Indoor Radon in EGFR- and BRAF-Mutated and ALK-Rearranged Non-Small-Cell Lung Cancer Patients.

BACKGROUND: Radon gas is the leading cause of lung cancer in the nonsmoking population. The World Health Organization (WHO) recommends indoor concentrations of < 100 Bq/m³. Several molecular alterations have been described in non-small-cell lung cancer (NSCLC), mainly in nonsmokers, with no risk factors identified. We studied the role of indoor radon in NSCLC patients harboring specific driver alterations. PATIENTS AND METHODS: We assessed the radon concentration from EGFR-, BRAF-mutated (m), and ALK-rearranged (r) NSCLC patients measured by an alpha-track detector placed in their homes between September 2014 and August 2015. Clinical characteristics were collected prospectively, and pathologic samples were reviewed retrospectively. RESULTS: Forty-eight patients were included (36 EGFRm, 10 ALKr, 2 BRAFm). Median radon concentration was 104 Bq/m³ (IQR 69-160) overall, and was 96 Bq/m³ (42-915) for EGFRm, 116 (64-852) for ALKr, and 125 for BRAFm, with no significant differences. Twenty-seven patients (56%) had indoor radon above WHO recommendations, 8 (80%) of 10 ALKr, 2 (100%) of 2 BRAFm, and 17 (47%) of 36 EGFRm. CONCLUSION: The median indoor radon concentration was above the WHO recommendations, with no differences between EGFR, ALK, and BRAF patients. Concentrations above the WHO recommendations were most common with ALKr and BRAFm. These findings should be validated in larger studies.

Estimating the economic consequences of an increased medication adherence due to a potential improvement in the inhaler technique with Spiromax® compared with Turbuhaler® in patients with moderate-to-severe chronic obstructive pulmonary disease in Spain.

OBJECTIVE: The objective of this study was to estimate the economic impact of the introduction of DuoResp® Spiromax®, budesonide/formoterol fixed-dose combination (FDC), focusing on an increase in medication adherence due to an enhancement of the inhalation technique for the treatment of COPD patients in Spain and 5 regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the time period of 2015-2018. This study aimed at evaluating the budget impact associated with the introduction of DuoResp Spiromax in comparison with Symbicort® Turbuhaler® and Rilast® Turbuhaler. National and regional data on COPD prevalence were obtained from the literature. Input data on health care resource utilization were obtained by clinical consultation. Resource included primary care visits, specialist visits, hospitalization, and emergency room visits as well as the length of hospital stay. Based on both pharmacological and health care resource costs, overall annual treatment cost per patient was estimated in EUR 2015. RESULTS: It was calculated that 130,777 adults were treated with budesonide/formoterol FDC delivered by a dry powder inhaler, Turbuhaler, in Spain in 2015. However, the target population decreases over the next 4 years. This pattern was observed in 4 regions, but for Andalusia, the treated population increased slightly. The overall budget savings in Spain with the market share of DuoResp Spiromax were estimated to be €6.01 million for the time period of 2015-2018. Region-specific data resulted in savings of €902,133 in Andalusia, €740,520 in Catalonia, €464,281 in Galicia, €748,996 in Madrid, and €495,812 in Valencia for the time period of 2015-2018. CONCLUSION: The introduction of budesonide/formoterol FDC delivered by Spiromax for COPD treatment is likely to contribute in a reduction of health care costs for Spain and in 5 Spanish regions. This model forecasts that Spain and these 5 Spanish regions were likely to have savings, which might be due to fewer days of hospitalization, avoided emergency room, and primary care visits.

Risk Factors of Poor Outcomes after Admission for a COPD Exacerbation: Multivariate Logistic Predictive Models.

