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1.
Int J Radiat Oncol Biol Phys ; 106(1): 90-99, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586665

RESUMO

PURPOSE: Our purpose was to develop predictive nomograms for overall survival (OS), progression-free survival (PFS), and time-to-progression (TTP) at 5 years in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: The study cohort included 714 ES-NSCLC patients treated with SABR from 2004-2015 with median follow-up of 59 months, divided into training and testing sets (8:2), with the former used for nomogram development. The least absolute shrinkage and selection operator were initially employed to screen for predictors of OS, PFS, and TTP, and identified predictors were subsequently applied toward Cox proportional hazards regression modeling. Significant predictors (P < .05) on multivariable regression were then used to develop nomograms, which were validated via evaluation of concordance indexes (C-index) and calibration plots. Finally, Kaplan-Meier method and Gray's test were employed to compare and confirm differences in outcomes among various groups and explore prognostic factors associated with local versus distant disease progression. RESULTS: Significant predictors of both OS and PFS at 5 years included age, sex, Charlson comorbidity index, diffusing capacity of carbon monoxide, systemic immune-inflammation index, and tumor size (P ≤ .01 for all). Eastern Cooperative Oncology Group performance status predicted for OS as well (P = .01), and both tumor size (P < .01) and minimum biological equivalent dose to 95% of planning target volume (PTV D95 BED10; P < .01) were predictive of TTP. The C-indexes for the OS, PFS, and TTP nomograms were 0.73, 0.68, and 0.60 in the training data set and 0.72, 0.66, and 0.59 in the testing data set, respectively. Tumor size > 2.45 cm and PTV D95 BED10 < 113 Gy were significantly associated with both local and distant progression. CONCLUSIONS: These prognostic nomograms can accurately predict for OS, PFS, and TTP at 5 years after SABR for ES-NSCLC and may thus help identify high-risk patients who could benefit from additional systemic therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Nomogramas , Radiocirurgia/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dióxido de Carbono/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Curva ROC , Análise de Regressão , Fatores Sexuais , Resultado do Tratamento
3.
N Engl J Med ; 381(10): 923-932, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483963

RESUMO

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Proteinose Alveolar Pulmonar/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico por imagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/imunologia , Capacidade de Difusão Pulmonar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Teste de Caminhada
4.
Folia Med (Plovdiv) ; 61(2): 204-212, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301664

RESUMO

INTRODUCTION: Exercise-induced desaturation is a common finding in patients with moderate and severe COPD. It is an important marker in the course of disease that has a prognostic value for mortality risk. AIM: To monitor over time COPD patients with and without desaturation during 6-minute walking test (6MWT) and to assess the stability of that phenomenon. MATERIALS AND METHODS: A 6MWT was administered to 70 patients with COPD which ranged in severity from stage 2A to stage 4D (GOLD 2011); the patients had a mean age of 64.5±10.1, mean pack-years - 38.8±21, FEV1% = 46.4%±15.7%, FVC% = 73.7%±1.3%, MRC = 2.31±0.84, CAT = 20.8±6.6. Oxygen saturation was monitored during the test; indications for desaturation were a decrease of SpO2 by ≥4% and a fall in SpO2 to ≤88% for at least 3 min. The patients were followed-up for mean 40.9±22.3 months and tests were repeated. RESULTS: Patients were divided into two groups based on the decrease in SpO2: Group A included patients with desaturation (n=35) and Group B - patients with no desaturation (n=35). In 66 of the patients the desaturation profile was stable over time. Only two patients, who did not desaturated at baseline, experienced desaturation in the follow-up 6MWT and another two patients, who desaturated at baseline, did not have it later in the follow-up. CONCLUSION: Desaturation is a phenomenon that is persistent over time. Based on the results, it could be concluded that exercise-induced desaturation is a major marker of a particular COPD phenotype.


