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AIMS: Pulmonary infections are more frequent in and associated with higher mortality in Cystic Fibrosis-Related Diabetes (CFRD) patients compared to CF patients without CFRD. Hyperglycaemia can lead to a higher vulnerability for infections. Aim of the study was to test whether the infection rate in well-controlled CFRD patients was similar to that in CF patients without CFRD. METHODS: This is a retrospective six-year cohort analysis on a consecutive series of 138 CF patients. They were categorized in two groups with CFRD or without CFRD. Pulmonary infection frequency was defined as the number of intravenous (IV) antibiotic treatments. Clinical factors associated with infection frequency were collected. RESULTS: CFRD was diagnosed in 54 (39%) CF patients of whom 44 (81%) achieved target value for glycaemic control (HbA1c 7.0% (⩽53mmol/mol)). Median frequency of IV antibiotics was 0 without CFRD and 3 episodes in patients with CFRD (rate ratio (RR) 2.9 (95% CI 1.6-5.2)). Multivariate analysis showed that frequency of IV antibiotics was significantly related to Pseudomonas aeruginosa colonization (RR 3.7) and lower lung function at baseline (RR 0.97) but not to CFRD by itself. CONCLUSIONS: In this cohort with overall strict glycaemic control, the frequency of IV antibiotics use was related to chronic infection and impaired lung function at baseline, but not to CFRD by itself. Although this study in itself does not prove beneficial effect of strict glycaemic control, it does emphasize the potential role of glycaemic control on infection frequency in CF patients.
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Antibacterianos/administración & dosificación , Fibrosis Quística/complicaciones , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus , Hiperglucemia/complicaciones , Enfermedades Pulmonares , Administración Intravenosa , Adolescente , Adulto , Análisis de Varianza , Glucemia/análisis , Estudios de Casos y Controles , Enfermedad Crónica , Diabetes Mellitus/metabolismo , Femenino , Hemoglobina Glucada/análisis , Índice Glucémico , Humanos , Hiperglucemia/prevención & control , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: In divers, conflicting results regarding the development of small airway disease and "large lungs" have been reported. PURPOSE: To analyze the changes in pulmonary function over time, the development of "large lungs" and to see whether the pulmonary function deviates from subjects with "non-large lungs." METHODS: It is a longitudinal cohort study from 1983 till 2013 in professional navy divers, in which lung functions tests were performed annually. RESULTS: In 1,260 navy divers, 8,149 pulmonary function tests were analyzed. The forced expiratory volume (FEV1) did not change except initially in those with abnormally low lung function (baseline value ⟨lower-limit-of-normal for the general population (LLN). In that group, FEV1 increased by 35 (SE 7) ml/year. For the entire cohort, the inspiratory vital capacity (iVC) increased by 73 ml/year (SE 25). In the ⟨LLN cohort, it increased by an additional 40 ml/year (SE 18). For the entire cohort, the FEV1/iVC annual drop was 0.37% (SE 0.9), but in the ⟨LLN cohort it increased by 0.25%/year (SE 0.04). For the entire cohort, the forced expiratory flow at 75% of expiration (FEF75) annual drop was 23 ml/s/year (SE 7), in contrast in the ⟨LLN cohort it increased by an additional 45 ml/second/year (SE 7). Of the navy divers, 6.3% showed "large lungs," but changes over time were not different from above except for an additional 0.2% (SE 0.1%) decline in FEV1/iVC. CONCLUSIONS: In professional navy divers, long-term pulmonary function changes (FEV1 and FEV1 /iVC and FEF75) are not different from those in the non-diving population. The iVC increases probably due to training effect.
