Nasal and bronchial airway reactivity in allergic and non allergic airway inflammation

In allergic or asthmatic airways disease, upper and lower airways show a uniform eosinophilic inflammation of the mucosa, and bronchial hyperreactivity is a common finding. To study the co- variation of mucosal reactivity in upper and lower airways, histamine challenges of both sites were performed in a group of patients with allergic rhinitis during non-season. Upper airways were monitored during challenge by the use of rhinostereometry, an optical technique that non-invasively measures nasal mucosa swelling. An increased histamine response was found in both nose and bronchi, and a subgroup of patients with non-specific nasal complaints reacted more strongly to histamine than patients without such problems, indicating that some patients with allergic rhinitis develop a permanent nasal hyperreactivity. By contrast, in patients with nasal polyposis, the nasal mucosa was non-reactive to histamine and thus did not differ from healthy volunteers in that respect, even though asthma and bronchial hyperreactivity was a common finding. Hence, although upper and lower airways mostly seem to react uniformly in allergic or asthmatic airway disease, non-specific reactivity may differ between the two sites. However, airway hyperreactivity was not restricted to the eosinophilic type of inflammation. Also in healthy volunteers exposed to swine dust by weighing pigs for 3 hours in a swine confinement building, a procedure known to induce an intense neutrophilic airway inflammation (organic dust toxic syndrome), both nasal and bronchial histamine reactivity were found to increase. In swine dust induced inflammation, neutrophils were found to rapidly migrate into the upper airways as detected by nasal lavage. Hence, there was reason to believe that the endothelial cells might be activated in this condition, and that endothelial cells, known controllers of leukocyte subset migration, also might influence the induction of airway hyperreactivity. Additional studies on swine dust exposed subjects revealed signs of activation of neutrophil/endothelial cell responses, i.e. changes of soluble adhesion levels, IL-8 and nitrate in peripheral blood. To further elucidate the role of endothelial cells in this type of inflammation, in vitro experiments were performed. Human umbilical vein endothelial cells were cultured and subsequently incubated with a swine dust extract. Cytokine secretion, expression of surface adhesion molecules and neutrophil adherence increased following swine dust stimulation, indicating that this dust directly induces neutrophil/endothelial cell interactions of importance for neutrophil accumulation in the airways

Optimizing diffusion-weighted magnetic resonance imaging for evaluation of lung tumors: A comparison of respiratory triggered and free breathing techniques

Purpose: The aim of this study was to compare respiratory-triggered (RT) and free breathing (FB) diffusion weighted imaging (DWI) techniques regarding apparent diffusion coefficient (ADC) measurements and repeatability in non-squamous non-small cell lung cancer (NSCLC) measuring the total tumor volume. Material and Methods: A total of 57 magnetic resonance imaging (MRI) examinations were analyzed. DWI was obtained by a single-shot spin-echo echo-planar imaging sequence, and for each MRI examination 2 consecutive RT and 2 consecutive FB DWI sequences were performed. Two radiologists independently read the images and made measurements. For each tumor the mean ADC value of the whole tumor volume was calculated. The difference in mean ADCs between FB and RT DWI was evaluated using the paired-sample t-test. The repeatability of ADC measurements related to imaging method was evaluated by intra class correlations (ICC) for each of the FB and RT DWI pairs. Results: There were no significant differences in mean ADCs between FB and RT (Reader 1 p = 0.346, Reader 2 p = 0.583). The overall repeatability of ADC measurement was good for both acquisition methods, with ICCs > 0.9. Subgroup analysis showed somewhat poorer repeatability in small tumors (50 ml or less) and tumors in the lower lung zones for the RT acquisition, with ICC as low as 0.72. Conclusions: No difference in ADC measurement or repeatability between FB and RT DWI in whole lesion ADC measurements of adenocarcinomas in the lung was demonstrated. The results imply that in this setting the FB acquisition method is accurate and possibly more robust than the RT acquisition technique. Key words: Magnetic resonance imaging, Diffusion weighted imaging, non-Small cell lung cance

Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma

Abstract Background Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR and rearrangement in the ALK genes identify specific subgroups of patients. Aim of this study was to investigate the role of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status on the risk of venous thromboembolism (VTE) in lung adenocarcinoma. Methods A retrospective longitudinal design was used. Patients with lung adenocarcinoma diagnosed and undergoing a mutational analysis at the Karolinska University Hospital, Stockholm, Sweden between January 2009 and September 2015 were divided in three subgroups based on their mutational status (EGFR-, ALK-mutated, unexposed group). Event-free time for VTE was assessed using Cox regression analysis based on mutation status and treatment received. Results Three hundred-ten patients were included. A VTE occurred in 70 (22.6%) patients. Mutation of EGFR was associated with a decreased risk of VTE (HR 0.46, 95% CI 0.23–0.94). Treatment with tyrosine kinase inhibitors (TKI) reduced the risk of VTE compared to other treatment strategies not including TKI (HR 0.42, 95% CI 0.29–0.79). Conclusions Our study suggests that patients with lung adenocarcinoma bearing a EGFR-mutation have a decreased risk of VTE compared with patients with other forms of lung adenocarcinoma. Targeted therapy with TKI alone or in combination with other treatments seems to reduce the risk of VTE compared to other treatments not including TKI

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007.

BACKGROUND: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. METHODS: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. RESULTS: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. CONCLUSIONS: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved