Browsing by Subject "COPD"

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  • Prokic, Ivana; Lahousse, Lies; de Vries, Maaike; Liu, Jun; Kalaoja, Marita; Vonk, Judith M.; van der Plaat, Diana A.; van Diemen, Cleo C.; van der Spek, Ashley; Zhernakova, Alexandra; Fu, Jingyuan; Ghanbari, Mohsen; Ala-Korpela, Mika; Kettunen, Johannes; Havulinna, Aki S.; Perola, Markus; Salomaa, Veikko; Lind, Lars; Arnlov, Johan; Stricker, Bruno H. C.; Brusselle, Guy G.; Boezen, H. Marike; van Duijn, Cornelia M.; Amin, Najaf (2020)
    Background Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis. Methods We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach. Results There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16,P = 5.6 x 10(- 4)in the discovery and OR = 1.30,P = 1.8 x 10(- 6)in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52-2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94-1.20). Conclusions Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.
  • Prokić, Ivana; Lahousse, Lies; de Vries, Maaike; Liu, Jun; Kalaoja, Marita; Vonk, Judith M; van der Plaat, Diana A; van Diemen, Cleo C; van der Spek, Ashley; Zhernakova, Alexandra; Fu, Jingyuan; Ghanbari, Mohsen; Ala-Korpela, Mika; Kettunen, Johannes; Havulinna, Aki S; Perola, Markus; Salomaa, Veikko; Lind, Lars; Ärnlöv, Johan; Stricker, Bruno H C; Brusselle, Guy G; Boezen, H. M; van Duijn, Cornelia M; Amin, Najaf (BioMed Central, 2020)
    Abstract Background Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis. Methods We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach. Results There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10− 4 in the discovery and OR = 1.30, P = 1.8 × 10− 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52–2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94–1.20). Conclusions Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.
  • Mattila, Tiina; Vasankari, Tuula; Rissanen, Harri; Knekt, Paul; Puukka, Pauli; Heliövaara, Markku (2018)
    Chronic obstructive pulmonary disease (COPD) has been associated with coronary mortality. Yet, data about the association between COPD and acute myocardial infarction (MI) remain scarce. We aimed to study airway obstruction as a predictor of MI and coronary mortality among 5576 Finnish adults who participated in a national health examination survey between 1978 and 1980. Subjects underwent spirometry, had all necessary data, showed no indications of cardiovascular disease at baseline, and were followed up through record linkage with national registers through 2011. The primary outcome consisted of a major coronary event-that is, hospitalization for MI or coronary death, whichever occurred first. We specified obstruction using the lower limit of normal categorization. Through multivariate analysis adjusted for potential confounding factors for coronary heart disease, hazard ratios (HRs) (with the 95% confidence intervals in parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79-1.42), 0.84 (0.54-1.31), and 1.40 (1.04-1.88), respectively, in those with obstruction compared to others. However, in women aged 30-49 obstruction appeared to predict a major coronary event, where the adjusted HR reached 4.21 (1.73-10.28). In conclusion, obstruction appears to predict a major coronary event in younger women only, whereas obstruction closely associates with the risk of coronary death independent of sex and age.
  • Mattila, Tiina; Vasankari, Tuula; Rissanen, Harri; Knekt, Paul; Sares-Jäske, Laura; Jääskeläinen, Tuija; Heliövaara, Markku (2019)
    Background and objective: Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort. Methods: We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles. Results: Both obstruction and low s-25(OH) D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40-0.80), respectively. Conclusions: In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.
  • Giordano, Luca; Farnham, Antoine; Dhandapani, Praveen K.; Salminen, Laura; Bhaskaran, Jahnavi; Voswinckel, Robert; Rauschkolb, Peter; Scheibe, Susan; Sommer, Natascha; Beisswenger, Christoph; Weissmann, Norbert; Braun, Thomas; Jacobs, Howard T.; Bals, Robert; Herr, Christian; Szibor, Marten (2019)
    Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage.
