Varhainen hengitystiesairaus nuorilla ja keski-ikäisillä tupakanpolttajilla

Chronic obstructive pulmonary disease (COPD) is an under-diagnosed and life-threatening progressive disease. Early symptoms of COPD include excessive sputum production and chronic cough. The primary risk factor of this disease in the western world is smoking. COPD is confirmed by spirometry, which does not totally reveal reversible airway obstruction. This study, conducted mainly in the Northern Finland, aimed to assess 1) smoking habits and smoking cessation in healthy middle-aged and young adults, 2) the prevalence of COPD and role of spirometry and prolonged respiratory symptoms in the diagnosis of COPD of smoking middle-aged adults, 3) the association of symptoms of chronic bronchitis with smoking habits in young adult males, and 4) to seek and to identify new potential biomarkers related to early COPD using non-hypothesis driven non-biased proteomics. A two-year prospective study included two visits to evaluate symptoms in healthy cigarette smokers, to screen new COPD cases and to assess the success of smoking cessation using motivational counselling and pharmacological therapies. In addition, a quantitative cross-sectional questionnaire survey was conducted in 1163 male conscripts during their military service in Northern Finland. A lung tissue proteomic approach was used to identify new COPD biomarkers. Spirometry revealed COPD by GOLD criteria in 11,0% and by national criteria in 15.3 % of originally asymptomatic chronic smokers. Further, chronic cough or sputum production was detected in 62.0% of the participants. After two years, 23.3% of adults had succeeded in quitting smoking. In young adults, 46.5% were daily smokers. The prevalence of self-reported chronic cough and sputum production was high in daily smokers (40.7%). The majority (60.2%) of the daily young smokers had made quit attempts and 46.9% of them had used nicotine replacement therapy (NRT). Based on the lung tissue proteomics, surfactant protein A (SP-A) was one of the most highly elevated spots in the COPD lung. The plasma SP-A concentration was higher both in chronic smokers and in COPD as compared to the non-smokers, and declined significantly during 2-year follow-up in those who succeeded to quit smoking compared to those who continued to smoke. To conclude there is remarkable burden of chronic bronchitis and COPD in the groups of chronic smokers who considered themselves as healthy. Motivational counselling seems to be successful, since over 23% of the adult smokers succeeded in stopping smoking. SP-A is a potential new biomarker for COPD although it needs further evaluation.Keuhkoahtaumatauti on kansantauti, jonka tärkein riski tekijä länsimaissa on tupakointi. Osa keuhkoahtaumatautia potevista on oireettomia, mutta tupakoijien pitkittynyt yskä ja sitkeä limaneritys saattavat viitata joko krooniseen keuhkoputkitulehdukseen tai keuhkoahtaumatautiin. Keuhkoahtaumatauti varmennetaan spirometria -tutkimuksella, jossa todetaan avaavalla lääkkeellä pääosin laukeamaton ahtauttava uloshengityksen tuuletusvaje. Tämän pääosin Pohjois-Suomessa tehdyn tutkimuksen kohdejoukkona olivat tupakoivat keski-ikäiset aikuiset ja tupakoivat varusmiehet. Tutkimuksessa selvitettiin 1) keuhkoahtaumataudin esiintyvyyttä päivittäin tupakoivien aikuisten keskuudessa, 2) kroonisen keuhkoputkitulehduksen oireiden esiintyvyyttä tupakanpolttajien keskuudessa, 3) tutkittavien onnistumista tupakoinnin lopettamisessa ja 4) löytöihin perustuvan proteomiikan keinoin mahdollisia keuhkoahtaumatautiin liittyviä biologisia merkkiaineita. Tutkittavista runsaalla kymmenellä prosentilla todettiin keuhkoahtaumatauti käyttäen kansainvälisiä ja kansallisia kriteereitä. Lisäksi 62 %:lla oli pitkittynyttä yskää ja/tai limaneritystä. Kahden vuoden seurannassa joka viides keski-ikäisistä tutkittavista (23,3 %) lopetti tupakoinnin. Kaiken kaikkiaan liki puolet (46,5 %) varusmiehistä olivat päivittäistupakoijia ja melkein joka toisella heistä (40,7 %) esiintyi pitkittynyttä yskää ja limaneritystä. Huomattava osa tupakoivista varusmiehistä oli tehnyt lopetusyrityksiä (60,2 %) ja 46,9 % heistä oli käyttänyt nikotiinikorvaustuotteita lopetusyrityksissään. Keuhkokudoksen proteomiikkaan perustuvien tutkimusten mukaan surfaktantti proteiini A (SP-A) on mahdollinen keuhkoahtaumatautiin liittyvä biomerkkiaine. Kohonneita SP-A pitoisuuksia todettiin keuhkoahtaumatautia potevien ysköksissä verrattuna vastaaviin kontrollinäytteiden pitoisuuksiin. Pitkään tupakoineiden tai keuhkoahtaumatautia potevien tutkittavien plasman SP-A pitoisuus oli korkeampi kuin vastaava pitoisuus tupakoimattomilla. Plasman SP-A pitoisuus laski tupakointinsa kahden vuoden seuranta-aikana lopettaneilla verrattuna tupakointiaan jatkavien vastaaviin arvoihin. Kroonisen keuhkoputkitulehdukseen viittaavat oireet ja keuhkoahtaumatauti ovat erittäin yleisiä itsensä oireettomaksi tuntevillakin pitkään tupakoineilla henkilöillä

