TY  - JOUR
AB  - BackgroundForced expiratory volume in one second (FEV1) characterizes the pathophysiology of COPD and different trajectories of FEV1 decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV1 and change in disease-specific and generic HRQL.MethodsWe analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV1 and to calculate mean changes in HRQL per FEV1 change categories [decrease (<= -100ml), no change, increase (>= 100ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV1 difference or change.ResultsWe observed a statistically significant deterioration in SGRQ (total score+1.3units) after 3 years, which was completely driven by the activity component (+4units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV1, 28% were recorded as no change in FEV1, and 13% experienced an increase. The relationship between HRQL and FEV1 was found to be approximately linear with decrease in FEV1 being statistically significantly associated with a deterioration in SGRQ (+3.20units). Increase in FEV1 was associated with improvements in SGRQ (-3.81units). The associations between change in FEV1 and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV1 and the SGRQ activity domain.ConclusionsDifference and change in FEV1 over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes.Trial registrationNCT01245933. Date of registration: 18 November 2010.
AU  - Lutter, J.
AU  - Jörres, R.A.*
AU  - Kahnert, K.*
AU  - Schwarzkopf, L.
AU  - Studnicka, M.*
AU  - Karrasch, S.
AU  - Schulz, H.
AU  - Vogelmeier, C.F.*
AU  - Holle, R.
C1  - 59244
C2  - 48680
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - Health-related quality of life associates with change in FEV1 in COPD: Results from the COSYCONET cohort.
JO  - BMC Pulm. Med.
VL  - 20
IS  - 1
PB  - Bmc
PY  - 2020
ER  - 

TY  - JOUR
AB  - Background: Asthma patients experience impairments in health-related quality of life (HRQL). Interventions are available to improve HRQL. EQ-5D-5L is a common generic tool used to evaluate health interventions. However, there is debate over whether the use of this measure is adequate in asthma patients.Methods: We used data from 371 asthma patients participating in a pulmonary rehabilitation (PR) program from the EPRA randomized controlled trial. We used four time points: T0 randomization, T1 start PR, T2 end PR, T3 3 months follow-up. We calculated floor and ceiling effects, intra-class correlation (ICC), Cohen's d, and regression analysis to measure the sensitivity to changes of EQ-5D-5 L (EQ-5D index and Visual Analog Scale (VAS)) and the disease-specific Asthma Quality of Life Questionnaire (AQLQ). Furthermore, we estimated the minimally important difference (MID). Based on the Asthma Control Test (ACT) scores, we defined three groups: 1. ACT-A (ACT> 19) controlled asthma, 2. ACT-B (14 < ACT <= 19) not well-controlled asthma, and 3. ACT-C (ACT <= 14) very poorly controlled asthma.Results: Only the EQ-5D index showed ceiling effects at T2 and T3 (32%). ICC (between T0 and T1) was moderate or good for all measures. Cohen's d at T2 and T3 was better at differentiating between ACT-A and ACT-B than between ACT-B and ACT-C. The EQ-5D index showed moderate effect sizes (0.63-0.75), while AQLQ showed large effect sizes (0.74-1,48). VAS was responsive to pronounced positive and negative ACT changes in every period, and AQLQ mostly to the positive changes, whereas the EQ-5D index was less responsive. We estimated a MID of 0.08 for the EQ-5D index, 12.3 for VAS, and 0.65 for AQLQ.Conclusion: All presented HRQL tools had good discriminatory power and good reliability. However, EQ-5D-5 L did not react very sensitively to small changes in asthma control. Therefore, we would suggest using supplementary measures in addition to EQ-5D-5 L to evaluate asthma-specific interventions more comprehensively.
AU  - Szentes, B.L.
AU  - Schultz, K.*
AU  - Nowak, D.*
AU  - Schüler, M.*
AU  - Schwarzkopf, L.
C1  - 59365
C2  - 48757
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - How does the EQ-5D-5L perform in asthma patients compared with an asthma-specific quality of life questionnaire?
JO  - BMC Pulm. Med.
VL  - 20
IS  - 1
PB  - Bmc
PY  - 2020
ER  - 

