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Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66-95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4-29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00-1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31-53)/8.9 months (95% CI: 7.6-11.8) and 91% (95% CI: 76-98)/12.2 months (95% CI: 9.2-14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.
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The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations are unknown. Elderly patients aged ≥75 years old with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria (n = 2), gastrointestinal perforation (n = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients with EGFR-positive NSCLC.
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Antineoplásicos/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Clorhidrato de Erlotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Relación Dosis-Respuesta a Droga , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/genética , MasculinoRESUMEN
BACKGROUND AND OBJECTIVE: The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM-ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM-ILD. METHODS: We conducted a prospective multicentre, open-label, randomized, 52-week phase 2 trial. Patients with PM/DM-ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention-to-treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE. RESULTS: Fifty-eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per-protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE. CONCLUSION: PSL plus TAC treatment may achieve a better short-term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long-term efficacy and safety of such treatment.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Ciclosporina/uso terapéutico , Dermatomiositis/complicaciones , Dermatomiositis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Prednisolona/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Tacrolimus/uso terapéuticoRESUMEN
Multidisciplinary discussion (MDD) requiring close communication between specialists (clinicians, radiologists and pathologists) is the gold standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). However, MDD by specialists is not always feasible because they are often separated by time and location. An online database would facilitate data sharing and MDD. Our aims were to develop a nationwide cloud-based integrated database containing clinical, radiological and pathological data of patients with IIPs along with a web-based MDD system, and to validate the diagnostic utility of web-based MDD in IIPs.Clinical data, high-resolution computed tomography images and lung biopsy slides from patients with IIPs were digitised and uploaded to separate servers to develop a cloud-based integrated database. Web-based MDD was performed using the database and video-conferencing to reach a diagnosis.Clinical, radiological and pathological data of 524 patients in 39 institutions were collected, uploaded and incorporated into the cloud-based integrated database. Subsequently, web-based MDDs with a pulmonologist, radiologist and pathologist using the database and video-conferencing were successfully performed for the 465 cases with adequate data. Overall, the web-based MDD changed the institutional diagnosis in 219 cases (47%). Notably, the MDD diagnosis yielded better prognostic separation among the IIPs than did the institutional diagnosis.This is the first study of developing a nationwide cloud-based integrated database containing clinical, radiological and pathological data for web-based MDD in patients with IIPs. The database and the web-based MDD system that we built made MDD more feasible in practice, potentially increasing accurate diagnosis of IIPs.
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Nube Computacional , Manejo de Datos/organización & administración , Neumonías Intersticiales Idiopáticas/diagnóstico , Comunicación Interdisciplinaria , Anciano , Biopsia , Bases de Datos Factuales , Diagnóstico Diferencial , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/mortalidad , Japón/epidemiología , Masculino , Persona de Mediana Edad , Patólogos , Pautas de la Práctica en Medicina , Neumólogos , Radiólogos , Análisis de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis. The role of ferritin in the pathogenesis of AE-IPF is not well known while serum ferritin is a key prognostic indicator for patients with clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia. OBJECTIVE: To elucidate the clinical importance of serum ferritin in patients with AE-IPF. METHODS: Thirty-seven patients (48 episodes), who were diagnosed with AE-IPF and treated at our hospital between 1997 and 2015, were retrospectively studied. RESULTS: Patients with AE-IPF had significantly higher levels of serum ferritin than baseline levels at the first diagnosis of IPF (P = 0.0017). Receiver operating characteristic analysis showed the cut-off value 174 ng/mL for the separation of AE (area under the curve, 0.700). No patients with AE-IPF were positive for anti- melanoma differentiation-associated gene 5 antibody. Patients with AE-IPF and higher ferritin (≥174 ng/mL) had lower %FVC and %DLCO before AE, and those with much higher ferritin (≥500 ng/mL) had significantly worse prognosis than those with lower ferritin (log-rank, P = 0.024). Immunohistochemical staining in autopsy specimens showed alveolar macrophages that were producing ferritin. Finally, in multivariate Cox proportional hazards analyses, serum ferritin level of ≥500 ng/mL was a significant worse prognostic factor (hazard ratio 5.280, P = 0.046). CONCLUSION: Higher serum ferritin may be related to a worse prognosis in patients with AE-IPF.
