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BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear. OBJECTIVES: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients. DESIGN: A multicenter prospective cohort study. METHODS: Serum samples were prospectively collected from five medical institutions, from patients with LAM (n = 40) and controls (n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p < 0.001). The serum VEGF-D levels were significantly higher in patients with LAM than those in the control group (median: 708.9 pg/mL vs 325.3 pg/mL, p < 0.001). In the ROC curve analysis, serum VEGF-D levels showed good predicting performance for LAM diagnosis (area under the curve = 0.918) with an optimal cut-off value of 432.7 pg/mL (sensitivity = 85.0%, specificity = 87.5%). When 800 pg/mL was used as the cut-off value, the specificity of serum VEGF-D for LAM diagnosis increased to 100.0%. CONCLUSION: Our results suggest that serum VEGF-D may be a useful biomarker for diagnosing LAM in Korean patients, similar to previous reports.
Blood test for diagnosis of lymphangioleiomyomatosis in Korea: role of vascular endothelial growth factor-DIn this study, we discuss a blood test to diagnose a rare lung disease, called lymphangioleiomyomatosis (LAM). LAM primarily affects women, especially during their childbearing years, and can cause serious lung problems such as damage and cyst (air-filled sac) formation. The blood test looks for a special protein in the blood, called vascular endothelial growth factor-D (VEGF-D). If someone has a lot of this protein, it usually means that they have LAM. We have found that when VEGF-D levels are high, the test can effectively separate LAM from other lung diseases. We also found that raising this threshold to higher levels made it much more likely to correctly distinguish a group of people who do not have the disease from patients with LAM. Our study is important because it's the first to show the usefulness of blood VEGF-D testing in Korean LAM patients, and because it suggests an easier and less inconvenient way for physicians to diagnose LAM in Koreans. Our findings are an important step in improving the management of Korean patients with LAM.
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Ensaio de Imunoadsorção Enzimática , Linfangioleiomiomatose , Fator D de Crescimento do Endotélio Vascular , Humanos , Feminino , Linfangioleiomiomatose/sangue , Linfangioleiomiomatose/diagnóstico , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Estudos de Casos e Controles , Curva ROC , Biomarcadores/sangue , Valor Preditivo dos Testes , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Estudos de Coortes , MasculinoRESUMO
Given the pleiotropic effects of statins beyond their lipid-lowering effects, there have been attempts to evaluate the role of statin therapy in IPF, but they have shown inconclusive results. Data from the National Health Insurance Service (NHIS) database of South Korea were used to investigate the effects of statin therapy on IPF. The IPF cohort consisted of a total of 10,568 patients who were newly diagnosed with IPF between 2010 and 2017. These patients were then matched in a 1:3 ratio to 31,704 subjects from a control cohort without IPF, with matching based on age and sex. A case-control study was performed to evaluate the association between statin use and the risk for IPF, and the multivariable analysis revealed that statin use was associated with a lower risk for IPF (adjusted OR 0.847, 95% CI 0.800-0.898). Using the IPF cohort, we also evaluated whether statin use at the time of diagnosis was associated with future clinical outcomes. The statin use at the time of IPF diagnosis was associated with improved overall survival (adjusted HR 0.779, 95% CI 0.709-0.856). Further prospective studies are needed to clarify the role of statin therapy in IPF.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Fibrose Pulmonar Idiopática , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos de Casos e Controles , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/epidemiologia , República da Coreia/epidemiologiaRESUMO
The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88-4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47-3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.
