Proteomics of exhaled breath condensate in stable COPD and non-COPD controls using tandem mass tags (TMTs) quantitative mass spectrometry: A pilot study.

Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow. Exhaled breath condensate (EBC) is now a safe and clinically significant measurement which has a huge potential to measure biomarkers in COPD. Previous studies profiled the pooled EBC samples from COPD or control participants due to technological limitations. In our study, 32 COPD patients and 28 control individuals were enrolled, and their EBC were collected. After matching with sex, age and smoking history, EBC samples of 19 COPD patients and 19 control individuals were analyzed using tandem mass tags (TMTs) quantitative mass spectrometry individually. A total of 257 proteins were identified. Compared with control group, 24 proteins (15 upregulated and 9 downregulated) were differentially expressed in COPD patients. The GO analysis of these differential proteins expressed mostly in the cytoplasm, and the KEGG analysis showed they had a predominant role in inflammatory response. And ACTB, UBC, TUBB and CCT2 involving in cell motility and cytoskeleton played important role in the interaction-net of these proteins. To sum up, we found some proteins might be novel biomarkers of EBC in COPD and TMTs was available to analyze proteomics in individual EBC samples. SIGNIFICANCE: It is still difficult to understand the mechanism of airway inflammation in COPD. Exhaled breath condensate(EBC) might be a great study object, but due to technological limitations, researchers preferred to use pooled EBC samples. This study analyzed individual EBC samples, which would deepen our understanding of the pathogenesis of COPD. And this method can be applied to individual EBC samples for further airway investigations of different purpose and different complexity.

Fractional Exhaled Nitric Oxide (FeNO) Combined with Pulmonary Function Parameters Shows Increased Sensitivity and Specificity for the Diagnosis of Cough Variant Asthma in Children.

BACKGROUND Cough variant asthma in children presents with a dry nonproductive cough. This study aimed to investigate the diagnostic value of fractional exhaled nitric oxide (FeNO) combined with small airway functional parameters in cough variant asthma. MATERIAL AND METHODS Children with asthma (n=136) were divided into a cough variant asthma (CVA) group (n=57; mean age, 8.03±2.1 years) and a non-cough variant asthma (nCVA) group (n=79; mean age, 8.61±1.7 years). In both groups, FeNO and other pulmonary function parameters were measured including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF), forced expiratory flow (FEF), and maximum expiratory flow at 25%, 50%, and 75% expired volume (MEF25, MEF50, and MEF75). Receiver-operating characteristic (ROC) curve analysis compared the sensitivity and specificity between the diagnostic parameters. RESULTS The FeNO values were significantly increased in the CVA group compared with the nCVA group (Z=6.890, p<0.001). The MMEF, MEF25, MEF50, and MEF75 values were significantly lower in the CVA group compared with the nCVA group (p=0.000, p=0.014, p=0.000, and p=0.000, respectively). The FeNO values were negatively correlated with MEF25, MEF50, and MMEF (ρ=-0.334, ρ=-0.257 and ρ=-0.276, respectively). FeNO was significantly more efficient diagnosing cough variant asthma comparing with pulmonary parameters (p<0.05), and was most sensitive and specific when combined with MMEF/MEF50 compared with single diagnostic parameters (p<0.05). CONCLUSIONS FeNO combined with pulmonary function parameters of MMEF/MEF50 showed increased sensitivity and specificity for the diagnosis of cough variant asthma.

Oscillating Positive Expiratory Pressure Therapy May Be Performed Poorly by Children With Cystic Fibrosis.

