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.

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.

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.

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.

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.

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.

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study.

BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9-3.8; P = 2.4 × 10-8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6-2.5; P = 9.7 × 10-9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6-2.7; P = 4.8 × 10-9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0-9.5; P = 7.1 × 10-9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.

End-of-life chemotherapy use at a Finnish university hospital: a retrospective cohort study.

BACKGROUND: Recent trends in the end-of-life (EOL) cancer care have suggested that the levels of treatment are becoming more aggressive. The aim of this single-center study was to evaluate the time from the last intravenous (IV) chemotherapy treatment to death and identify factors correlating with treatment closer to death. MATERIAL AND METHODS: The study included all patients diagnosed with cancer at Turku University Central Hospital between the years 2005 and 2013 (N = 38,982) who received IV chemotherapy during the last year of life (N = 3285). The cohort of patients and their respective clinical information were identified from electronic medical records. Statistical analysis was performed to assess and compare the treatment strategies, taking into account the patient's age, the year they were treated, and the type of cancer they were diagnosed with. RESULTS: A total of 11,250 cancer patients died during the observation time and one-third (N = 3285, 29.2%) of them had received IV chemotherapy during the last year of life. The time from the last IV chemotherapy regimen to death remained consistent across the follow-up time. During the last month of life, every third patient under the age of 50 years and only one-tenth of patients over the age of 80 years received IV chemotherapy. Hematological malignancies and lymphomas were treated closer to death when compared to other diagnostic groups. CONCLUSIONS: During the period of 9 years, the pattern of EOL IV chemotherapy treatment remained stable. Every third patient died at tertiary care. Only 7.2% of patients who received IV chemotherapy during the last year of life were treated 14 days before death, which is in line with international recommendations. However, significant variation in EOL treatment strategies between different diagnosis and age groups were identified.

Assessing the utilization of radiotherapy near end of life at a Finnish University Hospital: a retrospective cohort study.

BACKGROUND: Palliative radiotherapy can improve quality of life for cancer patients during the last months of life. However, very short life expectancy may devastate the benefit of the treatment. This single center study assesses the utilization of radiotherapy during the last weeks of life. MATERIAL AND METHODS: All cancer patients (N = 38,982) treated with radiotherapy (N = 11,395) in Turku University Central Hospital during 2005-2013 were identified in the database consisting of electronic patient records. One fourth (N = 2904, 25.5%) of the radiotherapy treatments were given during the last year of life. The last radiotherapy treatments and the time from the last radiotherapy treatment to death were assessed in regards to patients' age, cancer diagnosis, domicile, place of death and the treatment year. Treatments given during the last two weeks of life were also assessed regarding the goal of treatment and the reason for possible discontinuation. RESULTS: The median time from the last fraction of radiotherapy to death was 84 d. During the last two weeks before death (N = 340), pain (29.4%) was the most common indication for radiotherapy. Treatment was discontinued in 40.6% of the patients during the last two weeks of life, and worsening of general condition was the most common reason for discontinuity (70.3%). The patients receiving radiotherapy during the last weeks of life were more likely to die in tertiary care unit. During the last year of life single-fraction treatment was used only in 7% of all therapy courses. There was a statistically significant (p < .05) decrease in the median number of fractions in the last radiotherapy treatment between 2005-2007 (8 fractions) and 2011-2013 (6 fractions). CONCLUSIONS: Up to 70% of the treatments during the last two weeks of life were not delivered to alleviate pain and utilization of single fraction radiotherapy during the last year of life was infrequent. These observations suggest that practice of radiotherapy during the last weeks of life should be revisited.

Telemonitoring of CPAP therapy may save nursing time.

PURPOSE: Telemonitoring might enhance continuous positive airway pressure (CPAP) adherence and save nursing time at the commencement of CPAP therapy. We tested wireless telemonitoring (ResTraxx Online System®, ResMed) during the habituation phase of the CPAP therapy in obstructive sleep apnea syndrome (OSAS). METHODS: In total, 111 consecutive OSAS patients were enrolled. After CPAP titration, patients were followed with the telemonitoring (TM, N = 50) or the usual care (UC, N = 61). The TM group used fixed pressure CPAP device with and the UC group similar device without wireless telemonitoring. Patients and study nurses were unblinded. The evaluated end-points were hours of CPAP use >4 h/day, mask leak <0.4 L/s, and AHI <5/h. Nursing time including extra phone calls, visits, and telemonitoring time was recorded during the habituation phase. CPAP adherence was controlled in the beginning and at the end of the habituation phase and after 1-year of use. RESULTS: TM and UC groups did not differ in terms of patient characteristics. The average length of the habituation phase was 4 weeks in the TM group and fixed 3 months in the UC group. Median nursing time was 39 min (range 12-132 min) in the TM group and shorter compared to that of 58 min (range 40-180 min) (p < 0.001) per patient in the UC group. Both treatment groups had high CPAP usage hours (>4 h/day) and the change in usage at the end of the habituation phase did not differ between the groups (p = 0.39). Patients in both groups were equally satisfied with the treatment protocol. CPAP adherence (6.4 h in TM vs. 6.1 h in UC group, p = 0.63) and residual AHI (1.3 in TM vs. 3.2 in UC group, p = 0.04) were good in both groups at 1-year follow-up. CONCLUSIONS: Wireless telemonitoring of CPAP treatment could be relevant in closing the gap between the increasing demand and available health-care resources. It may save nursing time without compromising short- or long-term effectiveness of CPAP treatment in OSAS.

Individual FEV1 Trajectories Can Be Identified from a COPD Cohort.