Assuntos
Exercício , Hipóxia/metabolismo , Esforço Físico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Seguimentos , Volume Expiratório Forçado , Humanos , Hipóxia/fisiopatologia , Capacidade Inspiratória , Masculino , Pessoa de Meia-Idade , Pressão Parcial , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Capacidade Vital , Teste de Caminhada
5.
Arab J Gastroenterol ; 20(2): 81-85, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31182343

RESUMO

BACKGROUND/AIMS: Functional impairment is common among cirrhotic patients with refractory ascites, and improvement in functional impairment is an expected issue after paracentesis. The six-minute walk test (6MWT) is considered an objective test for functional activity. No published data have evaluated the 6MWT among cirrhotic patients with refractory ascites before and after large-volume paracentesis. The research aim was to assess the feasibility of performing the 6MWT among cirrhotic patients who had refractory ascites before and after large-volume paracentesis. MATERIALS AND METHODS: Thirty-one cirrhotic inpatients with refractory ascites were subjected to pulmonary function tests (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC) and diffusion lung capacity for carbon monoxide (DLCO) before and 48 h after therapeutic large-volume paracentesis. Dyspnoea as assessed by the Borg scale and functional capacity as assessed by the 6MWT were also evaluated. RESULTS: Prior to paracentesis, the mean values of FVC and FEV1 were lower than the predicted values, and a significant increase was observed after paracentesis. There was improvement in the mean DLCO values after paracentesis (P < 0.05). Regarding the 6MWT, significant increases in the walked distance (6MWD) (310.7 ±â€¯73 vs. 348.7 ±â€¯72.3 m) and oxygen saturation after paracentesis (P = 0.001) were observed. Significant improvement in the dyspnoea scale also occurred after paracentesis (P = 0.001). A significant positive correlation between the 6MWD before paracentesis and serum albumin levels was demonstrated (r = 0.373, P = 0.039). CONCLUSION: We found a decrease in pulmonary function and the 6MWD in patients who had refractory ascites, which improved significantly following large-volume paracentesis. The 6MWT is useful in detecting impaired functional capacity among cirrhotic patients.


Assuntos
Ascite/fisiopatologia , Ascite/cirurgia , Tolerância ao Exercício , Paracentese , Ascite/etiologia , Dispneia/etiologia , Feminino , Volume Expiratório Forçado , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Projetos Piloto , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Albumina Sérica/metabolismo , Capacidade Vital , Teste de Caminhada
6.
Medicine (Baltimore) ; 98(18): e15140, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045757

RESUMO

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a special form of spontaneous, chronic, progressive interstitial fibrotic pneumonia of unknown cause, and treatments for IPF have shown a poor prognosis. This study reports a new treatment, traditional Chinese medicine (TCM) therapy, for tonifying Qi-deficiency of lung-kidney in a 64-year-old patient with IPF. PATIENT CONCERNS: A 64-year-old man, who complained of cough and asthma, was diagnosed as IPF with mild impairment in lung function by thoracic high-resolution computed tomography and pulmonary function test. He received an 18-month N-acetylcysteine monotherapy but had no improvement in lung function. DIAGNOSES: IPF with mild impairment in lung function was diagnosed. INTERVENTIONS: The Chinese herbal medicine composition was decocted in 300 ml water for oral administration with 150 ml decoction twice daily in June 2017. OUTCOMES: The pulmonary function test showed that diffusing capacity for carbon monoxide had increased to 81% of predicted back to normal after 2-month TCM monotherapy. And diffusing capacity for carbon monoxide had increased to 89% of predicted, and forced expiratory volume in 1 s/forced vital capacity ratio increased to 92% at 14-month follow-up. No adverse events occurred during the 14 months of therapy and observation. LESSONS: The treatment by TCM therapy of tonifying lung-kidney's Qi-deficiency for IPF can improve the pulmonary function and reverse disease progression; it may be considered as a complementary treatment for IPF with mild-to-moderate impairment. However, the insights provided in this case report require further exploration and verification.