  • Hautala, Katja; Oinonen, Kirsi (Helsingfors universitet, 1997)
    Krooniset ärsytysperäiset hengitystiesairaudet ovat Suomessa hevosilla hyvin yleisiä. Pitkä sisäruokintakausi, huonolaatuiset rehut ja tallien usein heikko ilman laatu altistavat hevosia allergisille hengitystiesairauksille. Hevosten hengitystiesairauksien hoidossa käytetään paljon lääkeaineita, joiden vaikutuksista on hyvin vähän tutkittua tietoa. Tutkimuksessamme pyrittiin selvittämään asetyylikysteiinin vaikutuksia ja mukolyyttistä tehoa COPD:tä (chronic obstructive pulmonary disease) sairastavissa hevosissa. Tutkimukseen osallistui kymmenen hevosta, jotka tutkittiin neljä kertaa. Toisen ja kolmannen tutkimuskerran välillä hevosia lääkittiin kahden viikon ajan asetyylikysteiinillä (2.4 g suun kautta kahdesti päivässä). Jokaisella tutkimuskerralla hevosille tehtiin kliininen yleistutkimus ja ne tähystettiin. Tähystyksen yhteydessä hevosista otettiin makealimanäyte, josta määritettiin tiettyjen entsyymien (MMP9, kaseinaasi ja beta-glukuronidaasi) pitoisuudet sekä neutrofiilimäärä. Tutkimustulosten perusteella asetyylikysteiinillä ei todettu tilastollisesti merkittävää vaikutusta koeryhmän hevosten oireisiin. Yksittäisille hevosille hoidolla näyttäisi kuitenkin olleen positiivinen vaikutus.
  • Jalasto, Juuso (Helsingin yliopisto, 2020)
    Työperäinen altistuminen voi pahentaa jo olemassa olevan astman oireita tai aiheuttaa uutta työperäistä astmaa, ja sillä on osoitettu olevan myös merkitystä keuhkoahtaumataudin (COPD) synnyssä. Tämän tutkimuksen tarkoituksena oli tarkastella voivatko eroavaisuudet ammattiluokituksissa, työperäisessä altistumisessa ja tupakoinnissa vaikuttaa astman, COPD:n, hengitystieoireiden ja ilmateiden eosinofiilisen tulehduksen esiintyvyyteen. Tutkimuksessa tarkasteltiin myös kuinka eri ammattiluokittelut soveltuvat epidemiologiseen tutkimukseen. Kolmen Itämeren alueen valtion (Suomi, Viro ja Ruotsi) yhteistyönä toteutettiin vuosituhannen vaihteessa monikeskustutkimus, jossa tutkittaville tehtiin jokaisessa keskuksessa yhteneväinen lomakehaastattelu, spirometria sekä uloshengitysilman typpioksidimittaus (FENO). Tätä kolmesta maasta kerättyä aineistoa käytettiin nykyiseen tutkimukseen, jossa sitä tarkasteltiin kolmen eri ammattiluokittelun avulla. Lisäksi arvioitiin työperäistä altistumista altistematriisin (JEM) avulla. Iän, sukupuolen ja tupakoinnin mukaan säädetyssä monimuuttuja-analyysissa havaittiin tilastollisesti merkittävä riski kahdessa eri ammattiluokittelussa, jotka liittyivät ei-manuaaliseen työhön ja terveydenhoito- ja sosiaalialan töihin. Näissä ryhmissä oli myös korkea hengitystieoireiden esiintyvyys. Merkittävä COPD:n riski tuli ilmi kaikissa kolmessa luokitusjärjestelmässä manuaalisten töiden osalta ja työperäinen altistus aiheutti myös merkittävän COPD:n riskin sekä COPD:n liittyvien hengitystieoireiden riskin monimuuttuja-analyysissä. Uloshengitysilman typpioksidimittaustulokset erosivat esiintyvyyksiltään ammattiryhmissä mutta monimuuttuja-analyysissä ei havaittu merkittäviä riskejä kohonneen FENO:n suhteen. Eri ammattiluokituksilla oli erilainen kyky löytää tauteja, oireita ja työperäistä altistumista, ja tutkimuksen hyöty on auttaa sopivien työkalujen käyttämisessä tulevissa epidemiologissa tutkimuksissa, jotka tarkastelevat myös sosioekonomista näkökulmaa.
