Browsing by Subject "LUNG-FUNCTION"

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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.
  • Kalliola, Satu; Malmberg, L. Pekka; Malmstrom, Kristiina; Pelkonen, Anna S.; Mäkelä, Mika J. (2019)
    Background: Recurrent wheezing in early life is transient in most children. The significance of airway hyper-responsiveness (AHR) in persistence of respiratory symptoms from infancy to early childhood is controversial. Objective: We evaluated whether AHR in wheezy infants predicts doctor-diagnosed asthma (DDA) or AHR at the age of 6 years. Methods: Sixty-one wheezy infants (age 6-24 months) were followed up to the median age of 6 years. Lung function and AHR with methacholine challenge test were assessed at infancy and 6 years. The exercise challenge test was performed at the age of 6 years. Atopy was assessed with skin prick tests. Results: At 6 years, 21 (34%) of the children had DDA. Children with DDA had higher logarithmic transformed dose-response slope (LOGDRS) to methacholine in infancy than children without DDA (0.047 vs 0.025; P = .033). Furthermore, AHR to methacholine in infancy and at 6 years were associated with each other (r = 0.324, P = .011). Children with exercise-induced bronchoconstriction (EIB) at 6 years were more reactive to methacholine in infancy than those without EIB (P = .019). Conclusion: Increased AHR in symptomatic infants was associated with increased AHR, DDA, and EIB at median the age of 6 years, suggesting early establishment of AHR. (C) 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • Malmström, Kristiina; Lohi, Jouko; Malmberg, Leo Pekka; Kotaniemi-Syrjänen, Anne; Lindahl, Harry; Sarna, Seppo; Pelkonen, Anna S.; Mäkelä, Mika J. (2020)
    Abstract Background The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. Objective To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Methods Inclusion criteria: full-term, 3-23 months of age; doctor diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body pletysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analyzed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Results Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function correlated with AHR (p=0.047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (p=0.057 and 0.056 respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (p=0.031). Conclusions & Clinical Relevance These findings don not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.
  • 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.
  • Päivinen, Marja; Keskinen, Kari; Putus, Tuula; Kujala, Urho M.; Kalliokoski, Pentti; Tikkanen, Heikki O. (2021)
    Background Respiratory symptoms are common in competitive swimmers. However, among these and in swimmers at other activity levels the swimming distance, the total spent time in swimming halls and their medical background varies. Our objectives were, first, to assess their medical histories and the associations with respiratory symptoms among swimmers in different activity groups and then second, to study the pulmonary function findings and related medications in competitive swimmers who exercise in swimming hall environments the most. Methods First, 1118 participants consisting of 133 competitive-, 734 fitness- and 251 occasional swimmers answered questionnaires concerning their medical background, their respiratory symptoms in connection to swimming distance and their amount of time spent in swimming halls. Secondly, in 130 competitive swimmers, pulmonary function was tested by spirometry and a specific questionnaire was used to assess respiratory symptoms, medical histories and prescribed medication. Results Respiratory symptoms were reported by 18% of the studied swimmers. Competitive swimmers had significantly more symptoms than fitness- and occasional swimmers. Naturally competitive swimmers swum more than 2000 m and stayed by the pool more than 90 min, longer than the other activity groups of swimmers. Spirometry testing showed airway obstruction in 15 swimmers, which was 12% of the 130 competitive swimmers. 21 of them, had physician-diagnosed asthma and 16 of these individuals had prescribed medication for it. Conclusions Competitive swimmers had the highest swimming hall exposure and reported significantly more respiratory symptoms. A high prevalence of airway obstruction findings in competitive swimmers with asthma and allergies suggests a need for future recommendations for regular testing and special medical care for competitive swimmers.
  • Garcia-Larsen, Vanessa; Thawer, Narjis; Charles, David; Cassidy, Aedin; van Zele, Thibaut; Thilsing, Trine; Ahlström, Matti; Haahtela, Tari; Keil, Thomas; Matricardi, Paolo M.; Brozek, Grzegorz; Kowalski, Marek L.; Makowska, Joanna; Nizankowska-Mogilnicka, Ewa; Rymarczyk, Barbara; Loureiro, Carlos; Bom, Ana Todo; Bachert, Claus; Forsberg, Bertil; Janson, Christer; Toren, Kjell; Potts, James F.; Burney, Peter G. J. (2018)
    Background: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. Methods: A stratified random sample was drawn from the GA(2)LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC <LLN), and FEV1/FVC <LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA(2)LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. Results: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC <LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a -coeff 0.33; 0.10, 0.57 and a -coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. Conclusions: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.