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Buceo/fisiología , Volumen Espiratorio Forzado/fisiología , Personal Militar , Capacidad Vital/fisiología , Adulto , Femenino , Humanos , Estudios Longitudinales , Pulmón/patología , Pulmón/fisiopatología , Masculino , Tamaño de los Órganos , Pruebas de Función Respiratoria/estadística & datos numéricos , Fenómenos Fisiológicos Respiratorios , Factores de TiempoRESUMEN
PURPOSE: To determine inter-rater reliability of sarcoidosis-related computed tomography (CT) findings that can be used for scoring of thoracic sarcoidosis. MATERIALS AND METHODS: CT images of 51 patients with sarcoidosis were scored by five chest radiologists for various abnormal CT findings (22 in total) encountered in thoracic sarcoidosis. Using intra-class correlation coefficient (ICC) analysis, inter-rater reliability was analysed and reported according to the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria. A pre-specified sub-analysis was performed to investigate the effect of training. Scoring was trained in a distinct set of 15 scans in which all abnormal CT findings were represented. RESULTS: Median age of the 51 patients (36 men, 70%) was 43 years (range 26 - 64 years). All radiographic stages were present in this group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings. Sub-analysis for the best-trained observers demonstrated an ICC improvement for all abnormal findings and values above 0.60 for 16 of the 22 abnormalities. CONCLUSIONS: In our cohort, reliability between raters was acceptable for 16 thoracic sarcoidosis-related abnormal CT findings. KEY POINTS: ⢠Thoracic sarcoidosis is common; knowledge on reliability of CT scoring is limited. ⢠Scoring CT abnormalities in pulmonary sarcoidosis can achieve good inter-rater agreement. ⢠CT scoring validation in thoracic sarcoidosis is important for diagnostic and prognostic studies.
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Radiografía Torácica/métodos , Sarcoidosis Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Mannose-binding lectin (MBL)-deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL-deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL-deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL-deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL-deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL-deficient and -sufficient patients with RRTI. Eighteen MBL-deficient and 63 MBL-sufficient adult patients with RRTI were all vaccinated with the 23-valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL-sufficient and -deficient patients. Forty-three MBL-sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL-deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL-sufficient and -deficient patients. In conclusion, our study suggests that MBL-deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL-sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL-deficient patients with RRTI.
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Lectina de Unión a Manosa/deficiencia , Errores Innatos del Metabolismo/inmunología , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/inmunología , Streptococcus pneumoniae/inmunología , Adulto , Anticuerpos Antibacterianos/sangre , Femenino , Genotipo , Humanos , Inmunidad Humoral , Masculino , Lectina de Unión a Manosa/inmunología , Errores Innatos del Metabolismo/complicaciones , Persona de Mediana Edad , Infecciones Neumocócicas/etiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Pautas de la Práctica en Medicina , Recurrencia , Pruebas de Función Respiratoria , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/prevención & controlRESUMEN
BACKGROUND AND OBJECTIVE: The development of bronchiolitis obliterans syndrome (BOS) after lung transplantation is characterized by inflammation, remodeling and fibrosis. Both YKL-40 and matrix metalloproteinase (MMP)-9 have shown to be involved in these processes. We measured serial YKL-40 and MMP-9 serum levels in lung transplant recipients and assessed their usefulness as biomarker for BOS. Furthermore, we investigate the relationship between these two potential biomarkers of BOS and MMP-7. DESIGN: Ten patients with BOS (BOS(pos)) and 10 matched patients without BOS (BOS(neg)) were included. Serial serum samples were collected after lung transplantation and prior to BOS. YKL-40, MMP-9 and MMP-7 serum levels were determined by ELISA. RESULTS: The median concentrations of YKL-40 did not differ between BOS(pos) and BOS(neg) patients (p > 0.05). The median concentration of MMP-9 in BOS(pos) patients was significantly higher than in BOS(neg) patients (p < 0.0001). For MMP-9 as possible risk factor for BOS, a cut off value of 145 ng/ml has a sensitivity of 90% and a negative predictive value of 83%. Longitudinal analysis of YKL-40 and MMP-9 serum levels from the early post-transplant period onwards did not reveal a significant trend in time in both serum levels preceding BOS. In BOS(neg) patients MMP-9 showed an inverse relationship with MMP-7, that was absent in BOS(pos) patients. CONCLUSIONS: From the moment of transplantation onwards, patients who eventually developed BOS had significantly increased MMP-9 serum levels in comparison with patients who did not develop BOS. Therefore, increased MMP-9 serum levels might be useful as risk factor for BOS.