OBJECTIVE: We aim to make use of clinical spirometry data in order to identify individual COPD-patients with divergent trajectories of lung function over time. STUDY DESIGN AND SETTING: Hospital-based COPD cohort (N = 607) was followed on average 4.6 years. Each patient had a mean of 8.4 spirometries available. We used a Hierarchical Bayesian Model (HBM) to identify the individuals presenting constant trends in lung function. RESULTS: At a probability level of 95%, one third of the patients (180/607) presented rapidly declining FEV1 (mean -78 ml/year, 95% CI -73 to -83 ml) compared to that in the rest of the patients (mean -26 ml/year, 95% CI -23 to -29 ml, p ≤ 2.2 × 10(-16)). Constant improvement of FEV1 was very rare. The rapid decliners more frequently suffered from exacerbations measured by various outcome markers. CONCLUSION: Clinical data of unique patients can be utilized to identify diverging trajectories of FEV1 with a high probability. Frequent exacerbations were more prevalent in FEV1-decliners than in the rest of the patients. The result confirmed previously reported association between FEV1 decline and exacerbation rate and further suggested that in clinical practice HBM could improve the identification of high-risk individuals at early stages of the disease.

CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers.

Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA5/CHRNA3 locus) have been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer, and COPD. The aim of this candidate gene study was to study the locus among the Finnish COPD patients and long-term smokers with regard to COPD risk, smoking behavior, cancer, and all-cause mortality. Genotyping of rs1051730, the locus tagging SNP was done in two longitudinal cohorts: Finnish COPD patients (N = 575, 74% men) and long-term smokers, all men (N = 1911). Finnish population sample (N = 1730) was used as controls. The analyses were done using logistic and Cox regression. The main findings were that the minor allele increased the risk of COPD when compared to the Finnish population at large (OR = 1.4, 95% CI 1.2-1.7, p = 3.2 × 10-5). Homozygosity for the risk allele was associated in both cohorts with all-cause mortality (crude HR 2.2, 95% CI 1.2-3.8 and 1.3, 95% CI 1.1-1.5, respectively), with any type of cancer (crude OR 2.3, 95% CI 1.0-5.1) among the COPD patients and with the number of pack-years (crude OR 1.4, 95% CI 1.1-1.9) among the male smokers. CHRNA5/CHRNA3 locus tagged by rs1051730, which has been previously associated with several smoking related diseases was now shown to be associated also with increased all-cause mortality among long-term smokers with or without clinical COPD further emphasizing the clinical importance of the finding.

Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap.

The pathophysiological features of chronic obstructive pulmonary disease (COPD)-asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells. Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n=26), smokers (n=23), asthma (n=32), COPD (n=39) and COPD-asthma overlap patients (n=14). In patients with COPD-asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD-asthma overlap compared with COPD (p=0.00016) and could be used to differentiate patients with overlap from those with COPD. Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap.

Long-term smoking increases the need for acute care among asthma patients: a case control study.

BACKGROUND: To examine risk factors for asthma patients' emergency room (ER) visits in a well organized asthma care setting. METHODS: A random sample of 344 asthma patients from a Pulmonary Clinic of a University Hospital were followed through medical records from 1995 to 2006. All the ER visits due to dyspnea, respiratory infections, chest pain, and discomfort were evaluated. RESULTS: The mean age of the study population was 56 years (SD 13 years), 72% being women. 117 (34%) of the patients had had at least one ER visit during the follow-up (mean 0.5 emergency visits per patient year, range 0-7). Asthma exacerbation, lower and upper respiratory infections accounted for the 71% of the ER visits and 77% of the hospitalizations. The patients with ER visits were older, had suffered longer from asthma and more frequently from chronic sinusitis, were more often ex- or current smokers, and had lower lung function parameters compared to the patients without emergency visits. Previous (HR 1.9, CI 1.3-3.1) and current smoking (HR 3.6, CI 1.6-8.2), poor self-reported health related quality of life (HRQoL) (HR 2.5, CI 1.5-4), and poor lung function (FEV1<65%, HR 2.2, CI 1.3-3.7) remained independent risk factors for ER visits after adjustment for age and gender. CONCLUSIONS: Asthma patients who are or have been long-term smokers are more likely to require ER care compared to never smokers.

Co-morbidities are the key nominators of the health related quality of life in mild and moderate COPD.

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.

Bayesian predictors of very poor health related quality of life and mortality in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with increased mortality and poor health-related quality of life (HRQoL) compared with the general population. The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model. METHODS: The data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995-2006. The data set contained 49 potential predictor variables and two outcome variables: survival (dead/alive) and HRQoL measured with a 15D instrument (very poor HRQoL < 0.70 vs. typical HRQoL ≥ 0.70).In the first phase of model validation we randomly divided the material into a training set (n = 538), and a test set (n = 200). This procedure was repeated ten times in random fashion to obtain independently created training sets and corresponding test sets. Modeling was performed by using the training set, and each model was tested by using the corresponding test set, repeated in each training set. In the second phase the final model was created by using the total material and eighteen most predictive variables. The performance of six logistic regressions approaches were shown for comparison purposes. RESULTS: In the final model, the following variables were associated with mortality or very poor HRQoL: age at onset, cerebrovascular disease, diabetes, alcohol abuse, cancer, psychiatric disease, body mass index, Forced Expiratory Volume (FEV1) % of predicted, atrial fibrillation, and prolonged QT time in ECG. The prediction accuracy of the model was 77%, sensitivity 0.30, specificity 0.95, positive predictive value 0.68, negative predictive value 0.78, and area under the ROC curve 0.69. While the sensitivity of the model reminded limited, good specificity, moderate accuracy, comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches, and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients. CONCLUSION: We developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.