BACKGROUND: Oscillating positive expiratory pressure devices aid removal of excess secretions and reduce gas trapping in patients with hypersecretory pulmonary diseases, for example, cystic fibrosis. Oscillating positive expiratory pressure works when the patient exhales actively against a fixed resistor, which generates mean intrapulmonary pressures of 10-20 cm H2O with rapid fluctuations of at least 1 cm H2O from the mean. In this study, we evaluated the performance of oscillating positive expiratory pressure therapy by pediatric subjects with cystic fibrosis to determine adherence to target therapeutic pressures. METHODS: Twenty-one pediatric subjects were recruited. Each had a history of using an oscillating positive expiratory pressure device twice daily and had received standardized training and instructions from the same specialist physiotherapist. Performance was evaluated by using a flow and pressure sensor placed in-line between the participant's mouth and the device. The participants performed expirations as per their normal routine. RESULTS: None of the participants achieved target therapeutic pressure ranges during expiration. The mean ± SD pressure generated was 16.2 ± 6.8 cm H2O, whereas mean ± SD flow was 31.3 ± 8.9 L/min. The mean ± SD expiration length was 2.5 ± 1.4 s. CONCLUSIONS: Despite standardized instruction, the results demonstrated considerable variation among the participants and overall poor technique during use. Outcomes of this study indicated that airway clearance effects of oscillating positive expiratory pressure were compromised due to poor technique.

Efecto de la obstrucción de la vía aérea en la medición de la fracción de óxido nítrico exhalado / Effect of airway obstruction when testing exhaled nitric oxide fractionfeno

INTRODUCCIÓN: numerosos trabajos han intentado ver la aplicabilidad de la FeNO para el diagnóstico o para el control y regulación del tratamiento en el asma bronquial. Dado que el significado real de los valores de la FeNO en relación a la obstrucción bronquial sigue siendo incierto, intentar esclarecer esta circunstancia tiene un enorme interés en la práctica clínica diaria. MATERIAL Y MÉTODO: se realizó un estudio de corte trasversal de pacientes diagnosticados de asma leve-moderada, según criterios de la GEMA 2009, durante 9 meses. Se recogieron datos de control de asma (ACQ), FeNO basal, espirometría basal (FEV1), test de metacolina (PD20) y tras broncodilatación. En un subgrupo de pacientes se realizaron espirometrías seriadas. RESULTADOS: Se analizaron 48 asmáticos. La puntuación de ACQ fue de 1,7 ± 0,3 (0,7 - 2) puntos. El FEV1 basal fue 2,93 ± 0,8 (92 ± 16%). Al final del test de la metacolina, tanto el FEV1 como el FeNO caían significativamente respecto a los basales. Los pacientes que estaban en tratamiento con corticoides inhalados tenían unas cifras de FeNO menores que los que estaban sin corticoides: 21,4 ± 10 ppb, frente a 50,2 ± 29 ppb; p0,001. Se encontró una correlación significativa entre la disminución de FeNO, expresado en % del basal y la disminución de FEV1, expresado tanto en cifras absolutas como en % (R = 0,52 y 0,583, respectivamente). Se diseñó una curva ROC, recodificando la variable de disminución de FeNO en dos grupos, según disminuyesen más o menos de un 10% (área bajo la curva de 0,928, p < 0,001). Considerando como punto de corte un 18% de disminución de FEV1, se obtuvo una sensibilidad del 85% y una especificidad del 87%. No se encontraron diferencias en el subgrupo donde se realizaron maniobras espirométricas repetidas. CONCLUSIONES: Existe una afectación de la medida de la FeNO tras las variaciones agudas del calibre bronquial, con pruebas de metacolina y tras broncodilatadores, utilizando sistemas portátiles con sensor electroquímico, debiendo valorarse el impacto de estos hallazgos en el seguimiento de los pacientes asmáticos