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Adipoquinas/sangre , Biomarcadores/sangre , Bronquiolitis Obliterante/sangre , Lectinas/sangre , Metaloproteinasa 9 de la Matriz/sangre , Adulto , Bronquiolitis Obliterante/epidemiología , Proteína 1 Similar a Quitinasa-3 , Femenino , Humanos , Enfermedades Pulmonares/sangre , Trasplante de Pulmón , Masculino , Metaloproteinasa 7 de la Matriz/sangre , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVES: To determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation. METHODS: In 248 subjects (50 normal smokers; 50 mild obstruction; 50 moderate obstruction; 50 severe obstruction; 48 very severe obstruction) CT emphysema and CT air trapping were quantified on paired inspiratory and end-expiratory CT examinations using several available quantification methods. CT measurements were related to lung function (FEV(1), FEV(1)/FVC, RV/TLC, Kco) by univariate and multivariate linear regression analysis. RESULTS: Quantitative CT measurements of emphysema and air trapping were strongly correlated to airflow limitation (univariate r-squared up to 0.72, p < 0.001). In multivariate analysis, the combination of CT emphysema and CT air trapping explained 68-83% of the variability in airflow limitation in subjects covering the total range of airflow limitation (p < 0.001). CONCLUSIONS: The combination of quantitative CT air trapping and emphysema measurements is strongly associated with lung function impairment in current and former heavy smokers with a wide range of airflow limitation.
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Neoplasias Pulmonares/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Análisis de Varianza , Femenino , Volumen Espiratorio Forzado , Humanos , Hallazgos Incidentales , Modelos Lineales , Neoplasias Pulmonares/fisiopatología , Masculino , Flujo Espiratorio Máximo , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar/fisiopatología , Estudios Retrospectivos , Fumar/efectos adversos , Fumar/fisiopatología , Capacidad VitalRESUMEN
Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity.
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Biomarcadores/análisis , Pruebas Respiratorias/métodos , Espiración , Tamizaje Masivo/métodos , Enfisema Pulmonar/diagnóstico , Compuestos Orgánicos Volátiles/análisis , Anciano , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/metabolismoRESUMEN
PURPOSE: Fluor-18 fluorodeoxyglucose (18F-FDG) PET is able to demonstrate sarcoidosis activity. Ongoing pulmonary sarcoidosis activity can be reflected by a decline in pulmonary function tests (PFT). To assess whether diffuse metabolic activity of the lung parenchyma imaged by 18F-FDG PET predicts future pulmonary deterioration, 18F-FDG PET was compared with PFT. METHODS: In this retrospective cohort study, 43 newly diagnosed, sarcoidosis patients were analyzed. Based on 18F-FDG PET, patients were diagnosed with diffuse parenchymal disease activity, without or with immunosuppressive treatment, started after 18F-FDG PET was performed. As a control, sarcoidosis patients with mediastinal/hilar disease activity but without metabolic activity in the lung parenchyma were analyzed, all without treatment. Vital capacity (VC), forced expiratory volume (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) were analyzed per group at baseline, i.e., at the time 18F-FDG PET was performed, and after one year follow-up. RESULTS: At follow-up, a significant decrease in DLCO was found in untreated patients with diffuse parenchymal activity. No change in VC or FEV1 could be observed. Treated patients with parenchymal activity showed a significant increase in VC, FEV1 and DLCO, while patients without parenchymal activity did not show any change in PFT. CONCLUSIONS: In sarcoidosis, diffuse parenchymal disease imaged by 18F-FDG PET, predicts a future deterioration of DLCO when untreated. Treatment however, improves VC, FEV1 and DLCO significantly suggesting that 18F-FDG PET represents the pulmonary improvement that can be achieved. The absence of metabolic activity in the lung parenchyma justifies a wait-and-see policy.
