Pulmonary rehabilitation in lymphangioleiomyomatosis: a controlled clinical trial.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease frequently associated with reduced exercise capacity. The aim of this study was to assess safety and efficacy of pulmonary rehabilitation in LAM.This controlled clinical trial included 40 patients with LAM and a low physical activity level. The pulmonary rehabilitation programme comprised 24 aerobic and muscle strength training sessions and education. The primary outcome was exercise capacity (endurance time during a constant work rate exercise test). Secondary outcomes included health-related quality of life (St George's Respiratory Questionnaire (SGRQ)), 6-min walking distance (6MWD), dyspnoea, peak oxygen consumption (V'O2 ), daily physical activity (pedometer), symptoms of anxiety and depression, lung function and peripheral muscle strength (one-repetition maximum).The baseline characteristics were well balanced between the groups. The pulmonary rehabilitation group exhibited improvements in the following outcomes versus controls: endurance time (median (interquartile range) 169 (2-303) s versus -33 (-129-39) s; p=0.001), SGRQ (median (interquartile range) -8 (-16-2) versus 2 (-4-5); p=0.002) and 6MWD (median (interquartile range) 59 (13-81) m versus 20 (-12-30) m; p=0.002). Dyspnoea, peak V'O2 , daily physical activity and muscle strength also improved significantly. No serious adverse events were observed.Pulmonary rehabilitation is a safe intervention and improves exercise capacity, dyspnoea, daily physical activity, quality of life and muscle strength in LAM.

Pulmonary involvement in long-term mixed connective tissue disease: functional trends and image findings after 10 years.

OBJECTIVES: Interstitial lung disease (ILD) is highly prevalent in patients with mixed connective tissue disease (MCTD). However, little is known about the long-term progression of ILD in MCTD. The aims of this study were to describe pulmonary function test (PFT) and high-resolution computed tomography (HRCT) results in long-term MCTD patients, to measure changes in PFT and HRCT results over a 10-year period, and to ascertain correlations in functional and imaging data. METHODS: In this retrospective cohort study, comparison between baseline and follow-up PFT and HRCT data was performed for 39 unselected consecutive MCTD patients. RESULTS: At baseline, 51% of the patients had abnormal PFTs. Forced vital capacity (FVC) was slightly reduced at baseline (77% of predicted), but remained stable after 10 years. A relative decrease of 15% in the diffusion capacity for carbon monoxide (DLCO) was detected (from 84% to 71% of predicted, p<0.001). The median lower lobes ILD-HRCT score progressed from 7.5% at baseline to 11.2% at follow-up (p=0.02), and findings of traction bronchiolectasis and honeycombing increased (p<0.05). A moderate negative correlation was observed between functional parameters and quantification of image findings. CONCLUSIONS: Functional and radiologic alterations suggestive of ILD in long-term MCTD patients are prevalent, mild, and progressed slightly over time. The most sensitive parameters for detecting subtle progression of ILD in MCTD patients are trends in DLCO, quantification of lower-lobes disease by HRCT (lower-lobes %ILD-HRCT score), and qualitative analysis of HRCT imaging.

Exercise performance and dynamic hyperinflation in lymphangioleiomyomatosis.

RATIONALE: Lymphangioleiomyomatosis (LAM) is characterized by exercise performance impairment. Although airflow limitation is common, no previous studies have evaluated the prevalence and impact of dynamic hyperinflation (DH) in LAM. OBJECTIVES: To investigate the dynamic responses during maximal exercise and the prevalence, predictors, and repercussions of DH in LAM. METHODS: Forty-two patients with LAM performed symptom-limited incremental cycle exercise and pulmonary functions tests (PFTs) and were compared with 10 age-matched healthy women. Dyspnea intensity, inspiratory capacity, oxygen saturation, and cardiac, metabolic, and respiratory variables were assessed during exercise. Patients with LAM also performed a 6-minute walk test (6MWT). MEASUREMENTS AND MAIN RESULTS: Patients with LAM had higher baseline dyspnea, poorer quality of life, obstructive pattern, air trapping, and reduced diffusing capacity of carbon monoxide in PFTs. Although they had the same level of regular physical activity, their maximal exercise performance was reduced and was associated with ventilatory limitation, greater desaturation, and dyspnea. The prevalence of DH was high in LAM (55%), even in patients with mild spirometric abnormalities, and was correlated with airflow obstruction, air trapping, and diffusing capacity of carbon monoxide. Compared with the non-DH subgroup, the patients who developed DH had a ventilatory limitation contributing to exercise cessation on cycling and higher desaturation and dyspnea intensity during the 6MWT. CONCLUSIONS: Ventilatory limitation and gas exchange impairment are important causes of exercise limitation in LAM. DH is frequent in LAM, even in patients with mild spirometric abnormalities. DH was associated with the severity of disease, higher dyspnea, and lower oxygen saturation. In the 6MWT, desaturation and dyspnea were greater in patients with DH.

Lung cyst: an unusual manifestation of Niemann-Pick disease.

Niemann-Pick disease is a rare inherited autosomal recessive disorder, currently classified into six subtypes and characterized by the intracellular accumulation of sphingomyelin in the liver, spleen, lungs, bone marrow or brain. The main pulmonary abnormalities described in high-resolution computed tomography (HRCT) of the chest consist of thickening of the interlobular septa and ground-glass opacities. This case report describes a patient with subtype B Niemann-Pick disease characterized by cysts and ground-glass opacities that were detected on HRCT of the chest.