The aim of this study was to identify a multivariate model to predict poor outcomes after admission for exacerbation of chronic obstructive pulmonary disease (COPD).  We performed a multicenter, observational, prospective study. Patients admitted to hospital for COPD were followed up for 3 months. Relevant clinical variables at admission were selected. For each variable, the best cut-offs for the risk of poor outcome were identified using receiver operating characteristic (ROC) curves. Finally, a stepwise logistic regression model was performed. A total of 106 patients with a mean age of 71.1 (9.8) years were included. The mean maximum expiratory volume in the first second (FEV1)(%) was 45.2%, and the mean COPD assessment test (CAT) score at admission was 24.8 (7.1). At 3 months, 39 (36.8%) patients demonstrated poor outcomes: death (2.8%), readmission (20.8%) or new exacerbation (13.2%). Variables included in the logistic model were: previous hospital admission, FEV1 < 45%, Charlson ≥ 3, hemoglobin (Hb)<13 g/L, PCO2 ≥ 46 mmHg, fibrinogen ≥ 554 g/L, C-reactive protein (CRP)≥45 mg/L, leukocyte count < 9810 × 109/L, purulent sputum, long-term oxygen therapy (LTOT) and CAT ≥ 31 at admission. The final model showed that Hb < 13 g/L (OR = 2.46, 95%CI 1.09-6.36), CRP ≥ 45 mg/L (OR = 2.91, 95%CI: 1.11-7.49) and LTOT (3.07, 95%CI: 1.07-8.82) increased the probability of poor outcome up to 82.4%. Adding a CAT ≥ 31 at admission increased the probability to 91.6% (AUC = 0.75; p = 0.001). Up to 36.8% of COPD patients had a poor outcome within 3 months after hospital discharge, with low hemoglobin and high CRP levels being the risk factors for poor outcome. A high CAT at admission increased the predictive value of the model.

Factores asociados a la hospitalización por exacerbación de la enfermedad pulmonar obstructiva crónica / Factors associated with hospital admission for exacerbation of chronic obstructive pulmonary disease

Introducción: Las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EPOC) que precisan ingreso hospitalario tienen un gran impacto en la progresión de la enfermedad y generan un alto gasto sanitario. Método: Se trata de un estudio observacional, multicéntrico y transversal, con el objetivo de identificar los factores asociados a las hospitalizaciones por exacerbaciones de la EPOC. Se obtuvieron variables sociodemográficas, antropométricas, de calidad de vida, síntomas respiratorios, presencia de ansiedad y depresión, actividad física y pruebas de función pulmonar. Se analizó su asociación con el ingreso hospitalario mediante análisis multivariante con un modelo de regresión logística. Resultados: Se analizaron 127 pacientes, 50 (39%) de los cuales habían sido hospitalizados. El 93,7% fueron hombres, con una edad media de 67 años (DE=9) y un FEV1 del 41,9% (DE=15,3). En el primer modelo obtenido, la SpO2 basal, el índice BODE y las visitas a urgencias se asociaron con el ingreso, y el área bajo la curva (ABC) ROC fue de 0,809. En un segundo modelo incluimos solo variables de fácil obtención (sin la prueba de la marcha), y solo la SpO2 y las visitas previas a urgencias fueron significativas, con un ABC ROC de 0,783. Conclusiones: El ingreso hospitalario por exacerbación de la EPOC se asocia a peor SpO2, mayor puntuación del índice BODE y un mayor número de visitas al servicio de urgencias. En caso de no disponer de la prueba de caminar 6min, las otras dos variables ofrecen una capacidad discriminativa similar(AU)

Introduction: Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) that require hospital admission have a major impact on the progression of disease and generate high health costs. Method: A multi-center, cross-sectional, observational, study was conducted with the aim to identify factors associated with hospital admission in patients with COPD. We obtained data of socio-demographic and anthropometric characteristics, quality of life, respiratory symptoms, anxiety and depression, physical activity and pulmonary function tests. We analyzed their association with hospital admission with a multivariate analysis using a logistic regression model. Results: We analyzed 127 patients, 50 (39%) of whom had been hospitalized. 93.7% were men, mean age 67 years (SD=9) and a FEV1 of 41.9% (SD=15.3). In the first model obtained, the baseline SpO2, the BODE index and emergency room (ER) visits were associated with hospital admission and the area under the ROC curve (AUC) was 0.809. In a second model we included only variables readily available (without the 6 minutes walking test) and only the SpO2 and previous visits to the ER were significant with an AUC ROC 0.783. Conclusions: hospital admission for exacerbation of COPD is associated with poor SpO2, higher BODE index score and a greater number of visits to the ER. In case you do not have the 6 minutes walking test, the other two variables offer a similar discriminative ability(AU)