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Ferritinas/sangre , Fibrosis Pulmonar Idiopática/mortalidad , Helicasa Inducida por Interferón IFIH1/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Ferritinas/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/fisiopatología , Helicasa Inducida por Interferón IFIH1/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase is a target for cancer therapy, but there have been no reports about Skp2 as a target for IPF. Here we demonstrate that Skp2 is a promising therapeutic target for IPF. We examined whether disrupting Skp2 suppressed pulmonary fibrosis in a bleomycin (BLM)-induced mouse model and found that pulmonary fibrosis was significantly suppressed in Skp2-deficient mice compared with controls. The pulmonary accumulation of fibrotic markers such as collagen type 1 and fibronectin in BLM-infused mice was decreased in Skp2-deficient mice. Moreover, the number of bronchoalveolar lavage fluid cells accompanied with pulmonary fibrosis was significantly diminished. Levels of the Skp2 target p27 were significantly decreased by BLM-administration in wild-type mice, but recovered in Skp2-/- mice. In vimentin-positive mesenchymal fibroblasts, the decrease of p27-positive cells and increase of Ki67-positive cells by BLM-administration was suppressed by Skp2-deficency. As these results suggested that inhibiting Skp2 might be effective for BLM-induced pulmonary fibrosis, we next performed a treatment experiment using the Skp2 inhibitor SZL-P1-41. As expected, BLM-induced pulmonary fibrosis was significantly inhibited by SZL-P1-41. Moreover, p27 levels were increased by the SZL-P1-41 treatment, suggesting p27 may be an important Skp2 target for BLM-induced pulmonary fibrosis. Our study suggests that Skp2 is a potential molecular target for human pulmonary fibrosis including IPF.
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Antibióticos Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/metabolismo , Proteínas Quinasas Asociadas a Fase-S/antagonistas & inhibidores , Animales , Biomarcadores , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación de la Expresión Génica , Genotipo , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Fibrosis Pulmonar/patología , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismoRESUMEN
The known oncogene cyclin D1 (CCND1) participates in progression of the cell cycle from G1 to S-phase. Expression of cyclin D1 is frequently promoted in multiple human cancers including non-small cell lung cancer (NSCLC). However, a relationship between cyclin D1 expression and the prognosis of NSCLC has not been confirmed. NKX2-1 is a homeobox transcription factor involved in pulmonary development as a differentiation-promoting factor. In NSCLC, it acts as a metastasis suppressor and correlates with a good prognosis. Here, NKX2-1-binding motifs were identified in the cyclin D1 promoter, but it has not been clarified whether NKX2-1 is involved in cyclin D1 expression in NSCLC. To shed light on this issue, endogenous NKX2-1 was depleted in NSCLC cell lines, which resulted in decreased cyclin D1 mRNA and protein. In contrast, forced overexpression of NKX2-1 increased cyclin D1 levels. Moreover, NKX2-1 directly bound to the cyclin D1 promoter and enhanced its activity. Finally, using human NSCLC clinical specimens, it was determined that both NKX2-1 protein and mRNA were significantly correlated with cyclin D1 expression status in adenocarcinomas. These results indicate that NKX2-1 directly and positively regulates transcription of cyclin D1 Finally, expression of NKX2-1, but not cyclin D1, was significantly associated with metastatic incidence as an independent good prognostic factor of adenocarcinoma.Implications: NKX2-1-expressing adenocarcinomas, whereas NKX2-1 promoted cyclin D1 expression, may show good prognosis features by the metastasis inhibition potency of NKX2-1 regardless cyclin D1 expression. Mol Cancer Res; 15(10); 1388-97. ©2017 AACR.