Assuntos
Fibrose Pulmonar Idiopática/terapia , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Acetilcisteína/uso terapêutico , Monóxido de Carbono/metabolismo , Progressão da Doença , Expectorantes/uso terapêutico , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Rim/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar/efeitos dos fármacos , Testes de Função Respiratória/métodos , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos , Deficiência da Energia Yin
7.
Pancreatology ; 19(4): 519-523, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31036490

RESUMO

BACKGROUND: Only few studies have attempted to evaluate the pulmonary function in the early phase of acute pancreatitis (AP), although pulmonary dysfunction is the most frequent complication in the early phase of AP. We aimed to evaluate the changes in pulmonary function tests during the early phase of AP. METHODS: Prospective cohort study including 44 patients (52% men; median age 54 years) admitted with first attack of AP and 22 healthy controls. Patients underwent assessments on day 1, 2, 3, 6, and 10 as well as one month after discharge. Pulmonary function tests included the % predicted: forced expiratory volume during the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusion lung capacity (DLCO) and the ratio between DLCO and alveolar volume (DLCO/VA). RESULTS: In total, 9% developed severe acute pancreatitis, 7% died, and 14% required treatment at the intensive or semi-intensive care unit. From admission, patients had impaired FEV1, FVC, DLCO, and TLC compared with controls (p < 0.0001 in all analyses). Patients with CRP >150 mg/L had significantly lower lung function tests. One month after discharge, lung function tests improved but patients had lower FEV1 (p = 0.014), FVC (p = 0.022), TLC (p = 0.020), and DLCO (p < 0.001) compared with controls. CONCLUSION: This study found that patients with AP had evidence of pulmonary impairment from the first day after hospital admission. The impairment lasted several weeks after hospital discharge.


Assuntos
Pneumopatias/etiologia , Pneumopatias/patologia , Pancreatite/complicações , Pancreatite/patologia , Alvéolos Pulmonares/patologia , Doença Aguda , Adulto , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Troca Gasosa Pulmonar , Testes de Função Respiratória , Resultado do Tratamento
8.
Nagoya J Med Sci ; 81(1): 41-53, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30962654

RESUMO

We evaluated the progression of interstitial lung disease (ILD) by three-dimensional curved high-resolution computed tomography (3D-cHRCT) at a constant depth from the chest wall and compare the results to pulmonary function test (PFT) results on a follow-up assessment. We reviewed the patients with ILD who underwent HRCT and concurrent PFTs at least twice from April 2008 to December 2014. Forty-five patients with ILD were enrolled. 3D-cHRCT images of the lung at various depths from the chest wall were reconstructed, and total area (TA), high-attenuation area (HAA) >-500 HU, and %HAA ([HAA/TA] × 100) were calculated. The TA, HAA, and %HAA ratios (follow-up to baseline) were assessed for use in the diagnosis of physiologically progressive ILD (defined as; forced vital capacity [FVC] ratio <0.9 or %diffusing capacity of the lung for carbon monoxide [%DLCO] ratio <0.85 [follow-up to baseline]). Of all ratios obtained from 3D-cHRCT images at 5-30mm depths, the %HAA ratio at 20-mm had the largest area under the receiver operating characteristic curve (0.815, 95 % confidence interval 0.677-0.953). By univariate logistic regression analysis, TA, HAA, and %HAA ratios at 20-mm showed significant correlations with physiologically progressive ILD. 3D-cHRCT imaging performed in parallel with the chest wall offers novel quantitative parameters that are useful for following ILD.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imagem Tridimensional/métodos , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Curva ROC , Testes de Função Respiratória , Estudos Retrospectivos , Parede Torácica/diagnóstico por imagem , Parede Torácica/patologia , Capacidade Vital/fisiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-30880945