  • Mäntylä, Jarkko; Mazur, Witold; Törölä, Tanja; Bergman, Paula; Saarinen, Tuomas; Kauppi, Paula (2019)
    Background: By definition bronchiectasis (BE) means destructed structure of normal bronchus as a consequence of frequent bacterial infections and inflammation. In many senses, BE is a neglected orphan disease. A recent pan-European registry study, EMBARC, has been set up in order to better understand its pathophysiology, better phenotype patients, and to individualize their management. Aim: To examine the aetiology and co-morbidity of BE in the capital area in Finland. Methods: Two hundred five patients with BE diagnosis and follow up visits between 2016 and 2017 in Helsinki University Hospital were invited to participate in the study. Baseline demographics, lung functions, imaging, microbiological, and therapeutic data, together with co-morbidities were entered into EMBARC database. Clinical characteristics, aetiologic factors, co-morbidities, and risk factors for extensive BE were explored. Results: To the study included 95 adult patients and seventy nine percent of the BE patients were women. The mean age was 69 years (SD +/- 13). Asthma was a comorbid condition in 68% of the patients but in 26% it was estimated to be the cause of BE. Asthma was aetiological factor for BE if it had been diagnosed earlier than BE. As 41% BE were idiopathic, in 11% the disorder was postinfectious and others were associated to rheumatic disease, Alpha-1-antitrypsin deficiency, IgG deficiency and Kartagener syndrome. The most common co-morbidities in addition to asthma were cardiovascular disease (30%), gastroesophageal reflux disease (26%), overweight (22%), diabetes (16%), inactive neoplasia (15%), and immunodeficiency (12%). Extensive BE was found in 68% of BE patients in whom four or more lobes were affected. Risk factors for extensive BE were asthma (OR 2.7), asthma as aetiology for BE (OR 4.3), and rhinosinusitis (OR 3.1). Conclusions: Asthma was associated to BE in 68% and it was estimated as aetiology in every fourth patient. However, retrospectively, it is difficult to exclude asthma as a background cause in patients with asthma-like symptoms and respiratory infections. We propose asthma as an aetiology factor for BE if it is diagnosed earlier than BE. Asthma and rhinosinusitis were predictive for extensive BE.
  • Niemi, Anne; Tuominen, Riikka (Helsingfors universitet, 1992)
    Tutkimuksen tarkoituksena oli kehittää bronkoalveolaarinen huuhtelun suorittamista ja näytteiden laboratoriotekniikkaa sekä vertailla saatuja tuloksia keuhkobiopsioista saatuihin histopatologisiin muutoksiin. Keuhkonäytteet (28 kpl) kerättiin syksyllä 1991 Helsingin kaupungin teurastamolta. Bronkoalveolaarinen huuhtelu suoritettiin yleensä noin yhden tunnin sisällä hevosen teurastuksen jälkeen ja huuhtelunäytteistä määriteltiin totaalisolut ja solujen differentiaalilaskenta. Kenhkobiopsioita otettiin kuudesta eri kohdasta keuhkoista ja lisäksi näytteeksi otettiin yksi keuhkopala. Histopatologisten muutosten perusteella aineisto jaettiin neljään eri ryhmään, joiden sisällä analysoitiin em. totaalisolut ja solujen differentiaalilaskenta (tulokset%). Saatuja tuloksia vertailtiin Studentin t-testillä. Tällöin ei saatu tilastollisesti merkitseviä eroja (merkitsevyysraja 95 %) eri ryhmien välille. Lisäksi aineistoa käsiteltiin frekvenssianalyysilla, jolloin havaittiin neutrofiilien nousu ryhmissä II ja III 2/3-osassa näytteistä. Tämä löydös tukee aikaisempien tutkimusten tuloksia, joissa on havaittu neutrofiilien määrän nousua kroonisissa obstruktiivisissa keuhkosairauksissa (Vrins et al, 1991, Derksen et al. 1986).;Tutkimuksen tarkoituksena oli kehittää bronkoalveolaarinen huuhtelun suorittamista ja näytteiden laboratoriotekniikkaa sekä vertailla saatuja tuloksia keuhkobiopsioista saatuihin histopatologisiin muutoksiin. Keuhkonäytteet (28 kpl) kerättiin syksyllä 1991 Helsingin kaupungin teurastamolta. Bronkoalveolaarinen huuhtelu suoritettiin yleensä noin yhden tunnin sisällä hevosen teurastuksen jälkeen ja huuhtelunäytteistä määriteltiin totaalisolut ja solujen differentiaalilaskenta. Kenhkobiopsioita otettiin kuudesta eri kohdasta keuhkoista ja lisäksi näytteeksi otettiin yksi keuhkopala. Histopatologisten muutosten perusteella aineisto jaettiin neljään eri ryhmään, joiden sisällä analysoitiin em. totaalisolut ja solujen differentiaalilaskenta (tulokset%). Saatuja tuloksia vertailtiin Studentin t-testillä. Tällöin ei saatu tilastollisesti merkitseviä eroja (merkitsevyysraja 95 %) eri ryhmien välille. Lisäksi aineistoa käsiteltiin frekvenssianalyysilla, jolloin havaittiin neutrofiilien nousu ryhmissä II ja III 2/3-osassa näytteistä. Tämä löydös tukee aikaisempien tutkimusten tuloksia, joissa on havaittu neutrofiilien määrän nousua kroonisissa obstruktiivisissa keuhkosairauksissa (Vrins et al, 1991, Derksen et al. 1986).
