Air pollution and lung function among susceptible adult subjects: a panel study

BACKGROUND: Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. METHODS: Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM(10–2.5)) and fine (PM(2.5)) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO(2)), carbon monoxide (CO), ozone (O(3)), and sulphur dioxide (SO(2)) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. RESULTS: Decrements in lung function indices (FVC and/or FEV(1)) associated with increasing concentrations of PM(2.5), NO(2 )and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO(2 )was associated with a decrease in FEV(1). No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. CONCLUSION: This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function of the relatively young and mild asthmatics included in this study seems to worsen when ambient levels of NO(2 )increase

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7

Air quality and emergency pediatric care for symptoms of bronchial obstruction categorized by age bracket in Rio de Janeiro, Brazil Qualidade do ar e atendimentos pediátricos de emergência por sintomas de obstrução brônquica categorizados por faixas etárias no Rio de Janeiro, Brasil

The objective of this study was to estimate the association between levels of air pollutants and respiratory symptoms in children. An ecological time-series study was conducted between April 2002 and March 2003 with daily data on PM10, SO2, CO, NO2, and O3 and paediatric care in emergency rooms due to symptoms indicating bronchial obstruction. The potential confounding factors considered were: time trend, seasonality, meteorological variables, respiratory infections and the effects of weekends and holidays. A semi-parametric Poisson regression was used to model the time series. Splines (data smoothing functions), indicator variables and cubic polynomials were used to adjust the effects of the confounding variables. A 5% significance level was adopted for the study. A statistically significant increase of 6.7% in paediatric visits of children of less than 2 years of age was associated with PM10. A 3% positive association with O3 showed borderline significance (p < 0.06) in this age bracket. Our findings highlight the existence of an acknowledged public health problem in Rio de Janeiro, Brazil, and also emphasize the need to identify the principal sources of air pollutants.<br>O objetivo deste trabalho foi estimar a associação entre os níveis dos poluentes atmosféricos e sintomas respiratórios em crianças. Foi realizado um estudo ecológico de séries temporais, entre abril de 2002 e março de 2003, com dados diários de PM10, SO2, CO, NO2 e O3 e dos atendimentos pediátricos de emergência ocasionados por sintomas de obstrução brônquica. As variáveis de confusão foram: tendência temporal, sazonalidade, fatores meteorológicos, infecções respiratórias e os efeitos dos finais de semana e feriados. Regressão de Poisson semiparamétrica foi usada para modelar as séries temporais. Curvas suaves, splines, variáveis indicadoras e polinômios cúbicos foram empregadas para corrigir os efeitos dos fatores de confundimento. Foi adotado o nível de significância de 5%. Um incremento estatisticamente significativo dos atendimentos, de 6,7%, esteve associado com PM10 nas crianças menores do que dois anos. Associação positiva com o O3, em torno de 3%, nessa faixa etária, teve significado estatístico limítrofe (p < 0,06). Esses resultados evidenciam um problema de saúde pública não reconhecido no Rio de Janeiro, Brasil, que reforça a necessidade de identificação das principais fontes de poluição

Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity, and Inflammation in Adult Females

We previously observed greater ozone-induced lung function decrements in obese than non-obese women. Animal models suggest that obesity enhances ozone-induced airway reactivity and inflammation. In a controlled exposure study, we compared the acute effect of randomized 0.4ppm ozone and air exposures (2 h with intermittent light exercise) in obese (N = 20) (30<BMI<40Kg/m2) vs. non-obese (N = 20) (BMI<25Kg/m2) non-smoking 18–35 year old women. We measured spirometry and bronchial reactivity to inhaled methacholine (3h post-exposure). Inflammation and obesity markers were assessed in the blood (pre, 4h post, and 20h post exposures) and induced-sputum (4h post-exposures and on 24h pre-exposure training day, no exercise): measures of C reactive protein (CRP) (blood only), leptin (blood only), adiponectin, interleukins IL-6, IL-1b, and IL-8, and tumor necrosis factor alpha, and sputum cell differential cell counts. The pre- to post-exposure decrease in forced vital capacity after ozone (adjusted for the change after air exposure) was significantly greater in the obese group (12.5+/-7.5 vs. 8.0+/-5.8%, p<0.05). Post ozone exposure, 6 obese and 6 non-obese subjects responded to methacholine at ≤ 10mg/ml (the maximum dose); the degree of hyperresponsiveness was similar for the two groups. Both BMI groups showed similar and significant ozone-induced increases in sputum neutrophils. Plasma IL-6 was increased by exercise (4 hr post air exposure vs. pre) only in the obese but returned to pre-air exposure levels at 20hr post-exposure. Plasma IL-6 was significantly increased at 4hr post ozone exposure in both groups and returned to pre-exposure levels by 20h post-exposure. These results confirm our previous findings of greater post-ozone spirometric decrements in obese young women. However, acute ozone-induced airway reactivity to methacholine and airway inflammation did not differ by obesity at the exposure and exercise levels used

Methodology in the epidemiological research of respiratory diseases and environmental pollution Metodologia na pesquisa epidemiológica de doenças respiratórias e poluição ambiental

There are complex and diverse methodological problems involved in the clinical and epidemiological study of respiratory diseases and their etiological factors. The association of urban growth, industrialization and environmental deterioration with respiratory diseases makes it necessary to pay more attention to this research area with a multidisciplinary approach. Appropriate study designs and statistical techniques to analyze and improve our understanding of the pathological events and their causes must be implemented to reduce the growing morbidity and mortality through better preventive actions and health programs. The objective of the article is to review the most common methodological problems in this research area and to present the most available statistical tools used.<br>Existem problemas metodológicos diversos e complexos envolvidos no estudo clínico e epidemiológico de doenças respiratórias e seus fatores etiológicos. A associação do crescimento urbano, da industrialização e da deterioração ambiental com as doenças respiratórias torna necessário focalizar a atenção a esse campo de estudo com uma abordagem multidisciplinar. Devem ser implementados modelos de estudo e técnicas estatísticas adequadas para analisar e melhorar o entendimento sobre os eventos patológicos e suas causas e para reduzir a crescente morbimortalidade fazendo uso de medidas preventivas e melhores programas de saúde. O objetivo do artigo é revisar os problemas metodológicos mais comuns nessa área de pesquisa e apresentar os métodos estatísticos usados de maior acesso

Common and Rare EGFR and KRAS Mutations in a Dutch Non-Small-Cell Lung Cancer Population and Their Clinical Outcome

<p>Introduction: In randomly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI.</p><p>Patient and Methods: Clinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18-21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis.</p><p>Results: Tumors from 442 subsequent patients were analyzed. For 74 patients (17%) tumors were unsuitable for mutation analysis. Thirty-eight patients (10.9%) had EGFR mutations with 79% known activating mutations. One hundred eight patients (30%) had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR (n = 14), KRAS (n = 14) mutations and wild type EGFR/KRAS (n = 31) was not reached, 20 and 9 months, respectively.</p><p>Conclusion: One out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival.</p>