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Fibrose Pulmonar Idiopática , Enfisema Pulmonar , Humanos , Prognóstico , Progressão da Doença , Capacidade Vital , PulmãoRESUMO
Purpose To investigate quantitative CT (QCT) measurement variability in interstitial lung disease (ILD) on the basis of two same-day CT scans. Materials and Methods Participants with ILD were enrolled in this multicenter prospective study between March and October 2022. Participants underwent two same-day CT scans at an interval of a few minutes. Deep learning-based texture analysis software was used to segment ILD features. Fibrosis extent was defined as the sum of reticular opacity and honeycombing cysts. Measurement variability between scans was assessed with Bland-Altman analyses for absolute and relative differences with 95% limits of agreement (LOA). The contribution of fibrosis extent to variability was analyzed using a multivariable linear mixed-effects model while adjusting for lung volume. Eight readers assessed ILD fibrosis stability with and without QCT information for 30 randomly selected samples. Results Sixty-five participants were enrolled in this study (mean age, 68.7 years ± 10 [SD]; 47 [72%] men, 18 [28%] women). Between two same-day CT scans, the 95% LOA for the mean absolute and relative differences of quantitative fibrosis extent were -0.9% to 1.0% and -14.8% to 16.1%, respectively. However, these variabilities increased to 95% LOA of -11.3% to 3.9% and -123.1% to 18.4% between CT scans with different reconstruction parameters. Multivariable analysis showed that absolute differences were not associated with the baseline extent of fibrosis (P = .09), but the relative differences were negatively associated (ß = -0.252, P < .001). The QCT results increased readers' specificity in interpreting ILD fibrosis stability (91.7% vs 94.6%, P = .02). Conclusion The absolute QCT measurement variability of fibrosis extent in ILD was 1% in same-day CT scans. Keywords: CT, CT-Quantitative, Thorax, Lung, Lung Diseases, Interstitial, Pulmonary Fibrosis, Diagnosis, Computer Assisted, Diagnostic Imaging Supplemental material is available for this article. © RSNA, 2024.
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Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Idoso , Feminino , Humanos , Masculino , Modelos Lineares , Doenças Pulmonares Intersticiais/diagnóstico , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVE: Corticosteroids are commonly used for the treatment of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); however, the optimal initial dose of corticosteroids remains uncertain due to a lack of sufficient evidence. We evaluated whether the administration of a pulse dose of corticosteroids resulted in improved survival outcomes compared with conventional non-pulse dose of corticosteroids. METHODS: We retrospectively analysed 238 patients with AE-IPF treated with corticosteroids at a tertiary referral hospital between January 2013 and December 2021. Based on whether a pulse dose of corticosteroids (methylprednisolone of ≥250 mg/day or equivalent) was administered within 7 days of hospitalization for AE-IPF, the patients were divided into the pulse and non-pulse regimen groups. The survival outcomes were compared between the two groups using multivariable regression and propensity score-matched analyses. RESULTS: Among the 238 patients, 59 patients received pulse dose of corticosteroids, whereas 179 patients received conventional non-pulse dose of corticosteroids. After adjusting for the confounding factors related to the baseline clinical and radiographic severity, compared with the conventional non-pulse regimen, the pulse regimen of corticosteroids did not reduce the risk of mortality at the 3-month (aHR 0.84, 95% CI 0.45-1.38) or 12-month (aHR 0.96, 95% CI 0.60-1.25) follow-ups. Propensity score-matched analysis revealed similar results. CONCLUSION: The survival outcomes of patients with AE-IPF who received a pulse dose of corticosteroids did not differ from those of patients who received conventional non-pulse dose of corticosteroids. Further prospective studies are required to establish the optimal initial dose of corticosteroids for the treatment of AE-IPF.