  • Koskela, Jukka; Kilpeläinen, Maritta; Kupiainen, Henna Elina; Mazur, Witold; Sintonen, Harri; Boezen, Marike; Lindqvist, Ari; Postma, Dirkje; Laitinen, Tarja Helena (2014)
    BACKGROUND: Co-morbidities are common in chronic obstructive pulmonary disease (COPD). We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients. METHODS: Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis. The prevalence of their co-morbidities was compared with those of 5000 population controls. The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients. RESULTS: Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls. Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments. Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1. FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted). Poor HRQoL also predicted death during the next five years. CONCLUSIONS: The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD.
  • Hirvonen, Eveliina; Stepanov, Mikhael; Kilpeläinen, Maritta; Lindqvist, Ari; Laitinen, Tarja (2019)
    Introduction: Smoking has a significant impact on the development and progression of asthma and chronic obstructive pulmonary disease (COPD). Self-reported questionnaires and structured interviews are usually the only way to study patients' smoking history. In this study, we aim to examine the consistency of the responses of asthma and COPD patients to repeated standardised questions on their smoking habits over the period of 10 years. Methods: The study population consisted of 1329 asthma and 959 COPD patients, who enrolled in the study during years 2005-2007. A follow-up questionnaire was mailed to the participants 1, 2, 4, 6, 8, and 10 years after the recruitment. Results: Among the participants who returned three or more questionnaires (N = 1454), 78.5 % of the patients reported unchanged smoking status (never smoker, ex-smoker or current smoker) across the time. In 4.5% of the answers, the reported smoking statuses were considered unreliable/conflicting (first never smoker and, later, smoker or ex-smoker). The remainder of the patients changed their status from current smoker to ex-smoker and vice versa at least once, most likely due to struggling with quitting. COPD patients were more frequently heavy ex- or current smokers compared to the asthma group. The intraclass coefficient correlations between self-reported starting (0.85) and stopping (0.94) years as well as the consumption of cigarettes (0.74) over time showed good reliability among both asthma and COPD patients. Conclusion: Self-reported smoking data among elderly asthma and COPD patients over a 10-year follow-up is reliable. Pack years can be considered a rough estimate for their comprehensive consumption of tobacco products over time. We also observed that the questionnaire we used was not designed for dynamic changes in smoking which are rather common among heavy smokers especially when the follow-up time is several years, as in our study.
  • Lassmann-Klee, Paul G.; Lehtimäki, Lauri; Lindholm, Tuula; Malmberg, Leo Pekka; Sovijärvi, Anssi R. A.; Piirilä, Päivi Liisa (2019)
    In clinical practice, assessment of expiratory nitric oxide (F-ENO) may reveal eosinophilic airway inflammation in asthmatic and other pulmonary diseases. Currently, measuring of F-ENO is standardized to exhaled flow level of 50 ml s(-1), since the expiratory flow rate affects the F-ENO results. To enable the comparison of F-ENO measured with different expiratory flows, we firstly aimed to establish a conversion model to estimate F-ENO at the standard flow level, and secondly, validate it in five external populations. F-ENO measurements were obtained from 30 volunteers (mixed adult population) at the following multiple expiratory flow rates: 50, 30, 100 and 300 ml s(-1), after different mouthwash settings, and a conversion model was developed. We tested the conversion model in five populations: healthy adults, healthy children, and patients with COPD, asthma and alveolitis. F-ENO conversions in the mixed adult population, in healthy adults and in children, showed the lowest deviation between estimated FENO from 100 ml s(-1) and measured F-ENO at 50 mL s(-1): -0 center dot 28 ppb, -0 center dot 44 ppb and 0 center dot 27 ppb, respectively. In patients with COPD, asthma and alveolitis, the deviation was -1 center dot 16 ppb, -1 center dot 68 ppb and 1 center dot 47 ppb, respectively. We proposed a valid model to convert F-ENO in healthy or mixed populations, as well as in subjects with obstructive pulmonary diseases and found it suitable for converting F-ENO measured with different expiratory flows to the standard flow in large epidemiological data, but not on individual level. In conclusion, a model to convert F-ENO from different flows to the standard flow was established and validated.
