. CONCLUSIONS: This data reinforces the role of LT for LAM patients with end-stage disease. The use of sirolimus seems to be safe before LT and the occurrence of complications after LT, including those LAM-related, should be continuously monitored.