Maritta Kilpeläinen

Overlap Syndrome of Asthma and COPD Predicts Low Quality of Life

Background. In clinical practice, patients whose airway disease shares features of both asthma and chronic obstructive pulmonary disease (COPD) remain poorly recognized. Material and methods. The study population consisted of 1546 patients with a diagnosis of asthma or COPD or both. Based on patient-reported outcomes and retrospective medical record data, the study population was divided into three groups: (1) asthma only, (2) COPD only, and (3) both asthma and COPD (overlap syndrome group). We evaluated patient characteristics associated with health-related quality of life (HRQoL). Results. In many respects, the overlap group fell between the asthma and COPD groups. In the overlap group, however, HRQoL was the poorest of all. In the logistic regression model, with the asthma group as the reference, both the overlap and the COPD group showed higher risk for low HRQoL [odd ratio (OR): 1.9; 95% confidence interval (CI): 1.2–3.2; and OR: 1.8, 95% CI: 1.0–3.2; respectively]. In addition, female gender, obesity, duration of disease, disability pension, and coexisting cardiovascular disease were associated with low HRQoL across the study population. Conclusions. Patients with overlapping asthma and COPD differed from those patients with asthma or COPD only. Overlap syndrome was associated with low HRQoL.

Prevalence of nickel allergy among Finnish university students in 1995

Nickel allergy was studied in a sample of 1st‐year university students starting their studies in 1995. A total of 296 subjects (72%) of 413 invited participated in the clinical examination, and 284, 96 male and 188 female, were patch tested (69%). A history of nickel sensitization was enquired for. Prick tests and serum specific IgE levels were determined. Occurrence of atopic dermatitis, hand eczema, and current exposure to metals were recorded. Nickel allergy was encountered in 39% of all female students, in 42% of females with pierced skin, and in 14% of females without pierced skin. The corresponding figures for males were 3%, 7% and 3%. In the multiple regression analysis, the risk factors for nickel allergy were female sex (OR 8.1, p<0.01), current metal exposure at examination (OR 4.1, p<0.01) and skin piercing (OR 3.6, p<0.05). Positive prick tests or elevated IgE levels to common allergens were not significantly associated with nickel allergy. In female students, the prevalence of nickel allergy has increased from 13% in 1986 to 39%. The prevalence among males has remained low at 3%. The results indicate that, in addition to skin piercing, current metal contacts are important risk factors for nickel allergy. This finding gives support to the EU Nickel Directive.

IL‐12 up‐regulates T‐bet independently of IFN‐γ in human CD4+ T cells

T‐bet is an important Th1 driving transcription factor regulated by IFN‐γ/STAT1 pathway. T‐bet turns on IFN‐γ transcription in CD4+ T cells and T‐bet‐deficient cells fail to differentiate to Th1 direction. Previous reports have characterized function of T‐bet mainly in murine cells and very little is known about its functions in human cells. Here, we studied T‐bet expression kinetics in parallel with GATA3 during Th1/Th2 polarization. We demonstrate that in addition to CD3/CD28 activation, cytokines IL‐12 and IFN‐α in the presence of neutralizing anti‐IFN‐γ enhanced T‐bet mRNA and protein expression in human CD4+ cells. T‐bet is known to be a potent inducer of IFN‐γ. Even though IFN‐γ and IL‐12 stimulation induced similar levels of T‐bet protein in human CD4+ cells, IFN‐γ‐treated cells produced considerably less IFN‐γ than cells treated with IL‐12. Therefore, high T‐bet protein expression does not necessarily correlate with IFN‐γ production. In addition, we show that the immunosuppressive cytokine TGF‐β inhibits T‐bet and GATA3 protein expression only if it is present prior to primary T cell activation and is maintained in the cultures during the early polarization of Th1/Th2 cells. In conclusion, we report new insights into the cytokine regulation of T‐bet in human CD4+ T cells.

Physical inactivity in COPD and increased patient perception of dyspnea

Objective: To study patients’ levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD). Methods: A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005. The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion. Results: A total of 50% of the participants reported exercising > 2 times a week throughout the year. The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices. Year-round activity was better maintained among patients who exercised both indoors and outdoors. Training activity was significantly correlated with patients’ reported subjective dyspnea (r = 0.32, P < 0.001), health-related quality of life (r = 0.25, P < 0.001), mobility score (r = 0.37, P < 0.001), and bronchial obstruction (r = 0.18, P < 0.001). Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index. Irrespective of the level of severity of patients’ COPD, the most significant barrier to exercising was the subjective sensation of dyspnea. Conclusion: When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities.

Real-world clinical data identifies gender-related profiles in chronic obstructive pulmonary disease.