  • Koivunen, Anna-Liisa; Rantala, Anu-Riikka (Helsingfors universitet, 1994)
    Kirjallisuuskatsauksessa käsitellään hevosen hengitysteiden anatomiaa ja fysiologiaa, sekä COPD:n patogeneesiä, histopatologiaa ja kliinistä kuvaa. Lisäksi esitellään erilaisia COPD-potilaan tutkimuksessa käytettaviä; menetelmiä. Tutkimusosassa oli tarkoituksena selvittää, kuinka suuria vuodenaikaisvaihteluita yksittäisen hevosen hengitysteissä tapahtuu, sekä selvittää, mitkä tutkimusmenetelmät soveltuvat parhaiten COPD:n asteen arviointiin. Erityisesti kiinnitettiin huomiota trakealimanäytteiden entsyymiarvoihin. Tutkimusosuus suoritettiin Ypäjän Hevostaloudentutkimusasemalla. Kokeessa oli mukana 19 hevosta, joita seurattiin vuoden ajan n. kuuden viikon välein. Jokaisella tutkimuskerralla hevosille suoritettiin kliininen yleistutkimus, intrapleuraalisen paineen mittaus sekä endoskopointi. Endoskopoinnin yhteydessä hevosilta otettiin trakealimanäytteet, joista tutkittiin solukuva sekä tietyt entsyymipitoisuudet (NAGaasi, beeta-glukuronidaasi, trypsiini-inhibiittori, plasmiini ja plasminogeeni ). Verinäytteistätutkittiin mm. yleisimmät tulehdusparametrit (fibrinogeeni, leukosyytit ) sekä happiosapainearvot. COPD-oireiden vuodenaikaisvaihtelu oli selvästi havaittavissa. Sekä kliiniset oireet, että erilaiset COPD:n määrityksessä käytettävät parametrit olivat korkeimmillaan kevättalvella. Entsyymeistä beeta-glukuronidaasi osoittautui lupaavaksi parametriksi hevosten hengitystiesairauksien asteen määrityksessä. Beeta-glukuronidaasiarvot olivat merkitsevästi kohonneet silloin, kun hevonen oli intrapleuraalipaineen, veri-alveolieron ja trakealiman neutrofiilimäärän perusteella määritelty sairaaksi.
  • Sundar, Isaac K.; Yin, Qiangzong; Baier, Brian S.; Yan, Li; Mazur, Witold; Li, Dongmei; Susiarjo, Martha; Rahman, Irfan (2017)
    Background: Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip. Results: Our data revealed that the differentially methylated genes were related to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer, and nNOS signaling in neurons), disease and disorders (organismal injury and abnormalities, cancer, and respiratory disease), and molecular and cellular functions (cell death and survival, cellular assembly and organization, cellular function and maintenance) in patients with COPD. The genome-wide DNA methylation analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1, ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were further validated by pyrosequencing. Pyrosequencing validation confirmed hyper-methylation in smokers and patients with COPD as compared to non-smokers. However, we did not detect significant differences in DNA methylation for TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes observed in the genome-wide analysis. Conclusions: Our study suggests that DNA methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as epigenetic signatures in smokers and patients with COPD if the same is validated in a larger cohort. Future studies are required to correlate DNA methylation status with transcriptomics of selective genes identified in this study and elucidate their role and involvement in the progression of COPD and its exacerbations.