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Fluorodesoxiglucosa F18 , Pulmón/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Sarcoidosis Pulmonar/diagnóstico por imagen , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón/metabolismo , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Países Bajos , Valor Predictivo de las Pruebas , Pronóstico , Capacidad de Difusión Pulmonar , Pruebas de Función Respiratoria , Estudios Retrospectivos , Sarcoidosis Pulmonar/metabolismo , Sarcoidosis Pulmonar/fisiopatología , Sarcoidosis Pulmonar/terapia , Índice de Severidad de la Enfermedad , Factores de Tiempo , Capacidad VitalRESUMEN
A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV1/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV1/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV1/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.
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Monóxido de Carbono/metabolismo , Capacidad de Difusión Pulmonar , Enfisema Pulmonar/fisiopatología , Fumar/fisiopatología , Progresión de la Enfermedad , Volumen Espiratorio Forzado , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfisema Pulmonar/diagnóstico por imagen , Espirometría , Tomografía Computarizada por Rayos X , Capacidad VitalAsunto(s)
Volumen Espiratorio Forzado , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/mortalidad , Espirometría/estadística & datos numéricos , Espirometría/normas , Anciano , Humanos , Masculino , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Curva ROC , Valores de ReferenciaRESUMEN
The mainstay of the diagnosis of asthma is the presence of reversible airway obstruction. Exhaled NO levels are increased in asthma, in close relationship with the amount of airway inflammation, and may be used for monitoring the disease and adjusting therapy. In this study we investigated the role of eNO as a diagnostic for asthma, compared with the FEV1-reversibility and the PC20 (20% decrease of the FEV1 in the bronchial histamine provocation test), in two independent centers, on an unselected population. ENO measurements were performed with chemoluminesence technique in one center and with an electrochemical device in the other. Only after correction for so-called nuisance factors (allergy, use of inhaled steroids, recent infection, smoking, sex and the use of nitrate food) the eNO appeared as a diagnostic with equal power as the FEV1-reversibility and the PC20. Therefore, screening for asthma in our study population, with the eNO measurement, is a simple, fast and safe strategy.
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Asma/diagnóstico , Hiperreactividad Bronquial/diagnóstico , Pruebas de Provocación Bronquial/métodos , Histamina , Óxido Nítrico , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Derivación y ConsultaRESUMEN
The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary capillary blood volume and equals the membrane diffusing capacity. Therefore the DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA) and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly selected heavy smokers. Subjects with areas > or =1% of the total lung volume showing an attenuation <-950 Hounsfield Units were considered to have emphysema. In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94 subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive predictive value of KNO however was low (34.7%), while the negative predictive value of KNO was very high (98.2%), indicating an emphysema exclusion test. The DLNO/DLCO ratio is significantly higher in the study group compared to normal subjects.
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Óxido Nítrico/metabolismo , Capacidad de Difusión Pulmonar/métodos , Enfisema Pulmonar/diagnóstico , Fumar/efectos adversos , Anciano , Métodos Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Enfisema Pulmonar/fisiopatología , Espirometría/métodosRESUMEN
BACKGROUND: Free O2- radicals may cause precapillary sphincter abnormalities, resulting in epistaxis in hemizygous knockout mice for Endoglin. The objective of this study was to test if antioxidants, like N-acetylcysteine (NAC), are have a role in the treatment of epistaxis in hereditary hemorrhagic telangiectasia (HHT). METHODS: Forty-three patients participated in this study taking NAC 600 mg t.i.d for 12 weeks. Patients registered frequency, severity and duration of epistaxis and private and work-related quality of life (QOL), using a diary for two 6 weeks periods. The first period was prior to starting treatment and the second started after 6 weeks using NAC. RESULTS: There was a decrease infrequency (p < 0.01) and severity (p < 0.01) of epistaxis during the day. The improvement was most remarkable in male patients and patients with an ENDOGLIN mutation. In women and patients with an ALK-1 mutation, only a trend for improvement was found. Nocturnal epistaxis did not improve. The effect of epistaxis on the ability to work (p = 0.02) was reduced. CONCLUSION: This pilot study was conducted to investigate whether animal experiments can be translated to humans with HHT regarding epistaxis. The positive results with NAC are promising and justify a randomised clinical trial.