RESUMO

Purpose: Ultrafine particles (UFP) are toxic due to their small size and penetration into deeper lung compartments. We aimed to evaluate the exhaled breath condensate (EBC)-UFP content as a reflection of inflammation and oxidative stress status in COPD patients and as an exacerbation risk marker. Methods: EBC was collected by conventional methods. Particles were analyzed with NanoSight LM20. EBC carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA kits. Study population (58 COPD patients and 40 healthy smoker and non-smoker controls) underwent spirometry, diffusion capacity, EBC testing, and blood sampling. Results: Absolute eosinophil count, C-reactive protein (CRP), and lactate dehydrogenase in serum were elevated in the COPD group compared with the controls (224 U/L, 5 mg/L, and 391 U/L vs 154 U/L, 3 mg/L, and 330 U/L, P=0.009, P=0.05, and P=0.004, respectively). COPD patients had lower UFP concentrations in EBC compared with controls (0.24 E8/mL vs 0.51 E8/mL, P≤0.001). A mirror image was detected in serum: COPD patients had higher UFP concentrations compared with controls (9.8 E8/mL vs 6.7 E8/mL, respectively, P=0.03). EBC carbonyl and 8-OHdG levels were higher among COPD patients compared with controls (5.1 per 1 µg/mL protein and 0.036 ng/mL vs 0.41 per 1 µg/mL protein and 0.003 ng/mL, P=0.001 and P≤0.001, respectively). EBC UFP concentrations were negatively correlated with pack years (R=-0.44, P ≤0.001) and positively correlated with FEV1 and diffusing lung capacity for carbon monoxide (R=0.46, 0.23, P ≤0.001 and P=0.04, respectively). Low EBC UFP concentrations (≤0.18 E8/mL) and CRP levels ≥5 mg/L were independent predictors of the frequent exacerbator phenotype (OR 3.6; 95% CI: 1.06-7.97; P=0.04 and OR 4.4; 95% CI: 1.24-10.2; P=0.02, respectively). Conclusion: UFP content in EBC reflects the inflammatory state of airways. Low UFP concentrations in EBC and high in serum of COPD patients support our hypothesis that increased epithelial permeability could be the mechanism behind those findings.


Assuntos
Expiração , Mediadores da Inflamação/sangue , Inflamação/sangue , Pulmão/metabolismo , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/sangue , Adulto , Idoso , Biomarcadores/sangue , Testes Respiratórios , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Nível de Saúde , Humanos , Inflamação/diagnóstico , Inflamação/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Valor Preditivo dos Testes , Carbonilação Proteica , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Espirometria
10.
Int Heart J ; 60(2): 366-373, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30799383

RESUMO

The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.


Assuntos
Monóxido de Carbono/análise , Insuficiência Cardíaca/diagnóstico , Capacidade de Difusão Pulmonar/métodos , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Testes de Função Respiratória/métodos , Volume Sistólico
11.
Int J Rheum Dis ; 22(5): 921-928, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30746850

RESUMO

AIM: Pulmonary arterial hypertension (PAH) is a complex and devastating complication of systemic lupus erythematosus (SLE). We sought to describe the baseline characteristics of right heart catheterization (RHC)-confirmed SLE-associated PAH and identify risk factors for PAH in SLE patients. METHODS: A multicenter, cross-sectional study was conducted using the Chinese SLE Treatment and Research group (CSTAR) registry. Baseline data for patients with SLE-associated PAH and SLE patients without PAH were collected and compared. Risk factors for PAH among patients with SLE were identified. RESULTS: A total of 292 patients with SLE-associated PAH were enrolled. RHC was used to reveal hemodynamic features, including mean pulmonary arterial pressure (46.2 ± 12.0 mm Hg), pulmonary arterial wedge pressure (7.84 ± 3.92 mm Hg), pulmonary vascular resistance (10.86 ± 5.57 Wood units), and cardiac index (2.77 ± 0.91 L/min × m2 ). A multivariate logistic regression analysis showed that serositis (odds ratio [OR] = 5.524, 95% CI 3.605-8.465, P < 0.001), anti-ribonucleoprotein (RNP) antibody positivity (OR = 13.332, 95% CI 9.500-18.710, P < 0.001), and diffusion capacity of carbon monoxide in the lung (DLCO)/%Pred <70% (OR = 10.018, 95% CI 6.619-15.162, P < 0.001) were independent predictors of PAH. We recommend using transthoracic echocardiography (TTE) to perform early screening of SLE patients who have serositis, anti-RNP antibody positivity, or DLCO/%Pred <70%. RHC is suggested for patients suspected of having PAH. Once a diagnosis of SLE-PAH is confirmed, evaluation and treatment should immediately begin. CONCLUSION: Overall, we recommend performing early screening using TTE in SLE patients with serositis, anti-RNP antibodies, or a DLCO/%Pred <70%, even for patients in a relatively stable condition according to SLE disease activity index.