  • Tischer, Christina; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Flexeder, Claudia; Roponen, Marjut; Hyvarinen, Anne; Renz, Harald; Frey, Urs Peter; Fuchs, Oliver; Pekkanen, Juha (2021)
    Background Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. Methods Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.
  • Ilmarinen, Pinja; Juboori, Hind; Tuomisto, Leena E.; Niemelä, Onni; Sintonen, Harri; Kankaanranta, Hannu (2019)
    Health-related quality of life (HRQoL) is a well-established aspect of health that can be measured by both disease-specific and general instruments. The effect of uncontrolled asthma on generic HRQoL has not been shown in patients with clinically confirmed adult-onset asthma and with asthma control defined according to the Global Initiative for Asthma, so the aim of this study was to determine this. In the 12-year follow-up cohort of the Seinajoki Adult Asthma Study (n = 203), patients with uncontrolled and partially controlled asthma had lower generic HRQoL as determined by 15D compared to the controlled group. On 10 out of 15 dimensions of 15D, the mean scores were significantly lower in patients with uncontrolled asthma compared with those with controlled asthma. The affected dimensions were mobility, breathing, sleeping, usual activities, mental function, discomfort and symptoms, depression, distress, vitality and sexual activity. In the Tobit regression analysis, a poorer 15D score was associated with uncontrolled asthma, lower postbronchodilator FEV1, female sex, depression, treated dyspepsia and poorer 15D score at diagnosis. Our results show that uncontrolled asthma affects everyday life in several aspects, including previously unknown components such as sexual activity and vitality.
  • Elonheimo, Hanna Maria; Mattila, Tiina; Andersen, Helle Raun; Bocca, Beatrice; Ruggieri, Flavia; Haverinen, Elsi; Tolonen, Hanna (2022)
    Chronic obstructive pulmonary disease (COPD) is a slowly developing non-communicable disease (NCD), causing non-reversible obstruction and leading to marked morbidity and mortality. Besides traditional risk factors such as smoking, some environmental substances can augment the risk of COPD. The European Human Biomonitoring Initiative (HBM4EU) is a program evaluating citizens' exposure to various environmental substances and their possible health impacts. Within the HBM4EU, eighteen priority substances or substance groups were chosen. In this scoping review, seven of these substances or substance groups are reported to have an association or a possible association with COPD. Main exposure routes, vulnerable and high-exposure risk groups, and matrices where these substances are measured are described. Pesticides in general and especially organophosphate and carbamate insecticides, and some herbicides, lead (Pb), and polycyclic aromatic hydrocarbons (PAHs) showed an association, and cadmium (Cd), chromium (Cr and CrVI), arsenic (As), and diisocyanates, a possible association with COPD and/or decreased lung function. Due to long latency in COPD's disease process, the role of chemical exposure as a risk factor for COPD is probably underestimated. More research is needed to support evidence-based conclusions. Generally, chemical exposure is a growing issue of concern, and prompt action is needed to safeguard public health.
  • Aschard, Hugues; Tobin, Martin D.; Hancock, Dana B.; Skurnik, David; Sood, Akshay; James, Alan; Smith, Albert Vernon; Manichaikul, Aniw; Campbell, Archie; Prins, Bram P.; Hayward, Caroline; Loth, Daanw; Porteous, David J.; Strachan, David P.; Zeggini, Eleftheria; O'Connor, George T.; Brusselle, Guy G.; Boezen, H. Marike; Schulz, Holger; Deary, Ian J.; Hall, Ian P.; Rudan, Igor; Kaprio, Jaakko; Wilson, James F.; Wilk, Jemma B.; Huffman, Jennifer E.; Zhao, Jing Hua; de Jong, Kim; Lyytikainen, Leo-Pekka; Wain, Louise V.; Jarvelin, Marjo-Riitta; Kahonen, Mika; Fornage, Myriam; Polasek, Ozren; Cassano, Patricia A.; Barr, R. Graham; Rawal, Rajesh; Harris, Sarah E.; Gharib, Sina A.; Enroth, Stefan; Heckbert, Susan R.; Lehtimaki, Terho; Gyllensten, Ulf; Jackson, Victoria E.; Gudnason, Vilmundur; Tang, Wenbo; Dupuis, Josee; Artigas, Maria Soler; Joshi, Amit D.; London, Stephanie J.; Understanding Soc Sci Grp (2017)
    Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
  • Adults Born Preterm Int Collaborat; Doyle, Lex W.; Andersson, Sture; Bush, Andy; Cheong, Jeanie L. Y.; Clemm, Hege; Evensen, Kari Anne I.; Gough, Aisling; Halvorsen, Thomas; Hovi, Petteri; Kajantie, Eero; Lee, Katherine J.; McGarvey, Lorcan; Narang, Indra; Näsänen-Gilmore, Pieta; Steinshamn, Sigurd; Vollsaeter, Maria; Vrijlandt, Elianne J. L. E. (2019)
    Background Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at 2499 g) or at term. Methods We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. Findings Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3.4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0.06 [SD 1.03] vs -0.81 [1.33], mean difference -0.78 [95% CI -0.96 to -0.61], p Interpretation Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