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Acetilcisteína/uso terapéutico , Epistaxis/etiología , Epistaxis/prevención & control , Depuradores de Radicales Libres/uso terapéutico , Calidad de Vida , Telangiectasia Hemorrágica Hereditaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Índice de Severidad de la Enfermedad , Factores Sexuales , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with a high mortality rate. As lung transplantation is the only therapeutic option, it is important to predict survival. OBJECTIVE: This study evaluates the clinical value of surfactant protein-D as a marker of prognosis in patients with idiopathic pulmonary fibrosis. DESIGN: Surfactant protein-D was measured in serum of 72 patients and 305 healthy controls. The optimal cut-off level to define unfavourable prognosis was determined using a ROC analysis. A Cox's proportional Hazards model was used to evaluate variables that were significant predictors of survival. RESULTS: Serum levels of surfactant protein-D were significantly higher in patients than in controls. ROC analysis showed 460 ng/ml to be the optimal cut-off level to discriminate survivor from non-survivors after 1 year. Patients with high levels (> 460 ng/ml) had a median survival time of 13 months, compared to 67 months in the group with low levels (< 460 ng/ml). Surfactant protein-D showed to be a significant predictor of prognosis, even when corrected for age, sex, smoking, and lung function. CONCLUSION: The measurement of surfactant protein-D in serum of patients with idiopathic pulmonary fibrosis might be a clinically relevant tool to predict survival.
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Líquido del Lavado Bronquioalveolar/química , ADN/genética , Fibrosis Pulmonar Idiopática/mortalidad , Polimorfismo Genético , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Adulto , Alelos , Biomarcadores/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Genotipo , Humanos , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Proteína D Asociada a Surfactante Pulmonar/genética , Curva ROC , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We present a new, off-line breath collection and analysis method, suitable for large screening studies. The breath collection system is based on the guidelines of the American Thoracic Society for the sampling of exhaled NO. Breath containing volatile gases is collected in custom-made black-layered Tedlar bags and analyzed by proton-transfer reaction mass spectrometry (PTR-MS). The collection method and data analysis is validated for its accuracy, precision, selectivity, limits of detection, sensitivity and reproducibility. Consecutive fillings of five bags by the same person gave reproducible results to within 12% relative standard deviation (RSD) for methanol, acetaldehyde, acetone and water content from breath, whereas isoprene was constant to within 30% RSD. In an exploratory small-scale case-control study, we monitor the exhaled breath of 11 lung cancer patients on the day before surgery. The control group consisted of 57 age-matched subjects, the so-called 'healthy smokers'. This study is used as an example of the use of the system presented here.
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Pruebas Respiratorias/métodos , Neoplasias Pulmonares/metabolismo , Fumar/metabolismo , Biomarcadores/metabolismo , Pruebas Respiratorias/instrumentación , Estudios de Casos y Controles , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Tamizaje Masivo/métodos , Espectrometría de Masas/métodos , Persona de Mediana Edad , Proyectos Piloto , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIMS: For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes. METHODS: In a randomized single-blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 microm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17-BMP) were measured by liquid chromatography plus mass spectrometry. RESULTS: Aerosols with MMADs of 1.5 microm, 2.5 microm, and 4.5 microm gave mean maximum concentrations (C(max)) of 17-BMP of 475 pg ml(-1), 1300 pg ml(-1), and 1161 pg ml(-1), respectively. The area under the curve (AUC) values of 17-BMP for MMADs of 1.5 microm, 2.5 microm, and 4.5 microm were 825 pg ml(-1) h, 2629 pg ml(-1) h, and 2276 pg ml(-1) h, respectively. The mean terminal half-time of 17-BMP for all three aerosol sizes was around 1.5 h. CONCLUSIONS: Monodisperse BDP aerosols with a MMAD of 1.5 microm gave two-three fold lower values for C(max) and AUC than those with MMADs of 2.5 and 4.5 microm.