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Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Ciclina D1/genética , Neoplasias Pulmonares/genética , Factor Nuclear Tiroideo 1/metabolismo , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Sitios de Unión , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Ciclina D1/química , Ciclina D1/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Metástasis de la Neoplasia , Pronóstico , Regiones Promotoras Genéticas , Análisis de Supervivencia , Factor Nuclear Tiroideo 1/genéticaRESUMEN
PURPOSE: Small airway disease (SAWD) in patients with interstitial lung disease (ILD) is often assessed by high-resolution computed tomography (HRCT). However, frequent HRCT examinations result in a high level of radiographic exposure. This study investigated the utility of the forced oscillation technique (FOT) to evaluate SAWD in patients with ILD. METHODS: Broadband FOT using a commercially available device (MostGraph-01) and pulmonary function tests (PFT) were performed in 90 patients with ILD. HRCT images taken within 3 months were reviewed. The patients were divided into two groups according to the presence or absence of SAWD findings detected by HRCT. Clinical characteristics, PFT, and FOT between the two groups were compared. RESULTS: Of the 90 patients with ILD, 19 were classified as having SAWD findings (the presence group) and 71 as not having SAWD findings (the absence group). There were no significant differences in parameters of PFT between the two groups. The presence group had higher absolute values of reactance at 5 Hz (X5), resonant frequency (Fres), and low-frequency reactance area (ALX) than did the absence group. A within-breath change analysis demonstrated that the change in X5, Fres, and ALX between expiration and inspiration (ΔX5, ΔFres, ΔALX, respectively) was significantly different between the groups. A univariate analysis revealed that X5, Fres, ALX, ΔX5, ΔFres, ΔALX were significantly associated with the presence of SAWD findings. Multivariate analysis validated that Fres was related to the presence of SAWD findings. CONCLUSIONS: The FOT may be useful in detecting and evaluating SAWD in patients with ILD. TRIAL REGISTRATION: UMIN 000020733.
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Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Obstructivas/fisiopatología , Mecánica Respiratoria , Adulto , Anciano , Anciano de 80 o más Años , Resistencia de las Vías Respiratorias , Área Bajo la Curva , Espiración , Femenino , Humanos , Inhalación , L-Lactato Deshidrogenasa/sangre , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Obstructivas/diagnóstico por imagen , Enfermedades Pulmonares Obstructivas/etiología , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Valor Predictivo de las Pruebas , Proteína D Asociada a Surfactante Pulmonar/sangre , Curva ROC , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Angiopoietin (Ang) -1 and -2 are glycoproteins that play roles in vascular development, angiogenesis, and lung vascular permeability. Although the serum concentrations of Ang-1 and -2 have been evaluated in patients with sepsis, those in patients with idiopathic pulmonary fibrosis (IPF) have received less attention. OBJECTIVE: To elucidate the clinical significance of Ang-1 and -2 in patients with IPF. METHODS: Seventy-five patients with IPF were retrospectively studied. Serum concentrations of Ang-1 and -2 at diagnosis of IPF were measured by enzyme-linked immunosorbent assay. The relationships of the Ang-1 and -2 concentrations with pulmonary function test results, high-resolution computed tomography findings, histologic findings, occurrence of acute exacerbation of IPF (AE-IPF), and prognosis were evaluated. RESULTS: The median patient age was 68 year-old and the median observation period was 44 months. IPF patients with high Ang-2 concentrations showed a significantly lower forced vital capacity (FVC) (2.28 vs. 2.69 L, respectively; p = 0.047) and lower percent diffusion lung capacity for carbon monoxide (%DLCO) (61.4 vs. 81.4%, respectively; p = 0.015) than patients with low Ang-2 concentrations. Serum Ang-2 concentrations were negatively correlated with %DLCO (r = -0.375, p = 0.021) and the change in %FVC in 12 months (r = -0.348, p = 0.043). The Ang-2 concentration was significantly higher in several patients with AE-IPF than in patients in stable condition (p = 0.011). Finally, patients with high Ang-2 concentrations showed a significantly worse prognosis than those with low Ang-2 concentrations (log-rank p = 0.039). Multivariate analysis showed that the serum Ang-2 concentration, but not the Ang-1 concentration, was a significant prognostic factor in patients with IPF (hazard ratio 1.439, p = 0.028). CONCLUSION: Increases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.