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Pneumonias Intersticiais Idiopáticas , Fibrose Pulmonar Idiopática , Humanos , Progressão da Doença , Estudos Retrospectivos , Resultado do Tratamento , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Corticosteroides/uso terapêuticoRESUMO
OBJECTIVES: To develop and validate a deep learning-based prognostic model in patients with idiopathic pulmonary fibrosis (IPF) using chest radiographs. METHODS: To develop a deep learning-based prognostic model using chest radiographs (DLPM), the patients diagnosed with IPF during 2011-2021 were retrospectively collected and were divided into training (n = 1007), validation (n = 117), and internal test (n = 187) datasets. Up to 10 consecutive radiographs were included for each patient. For external testing, three cohorts from independent institutions were collected (n = 152, 141, and 207). The discrimination performance of DLPM was evaluated using areas under the time-dependent receiver operating characteristic curves (TD-AUCs) for 3-year survival and compared with that of forced vital capacity (FVC). Multivariable Cox regression was performed to investigate whether the DLPM was an independent prognostic factor from FVC. We devised a modified gender-age-physiology (GAP) index (GAP-CR), by replacing DLCO with DLPM. RESULTS: DLPM showed similar-to-higher performance at predicting 3-year survival than FVC in three external test cohorts (TD-AUC: 0.83 [95% CI: 0.76-0.90] vs. 0.68 [0.59-0.77], p < 0.001; 0.76 [0.68-0.85] vs. 0.70 [0.60-0.80], p = 0.21; 0.79 [0.72-0.86] vs. 0.76 [0.69-0.83], p = 0.41). DLPM worked as an independent prognostic factor from FVC in all three cohorts (ps < 0.001). The GAP-CR index showed a higher 3-year TD-AUC than the original GAP index in two of the three external test cohorts (TD-AUC: 0.85 [0.80-0.91] vs. 0.79 [0.72-0.86], p = 0.02; 0.72 [0.64-0.80] vs. 0.69 [0.61-0.78], p = 0.56; 0.76 [0.69-0.83] vs. 0.68 [0.60-0.76], p = 0.01). CONCLUSIONS: A deep learning model successfully predicted survival in patients with IPF from chest radiographs, comparable to and independent of FVC. CLINICAL RELEVANCE STATEMENT: Deep learning-based prognostication from chest radiographs offers comparable-to-higher prognostic performance than forced vital capacity. KEY POINTS: ⢠A deep learning-based prognostic model for idiopathic pulmonary fibrosis was developed using 6063 radiographs. ⢠The prognostic performance of the model was comparable-to-higher than forced vital capacity, and was independent from FVC in all three external test cohorts. ⢠A modified gender-age-physiology index replacing diffusing capacity for carbon monoxide with the deep learning model showed higher performance than the original index in two external test cohorts.
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Aprendizado Profundo , Fibrose Pulmonar Idiopática , Radiografia Torácica , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/mortalidade , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Idoso , Radiografia Torácica/métodos , Pessoa de Meia-Idade , Capacidade VitalRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.
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Fibrose Pulmonar Idiopática , Células-Tronco Mesenquimais , Humanos , Animais , Camundongos , Administração Intravenosa , Macrófagos , Monócitos , Bleomicina , Modelos Animais de DoençasRESUMO
BACKGROUND: Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure, fatal infectious complications have been reported. However, adequate preventive strategies have not been determined. We aimed to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. METHODS: In this single-center, assessor-blinded, parallel-group randomized controlled trial, we randomly assigned adult participants undergoing EBUS-TBNA using a convex probe to gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA or to receive usual care (no chlorhexidine mouthrinse). Aspiration needle wash samples were collected immediately after completion of EBUS-TBNA by instilling sterile saline into the used needle. The primary outcome was colony forming unit (CFU) counts per mL of needle wash samples in aerobic cultures. Secondary outcomes were CFU counts per mL of needle wash samples in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. RESULTS: From January 2021 to June 2021, 106 patients received either chlorhexidine mouthrinse (n = 51) or usual care (n = 55). The median CFU counts of needle wash samples in aerobic cultures were not significantly different in the two groups (10 CFU/mL vs 20 CFU/mL; P = 0.70). There were no significant differences between the groups regarding secondary outcomes, including median CFU counts in anaerobic cultures (P = 0.41) and fever within 24 hours after EBUS-TBNA (11.8% vs 5.6%, P = 0.31). There were no infectious complications within 4 weeks in both groups. CONCLUSIONS: Chlorhexidine mouthrinse did not reduce CFU counts in needle wash samples of EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04718922 . Registered on 22/01/2021.
