Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

OBJECTIVES: Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). METHODS: Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. RESULTS: Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. CONCLUSION: Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Use of electronic health record data mining for heart failure subtyping.

OBJECTIVE: To assess whether electronic health record (EHR) data text mining can be used to improve register-based heart failure (HF) subtyping. EHR data of 43,405 individuals from two Finnish hospital biobanks were mined for unstructured text mentions of ejection fraction (EF) and validated against clinical assessment in two sets of 100 randomly selected individuals. Structured laboratory data was then incorporated for a categorization by HF subtype (HF with mildly reduced EF, HFmrEF; HF with preserved EF, HFpEF; HF with reduced EF, HFrEF; and no HF). RESULTS: In 86% of the cases, the algorithm-identified EF belonged to the correct HF subtype range. Sensitivity, specificity, PPV and NPV of the algorithm were 94-100% for HFrEF, 85-100% for HFmrEF, and 96%, 67%, 53% and 98% for HFpEF. Survival analyses using the traditional diagnosis of HF were in concordance with the algorithm-based ones. Compared to healthy individuals, mortality increased from HFmrEF (hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.24-2.95) to HFpEF (2.28; 1.80-2.88) to HFrEF group (2.63; 1.97-3.50) over a follow-up of 1.5 years. We conclude that quantitative EF data can be efficiently extracted from EHRs and used with laboratory data to subtype HF with reasonable accuracy, especially for HFrEF.

Survival with lung cancer in Finland has not improved during 2007-2019-a single center retrospective population-based real-world study.

OBJECTIVES: According to the CONCORD-3 study, the 5-year survival rate of lung cancer patients in Finland has not improved during the twenty-first century. In the present study, we evaluated the survival trends of lung cancer patients diagnosed and treated in one of the five university hospitals in Finland to determine possible explanatory factors behind the lack of improved survival. MATERIAL AND METHODS: This retrospective population-based study included all lung cancer patients diagnosed in Tampere University Hospital in 2007-2019 (N = 3041). The study population was divided into two subcohorts: the patients diagnosed in 2007-2012 and those diagnosed in 2013-2019. The two subcohorts were then compared to analyze the temporal changes in survival and the distribution of prognostic factors. RESULTS: A comparison of the patients diagnosed in 2007-2012 and 2013-2019 showed that the patients' overall survival had remained unchanged. The median overall survival was 8.7 months in the earlier subcohort and 9.2 months in the later subcohort. The respective 5-year survival rates were 16.6% and 17.8%, and these differences were not statistically significant. The proportion of stage IV patients (approximately 59% in both subcohorts) and their risk of death were similar for the two subcohorts. According to the regression analysis, male gender, advanced stage, and poor Eastern Cooperative Oncology Group performance status were independent risk factors for death, while a never-smoking status and mutation-positive disease were associated with a decreased risk of death, but only in the later cohort. CONCLUSION: Echoing the results of CONCORD-3, this study confirmed that the real-world survival of unselected lung cancer populations in Finland has not improved over the last 15 years, mainly because of the unchanged proportions of patients with late-stage lung cancer. This calls for earlier recognition of lung cancer, achieved by screening and increasing awareness of the disease.

Genetic Associations and Architecture of Asthma-COPD Overlap.

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 × 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 × 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.

Improved risk prediction of chemotherapy-induced neutropenia-model development and validation with real-world data.

BACKGROUND: The existing risk prediction models for chemotherapy-induced febrile neutropenia (FN) do not necessarily apply to real-life patients in different healthcare systems and the external validation of these models are often lacking. Our study evaluates whether a machine learning-based risk prediction model could outperform the previously introduced models, especially when validated against real-world patient data from another institution not used for model training. METHODS: Using Turku University Hospital electronic medical records, we identified all patients who received chemotherapy for non-hematological cancer between the years 2010 and 2017 (N = 5879). An experimental surrogate endpoint was first-cycle neutropenic infection (NI), defined as grade IV neutropenia with serum C-reactive protein >10 mg/l. For predicting the risk of NI, a penalized regression model (Lasso) was developed. The model was externally validated in an independent dataset (N = 4594) from Tampere University Hospital. RESULTS: Lasso model accurately predicted NI risk with good accuracy (AUROC 0.84). In the validation cohort, the Lasso model outperformed two previously introduced, widely approved models, with AUROC 0.75. The variables selected by Lasso included granulocyte colony-stimulating factor (G-CSF) use, cancer type, pre-treatment neutrophil and thrombocyte count, intravenous treatment regimen, and the planned dose intensity. The same model predicted also FN, with AUROC 0.77, supporting the validity of NI as an endpoint. CONCLUSIONS: Our study demonstrates that real-world NI risk prediction can be improved with machine learning and that every difference in patient or treatment characteristics can have a significant impact on model performance. Here we outline a novel, externally validated approach which may hold potential to facilitate more targeted use of G-CSFs in the future.

Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.

The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.

Documentation of the patient's smoking status in common chronic diseases - analysis of medical narrative reports using the ULMFiT based text classification.

INTRODUCTION: Smoking cessation is essential part of a successful treatment in many chronic diseases. Our aim was to analyse how actively clinicians discuss and document patients' smoking status into electronic health records (EHR) and deliver smoking cessation assistance. METHODS: We analysed the results using a combination of rule and deep learning-based algorithms. Narrative reports of all adult patients, whose treatment started between years 2010 and 2016 for one of seven common chronic diseases, were followed for two years. Smoking related sentences were first extracted with a rule-based algorithm. Subsequently, pre-trained ULMFiT-based algorithm classified each patient's smoking status as a current smoker, ex-smoker, or never smoker. A rule-based algorithm was then again used to analyse the physician-patient discussions on smoking cessation among current smokers. RESULTS: A total of 35,650 patients were studied. Of all patients, 60% were found to have a smoking status in EHR and the documentation improved over time. Smoking status was documented more actively among COPD (86%) and sleep apnoea (83%) patients compared to patients with asthma, type 1&2 diabetes, cerebral infarction and ischemic heart disease (range 44-61%). Of the current smokers (N=7,105), 49% had discussed smoking cessation with their physician. The performance of ULMFiT-based classifier was good with F-scores 79-92. CONCLUSION: Ee found that smoking status was documented in 60% of patients with chronic disease and that the clinician had discussed smoking cessation in 49% of patients who were current smokers. ULMFiT-based classifier showed good/excellent performance and allowed us to efficiently study a large number of patients' medical narratives.

Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers.

OBJECTIVES: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. METHODS: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. RESULTS: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. CONCLUSION: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Development of self-assessed work ability among middle-aged asthma patients-a 10 year follow-up study.

OBJECTIVE: The prevalence of asthma has been growing among working age people over the last decades. In this study, we examine the development of Work Ability Score (WAS) among middle-aged asthmatics in a longitudinal setting, in order to find risk factors for poor development. METHODS: We followed the development of WAS trends during 10 years in a cohort of 529 middle-aged asthmatics, who were active in working life. Follow-up questionnaires were mailed in years 1, 2, 4, 6, 8, and 10. To study the development of WAS over time, we computed the discrete Frechet distance, which describes the similarity between the shapes of WAS curves. RESULTS: Sixty-eight percent of the patients' WAS remained good or excellent throughout the follow-up period, while 24% of the patients WAS trend remained moderate. However, in 8%, the WAS was poor already in baseline and decreased further throughout the study. Using logistic regression, the moderate/poor development was associated significantly with high body mass index (BMI), pack years, adult onset asthma, physically strenuous work, number of co-morbidities, especially in psychiatric conditions, hypertension, and gastroesophageal reflux disease(GERD). When the model was adjusted for age and gender, adulthood onset of asthma and pack years lost their significance. Based on medication (high dose of inhaled corticosteroids (ICS) and second controller in use), 8% of the patients had severe asthma. CONCLUSION: In the great majority of middle-aged asthma patients WAS remained stable throughout the follow-up period. However, 8% of the patients, who had more severe asthma and multiple co-morbidities, showed significantly poorer outcomes.

High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study.

OBJECTIVES: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines. MATERIALS AND METHODS: 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available. RESULTS: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB ≥ 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002). CONCLUSION: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.

Motor vehicle accidents in CPAP-compliant obstructive sleep apnea patients-a long-term observational study.