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Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Fibrosis Pulmonar Idiopática/sangre , Pulmón/metabolismo , Anciano , Anciano de 80 o más Años , Inductores de la Angiogénesis , Monóxido de Carbono/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Pulmón/irrigación sanguínea , Pulmón/patología , Masculino , Persona de Mediana Edad , Pronóstico , Capacidad de Difusión Pulmonar/fisiología , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis and there is currently no effective treatment for this condition. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) improves oxygenation, but it is unclear whether treatment of AE-IPF with PMX-DHP affects survival. This study elucidated the effectiveness and safety of PMX-DHP for the treatment of AE-IPF. METHODS: This study included 31 patients with 41 episodes of AE-IPF. All patients received steroids. Of 31, 14 patients (20 episodes) were treated with PMX-DHP. The laboratory and physiological test results after the start of therapy and survival were retrospectively compared between patients treated with and without PMX-DHP. RESULTS: Patients treated with PMX-DHP had a significantly greater change in PaO2/FiO2 ratio (mean ± SEM, 58.2 ± 22.5 vs. 0.7 ± 13.3, p = 0.034) and a smaller change in white blood cell count (-630 ± 959 /µL vs. 4500 ± 1190 /µL, p = 0.002) after 2 days of treatment than patients treated without PMX-DHP. The 12-month survival rate was significantly higher in patients treated with PMX-DHP (48.2% vs. 5.9%, p = 0.041). PMX-DHP was effective in patients with more severe underlying disease (GAP stages II or III; 12-month survival rate 57.1% with PMX-DHP vs. 0% without PMX-DHP, p = 0.021). Treatment with PMX-DHP was an independent predictor of better prognosis (hazard ratio 0.345, p = 0.037). Mild pulmonary thromboembolism occurred in one patient treated with PMX-DHP. CONCLUSIONS: Treatment of AE-IPF with PMX-DHP is tolerable and improves 12-month survival.
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Antibacterianos/uso terapéutico , Hemoperfusión/métodos , Fibrosis Pulmonar Idiopática/terapia , Proteínas Inmovilizadas/uso terapéutico , Polimixina B/uso terapéutico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/inmunología , Recuento de Leucocitos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and often coexists with asthma or chronic obstructive pulmonary disease (COPD); however, it is unknown whether there are differences in the effect of GERD on these diseases. The purpose of this study was to assess the difference in the effect of GERD on cough-related quality of life and disease status in asthma and COPD in a real-world setting. METHODS: Subjects were 132 patients with overall controlled asthma and 102 patients with stable COPD. They completed the frequency scale for symptoms of GERD (FSSG), a validated Japanese questionnaire for GERD, the Leicester Cough Questionnaire (LCQ), and the Asthma Control Test (ACT) or COPD assessment test (CAT) questionnaires. RESULTS: We found that 29 (22.0%) patients with asthma and 22 (21.6%) patients with COPD had GERD. There was no difference in the FSSG scale between the diseases. The patients with GERD, regardless of having asthma or COPD, had lower LCQ scores affecting all health domains and lower ACT or higher CAT scores than those without GERD. Overall, the patients with COPD had lower LCQ scores regardless of the presence or absence of GERD. The FSSG scale was negatively correlated with the LCQ total score in asthma and in COPD. In contrast, the FSSG scale was positively correlated with the CAT score but not with the ACT score. CONCLUSIONS: Patients with GERD had impaired cough-related quality of life, poor asthma control or more symptoms and impacts of COPD.