Factors associated with hospital admission for exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) that require hospital admission have a major impact on the progression of disease and generate high health costs. METHOD: A multi-center, cross-sectional, observational, study was conducted with the aim to identify factors associated with hospital admission in patients with COPD. We obtained data of socio-demographic and anthropometric characteristics, quality of life, respiratory symptoms, anxiety and depression, physical activity and pulmonary function tests. We analyzed their association with hospital admission with a multivariate analysis using a logistic regression model. RESULTS: We analyzed 127 patients, 50 (39%) of whom had been hospitalized. 93.7% were men, mean age 67 years (SD=9) and a FEV1 of 41.9% (SD=15.3). In the first model obtained, the baseline SpO(2), the BODE index and emergency room (ER) visits were associated with hospital admission and the area under the ROC curve (AUC) was 0.809. In a second model we included only variables readily available (without the 6 minutes walking test) and only the SpO(2) and previous visits to the ER were significant with an AUC ROC 0.783. CONCLUSIONS: hospital admission for exacerbation of COPD is associated with poor SpO(2), higher BODE index score and a greater number of visits to the ER. In case you do not have the 6 minutes walking test, the other two variables offer a similar discriminative ability.

Tumor necrosis factor alpha as a marker of systemic and local inflammation in "healthy" smokers.

BACKGROUND: Tobacco smoking induces a local and systemic inflammatory reaction and also a decline in pulmonary function. There are some novel noninvasive methods to measure the degree of inflammatory bronchial reaction, including the exhaled breath condensate (EBC) in which several inflammatory markers can be measured, including tumor necrosis factor alpha (TNF-alpha). There is a clear clinical need to develop methods that allow early detection of smokers at risk of losing pulmonary function. OBJECTIVES: THE AIMS OF THE PRESENT STUDY ARE: 1) to show that smokers show higher levels of TNF-alpha both in serum and EBC; 2) to analyze the possible influence of gender, age, and weight on this parameter; and 3) to determine a possible association between smoking and pulmonary function parameters and TNF-alpha levels. MATERIAL AND METHODS: We have prospectively analyzed two cohorts of smokers and non-smokers subjects without any chronic or acute disease (within eight weeks of study initiation). We have performed pulmonary function tests with bronchodilators and also collected EBC and blood samples before smoking cessation. Statistical analysis was performed with SPSS 11.0 for Windows Statistical Package. RESULTS: The study has enrolled 17 patients (8 smokers), 50% of whom were females. Mean age was 38.59 years old (standard deviation, 7.4). The mean number of cigarettes smoked in the smoker group was 26.14 (11.29) cigarettes/day and the mean age when tobacco first began was 15.14 (2.04) years. We have not been able to show any significant differences in TNF-alpha levels according to age or weight. For the whole series we have not found any significant influence of gender in TNF-alpha levels, but after dividing the series in smokers and nonsmokers, we have shown higher levels of TNF-alpha in serum (5.59 [0.26] pg/mL vs 5.56 [0.37] pg/mL; nonsignificant [NS]) and EBC (4.94 [0.41] pg/mL vs 4.22 [0.36] pg/mL; p = 0.031) in male smokers. On the other hand, nonsmoking females showed slightly higher TNF-alpha levels in serum (5.70 [0.50] pg/mL vs 5.42 [0.29] pg/mL; NS) and EBC (4.54 [0.92] vs 4.11 [0.41 pg/mL]; NS). Smokers had higher TNF-alpha levels in EBC (4.46 [0.58] pg/mL vs 4.34 [0.62] pg/mL; NS), while serum TNF-alpha levels were slightly higher in nonsmokers (5.52 [0.56] pg/mL vs 5.50 [0.27] pg/mL; NS). We have not demonstrated any association between tobacco consumption and TNF-alpha levels. We have not shown any significant relation between pulmonary function and the studied parameters, with only a modest association between forced expiratory volume at one second and forced vital capacity and TNF-alpha levels in EBC. CONCLUSION: Smokers show higher TNF-alpha levels in EBC. Among smokers, males show higher levels of TNF in serum and EBC. We have not confirmed any significant influence of age or weight on TNF-alpha levels. These levels do not seem to be influenced either by the amount of tobacco or the time since habit began. We have shown a modest relation between pulmonary function and TNF-alpha levels in EBC.