  • SpiroMeta Consortium; Int COPD Genetics Consortium; Understanding Soc Sci Grp (2019)
    Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P <5 x 10(-8); 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
  • Wang, Tong; Wang, Weijing; Li, Weilong; Duan, Haiping; Xu, Chunsheng; Tian, Xiaocao; Zhang, Dongfeng (2021)
    Background Previous studies have determined the epigenetic association between DNA methylation and pulmonary function among various ethnics, whereas this association is largely unknown in Chinese adults. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and pulmonary function among middle-aged Chinese monozygotic twins. Methods The monozygotic twin sample was drawn from the Qingdao Twin Registry. Pulmonary function was measured by three parameters including forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear mixed effect model was used to regress the methylation level of CpG sites on pulmonary function. After that, we applied Genomic Regions Enrichment of Annotations Tool (GREAT) to predict the genomic regions enrichment, and used comb-p python library to detect differentially methylated regions (DMRs). Gene expression analysis was conducted to validate the results of differentially methylated analyses. Results We identified 112 CpG sites with the level of P < 1 x 10(-4) which were annotated to 40 genes. We identified 12 common enriched pathways of three pulmonary function parameters. We detected 39 DMRs located at 23 genes, of which PRDM1 was related to decreased pulmonary function, and MPL, LTB4R2, and EPHB3 were related to increased pulmonary function. The gene expression analyses validated DIP2C, ASB2, SLC6A5, and GAS6 related to decreased pulmonary function. Conclusion Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on pulmonary function. Several CpG sites, genes, biological pathways and DMRs are considered as possible crucial to pulmonary function.
  • Bajc, M.; Chen, Y.; Wang, J.; Li, X. Y.; Shen, W. M.; Wang, C. Z.; Huang, H.; Lindqvist, A.; He, X. Y. (2017)
    Introduction: Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool. We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent. Methods: 94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry. Ventilation and perfusion defects were analyzed blindly according to the European guidelines. Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease. Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry. Results: Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients. Emphysema was identified in 81 patients. Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor. The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages (r=0.63 and -0.60, respectively, P <0.0001). V/P SPECT identified pulmonary embolism in 30 patients (32%). A pattern typical for heart failure was present in 26 patients (28%). Parenchymal changes typical for pneumonia or lung tumor were present in several cases. Conclusion: V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity. Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities. The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis.
  • Andersen, Heidi; Ilmarinen, Pinja; Honkamäki, Jasmin; Tuomisto, E. Leena; Hisinger-Mölkänen, Hanna; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Sovijärvi, Anssi; Piirilä, Päivi; Kankaanranta, Hannu (2021)
    Purpose: Asthma is a heterogeneous disease, and factors associated with different asthma phenotypes are poorly understood. Given the higher prevalence of farming exposure and late diagnosis of asthma in more rural Western Finland as compared with the capital of Helsinki, we investigated the relationship between childhood farming environment and age at asthma diagnosis. Methods: A cross-sectional population-based study was carried out with subjects aged 2069 years in Western Finland. The response rate was 52.5%. We included 3864 participants, 416 of whom had physician-diagnosed asthma at a known age and with data on the childhood environment. The main finding was confirmed in a similar sample from Helsinki. Participants were classified as follows with respect to asthma diagnosis: early diagnosis (011 years), intermediate diagnosis (12-39 years), and late diagnosis (40-69 years). Results: The prevalence of asthma was similar both without and with childhood exposure to a farming environment (11.7% vs 11.3%). Allergic rhinitis, family history of asthma, exsmoker, occupational exposure, and BMI >= 30 kg/m(2) were associated with a higher likelihood of asthma. Childhood exposure to a farming environment did not increase the odds of having asthma (aOR, 1.10; 95% CI, 0.87-1.40). It did increase the odds of late diagnosis (aOR, 2.30; 95% CI, 1.12-4.69), but the odds were lower for early (aOR, 0.49; 95% CI, 0.30-0.80) and intermediate diagnosis of asthma (aOR, 0.75; 95% CI, 0.47-1.18). Conclusion: Odds were lower for early diagnosis of asthma and higher for late diagnosis of asthma in a childhood farming environment. This suggests a new hypothesis concerning the etiology of asthma when it is diagnosed late.