Risk of breast cancer in patients with lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare metastasizing pulmonary disease that shares some clinical, cellular, and molecular similarities with metastatic breast cancer to lung. LAM cells have been identified circulating in various body fluids of patients and, intriguingly, diverse evidence indicates that these cells may originate from a different organ to the lung. Following on from these observations, we hypothesized the existence of a common risk basis between LAM and breast cancer, and suggested increased risk of breast cancer among LAM patients. Here, by studying two additional LAM cohorts with more detailed epidemiological, life-style, and disease-related data, we show consistent results; a potential excess of estrogen-receptor-positive young breast cancer cases in LAM. This observation further suggests the need of prospective studies to precisely assess the association between both diseases.

Characterization of lymphangioleiomyomatosis patients with discordance between spirometric and diffusion measurements of pulmonary function.

Background: A subset of lymphangioleiomyomatosis (LAM) patients present with normal FEV1 and FVC but with reduced DLCO. Patients with an isolated reduction in DLCO in other diseases appear to be at higher risk for pulmonary hypertension and worse survival but this has not been previously described in LAM patients. Objective: To characterize the prevalence and clinical progression of LAM patients who present with discordantly low DLCO. Methods: This was a retrospective cohort study of LAM patients in two centers in the United States and Brazil. Discordant DLCO was defined as FEV1 >80% predicted, FVC >80% predicted, and DLCO<80% predicted. We compared the rate of decline in pulmonary function, pulmonary artery to aorta (PA-A) ratio, and VEGF-D levels in patients with concordant and discordant DLCO. Results: The overall prevalence of discordant DLCO was 26.0%. Patients with discordant DLCO did not have a higher rate of yearly decline in FEV1 (-1.0±0.6 vs -1.0±0.6, p=0.50), FVC (-1.0±0.7 vs -0.3±0.8, p=0.54), or DLCO (-2.2±0.9 vs -1.6±0.6, p=0.79). They did not have higher rates of PA-A ratio>1 (23.3% vs 20.1%, p=1.00). Patients with discordant DLCO did not have higher levels of VEGF-D (1214±1256 pg/mL vs 1706±1214 pg/mL, p=0.07). Conclusions: LAM patients who present with a discordantly low DLCO do not appear to have different rates of decline in pulmonary function. Additional biological and radiographic markers are needed to more fully characterize this population. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 206-212).

Pulmonary hypertension in lymphangioleiomyomatosis: prevalence, severity and the role of carbon monoxide diffusion capacity as a screening method.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is included within group 5 of the current PH classification (unclear multifactorial mechanisms). However, data regarding the occurrence of PH in LAM are scarce. The aims of the study were to describe the prevalence and characteristics of PH in a large cohort of LAM patients with different levels of severity, and to evaluate the role of echocardiography and carbon monoxide diffusion capacity (DLCO) as screening methods for PH in LAM. METHODS: One hundred five LAM patients underwent transthoracic echocardiography, pulmonary function tests (PFTs) and 6-min walk test (6MWT). Patients with a suspicion of PH on echocardiography, defined by the presence of estimated systolic pulmonary artery pressure (PAP) over 35 mmHg or PFT showing DLco below 40% of the predicted value, underwent right heart catheterisation to confirm the diagnosis of PH. RESULTS: Eight patients (7.6%) had PH confirmed on right heart catheterisation, six patients (5.7%) had a pre-capillary pattern and two patients (1.9%) had a post-capillary profile. Only one patient (1%) had mean PAP over 35 mmHg. Patients with PH had lower FEV1 and DLCO in PFTs and greater oxygen desaturation and dyspnea intensity during 6MWT compared with those without PH. In 63% of the patients with confirmed PH, the right heart catheterisation was performed based only on DLCO result. CONCLUSIONS: The prevalence of PH is low in LAM patients. Pulmonary hypertension in LAM is typically mild and significantly associated with pulmonary parenchymal involvement. Carbon monoxide diffusion capacity significantly improved the identification of PH in LAM patients.

Pneumonite de hipersensibilidade crônica / Chronic hypersensitivity pneumonitis

A pneumonite de hipersensibilidade é uma síndrome com apresentação clínica variável, cuja inflamação no parênquima pulmonar é causada pela inalação de antígenos específicos em indivíduos previamente sensibilizados. A forma crônica da doença cursa com dispneia e fibrose progressivas, padrão restritivo em testes funcionais pulmonares e pior prognóstico, representando um desafio diagnóstico no diferencial com outras pneumopatias intersticiais idiopáticas. Recentes estudos permitiram um maior entendimento sobre a fisiopatogênese, especificamente no estudo da suscetibilidade genética e na modulação da resposta imune frente a determinados antígenos. A TCAR tem permitido correlações cada vez mais fidedignas com os achados histológicos, podendo muitas vezes evitar a biópsia cirúrgica. Pelo aspecto tomográfico, muitas vezes indistinguível entre aquele de pneumonia intersticial não específica e o de pneumonia intersticial usual, um inquérito sobre exposições sempre deve ser ativamente buscado na investigação clínica dos pacientes com doenças intersticiais fibrosantes. Recentemente, formas de exacerbação aguda semelhantes à fibrose pulmonar idiopática também foram descritas e se associam a um pior prognóstico. O diagnóstico precoce permite o tratamento com o afastamento da exposição e eventual uso de medicação anti-inflamatória. Ainda faltam estudos sobre o real papel da utilização de imunossupressores e corticosteroides no tratamento dessa doença