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Neoplasias Pulmonares , Antissépticos Bucais , Adulto , Humanos , Broncoscopia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Febre , LinfonodosRESUMO
BACKGROUND: Antifibrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fibrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifibrotic therapy have not been identified. Therefore, we aimed to evaluate the prognostic efficacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifibrotic therapy. METHODS: The clinical data of 188 patients with IPF who initiated antifibrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, diffusing capacity for carbon monoxide ≥ 15%, acute exacerbation, or deaths during 6 months after antifibrotic therapy. RESULTS: The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2-9.8 months). There was no difference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥ 500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confidence interval 1.005-1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve = 0.707; P < 0.012). CONCLUSIONS: Our data suggest that the relative change in KL-6 over 1 month might be useful for predicting DP in patients with IPF receiving antifibrotic therapy when baseline KL6 is high.
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Fibrose Pulmonar Idiopática , Humanos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Mucina-1 , Capacidade Vital , Curva ROC , Razão de Chances , BiomarcadoresRESUMO
BACKGROUND: Although single-cell RNA sequencing of xenograft samples has been widely used, no comprehensive bioinformatics pipeline is available for human and mouse mixed single-cell analyses. Considering the numerous homologous genes across the human and mouse genomes, misalignment errors should be evaluated, and a new algorithm is required. We assessed the extents and effects of misalignment errors and exonic multi-mapping events when using human and mouse combined reference data and developed a new bioinformatics pipeline with expression-based species deconvolution to minimize errors. We also evaluated false-positive signals presumed to originate from ambient RNA of the other species and address the importance to computationally remove them. RESULT: Error when using combined reference account for an average of 0.78% of total reads, but such reads were concentrated to few genes that were greatly affected. Human and mouse mixed single-cell data, analyzed using our pipeline, clustered well with unmixed data and showed higher k-nearest-neighbor batch effect test and Local Inverse Simpson's Index scores than those derived from Cell Ranger (10 × Genomics). We also applied our pipeline to multispecies multisample single-cell library containing breast cancer xenograft tissue and successfully identified all samples using genomic array and expression. Moreover, diverse cell types in the tumor microenvironment were well captured. CONCLUSION: We present our bioinformatics pipeline for mixed human and mouse single-cell data, which can also be applied to pooled libraries to obtain cost-effective single-cell data. We also address misalignment, multi-mapping error, and ambient RNA as a major consideration points when analyzing multispecies single-cell data.
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Biologia Computacional , Genoma , Algoritmos , Animais , Genômica , Humanos , Camundongos , RNARESUMO
Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6-along with baseline P/F ratio and CRP levels-was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD.
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Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Idoso , Biomarcadores , Humanos , Masculino , Mucina-1 , Oxigênio , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS: The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases. METHODS: This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George's Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity. RESULTS: Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without. CONCLUSION: The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.
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Asma , Fibrose Pulmonar Idiopática , Doença Pulmonar Obstrutiva Crônica , Tosse , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/epidemiologia , Prevalência , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear. OBJECTIVE: This study aimed to identify a key cellular player of air pollutant-induced asthma exacerbation and development. METHODS: We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry and RNA-Seq analysis. The roles of sialic acid-binding, Ig-like lectin F (SiglecF)-positive neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies. RESULTS: DEP exposure induced a unique population of lung granulocytes that coexpressed Ly6G and SiglecF. These cells differed phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEPs induces the local release of adenosine triphosphate, which is a damage-associated molecular pattern signal. Adenosine triphosphate promotes the expression of SiglecF on neutrophils, and these SiglecF+ neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8- (which corresponds to murine SiglecF) expressing neutrophils, and we found it in patients with asthma-chronic obstructive pulmonary disease overlap. CONCLUSION: The SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting this population could reverse or ameliorate asthma.