This study aims to compare diagnostic and clinical outcomes of Chronic Obstructive Pulmonary Disease (COPD) from the gender perspective using retrospective health care data and patient reported outcomes in a real-world setting. An electronic database was constructed from complete medical records of 844 COPD patients who were recruited in Helsinki and Turku University Central Hospitals during the years 2005—07. The patients were identified from the hospital discharge registries by ICD10 code J44.8 in the age group of 18–75 years of age. The medical history was obtained from all healthcare providers who had treated these patients during the previous 5-10 years; the study intends to continue their follow-up annually for the next 10 years. Thirty-six percent (N = 266) of the participants were women. The COPD diagnosis had been made at the same age for both genders. Women, however, reported significantly less pack-years than men. Compared to the men, the women displayed less advanced airway obstruction, but more severe gas transfer impairment. Parenchymal damage when evaluated by diffusion capacity correlated significantly stronger with FEV1 (% of predicted) in women than men. The BMI index of the women was lower than that of the men. Cardiovascular diseases, diabetes and alcoholism were significantly more common in men, but women suffered more psychiatric conditions, especially depression. This cohort showed several significant gender dependent differences in the clinical presentation that need to taken under consideration in the assessment of COPD progression and the disease management.

Comparison between the disease-specific Airways Questionnaire 20 and the generic 15D instruments in COPD

BackgroundGiven that the assessment of health-related quality of life (HRQoL) is an essential outcome measure to optimize chronic obstructive pulmonary disease (COPD) patient management, there is a need for a short and fast, reliable and valid instrument for routine use in clinical practice. The objective of this study was to analyse the relationship between the disease-specific Airways questionnaire (AQ20) and the generic 15D health-related quality of life (HRQoL) instrument simultaneously in a large cohort of patients with COPD. We also compare the HRQoL of COPD patients with that of the general population.MethodsThe AQ20 and 15D were administered to 739 COPD patients representing an unselected hospital-based COPD population. The completion rates and validity of, and correlations among the questions and dimension scores were examined. A factor analysis with varimax rotation was performed in order to find subsets of highly correlating items of the questionnaires.ResultsThe summary scores of AQ20 and 15D were highly correlated (r = - 0.71, p < 0.01). In AQ20 over 50% of patients reported frequent cough, breathlessness during domestic work, and chest problem limiting their full enjoyment of life. 15D results showed a noteworthy decrease of HRQoL in breathing, mobility, sleeping, usual activities, discomfort and symptoms, vitality, and sexual activity (scores ≤ 0.75). Compared to the age- and gender-standardized Finnish general population, the COPD patients were statistically significantly worse off on 13 of 15 dimensions.ConclusionsThe AQ20 and 15D summary scores are comparable in terms of measuring HRQoL in COPD patients. The data support the validity of 15D to measure the quality of life in COPD. COPD compromises the HRQoL broadly, as reflected by the generic instrument. Both questionnaires are simple and short, and could easily be used in clinical practice with high completion rates.

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

BackgroundChronic 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.MethodsThe 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.ResultsIn 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.ConclusionWe developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.

Longitudinal HRQoL shows divergent trends and identifies constant decliners in asthma and COPD

BACKGROUND/AIM Monitoring of lung function alone does not adequately identify the high-risk patients among elderly asthma and COPD cohorts. The additional value of Health-Related Quality of Life (HRQoL) development in the detection of patients with a disabling disease in clinical practice is unclear. The aim of this study was to statistically examine the individual development of HRQoL measured using respiratory-specific AQ20 and generic 15D questionnaires. MATERIALS AND METHODS The HRQoL of COPD (N = 739) and asthma (N = 1329) patients was evaluated at 0, 1, 2, and 4 years after recruitment. To determine a five-year HRQoL change for each patient we used mixed-effects modelling for linear trend. RESULTS In COPD, the majority (60-80%) of the individuals showed declining trend, whereas in asthma, the majority (46-71%) showed no attenuation in HRQoL. The proportion of constant decliners was estimated higher with the 15D both in asthma (6.3%) and COPD (6.3%) than with AQ20 (3.5 and 4.5%, respectively). The first measurement of HRQoL was found to predict future development of HRQoL. In asthma, obesity-related diseases such as hypertension, diabetes and gastro-esophageal reflux disease best explained the decline, whereas in COPD, age and the level of bronchial obstruction were the main determinants. CONCLUSION Based on the five-year follow-up, the HRQoL trends significantly diverging from each other could be identified both among the asthma and COPD patients. Compared to cross-sectional HRQoL, the HRQoL trend over a clinically relevant period of time allows us to ignore, to a great extent, the random error of self-assessed HRQoL and thus, it may offer a more accurate measure to describe the disease process.

CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers

Abstract 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.

Individual FEV1 Trajectories Can Be Identified from a COPD Cohort

Abstract 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.