Toll-like receptor expression in smokers with and without COPD

SummaryIntroductionChronic obstructive pulmonary disease (COPD) is characterized by non-reversible airflow limitation and systemic engagement. Bacterial colonization in the lungs is common in COPD-patients and may be associated with frequent acute exacerbations. Pattern-recognition receptors (PRRs), like Toll-like receptor 2 (TLR2), TLR4 and CD14 are expressed on most immunologic active cell types and are most likely of importance in COPD patho-physiology.Material and methodsTwenty smokers with and 20 without COPD and 20 healthy non-smokers participated in the study. At two visits, induced sputum was collected after spirometry, blood was sampled and bronchoscopy with bronchoalveolar lavage was performed. Expression of TLR2, TLR4 and CD14 on different cell types and soluble receptors were assessed in the different compartments.ResultsExpression of TLR2 was lower on sputum neutrophils and soluble TLR2 (sTLR2) was higher in the supernatant in the COPD group, indicating a down regulation of TLR2 at the transit from blood to sputum. Expression of CD14 on sputum neutrophils and gene expression of CD14 on alveolar macrophages was up-regulated in the two smoking groups compared with non-smokers. No differences between the groups were found regarding TLR4 expression.ConclusionsPattern-recognition receptors (PRRs), that are expected to make a first line of defense against invading micro-organisms, are differently regulated in smokers with COPD compared with smokers without airflow limitation and non-smokers. This is likely of importance in COPD patho-physiology, in particular for exacerbations, which often are caused by micro-organisms

Genomgång och strategisk utvärdering av HÄMI-serien ”Cancerframkallande ämnen i tätortsluft”

Institutet för Miljömedicin har av Naturvårdsverket fått i uppdrag att genomföra en strategisk utvärdering av HÄMI-serien ”Cancerframkallande ämnen i tätortsluft”. För att genomföra utvärderingen har vi studerat samtliga mätrapporter som publicerats inom projektet, gjort litteratursökning gällande vetenskapligt publicerade artiklar och grå litteratur, samt genomfört en semi-strukturerad intervju med samtliga utförare inom projektet. Utvärderingen har framförallt fokuserat på: lokalisering och omfattning av ingående städer, antal och urval av individer som ska ingå i studien, kvalitetssäkring av analysmetodik och jämförbarheten av analyser vid olika laboratorier, synligheten av projektet som helhet och en genomgång av möjliga nya ämnen och provtagningsmetoder som skulle kunna ingå. Baserat på detta ges ett fåtal rekommendationer för seriens utveckling och revidering. Våra slutsatser kan sammanfattas som att det finns goda förutsättningar för att synliggöra projektet bättre genom att sammanställa och publicera tidstrendsanalyser och populärvetenskapliga rapporter på NV’s hemsida. Dessutom bör NV överväga vikten av slumpartat urval av tvärsnittsbefolkningen vid rekrytering av deltagare då deltagarfrekvensen systematiskt minskat till ca 30%, alternativt bör man införa viktningsfaktorer så att deltagarnas svar följer den nationella proportionen av befolkningen, vilket är av särskild vikt för rökning. Vidare bör nyttan av upprepade mätningar sättas i förhållande till möjlighet att med dessa resurser utföra pumpad provtagning för black carbon (sot) för att få tidsupplöst information om förbränningspartiklar genererade av trafik, istället för att fortsätta mäta NO2, vilket inom projektet inte visat sig vara den proxy som man önskat för trafikrelaterade luftföroreningar. Inkludering av black carbon medger att en annan viktig faktor för befolkningens hälsa kan mätas, även om den ännu inte är klassad som cancerframkallande av IARC

Heated Tobacco Products: Insights into Composition and Toxicity

Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have reported short-term pathophysiological effects of HTP use. Currently available HTP toxicity data are mainly on the pulmonary and cardiovascular systems. Moreover, there are no long-term toxicity data and, therefore, the claims of the tobacco industry regarding HTPs as a safer alternative to traditional combustible cigarettes are unsubstantiated. Furthermore, HTP aerosol contains the highly addictive substance nicotine, which is harmful to the adolescent brain, developing foetuses, pregnant women, and also adults. Hence, comprehensive studies addressing the safety profiling related to long-term HTP use are warranted. With this background, the following review summarizes the current state of knowledge on HTP toxicity on four broad lines: composition of mainstream HTP aerosol compared to traditional combustible cigarette smoke, biomarkers of HTP exposure, health effects of HTP exposure, and the harm reduction aspect

Concentration of sST2 in serum before and after exposure in a pig barn and a LPS challenge.

<p>Concentration of sST2 in serum before and after exposure in a pig barn and a LPS challenge in 11 farmers and 12 healthy non-exposed control subjects. Horizontal lines indicate median values. § indicate p<0.05 for pre- and post-exposure comparisons.</p

Concentration of sTLR2 and sCD14 in sputum and correlation between sputum sCD14 and TLR4 expression on blood neutrophils.

<p>Concentration of sTLR2 (A) and sCD14 (B) in sputum (controls n = 14 and farmers n = 14). P-values indicate differences between the farmers and controls. A negative correlation between sputum sCD14 and TLR4 expression on blood neutrophils (C), and a positive correlation between sCD14 and macrophages number in sputum in farmers (D).</p

Cadmium in tobacco smokers: a neglected link to lung disease?

Cadmium in tobacco smoke may contribute to the development of pulmonary emphysema. However, there is poor understanding of the mechanisms behind the pathogenic role of cadmium in this and other smoking-related lung diseases. The traditional focus on the total body burden of cadmium, estimated through analysis of urine, may not fully reflect the local burden of cadmium, since it is inhaled by smokers. Thus, assessing the local accumulation of cadmium in the lungs appears more relevant, given that there is tissue-specific retention of cadmium. In this review, we outline the principal sources of cadmium exposure and the clinical effects of occupational exposure. In addition, we review evidence on local cadmium and its association with alterations in innate immunity in tobacco smokers. Moreover, we scrutinise the data on cadmium as a cause of lung disease in translational models. We conclude that cadmium may contribute to smoking-related lung diseases, possibly via an altered redox balance and by making macrophages dysfunctional. However, there is a need for new studies on local cadmium levels and their relation to pathology in long-term tobacco smokers, as well as for more in-depth studies on cellular and molecular mechanisms, to elucidate the importance of cadmium in smoking-related lung diseases

Release of IL-6 and TNF after <i>ex vivo</i> stimulation of peripheral blood.

<p>Release of IL-6 and TNF after <i>ex vivo</i> stimulation of peripheral blood with TNF, LPS, Pam3Cys or pig barn dust (controls n = 13 and farmers n = 14). § indicates p<0.05 and ‡ indicates p<0.01 compared with medium control.</p