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Poluentes Atmosféricos , Asma , Trifosfato de Adenosina/metabolismo , Poluentes Atmosféricos/toxicidade , Animais , Humanos , Inflamação/metabolismo , Pulmão , Camundongos , Neutrófilos/patologia , Emissões de Veículos/toxicidadeRESUMO
BACKGROUND: Smoking has been considered an important risk factor for idiopathic pulmonary fibrosis (IPF) incidence. However, there are no population-based large-scale studies demonstrating the effects of smoking on the development of IPF. We aimed to evaluate the effect of smoking on IPF development using a nationwide population-based cohort. METHODS: Using the Korean National Health Information Database, we enrolled individuals who had participated in the health check-up service between 2009 and 2012. Participants having a prior diagnosis of IPF were excluded. The history of smoking status and quantity was collected by a questionnaire. We identified all cases of incident IPF through 2016 on the basis of ICD-10 codes for IPF and medical claims. Cox proportional hazards models were used to calculate the adjusted HR (aHR) of the development of IPF. RESULTS: A total of 25 113 individuals (0.11%) with incident IPF were identified out of 23 242 836 participants registered in the database. The risk of IPF was significantly higher in current and former smokers than in never smokers, with an aHR of 1.66 (95% CI 1.61 to 1.72) and 1.42 (95% CI 1.37 to 1.48), respectively. Current smokers had a higher risk of IPF than former smokers (aHR 1.17, 95% CI 1.13 to 1.21). The risk of IPF development increased as the smoking intensity and duration increased. CONCLUSION: Smoking significantly increased the risk of IPF development. Current smokers had a higher risk of IPF than former smokers. A dose-response relationship was observed between smoking and the development of IPF.
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Fibrose Pulmonar Idiopática , Fumar , Estudos de Coortes , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/etiologia , Incidência , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar TabacoRESUMO
BACKGROUND/AIMS: Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF. METHODS: This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). RESULTS: The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was -6.56% (95% confidence interval [CI], -9.26 to -3.87) per year before, but -4.43% (95% CI, -5.87 to -3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was -4.96% (95% CI, -6.82 to -3.09) per year before, but -1.79% (95% CI, -2.75 to -0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II-III than in the stage I group. CONCLUSION: The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.
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Fibrose Pulmonar Idiopática , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Capacidade VitalRESUMO
BACKGROUND: The intensive care unit (ICU) staffing model affects clinical outcomes of critically ill patients. However, the benefits of a closed unit model have not been extensively compared to those of a mandatory critical care consultation model. METHODS: This retrospective before-after study included patients admitted to the medical ICU. Anthropometric data, admission reason, Acute Physiology and Chronic Health Evaluation II score, Eastern Cooperative Oncology Group grade, survival status, length of stay (LOS) in the ICU, duration of mechanical ventilator care, and occurrence of ventilator-associated pneumonia (VAP) were recorded. The staffing model of the medical ICU was changed from a mandatory critical care consultation model to a closed unit model in September 2017, and indices before and after the conversion were compared. RESULTS: A total of 1,526 patients were included in the analysis. The mean age was 64.5 years, and 954 (62.5%) patients were men. The mean LOS in the ICU among survivors was shorter in the closed unit model than in the mandatory critical care consultation model by multiple regression analysis (5.5 vs. 6.7 days; p = 0.005). Central venous catheter insertion (38.5% vs. 51.9%; p < 0.001) and VAP (3.5% vs. 8.6%; p < 0.001) were less frequent in the closed unit model group than in the mandatory critical care consultation model group. After adjusting for confounders, the closed unit model group had decreased ICU mortality (adjusted odds ratio 0.65; p < 0.001) and shortened LOS in the ICU compared to the mandatory critical care consultation model group. CONCLUSION: The closed unit model was superior to the mandatory critical care consultation model in terms of ICU mortality and LOS among ICU survivors.
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Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
Most epidemiologic studies of patients with idiopathic pulmonary fibrosis (IPF) have been conducted in North America and Europe. Moreover, there are limited data concerning the cause of death and cause-specific mortality rate of IPF patients in population-based studies. We analyzed information from the Korean National Health Insurance Service database from 2006 to 2016. Patients with a diagnosis code of IPF were extracted from the database and we included those who satisfied the narrow definition of IPF diagnosis. Age- and sex-matched controls were randomly selected at a case-to-control rate of 1:3. We included 42,777 patients newly diagnosed with IPF during the study period. Their mean age was 64.6 years, and 65.4% were male. The age-standardized mortality rates were 85.66 (95% confidence interval [CI] 84.45-86.89) per 1000 person-years. The survival rates of IPF patients 1, 2, 3, 5, and 10 years after IPF diagnosis were 84.5%, 77.4%, 71.9%, 62.9%, and 48.4%, respectively. The standardized mortality ratio of IPF patients compared to that of the normal population was 4.66. The leading cause of death in IPF patients was respiratory causes, followed by cancer. Patients with IPF in Korea showed significantly higher mortality compared to the general population.
Assuntos
Fibrose Pulmonar Idiopática/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Causas de Morte , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: While extreme sleep duration negatively affects mortality and health-related quality of life (HRQOL) in general populations, the relationship remains uncertain in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To evaluate the association between sleep duration and mortality and HRQOL in patients with COPD. METHODS: We analyzed 3,349 participants with COPD enrolled in the 2007-2015 Korea National Health and Nutrition Examination Survey (KNHANES). Participants aged 40 years or older with a smoking history and prebronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7 were eligible. The participants were categorized as short sleepers (<6 h), 6-8 h, and long sleepers (>8) according to self-reported sleep duration. The outcome variables were all-cause mortality and HRQOL. HRQOL was measured using the European Quality of Life-5 Dimensions (EQ-5D) index. RESULTS: During a median of 6.5 years, 386 (11.5%) participants died. In unadjusted Cox regression analysis, short sleepers with COPD had an increased risk of death (hazard ratio, 1.35; 95% confidence interval [CI]: 1.07-1.71). However, this association was not significant after adjusting for sociodemographic factors, BMI, FEV1, and comorbidities. In unadjusted and adjusted multiple linear regression, short sleepers had significantly worse HRQOL. The adjusted means of the EQ-5D index were 0.88 (95% CI: 0.87-0.89) for short sleepers, 0.90 (95% CI: 0.90-0.91) for 6- to 8-h sleepers, and 0.89 (95% CI: 0.87-0.91) for long sleepers (p = 0.01). CONCLUSIONS: In patients with COPD, sleep duration was not associated with all-cause mortality. However, short sleep duration was significantly associated with worse HRQOL.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Volume Expiratório Forçado , Humanos , Inquéritos Nutricionais , SonoRESUMO
BACKGROUND AND OBJECTIVE: IPF shares common risk factors and has pathogenic similarities with cancer. However, limited population-based data are available on cancer risk among patients with IPF. Herein, we investigated whether IPF is associated with an increased risk for cancer incidence from a nationwide database in South Korea. METHODS: In this population-based cohort study, patients with IPF were enrolled from 2009 to 2014, and matched controls were randomly selected at a control-to-case ratio of 3:1. In both groups, individuals diagnosed with any malignancy before the index date were excluded. The incidence rates of cancer were measured as the number of events per 1000 person-years. Multivariable Cox regression models were used to assess the cancer incidence risk. RESULTS: This study included 25 241 patients with IPF and 75 723 matched controls. The overall cancer incidence in patients with IPF was 29.0 cases per 1000 person-years, and it was significantly higher in the IPF group than in the non-IPF group (HR, 2.09; 95% CI, 1.96-2.16). Lung cancer showed the highest HR (5.89; 95% CI, 5.40-6.42), followed by lymphoma, skin, uterine cervical, multiple myeloma, thyroid, leukaemia, pancreatic, liver and prostate cancer. Moreover, adjustment for the effects of smoking and other cancer-associated covariates had little effect on the HR of overall and specific cancers. CONCLUSION: The cancer incidence risk was higher in the IPF group than in the non-IPF group. Therefore, healthcare providers should be aware of this risk when treating patients with IPF.