Assuntos
Pressão Arterial , Hipertensão Pulmonar/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Artéria Pulmonar/fisiopatologia , Adulto , Anticorpos Antinucleares/sangue , Cateterismo Cardíaco , China/epidemiologia , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Ribonucleoproteínas/imunologia , Fatores de Risco , Serosite/epidemiologia
12.
ESC Heart Fail ; 6(2): 379-387, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784223

RESUMO

AIMS: Patients with heart failure (HF) are known to have a reduced pulmonary diffusion capacity for carbon monoxide (DLCO ), but little is known about how lung function relates to central haemodynamics. The aim of this study was to investigate the association between haemodynamic variables and pulmonary diffusion capacity adjusted for alveolar volume in congestive HF patients and to analyse how predicted DLCO /VA affects mortality in relation to the haemodynamic status. METHODS AND RESULTS: We retrospectively studied right heart catheterization (RHC) and lung function data on 262 HF patients (mean age 51 ± 13 years) with a left ventricular ejection fraction < 45% referred non-urgently for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD). Univariate and multivariate linear regression models were constructed to examine the associations between predicted values of DLCO /VA , forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 ), and haemodynamic parameters [pulmonary capillary wedge pressure (PCWP), central venous pressure, cardiac index, mean pulmonary artery pressure, and mean arterial pressure] as well as other factors known to affect lung function in HF. FEV1 was reduced to <80% of predicted value in 55% of the population, and DLCO/ VA was reduced in 63% of the population. DLCO /VA correlated positively with pulmonary capillary wedge pressure in both univariate and multivariate analyses for all included patients (P < 0.001 and P = 0.045, respectively) and a restricted population of patients with the shortest time between RHC and lung function testing (P = 0.005, P = 0.015). DLCO /VA predicted mortality in multivariate models [hazard ratio 1.5 (1.1-2.1)] but not the combined endpoint of death, LVAD implantation, or HTX. There was no significant correlation between haemodynamics and predicted FVC or FEV1 . CONCLUSIONS: Pulmonary diffusion capacity correlates positively with left ventricular fillings pressures, and reduced values predict increased mortality in patients with HF. This might be driven by increased lung capillary volume in patients with pulmonary congestion.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Circulação Pulmonar/fisiologia , Capacidade de Difusão Pulmonar , Pressão Propulsora Pulmonar/fisiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Função Ventricular Esquerda
13.
Arthritis Rheumatol ; 71(6): 972-982, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30624031

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc-associated ILD. METHODS: Serum samples from a combined cohort of SSc patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme-linked immunosorbent assay for concentrations of lung epithelial-derived surfactant protein D (SP-D), Krebs von den Lungen 6 glycoprotein (KL-6), CCL18, and OX40 ligand (OX40L). Lung fibrosis was measured by high-resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean ± SD follow-up 3.2 ± 4.4 years) were investigated. RESULTS: In SSc patients at baseline, serum levels of KL-6 correlated with the forced vital capacity (FVC) (r = -0.317, P < 0.001), diffusing capacity for carbon monoxide (r = -0.335, P < 0.001), and extent of lung fibrosis (r = 0.551, P < 0.001). In multivariate analyses, serum levels of KL-6 and SP-D, but not CCL18 and OX40L, were associated with lung fibrosis (odds ratio [OR] 2.41, 95% confidence interval [95% CI] 1.43-4.07 [P = 0.001] and OR 3.15, 95% CI 1.81-5.48 [P < 0.001], respectively). In SSc patients with ILD at baseline, longitudinal, multivariate analyses showed that CCL18 serum levels were an independent predictor of a >10% decrease in the FVC (hazard ratio [HR] 2.90, 95% CI 1.25-6.73; P = 0.014) and de novo development of extensive disease (HR 3.71, 95% CI 1.02-13.52; P = 0.048). Matrix-based logistic regression models for the diagnosis and prognosis of SSc-associated ILD were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of SP-D (for diagnosis) and serum levels of CCL18 (for progression of disease). CONCLUSION: These results show that SP-D is a relevant diagnostic biomarker for SSc-associated ILD, whereas KL-6 could be used to assess the severity of lung fibrosis. CCL18 appears to be a potential predictive marker for progression of ILD in SSc.