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Antiasmáticos/farmacocinética , Asma/metabolismo , Beclometasona/análogos & derivados , Beclometasona/farmacocinética , Tamaño de la Partícula , Administración por Inhalación , Adolescente , Adulto , Aerosoles , Antiasmáticos/sangre , Área Bajo la Curva , Asma/sangre , Beclometasona/sangre , Disponibilidad Biológica , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
AIM OF THE STUDY: The diffusion capacity of the lung for carbon monoxide (DL(CO)) is an important tool in the diagnosis and follow-up of patients with pulmonary diseases. In case of a decreased DL(CO) the K(CO), defined as DL(CO)/V(A) (V(A) is alveolar volume), can differentiate between normal alveolocapillary membrane (normal K(CO)) and abnormal alveolocapillary membrane (low K(CO)). The latter category consists of decreased surface of the membrane, increased thickness or decreased perfusion of ventilated alveoli. The V(A)/TLC (TLC is total lung capacity determined by whole body plethysmography) can partially differentiate between these categories. The aim of this study was to investigate the diagnostic value of the specific diffusion disturbances, which can be constructed by combining the DL(CO), K(CO) and V(A)/TLC. METHODS: In 460 patients the diagnosis made by clinicians were fitted into five diagnostic categories: asthma, chronic obstructive pulmonary disease (COPD), treatment effects of haematologic malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These categories were linked to the pattern of diffusion disturbance. RESULTS: Almost all patients with asthma have a normal DL(CO), most patients in the other groups do not have the expected pattern of diffusion disturbance, especially in the group with DPLD a bad match is observed. CONCLUSION: In this study the pattern of diffusion disturbance is of limited use in establishing a diagnosis. The use of the K(CO) next to the DL(CO) has no additional diagnostic value. Regional ventilation-perfusion inequality probably forms an important underlying mechanism of decreased DL(CO).
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Barrera Alveolocapilar/patología , Monóxido de Carbono/metabolismo , Enfermedades Pulmonares/diagnóstico , Capacidad de Difusión Pulmonar/efectos de la radiación , Capacidad Pulmonar Total/efectos de la radiación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Difusión , Femenino , Volumen Espiratorio Forzado , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Capacidad VitalRESUMEN
BACKGROUND: The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He)). OBJECTIVES: The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts. METHODS: We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous. RESULTS: A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively). CONCLUSION: We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.
Asunto(s)
Helio/farmacocinética , Mediciones del Volumen Pulmonar , Alveolos Pulmonares/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Administración por Inhalación , Adulto , Anciano , Anciano de 80 o más Años , Enfisema , Femenino , Helio/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Valores de Referencia , Fumar/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
The aim of asthma treatment is optimal disease control. Poor asthma control results in considerable patient morbidity, as well as contributing to the considerable burden placed by the disease on healthcare budgets. There is a need for costs to be carefully scrutinised, with the switching of patients to inhaler devices with lower acquisition costs likely to be increasingly considered. However, before such practice becomes widespread, it is important to establish whether or not this could adversely impact on patients and the level of disease control. For approval to have been given, all marketed inhalers must have satisfied current regulatory requirements for devices. Full preclinical and clinical development programmes are not required when application is made for authorisation to market a new inhaler containing an existing chemical entity, although clinical equivalence testing must be used. Both beneficial and adverse effects should be tested, and the limits of equivalence must be clearly defined, based on therapeutic relevance. It should be noted that equivalence studies are invalid when the end point is not responding (i.e. at the top of the dose-response curve) and when equivalence limits approach or are equal to the magnitude of the drug effect. Approval on the basis of regulations designed to safeguard quality of dry powder inhalers does not mean that devices are interchangeable. When using an inhaler, there are many stages between the patient and the therapeutic effect, involving device design, pharmaceutical performance and patient behaviour. Regulations governing new devices cover only a few of the many factors affecting disease control. Furthermore, clinical trials to assess equivalence may not take into account factors in patient behaviour or variations in patient inhaler technique that may affect use of devices in real-life situations. When assessing the consequences of interchangeable use of dry powder inhalers on healthcare costs, it is important to ensure that the acquisition cost of the devices is not the only cost considered. Other costs that should be considered include the cost of time spent demonstrating to the patient how to use the new device, the cost of additional physician visits to address patient concerns and the management costs if disease control is adversely affected.