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Asma/epidemiología , Tos/epidemiología , Tos/etiología , Reflujo Gastroesofágico/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Calidad de Vida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/fisiopatología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The composite physiologic index (CPI), which is derived from FEV1, FVC, and diffusing capacity, has been developed to predict the extent of fibrosis on high-resolution computed tomography (HRCT). However, the relevance to the forced oscillation technique (FOT) is not fully understood. We hypothesized that FOT would independently predict the CPI in interstitial lung disease (ILD). In this cross-sectional study we assessed the relationship between pulmonary function tests, forced oscillatory parameters, and the degree of fibrosis in ILD. Spirometry, evaluation of diffusing capacity for carbon monoxide, and the broadband frequency FOT were performed in 93 patients with a clinical/HRCT diagnosis of ILD. The CPI was calculated and fibrosis extent was measured by HRCT and scored. Univariate analyses revealed that, of the forced oscillatory parameters, inspiratory resonant frequency best correlated with FVC, FEV1, diffusing capacity, CPI, and fibrosis score. In multiple regression analyses, CPI was independently predicted by inspiratory resonant frequency and fibrosis score (model R(2)=0.405, p<0.0001).
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Volumen Espiratorio Forzado/fisiología , Inhalación/fisiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Enfisema/etiología , Enfisema/patología , Femenino , Fibrosis/etiología , Fibrosis/patología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Pruebas de Función Respiratoria , Estudios Retrospectivos , Espirometría , Tomógrafos Computarizados por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. EFL can be measured by the forced oscillation technique (FOT); however, the relevance to clinical parameters is not fully understood. We hypothesized that emphysema extent and pulmonary function would contribute independently to the degree of EFL. METHODS: Broadband frequency FOT and pulmonary function tests were performed in 74 patients with COPD to derive respiratory system resistance (Rrs) and reactance (Xrs), and the EFL index as expressed by the differences between inspiratory and expiratory phases of Xrs at 5 Hz (ΔX5). Emphysema extent was measured by high-resolution computed tomography and scored. RESULTS: On the basis of the median value of ΔX5 (0.55 cmH2O/L/s), patients were classified into a high or low EFL index group. In multivariate regression analyses, a high EFL index was independently predicted by emphysema score, peripheral airway obstruction (forced expiratory flow between 25% and 75% of forced vital capacity), hyperinflation (functional residual capacity), and airway caliber (whole-breath Rrs at 5 Hz). CONCLUSIONS: EFL measured by FOT is a global measure of COPD that has separable etiologies and is useful for evaluating the disease condition.
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Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Espiración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar/etiología , Enfisema Pulmonar/fisiopatología , Pruebas de Función Respiratoria , Adulto JovenRESUMEN
PURPOSE: Recently, the clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices, including the impulse oscillation system and MostGraph. We investigated the usefulness of color 3D imaging of respiratory impedance in asthma using MostGraph. METHODS: Whole-breath and within-breath respiratory system resistance (Rrs) and reactance (Xrs) were measured in 78 patients with asthma. Color 3D images were classified into three patterns: the chronic obstructive pulmonary disease (COPD)-like pattern (high values of Rrs and Xrs with a marked respiratory cycle and frequency dependence), the asthma pattern (moderately high Rrs over the entire frequency and a respiratory cycle with slight Xrs changes), and a normal-like pattern (low Rrs and Xrs with few within-breath changes). The classification was performed by three researchers, who were unaware of the clinical information, and the clinical characteristics were compared among the three groups. RESULTS: Color 3D imaging provided a COPD-like pattern in 25 patients, an asthma pattern in 39 patients, and a normal-like pattern in 14 patients. Patients with the COPD-like pattern were predominantly female with a higher body mass index, lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and higher Rrs and Xrs values (whole-breath and within-breath variation). Those with the normal pattern had higher FEV1 and FVC, and a lower single-breath nitrogen washout slope. There were no differences in asthma control or exhaled nitric oxide levels among the three groups. CONCLUSIONS: These results suggest that color 3D imaging of respiratory impedance may show asthma phenotypes.