  • Andersen, Heidi; Ilmarinen, Pinja; Honkamäki, Jasmin; Tuomisto, Leena E.; Piirilä, Päivi; Hisinger-Mölkänen, Hanna; Sovijärvi, Anssi; Backman, Helena; Lundback, Bo; Rönmark, Eva; Lehtimäki, Lauri; Kankaanranta, Hannu (2021)
    Background Difference in dyspnea mMRC >= 2 between Finnish speaking and Swedish-speaking populations in Finland has not been previously studied. Methods In February 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland with a response rate of 52.3%. The registered native language of each subject determined whether questionnaire in Finnish or Swedish was applied. Multiple logistic regression was performed to calculate Odds Ratios (OR) with 95% CI for the simultaneous effects of independent variables on dyspnea mMRC >= 2. Results Of all participants, 2780 (71.9%) were Finnish speakers and 1084 (28.1%) were Swedish speakers. Finnish speakers had a higher prevalence of dyspnea mMRC >= 2 (11.1% vs 6.5% p <0.001) when compared to Swedish speakers. Finnish speakers smoked more often, had higher BMI, spent less time moving during the day, had more often occupational exposure to vapours, gases, dusts or fumes (VGDF), and had lower socioeconomic status based on occupation. Significant risk factors for dyspnea mMRC >= 2 were COPD (OR = 10.94), BMI >35 (OR = 9.74), asthma (OR = 4.78), female gender (OR = 2.38), older age (OR = 2.20), current smoking (OR = 1.59), and occupational exposure to VGDF (OR = 1.47). Conclusions Swedish speakers had less dyspnea mMRC >= 2 which is explained by a healthier lifestyle. Smoking, obesity, and occupational exposures should be in focus to improve respiratory health.
  • Bajc, Marika; Schümichen, Carl; Grüning, Thomas; Lindqvist, Ari; Le Roux, Pierre-Yves; Alatri, Adriano; Bauer, Ralf W.; Dilic, Mirza; Neilly, Brian; Verberne, Hein J.; Delgado Bolton, Roberto C.; Jonson, Bjorn (2019)
    These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/P-SPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/P-SPECT an essential method for the diagnosis of PE. When V/P-SPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/P-SPECT interpretation are discussed. In conclusion, V/P-SPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.
  • Rossi, Vilma; Salimäki, Johanna; Sandler, Charlotta; Airaksinen, Marja; Kauppi, Paula (2021)
    Objectives: The objective of this study was to examine how Inhalation Technique Assessment Service (ITAS) by community pharmacies affect patients' inhalation techniques when using the Respimat (R) soft mist inhaler. The inhaler was simultaneously updated into a reusable inhaler. The study focused on the Respimat (R) inhaler because its use is known to be challenging for patients. Methods: The study was performed as a pre-post design in 33 community pharmacies (CPs) in Finland. Patients' inhalation technique was assessed before ITAS (baseline) and immediately after ITAS (follow-up 1). Follow-up 2 was performed when the patient came to the pharmacy for a refill (1-3 months after the baseline and the followup 1). A Respimat specific twenty item checklist was used to assess inhalation technique. The checklist included 1) preparation steps before the first use of the Respimat (R) inhaler (8 items) and 2) daily use steps of the Respimat (R) inhaler (12 items). After ITAS, the patients received a brief questionnaire to assess their asthma/ COPD history. Results: A total of 228 patients were enrolled at the first visit (mean age 67.8 years, 61.0% female, 85.5% had previous Respimat (R) use experience) and 42 of them attended the follow-up 2, 1-3 months later (mean age 70.1 years, 69.0% female, 92.9% had previous Respimat (R) use experience. The median number of the steps performed correctly increased from 17/20 at the baseline to all the 20 steps at the follow-up 1 (p < 0.001). At the baseline, 27.6% of the patients (n = 228) performed all preparation steps correctly, while 87.3% at the follow-up 1 and 71.4% at the follow-up 2. The percentage of the patients with acceptable inhalation technique (all critical daily use steps correct) increased from 69.7% at the baseline to 93.0% at the follow-up 1 (p < 0.001). The corresponding figure at the follow-up 2 was 69.0%. At the baseline, 30.3% of patients had optimal inhalation technique (all daily use steps correct). At the follow-up 1 corresponding figure was 85.1%, and 54.8% at the followup 2. Conclusions: A pharmacist-led intervention significantly improved asthma and COPD patients' inhalation technique with the Respimat (R) inhaler. Significant improvements were found in the daily use steps and the preparation steps before the first use.
