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.

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.

Characterization and outcomes of pulmonary alveolar proteinosis in Brazil: a case series.

OBJECTIVE: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. METHODS: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. RESULTS: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. CONCLUSIONS: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.

Characterization and outcomes of pulmonary alveolar proteinosis in Brazil: a case series / Proteinose alveolar pulmonar: caracterização e desfechos em uma série de casos no Brasil

ABSTRACT Objective: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. Methods: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. Results: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. Conclusions: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.

RESUMO Objetivo: A proteinose alveolar pulmonar (PAP) é uma doença rara, caracterizada pelo acúmulo alveolar de substância surfactante, composta por proteínas e lipídios. É causada por um déficit de atividade macrofágica, cujo principal tratamento é a lavagem pulmonar total (LPT). Relatamos a seguir a experiência de um centro de referência brasileiro em PAP. Métodos: Estudo retrospectivo com a avaliação de pacientes com PAP acompanhados entre 2002 e 2016. Informações sobre história clínica, métodos diagnósticos, tratamentos realizados e desfechos, incluindo dados de função pulmonar, sobrevida e presença de complicações, foram analisados. Resultados: Foram incluídos 12 pacientes (8 mulheres), com média de idade de 41 ± 15 anos. A maioria dos pacientes foi diagnosticada por LBA e biópsia transbrônquica. A média do número de LPT realizadas por paciente foi de 2,8 ± 2,5. Um terço dos pacientes não foi submetido à LPT. Quatro pacientes (33,3%) apresentaram infecções associadas (criptococose, em 2; nocardiose, em 1; e tuberculose, em 1) e houve 2 óbitos (16,6%): 1 por adenocarcinoma lepídico e 1 por complicações na indução anestésica pré-LPT. Não houve diferença significativa entre os dados funcionais; porém houve uma tendência de aumento da SpO2 ao se comparar os dados iniciais aos do final do seguimento. A mediana de seguimento foi de 45 meses (1-184 meses), com taxa de sobrevida em 5 anos de 82%. Conclusões: Pelo que sabemos, esta é a maior série de casos de PAP no Brasil. A taxa de sobrevida foi semelhante à encontrada em outros centros. A LPT ainda é o tratamento de escolha para pacientes sintomáticos e hipoxêmicos. Deve-se atentar para complicações, especialmente infecções oportunistas.