INTRODUCTION: several studies have tried to implementFeNOfor diagnosis or to control and regulate bronchial asthma treatments. Given that the significance of FeNO values regardingbronchial obstruction continues to be uncertain, clarifying this circumstance is extremely interesting for daily clinical practice. MATERIAL AND METHOD: across-sectional study was carried out with patients who were diagnosed with mild to moderate asthma, in keeping with the GEMA 2009 criteria, for 9 months. Asthma control data was collected (ACQ), basal FeNO, basal spirometry (FEV1), methacholine test (PD20) and post-bronchodilation. In a sub-group of patients, serial spirometry was carried out. RESULTS: 48 asthmatic patients were analyzed. The ACQ score was 1.7 ± 0.3 (0.7 - 2) points. Basal FEV1 was 2.93 ± 0.8 (92 ± 16%). Upon concluding the methacholine test, both FEV1 andFeNOfell significantly with regards to basal values. Patients treated with inhaled corticosteroids had lower FeNOlevels thanthose not oncorticosteroids: 21.4 ± 10 ppb, compared to 50.2 ± 29 ppb; p < 0.001. A significant correlation was seen between the decrease in FeNO, expressed in percentage of basal values, and the decrease of FEV1, expressed both in absolute values as well as in percentages, R = 0.52 and 0.583, respectively). A ROC (receiver operative curve) analysis was performed, recoding the decreased variable for FeNOinto two groups, based on a reduction of more or less than 10% (area under the curve was 0.928, p <0.001).A 18% cutoff for FEV1 decline had a 85% sensitivity and 87% specificity. No differences were found in the sub-group where repeated spirometrictests were performed. CONCLUSIONS: there is anaffectationwhen measuring FeNOafter acute variations of the bronchial caliber, with methacholine tests and after bronchodilators, using portable systems with electrochemical sensors. The impact of these findings for the follow-up of asthmatic patients must be assessed

Estudio de pacientes con sospecha de asma bronquial remitidos desde Atención Primaria. Análisis del diagnóstico final y utilidad del test de broncodilatación / Studying patients with possible bronchial asthma. Analysis of the final diagnosis and the usefulnessof bronchodilatort testing

INTRODUCCIÓN: el asma es un trastorno inflamatorio crónico de la vía aérea que cursa con obstrucción e hiperrespuesta bronquial y no existe un 'patrón oro' para su diagnóstico. OBJETIVO: estudiar, según el algoritmo diagnóstico de GEMA, la utilidad del test broncodilatador (BD), las características (clínicas, funcionales, parámetros de inflamación) según el resultado del test y las diferencias de los pacientes diagnosticados de asma de aquéllos con otros diagnósticos finales ('pseudoasmas'). METODOLOGÍA: se incluyeron pacientes derivados a consultas especializadas de Neumología con sospecha clínica de asma. Se recogieron datos clínicos y se realizó espirometría con test BD y determinación de niveles de óxido nítrico exhalado (FENO). Cuando el test BD fue negativo, se efectuó prueba de provocación con metacolina o manitol. Los pacientes fueron revisados al mes y a los 6 meses para confirmar el diagnóstico de asma. RESULTADOS: se estudiaron 133 pacientes (edad media 35,6 [11]). Fueron 92 los diagnosticados de asma bronquial y 41 (30,8%) de otras patologías, siendo el goteo nasal posterior la más frecuente. De los 92 asmáticos, presentaron test BD positivo 61 (66,3% de los asmáticos, 45,8% del total). En los 31 casos con test BD negativo, el diagnóstico se hizo por prueba de provocación. Los pacientes con prueba BD positiva presentaban mayor gravedad, afectación funcional y peor control del asma, mayor consumo acumulado de tabaco, habiendo una mayor proporción de hombres. Los casos con test negativo presentaron valores de FENO >30 ppb en el 19% de los casos. CONCLUSIONES: en pacientes previamente no tratados, la prueba broncodilatadora es positiva en un porcentaje alto, siendo aquéllos con patología más grave y peor control. En los casos en que es negativa, puede ser útil la determinación de niveles de FENO. Más de un 30% de pacientes derivados con sospe-cha de asma, finalmente fueron diagnosticados de otras pato-logías, entre las que destaca el goteo nasal posterior