  • Katajisto, Milla; Laitinen, Tarja (2017)
    Aims: To study the short- and long-term results of pulmonary rehabilitation (PR) given in the Helsinki University Heart and Lung Center and to understand the hospital resources used to treat severe COPD exacerbations in the city of Helsinki. Materials and methods: Seventy-eight inactive patients with severe COPD were recruited for a PR course; three of them did not finish the course. The course took 6-8 weeks and included 11-16 supervised exercise sessions. Using electronic medical records, we studied all COPD patients with hospital admission in the city of Helsinki in 2014, including COPD diagnosis, criteria for exacerbation, and potential exclusion/inclusion criteria for PR. Results: Seventy-five of the patients finished the PR course and 92% of those patients showed clinically significant improvement. Their hospital days were reduced by 54% when compared to the year before. At 1 year after the course, 53% of the patients reported that they have continued with regular exercise training. In the city of Helsinki, 437 COPD patients were treated in a hospital due to exacerbation during 2014. On the basis of their electronic medical records, 57% of them would be suitable for PR. According to a rough estimate, 10%-20% hospital days could be saved annually if PR was available to all, assuming that the PR results would be as good as those shown here. Conclusions: The study showed that in a real-world setting, PR is efficient when measured by saved hospital days in severe COPD. Half of the patients could be motivated to continue exercising on their own.
  • John, Catherine; Guyatt, Anna L.; Shrine, Nick; Packer, Richard; Olafsdottir, Thorunn A.; Liu, Jiangyuan; Hayden, Lystra P.; Chu, Su H.; Koskela, Jukka T.; Luan, Jian'an; Li, Xingnan; Terzikhan, Natalie; Xu, Hanfei; Bartz, Traci M.; Petersen, Hans; Leng, Shuguang; Belinsky, Steven A.; Cepelis, Aivaras; Cordero, Ana I. Hernandez; Obeidat, Ma'en; Thorleifsson, Gudmar; Meyers, Deborah A.; Bleecker, Eugene R.; Sakoda, Lori C.; Iribarren, Carlos; Tesfaigzi, Yohannes; Gharib, Sina A.; Dupuis, Josee; Brusselle, Guy; Lahousse, Lies; Ortega, Victor E.; Jonsdottir, Ingileif; Sin, Don D.; Bosse, Yohan; van den Berge, Maarten; Nickle, David; Quint, Jennifer K.; Sayers, Ian; Hall, Ian P.; Langenberg, Claudia; Ripatti, Samuli; Laitinen, Tarja; Wu, Ann C.; Lasky-Su, Jessica; Bakke, Per; Gulsvik, Amund; Hersh, Craig P.; Hayward, Caroline; Langhammer, Arnulf; Brumpton, Ben; Stefansson, Kari; Cho, Michael H.; Wain, Louise; Tobin, Martin D. (2022)
    BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 x 10(-6)) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 x 10(-8)) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.
  • the AANZDEM and EuroDEM study groups; Kelly, Anne-Maree; Van Meer, Oene; Laribi, Said (2020)
    Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are common in emergency departments (ED). Guidelines recommend administration of inhaled bronchodilators, systemic corticosteroids and antibiotics along with non-invasive ventilation (NIV) for patients with respiratory acidosis. Aim: To determine compliance with guideline recommendations for patients treated for COPD in ED in Europe (EUR) and South East Asia/Australasia (SEA) and to compare management and outcomes. Methods: In each region, an observational prospective cohort study was performed that included patients presenting to ED with the main complaint of dyspnoea during three 72-h periods. This planned sub-study included those with an ED primary discharge diagnosis of COPD. Data were collected on demographics, clinical features, treatment, disposition and in-hospital mortality. We determined overall compliance with guideline recommendations and compared treatments and outcome between regions. Results: A total of 801 patients was included from 122 ED (66 EUR and 46 SEA). Inhaled bronchodilators were administered to 80.3% of patients, systemic corticosteroids to 59.5%, antibiotics to 44 and 60.6% of patients with pH Conclusion: Compliance with guideline recommended treatments, in particular administration of corticosteroids and NIV, was sub-optimal in both regions. Improved compliance has the potential to improve patient outcome.