PURPOSE: Obstructive sleep apnea (OSA) has been associated with a 2- to 7-fold risk of motor vehicle accidents (MVAs). Continuous positive airway pressure (CPAP) treatment may reduce MVA risk. We further explored this issue in long-term CPAP users and untreated controls. METHODS: We used both before-after and case-control study designs. The observational cohort consisted of CPAP-treated and untreated patients matched for gender, age, and apnea-hypopnea index. All MVAs reported to the police were identified. RESULTS: A total of 2060 patients (75.8% male, mean age 56.0 ± 10.5 years) were included. The CPAP-treated patients (N = 1030) were screened for MVAs for a median of 9.0 years before and after treatment. The median CPAP usage was 6.4 h/day. The control patients (N = 1030) were screened for MVAs for a median of 6.5 years after discontinuation of CPAP. No significant differences were observed between the incidences of MVAs per 1000 person years before treatment (3.2), after treatment (3.9), or in controls (2.6). Compared with controls, patients who had MVA after treatment had a higher body mass index (BMI), but did not differ in terms of other baseline characteristics, sleep study data, or accident conditions. In the majority of these patients, daytime sleepiness was reduced, whereas BMI tended to increase during treatment. CONCLUSIONS: The MVA incidence did not change after CPAP treatment. Among the patients who had MVA, BMI was the only baseline characteristic that differed between the groups and tended to further increase after CPAP treatment. Differences in sleep study data or accident conditions were not observed.

Forced Vital Capacity (FVC) decline, mortality and healthcare resource utilization in idiopathic pulmonary fibrosis.

Aim of the study: Potential care implications of antifibrotic reimbursement restrictions were studied by forced vital capacity (FVC) decline, mortality and specialty care related healthcare resource utilization in patients with idiopathic pulmonary fibrosis (IPF). Material and methods: IPF patients were identified from the electronic medical records of the Hospital District of Southwest Finland between 2005 and 2017. Text-mining was used for patient identification to exclude other interstitial lung diseases (ILD) from the cohort. FVC reimbursement restriction (FVC 50-90%) was used for stratification. Results: Out of all patients with ILD, 27% (N = 266) were identified to have IPF. At baseline, 24% presented with FVC>90% and 63% with FVC 50-90% predicted. FVC at diagnosis did not improve during the study period. Median survival decreased by severity from 6.7 years in FVC>90% at baseline to 0.7 years in patient with FVC<50% predicted. In the FVC>90% group, 14% died before a change in FVC category could be noted. Overall, 4.7 million euro worth of specialty care resources were spent on IPF patients. The highest cost driver was inpatient days. Conclusions: IPF is associated with a high burden of disease, and reimbursement restrictions are in conflict with early care. As there are antifibrotic treatment options for IPF patients, early diagnosis is important.

Retrospective Evaluation of Lung Adenocarcinoma Patients Progressing on 1st Line Chemotherapy.

Background and Objectives: Evaluation of data from electronic health care records could help in guiding towards more rational drug treatments. This single center study evaluated clinical characteristics that could be associated with disease progression. Methods: This was a real world data (RWD) study using existing data from the registries of a university hospital. Patients had lung adenocarcinoma and they had received 1st line treatment. Treatment patterns and survival parameters were characterized and clinical characteristics of the patients were evaluated together with their association with disease progression. Results: 80 stage III/IV patients fulfilling inclusion criteria were identified. Mean age was 62 years and 61% were men. In total, 65% were current smokers and 82% had performance status (ECOG) 0/1. Median progression free survival (mPFS) and median overall survival (mOS) for stage III and IV patients were 8.5 and 5.4 months, and 21.9 and 8.6 months, respectively. The study found that 69% of patients progressed within 9 months from the start of the 1st line treatment. Poor performance status (ECOG 3), male gender, and smoking suggested faster disease progression. Most had received cis/carboplatin-based treatment in the 1st line. Cisplatin regimens were associated with more complete responses and better PFS and OS than the carboplatin ones. Conclusions: By combining algorithmic and manual validation of electronic health care records, clinically valid characteristics and outcomes could be evaluated and presented. This approach forms a basis for tools such as quality registries that can guide treatment decisions.

The Burden Of Chronic Obstructive Pulmonary Disease (COPD) In Finland: Impact Of Disease Severity And Eosinophil Count On Healthcare Resource Utilization.