INTRODUCTION: asthma is the chronic inflammation of the airways that presents bronchial obstruction and hyper-response. There is no 'golden rule' to diagnose this disease. OBJECTIVE: Based on the GEMA (Spain's Guideline for Asthma Management) diagnostic algorithm, the usefulness of the bronchodilator test (BD) was studied, as were the circumstances (clinical, functional, inflammatory parameters) based on test results and the differences between patients diagnosed with asthma and those with another final diagnosis (Pseudo-asthma). METHODOLOGY: this study included patients who were thought to have asthma and referred to a respiratory specialist. Clinical data was collected and a spirometry performed with a bronchodilator (BD) test; fractional exhaled nitric oxide (FENO) levels were determined. When the BD test was negative, a methacholine or mannitol challenge test was performed. Patients were seen again after a month and then after six months to confirm the asthma diagnosis. RESULTS: 133 patients were studied (mean age 35.6[11]). 92 were diagnosed with bronchial asthma and 41 (30.8%) with other pathologies; post-nasal drip being the most frequent. Of the 92 patients with asthma, 61 had a positive BD test (66.3% of those with asthma, 45.8% of the total). Of the 31 cases with a negative BD test, the diagnosis was reached using the challenge test. Patients with a positive BD test showed greater severity, with functional affection and poorer asthma control, a greater accumulated prevalence of tobacco, with males being a higher percentage. Cases with a negative test presented FENO values >30 ppb in 19% of the cases. CONCLUSIONS: in previously untreated patients, the BD test was positive in a higher percentage of patients, with them showing more serious pathologies and worse control. In negative cases, it could be useful to determine the FENO level. More than 30% of the referral patients suspected of having asthma were, in the end, diagnosed with other pathologies, including post-nasal drip

Monitoring lung aeration during respiratory support in preterm infants at birth.

BACKGROUND: If infants fail to initiate spontaneous breathing, resuscitation guidelines recommend respiratory support with positive pressure ventilation (PPV). The purpose of PPV is to establish functional residual capacity and deliver an adequate tidal volume (VT) to achieve gas exchange. OBJECTIVE: The aim of our pilot study was to measure changes in exhaled carbon dioxide (ECO2), VT, and rate of carbon dioxide elimination (VCO2) to assess lung aeration in preterm infants requiring respiratory support immediately after birth. METHOD: A prospective observational study was performed between March and July 2013. Infants born at <37 weeks gestational age who received continuous positive airway pressure (CPAP) or PPV immediately after birth had VT delivery and ECO2 continuously recorded using a sensor attached to the facemask. RESULTS: Fifty-one preterm infants (mean (SD) gestational age 29 (3) weeks and birth weight 1425 (592 g)) receiving respiratory support in the delivery room were included. Infants in the CPAP group (n = 31) had higher ECO2 values during the first 10 min after birth compared to infants receiving PPV (n = 20) (ranging between 18-30 vs. 13-18 mmHg, p<0.05, respectively). At 10 min no significant difference in ECO2 values was observed. VT was lower in the CPAP group compared to the PPV group over the first 10 min ranging between 5.2-6.6 vs. and 7.2-11.3 mL/kg (p<0.05), respectively. CONCLUSIONS: Immediately after birth, spontaneously breathing preterm infants supported via CPAP achieved better lung aeration compared to infants requiring PPV. PPV guided by VT and ECO2 potentially optimize lung aeration without excessive VT administered.

Lung clearance index during hospital admission in school-age children with cystic fibrosis.

BACKGROUND: There is currently limited information regarding lung clearance index (LCI) and its response to treatment of pulmonary exacerbations in CF. We aimed to examine the utility of LCI for assessing short term clinical response to IV antibiotic therapy in school-age children with CF. METHODS: Subjects experiencing exacerbations and hospitalised for IV antibiotics performed both multiple breath nitrogen washout (MBNW) and spirometry on admission to hospital and prior to discharge. RESULTS: 27 patients (aged 6-20 years) had paired data for MBNW and spirometry. Mean LCI reduced from 12.18 to 11.65 (4.4%) by time of discharge and FEV1z-score improved from -3.05 to -2.86 (6.2%). Overall, LCI improved in n=15 (55%) patients compared with n=18 (67%) where FEV1 improved. CONCLUSIONS: In summary, these findings do not support the use of LCI (or indeed, FEV1) to gauge the short term clinical response to IV antibiotic therapy in school-age children with cystic fibrosis.