Assuntos
Quimiocinas CC/sangue , Doenças Pulmonares Intersticiais/sangue , Mucina-1/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Receptores OX40/sangue , Escleroderma Sistêmico/sangue , Idoso , Biomarcadores/sangue , Feminino , França , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Noruega , Prognóstico , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Tomografia Computadorizada por Raios X , Capacidade Vital
14.
Artigo em Inglês | MEDLINE | ID: mdl-30666101

RESUMO

There is evidence that iron plays a key role in the adequate functioning of skeletal muscle. While it has been demonstrated that nonanemic iron deficiency (NAID) affects exercise tolerance and response to exercise training in patients with COPD, the impact on daily physical activities (DPAs) remains unknown. Eighteen COPD patients with NAID (ferritin <100 ng/mL or ferritin 100-299 ng/mL with a transferrin saturation <20%) and 18 COPD patients without this abnormality, matched for age, gender, and the degree of airflow limitation (control group), were enrolled to the study. The primary outcome was the level of DPA assessed by accelerometers. Patients were (mean [SD]) 66 (7) years and were mostly male (70%) and former smokers (52%). Their forced expiratory volume at 1 second was 41 (16)% predicted, carbon monoxide diffusing capacity was 47 (14)% predicted and oxygen arterial pressure reached 70 (11) mmHg. DPA and the number of steps per day were lower in NAID COPD patients compared with controls (physical activity level 1.39 vs 1.59, P<0.05; and 4,402 vs 6,975 steps/day, P<0.05, respectively). The percentage of patients with increased time spent sitting per day (>6 hours) was higher in patients with NAID compared with controls (73% vs 37%, P<0.05). In addition, the percentage of patients doing moderate to vigorous physical activity per day (>3 metabolic equivalents of task, at least 30 minutes) was lower in this group (66% vs 100%, P<0.05). The presence of iron deficiency was associated with reduced DPA in COPD patients. Further studies are needed to evaluate iron reposition and their impact on the level of physical activity in these patients.


Assuntos
Tolerância ao Exercício , Exercício , Ferro/deficiência , Pulmão/fisiopatologia , Estado Nutricional , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Actigrafia/instrumentação , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ferritinas/sangue , Monitores de Aptidão Física , Volume Expiratório Forçado , Nível de Saúde , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Comportamento Sedentário , Fatores de Tempo , Transferrina/análise , Capacidade Vital
15.
Artigo em Inglês | MEDLINE | ID: mdl-30643400

RESUMO

Background and objective: The distance of 6-minute walk test (D6MWT) has been widely used in the assessment of functional status in patients with COPD, while very little attention has been paid to the role of steps of 6-minute walk test (S6MWT). The purpose of this study was to investigate the relationship between S6MWT and other physiologic parameters of COPD. Patients and methods: Seventy patients with stable COPD were enrolled consecutively in this cross-sectional study. Pulmonary function tests, including spirometry, impulse oscillometry (IOS) and the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), were carried out at rest. Quality of life was assessed by health-related quality of life (HRQoL) questionnaires, including modified Medical Research Council dyspnea scale (mMRC), St George's Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and Clinical Chronic Obstructive Pulmonary Questionnaire. Both steps and distance were measured in the following 6-minute walk test (6MWT). Results: Both S6MWT and D6MWT showed significant correlation with spirometry, IOS, DLCO parameters and HRQoL questionnaires score. Both pre- and post-6MWT inspiratory capacity showed significant correlation with S6MWT (ρ=0.338, P=0.004; ρ=0.359, P=0.002, respectively), whereas did not correlate with D6MWT (ρ=0.145, P=0.230; ρ=0.160, P=0.189, respectively). In stepwise multiple regression analysis, mMRC grade, age and CAT score remained as significant predictors in the final model for D6MWT (adjusted R 2=0.445, P<0.01). DLCO and CAT score remained as significant predictors in the final model for S6MWT (adjusted R 2=0.417, P<0.01). Conclusion: S6MWT is efficient in the evaluation of functional status and quality of life in COPD and has significant correlation with various parameters indicating disease severity. Additionally, S6MWT might be better in predicting lung hyperinflation in COPD compared with D6MWT.