Soluble receptor for advanced glycation end-products and progression of airway disease

Peer reviewe

Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction : A Prospective Study in Smokers with COPD

Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions. Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up. Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.Peer reviewe

Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction

Background: A significant number of young people start smoking at an age of 13-15, which means that serious smoking-evoked changes may have been occurred by their twenties. Surfactant proteins (SP) and matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to cigarette smoke induced lung remodelling and chronic obstructive pulmonary disease (COPD). However, the level of these proteins has not been examined during ageing or in young individuals with short smoking histories. Methods: Plasma levels of SP-A, SP-D, MMP-9, and TIMP-1 were measured by EIA/ELISA from young (18-23 years) non-smoking controls (YNS) (n = 36), smokers (YS) (n = 51), middle aged/elderly (37-77 years) non-smoking controls (ONS) (n = 40), smokers (OS) (n = 64) (FEV1/FVC >0.7 in all subjects) and patients with COPD (n = 44, 35-79 years). Results: Plasma levels of SP-A increased with age and in the older group in relation to smoking and COPD. Plasma SP-D and MMP-9 levels did not change with age but were elevated in OS and COPD as compared to ONS. The TIMP-1 level declined with age but increased in chronic smokers when compared to ONS. The clearest correlations could be detected between plasma SP-A vs. age, pack years and FEV1/FVC. The receiver operating characteristic (ROC) curve analysis revealed SP-A to be the best marker for discriminating between patients with COPD and the controls (area under ROC curve of 0.842; 95% confidence interval, 0.785-0.899; p <0.001). Conclusions: Age has a significant contribution to potential markers related to smoking and COPD; SP-A seems to be the best factor in differentiating COPD from the controls.Peer reviewe

Environmental exposure as an independent risk factor of chronic bronchitis in northwest Russia

Peer reviewe

Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

Peer reviewe

Reporting data analysis methods in high-impact respiratory journals

Abstract Data analysis methods play an important role in respiratory research. We evaluated the application and complexity of data analytical methods in high-impact respiratory journals and compared the statistical reporting in these respiratory articles with reports published in other eminent medical journals. This study involved a total of 160 papers published in 2015 in the European Respiratory Journal, American Journal of Respiratory and Critical Care Medicine, Chest and Thorax, and 680 papers published between 2007–2015 in other medical journals including the Lancet and New England Journal of Medicine. We manually reviewed the articles to determine the way in which they reported the methods applied in data analysis. The statistical intensity in the respiratory journals was equal to that in eminent medical journals. Traditional ways of testing statistical significance were widely used in respiratory articles. Statistical procedures were not always described in sufficient detail, and the prominent respiratory journals did not display different profiles with respect to their statistical content. Readers of the prominent respiratory journals need to possess a substantial level of statistical expertise if they wish to critically evaluate the design, methodology, data analysis and interpretation of the findings published in these journals