Purpose: The burden associated with chronic obstructive pulmonary disease (COPD) is substantial. The objectives of this study were to describe healthcare resource utilization (HCRU) and HCRU-associated costs in patients with COPD in Finland, according to disease severity and blood eosinophil count (BEC). Patients and methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from the specialist care hospital register. Data extraction was from first hospital visit with a COPD diagnosis (index date) from January 1, 2004 until December 31, 2015 or death. Patients (aged >18 years with ≥1 report of post-bronchodilation forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) were categorized as having non-severe or severe COPD (FEV1 >50% or ≤50% of reference, respectively). Patients who were initially non-severe but progressed to severe were classified as having progressing COPD. Patients without spirometry registry data were classified as having clinically verified COPD. Patients were grouped according to BEC (≥300 cells/µL, <300 cells/µL or BEC unknown). HCRU, estimated associated costs and mortality were evaluated according to COPD severity and BEC. Results: There were 9042 patients with COPD; 340 non-severe, 326 progressing, 394 severe, and 7982 clinically verified. BEC was available for 31.8% of patients. The mean follow-up time was 3.7-6.5 years in the classified patient-groups. All-cause mortality was 46% during follow-up. Severe COPD was associated with more COPD-related HCRU and higher mortality than non-severe COPD. Patients with BEC ≥300 cells/µL had higher overall HCRU but improved survival compared with those with BEC <300 cells/µL. Overall direct costs were similar across COPD severity categories, 3300-3900€/patient-year, although COPD-related costs were higher in patients with severe versus non-severe COPD. Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic COPD for patients in Finland.

Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.

Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 × 10-9 ) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 × 10-9 ) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.

Consistency and reliability of smoking-related variables: longitudinal study design in asthma and COPD.

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.

Nonfatal and fatal cardiovascular disease events in CPAP compliant obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea (OSA) is suggested to predispose to cardiovascular disease (CVD) events. It is uncertain whether compliance to continuous positive airway pressure (CPAP) treatment could attenuate the risk. We explored this issue in long-term CPAP users and untreated controls. METHODS: Retrospective observational cohort of CPAP-treated and control patients were pairwise matched for gender, age, and apnea-hypopnea index (AHI). The study end point was a composite of nonfatal and fatal CVD events. Cox regression model was used to determine the association between CPAP treatment and event-free survival. RESULTS: A total of 2060 patients (75.8% male, mean age 56.0 ± 10.5 years), of which 76.4% had moderate-severe OSA, were included. In the CPAP-treated group (N = 1030), the median use of CPAP was 6.4 h/day during a median follow-up of 8.7 years. The control group (N = 1030) was followed for a median of 6.2 years after the CPAP treatment had ended. The study end point occurred in 14.4% (N = 148) of the CPAP-treated and in 18.8% (N = 194) of the control patients (p = 0.006). Using the Cox regression model adjusted for gender, age, AHI, body mass index, and history of CVD, hypertension, type 2 diabetes, and chronic obstructive pulmonary disease at baseline, a beneficial association between CPAP treatment and CVD risk was observed (hazard ratio 0.64, confidence interval 95% 0.5-0.8, p < 0.001). CONCLUSIONS: CPAP treatment was associated with a decreased risk of nonfatal and fatal CVD events. Majority of the patients were compliant to CPAP. The association was demonstrated independent from common cardiovascular risk factors and AHI.

Predictors of New Airway Obstruction - An 11 Year's Population-Based Follow-Up Study.

In the present study we aimed to investigate the incidence and predictors of spirometry based airway obstruction in a representative population-based sample. Altogether 3,863 subjects, 1,651 males and 2,212 females aged ≥30 years had normal spirometry in year 2000. Fifty-three percent of them were never and 23% current smokers. A re-spirometry was performed 11 years later. Several characteristics, such as level of education, use of alcohol, physical activity, diet using Alternate healthy eating (AHEI) index, body mass index, circumwaist, sensitive C reactive protein (CRP) and cotinine of the laboratory values and co-morbidities including asthma, allergic rhinitis, sleep apnoea and chronic bronchitis, as potential risk factors for airway obstruction were evaluated. Using forced expiratory volume in one second/ forced vital capacity below the lower limit of normal, we observed 124 new cases of airway obstruction showing a cumulative 11-year incidence of 3.2% and corresponding to an incidence rate of 5.6/1,000 per year (PY). The incidence rate was higher in men than in women (6.3/1,000 PY vs. 5.0/1,000 PY, respectively). The strongest risk factors were current smoking (Odds ratio [OR] 2.5) and previously diagnosed asthma (OR 2.1). Sensitive CRP associated with the increased risk and high AHEI index with the decreased risk of airway obstruction. Using the similar study approach our findings on the incidence of airway obstruction are in line with the previously published figures in Europe. We were able to confirm the recent findings on the protective effect of healthy diet.