Assuntos
Tolerância ao Exercício , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Teste de Caminhada , Caminhada , Idoso , Estudos Transversais , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oscilometria , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Espirometria , Inquéritos e Questionários , Capacidade Vital
16.
Lung ; 197(2): 139-146, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30623243

RESUMO

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.


Assuntos
Linfangioleiomiomatose/sangue , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Brasil , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/fisiopatologia , Sistema Linfático/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Regulação para Cima
17.
J Clin Rheumatol ; 25(3): e12-e15, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29782426

RESUMO

OBJECTIVE: The aim of this study was to evaluate the association of nailfold videocapillaroscopy (NVC) changes and the presence and severity of interstitial lung disease (ILD) in systemic sclerosis. METHODS: This was a cross-sectional analysis of 48 systemic sclerosis patients (21 patients with ILD). The NVC characteristics considered were capillary organization, capillary loss (CL), avascular areas, enlarged and giant capillaries, hemorrhages, abnormally shaped capillaries, edema, and intermittent flux.We analyzed the association between NVC findings and (1) presence and extension of ILD and (2) percent predicted of forced vital capacity (FVC) and the carbon monoxide diffusing capacity (DLCO). RESULTS: Capillary loss and avascular areas showed a significant association with the presence of ILD (odds ratio, 18.57; 95% confidence interval [CI], 2.17-158.72 [p = 0.008]; and odds ratio, 4.64; 95% CI, 1.35-15.91 [p = 0.015], respectively). Receiver operating characteristic (ROC) curve analysis confirmed the association between CL and ILD (area under the ROC curve, 90.1%; 95% CI, 81.8-91.4). Avascular areas and CL were associated with a worse pulmonary function (FVC -18.1% [p = 0.034], DLCO -14.0% [p = 0.013]; and FVC -15.3% [p = 0.086], DLCO -12.3% [p = 0.049], respectively). No association was found between other NVC findings and ILD or lung function. CONCLUSIONS: Capillary loss and avascular area showed a significant association with the presence of ILD, supported by ROC curve analysis. These results may reinforce a prognostic role for NVC and a physiopathology mechanism for ILD based on vascular damage.


Assuntos
Capilares , Doenças Pulmonares Intersticiais , Angioscopia Microscópica/métodos , Escleroderma Sistêmico , Adulto , Idoso , Capilares/diagnóstico por imagem , Capilares/fisiopatologia , Monóxido de Carbono/análise , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Curva ROC , Reprodutibilidade dos Testes , Testes de Função Respiratória/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Capacidade Vital
18.
Dis Esophagus ; 32(3)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239639

RESUMO

A reduced forced expiratory volume in one second (FEV1) is a well-recognized risk factor for complications after esophagectomy. Lung diffusing capacity for carbon monoxide (DLCO) is not routinely integrated in the risk assessment of esophagectomy. The aim of this study is to evaluate the association of preoperative pulmonary function tests with major postoperative complications after esophagectomy for cancer. In order to achieve this aim, 459 patients with newly diagnosed esophageal cancer who underwent elective transthoracic (n = 352) or transhiatal (n = 107) surgical resection of the esophagus with cervical anastomosis between 2003 and 2015 were analyzed. Multivariable logistic regression analysis was performed to assess the association of preoperative pulmonary function tests (expressed as % of predicted) with major complications after esophagectomy, adjusted for previously identified predictors. Major complications were defined as Clavien-Dindo grade IIIb or higher. Of the 459 included patients, 114 (24.8%) developed major complications. In univariable analysis FEV1, forced vital capacity (FVC), vital capacity (VC), and DLCO were associated with major complications. After adjusting each pulmonary function test for age, American Society of Anesthesiologists (ASA) score, cardiac comorbidity, diabetes mellitus, peripheral vascular disease, and surgical approach, FVC (OR: 1.24 per 10% decrease; 95% CI: 1.06-1.45; P = 0.004), VC (OR: 1.19 per 10% decrease; 95% CI: 1.02-1.39; P = 0.025) and DLCO (OR: 1.16 per 10% decrease; 95%CI: 1.02-1.33; P = 0.025) remained predictive factors for major surgical complications. In multivariable analysis in which all pulmonary functions tests were combined, DLCO was the strongest predictor of major complications (OR: 1.14 per 10% increase; 95% CI: 1.01-1.30; P = 0.046). The ideal cut-off for DLCO% of predicted was determined at <84% (OR: 1.97; 95% CI: 1.28-3.03; P = 0.002). These data indicate that DLCO is an independent predictor of major complications after esophagectomy for cancer. This pulmonary function test deserves greater consideration in prediction research of major complications after esophagectomy.