  • Bianchi, L.; Porta, C.; Rinaldi, A.; Gazzaruso, C.; Fratino, P.; DeCata, P.; Protti, P.; Paltro, R.; Bernardi, L. (2017)
    Background: Cardiovascular (baroreflex) and respiratory (chemoreflex) control mechanisms were studied separately in diabetes, but their reciprocal interaction (well known for diseases like heart failure) had never been comprehensively assessed. We hypothesized that prevalent autonomic neuropathy would depress both reflexes, whereas prevalent autonomic imbalance through sympathetic activation would depress the baroreflex but enhance the chemoreflexes. Methods: In 46 type-1 diabetic subjects (7.0 +/- 0.9 year duration) and 103 age-matched controls we measured the baroreflex (average of 7 methods), and the chemoreflexes, (hypercapnic: ventilation/carbon dioxide slope during hyperoxic progressive hypercapnia; hypoxic: ventilation/oxygen saturation slope during normocapnic progressive hypoxia). Autonomic dysfunction was evaluated by cardiovascular reflex tests. Results: Resting oxygen saturation and baroreflex sensitivity were reduced in the diabetic group, whereas the hypercapnic chemoreflex was significantly increased in the entire diabetic group. Despite lower oxygen saturation the hypoxic chemoreflex showed a trend toward a depression in the diabetic group. Conclusion: Cardio-respiratory control imbalance is a common finding in early type 1 diabetes. A reduced sensitivity to hypoxia seems a primary factor leading to reflex sympathetic activation (enhanced hypercapnic chemoreflex and baroreflex depression), hence suggesting a functional origin of cardio-respiratory control imbalance in initial diabetes. (C) 2017 Elsevier B.V. All rights reserved.
  • Skaaby, Tea; Taylor, Amy E.; Jacobsen, Rikke K.; Paternoster, Lavinia; Thuesen, Betina H.; Ahluwalia, Tarunveer S.; Larsen, Sofus C.; Zhou, Ang; Wong, Andrew; Gabrielsen, Maiken E.; Bjorngaard, Johan H.; Flexeder, Claudia; Mannisto, Satu; Hardy, Rebecca; Kuh, Diana; Barry, Sarah J.; Mollehave, Line Tang; Cerqueira, Charlotte; Friedrich, Nele; Bonten, Tobias N.; Noordam, Raymond; Mook-Kanamori, Dennis O.; Taube, Christian; Jessen, Leon E.; McConnachie, Alex; Sattar, Naveed; Upton, Mark N.; McSharry, Charles; Bonnelykke, Klaus; Bisgaard, Hans; Schulz, Holger; Strauch, Konstantin; Meitinger, Thomas; Peters, Annette; Grallert, Harald; Nohr, Ellen A.; Kivimaki, Mika; Kumari, Meena; Voelker, Uwe; Nauck, Matthias; Voeizke, Henry; Power, Chris; Hypponen, Elina; Hansen, Torben; Jorgensen, Torben; Pedersen, Oluf; Salomaa, Veikko; Grarup, Niels; Langhammer, Arnulf; Romundstad, Pal R.; Skorpen, Frank; Kaprio, Jaakko; Munafo, Marcus R.; Linneberg, Allan (2017)
    Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0.68, 95% confidence interval (CI): 0.61, 0.76; P <0.001) and allergic sensitization (OR = 0.74, 95% CI: 0.64, 0.86; P <0.001), but similar asthma risk (OR = 1.00, 95% CI: 0.91, 1.09; P = 0.967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0.958, 95% CI: 0.920, 0.998; P = 0.041), a lower risk of allergic sensitization (OR = 0.92, 95% CI: 0.84, 1.02; P = 0.117), but higher risk of asthma (OR = 1.06, 95% CI: 1.01, 1.11; P = 0.020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
  • Toppila-Salmi, Sanna; Luukkainen, Annika T.; Xu, Baizhuang; Lampi, Jussi; Auvinen, Juha; Dhaygude, Kishor; Järvelin, Marjo-Riitta; Pekkanen, Juha (2020)
    Rationale: Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma. Objectives: To determine the association between prenatal ETS and adult onset asthma. Measurements and main results: The questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04-2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28-40.67) or past cough with wheeze (3.21, 95% CI 1.71-6.05). A significant association was detected between gestational smoke exposure and the offspring's forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA of RUNX1, gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11-14.52, adjusted p-value for interaction 0.10). Conclusion: Maternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV1/FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring's airways to ETS and its putative long-term effects.
  • Lassmann-Klee, Paul G.; Sundblad, Britt-Marie; Malmberg, Leo P.; Sovijarvi, Anssi R. A.; Piirilä, Päivi (2020)
    Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijarvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijarvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijarvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijarvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.