RESUMEN
A 55-year-old woman visited our hospital for an investigation of central bronchiectasis, mucoid impaction and infiltrative shadows on chest CT. She had a 10-year history of bronchial asthma; however, her adherence to treatment was poor. Based on the presence of peripheral blood eosinophilia and immediate cutaneous reactivity to Aspergillus fumigatus, the patient was clinically diagnosed with allergic bronchopulmonary aspergillosis. Her condition and CT findings improved with systemic corticosteroid therapy. It was found that the patient had not been sensitized to Aspergillus 10 years earlier, indicating that single testing is inadequate for the early diagnosis of this disease.
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Aspergilosis Broncopulmonar Alérgica/etiología , Bronquiectasia/etiología , Corticoesteroides/uso terapéutico , Alérgenos/inmunología , Anticuerpos Antifúngicos/sangre , Antígenos Fúngicos/inmunología , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergillus fumigatus/inmunología , Asma/complicaciones , Asma/inmunología , Bronquiectasia/inmunología , Femenino , Humanos , Hipersensibilidad Inmediata , Inmunoglobulina E/sangre , Persona de Mediana Edad , Pruebas Cutáneas , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
The nitrogen (N2) single-breath washout (SBW) test is a measure of ventilation distribution inhomogeneity and also a small airway function that offers complementary information to spirometry; however, the relevance to the forced oscillation technique (FOT) and pulmonary emphysema in COPD is not fully understood. We hypothesized that pulmonary functions, forced oscillatory parameters, and emphysema extent would contribute independently to the results of the SBW test. In this cross-sectional study we assessed the relationship between the phase III slope (delta N2) derived from N2 SBW and these parameters. Spirometry, lung volumes, N2 SBW, and the broadband frequency FOT were performed in 56 patients with COPD. Emphysema extent was measured by high-resolution computed tomography and scored. In multiple regression analyses, the delta N2 was independently predicted by forced vital capacity, resonant frequency, and emphysema score (R(2)=0.57, p<0.0001). The degree of ventilation inhomogeneity derived from N2 SBW is independently predicted by spirometry, lung mechanics, and the degree of emphysema.
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Pruebas Respiratorias/métodos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Pruebas de Función Respiratoria , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrógeno/análisis , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar/complicacionesRESUMEN
A 48-year-old man with a history of asthma visited our hospital for the investigation of a high density mass at the right hilum. Laboratory data revealed elevated serum carcinoembryonic antigen. A bronchoscopy was performed to rule out lung cancer; however, mucoid impaction was found without malignant or bacterial cells. On the basis of peripheral blood eosinophilia, elevated total serum IgE, and immediate cutaneous reactivity to Aspergillus fumigatus, he was diagnosed with allergic bronchopulmonary aspergillosis. The radiographic findings and serum carcinoembryonic antigen levels improved with corticosteroids. Pulmonary masses are uncommon findings and serum carcinoembryonic antigen may be a useful marker of the disorder.
RESUMEN
The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the lung mechanics measured by multi-frequency forced oscillation technique (FOT) among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41 patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20 Hz was significantly lower in patients with CPFE than in those with IP or COPD, irrespective of the severity of airflow limitation. Within-breath analyses of resistance revealed no difference among the 3 groups; however, the difference between inspiratory and expiratory phases of reactance at 5 Hz, which reflects expiratory flow limitation, in patients with CPFE was significantly higher than in those with IP and lower than in those with COPD. In conclusion, both emphysema and fibrosis affect lung mechanics in CPFE, leading to different findings from IP or COPD alone.