Assuntos
Neoplasias Esofágicas/fisiopatologia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Capacidade de Difusão Pulmonar , Testes de Função Respiratória/estatística & dados numéricos , Idoso , Neoplasias Esofágicas/cirurgia , Feminino , Volume Expiratório Forçado , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Valores de Referência , Fatores de Risco , Resultado do Tratamento
19.
Ann Rheum Dis ; 78(1): 122-130, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30409830

RESUMO

OBJECTIVE: To assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II. METHODS: SLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling. RESULTS: After a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data. CONCLUSION: In addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.


Assuntos
Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/mortalidade , Ácido Micofenólico/administração & dosagem , Escleroderma Sistêmico/mortalidade , Adulto , Monóxido de Carbono/análise , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
20.
Clin Rheumatol ; 38(3): 803-815, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30392161

RESUMO

OBJECTIVE: To study prognostic factors in different types of idiopathic inflammatory myopathies (IIM) associated with interstitial lung disease (ILD). PATIENTS AND METHODS: Multicenter retrospective study of a Spanish cohort of patients diagnosed with IIM. Patients were classified into four categories: polymyositis (PM), dermatomyositis (DM), antisynthetase syndrome (ASS), and overlap myositis (OM). Sociodemographic data, clinical characteristics, antibodies, and treatments were collected. Cox regression models were calculated to identify factors associated with mortality, the necessity for long-term oxygen therapy (LTOT), and deterioration in respiratory function tests (RFT). RESULTS: The number of patients included was 478, of whom 112 (23.4%) suffered from ILD: 17% PM, 16% DM, 45% ASS, and 22% OM. Factors associated with mortality in the multivariate analysis were clinically meaningful progression of ILD after 3 months (CMP 3m) (hazard ratio (HR) 9.48, p = 0.005), severe infections (HR 6.41, p = 0.016), heliotrope erythema (HR 31.1, p = 0.002), delay in diagnosis (HR 1.29; p = 0.011), and Raynaud's phenomenon (HR 11.9, p = 0.007). However, being female (HR 0.19, p = 0.044) and positivity solely for ANAs (HR 0.08, p = 0.008) presented a protective effect. CMP 3m (HR 22.7, p = 0.027) was associated with the need for LTOT, while basal aldolase (HR 0.90; p = 0.049) had a protective effect. Likewise, joint manifestations (HR 0.04, p = 0.034) were shown to reduce risk of deterioration in RFT. CONCLUSIONS: CMP 3m, severe infections, delay in diagnosis, heliotrope erythema, and Raynaud's phenomenon were identified as factors of poor prognosis in different IIM associated with ILD.


Assuntos
Doenças Pulmonares Intersticiais/fisiopatologia , Mortalidade , Miosite/fisiopatologia , Oxigenoterapia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Diagnóstico Tardio/estatística & dados numéricos , Dermatomiosite/epidemiologia , Dermatomiosite/imunologia , Dermatomiosite/fisiopatologia , Progressão da Doença , Eritema/epidemiologia , Feminino , Frutose-Bifosfato Aldolase/metabolismo , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Miosite/epidemiologia , Miosite/imunologia , Polimiosite/epidemiologia , Polimiosite/imunologia , Polimiosite/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Proteção , Capacidade de Difusão Pulmonar , Doença de Raynaud/epidemiologia , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Capacidade Vital , Adulto Jovem
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