TY  - JOUR
AB  - Background: Asthma and wheezing disorders in childhood and adulthood are clinically heterogeneous regarding disease presentation, natural course, and response to treatment. Deciphering common disease mechanisms in distinct subgroups requires harmonized molecular (endo-) phenotyping of both children and adult patients with asthma in a prospective, longitudinal setting. Methods: The ALL Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL) is a prospective, multi-center, observational cohort study with seven recruiting sites across Germany. Data are derived from four sources: (a) patient history from medical records, (b) standardized questionnaires and structured interviews, (c) telephone interviews, and (d) objective measurements. Objective measurements include amongst others lung function and quantitative assessment of airway inflammation and exhaled breath, peripheral blood, skin, nasal, pharyngeal, and nasopharyngeal swabs, nasal secretions, primary nasal epithelial cells, and induced sputum. In cases, objective measurements and biomaterial collection are performed regularly, while control subjects are only examined once at baseline. Discussion: The standardized and detailed collection of epidemiological and physiological data, and the molecular deep phenotyping of a comprehensive range of biomaterials in a considerable number of study participants across all ages are the outstanding characteristics of this multi-center cohort. Despite extensive biomaterial sampling, and a recruitment strategy that also includes pre-school children as young as 6 months, attrition is low. In children 83.9%, and in adults 90.5% attended the 12-month follow-up. The earliest time-point to include cases, however, is disease manifestation. Therefore, unraveling mechanisms that drive disease onset is limited, as this question can only be answered in a population-based birth cohort. Nonetheless, ALLIANCE offers a unique, integrative and inter-disciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood. Ultimately, this approach aims to translate its most significant findings into clinical practice, and to improve asthma transition from adolescence to adulthood. Trial registration:NCT02496468for pediatric arm, NCT02419274for adult arm.
AU  - Fuchs, O.*
AU  - Bahmer, T.*
AU  - Weckmann, M.*
AU  - Dittrich, A.M.*
AU  - Schaub, B.*
AU  - Roesler, B.*
AU  - Happle, C.*
AU  - Brinkmann, F.*
AU  - Ricklefs, I.*
AU  - Koenig, I.R.*
AU  - Watz, H.*
AU  - Rabe, K.F.*
AU  - Kopp, M.V.*
AU  - Hansen, G.*
AU  - von Mutius, E.
C1  - 54203
C2  - 45333
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: A longitudinal cohort study.
JO  - BMC Pulm. Med.
VL  - 18
IS  - 1
PB  - Bmc
PY  - 2018
ER  - 

TY  - JOUR
AB  - Following publication of the original article [1], the author flagged aspects of the article that affected readability of some of the article's scientific content.
AU  - Fuchs, O.*
AU  - Bahmer, T.*
AU  - Weckmann, M.*
AU  - Dittrich, A.M.*
AU  - Schaub, B.*
AU  - Rösler, B.*
AU  - Happle, C.*
AU  - Brinkmann, F.*
AU  - Ricklefs, I.*
AU  - König, I.R.*
AU  - Watz, H.*
AU  - Rabe, K.F.*
AU  - Kopp, M.V.*
AU  - Hansen, G.*
AU  - von Mutius, E.
C1  - 54764
C2  - 45863
CY  - Campus, 4 Crinan St, London N1 9xw, England
SP  - 165
TI  - Correction to: The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: a longitudinal cohort study.
JO  - BMC Pulm. Med.
VL  - 18
IS  - 1
PB  - Bmc
PY  - 2018
ER  - 

TY  - JOUR
AB  - Spirometric indices as well as other respiratory and functional parameters decline with age, but the link between the changes is not well studied. We assessed their relationship in elderly subjects with either good or poor spirometric parameters to reveal whether different domains of lung function show comparable differences between the two groups. Among subjects of the population-based KORA-Age cohort (n=935, 65-90y; 51% male) two groups were selected from either the lower (LED; n=51) or the upper (UED; n=72) end of the FEV1 distribution. All subjects did not have a history of lung disease and were non-smokers at the time of the study. Measurements included spirometry, body plethysmography, diffusing capacity for NO and CO, respiratory pump function and exhaled NO (FeNO). In addition, 6-minute walking distance as a functional overall measure, as well as telomere length of blood leukocytes and serum 8-hydroxydeoxyguanosine (8-OHdG) as potential markers of overall biological ageing and stress were determined. In the majority of parameters, LED subjects showed significantly impaired values compared to UED subjects. Differences in spirometric parameters, airway resistance and respiratory pump function ranged between 10% and more than 90% in terms of predicted values. In contrast, volume-related CO and NO diffusing capacity showed differences between groups of lower than 5%, while telomere length, 8-OHdG and FeNO were similar. This was reflected in the differences in functional age as derived from prediction equations. In elderly subjects without a history of lung disease the differences in lung-mechanical parameters of spirometry and body plethysmography were higher than those of gas exchange. Thus, the concept of a general functional “lung age” might be inadequate and specific terms such as “spirometric age” should be preferred.
AU  - Karrasch, S.
AU  - Behr, J.*
AU  - Huber, R.M.*
AU  - Nowak, D.*
AU  - EUMODIC Consortium (Peters, A.
AU  - Holle, R.
AU  - Schulz, H.
AU  - Leidl, R.
AU  - Meisinger, C.
AU  - Strauch, K.)
AU  - Peters, S.*
AU  - Jörres, R.A.*
C1  - 50146
C2  - 42034
TI  - Heterogeneous pattern of differences in respiratory parameters between elderly with either good or poor FEV1.
JO  - BMC Pulm. Med.
VL  - 18
PY  - 2018
ER  - 

TY  - JOUR
AB  - BACKGROUND: In lung disease, physical activity (PA) yields beneficial health effects, but its association with the function of healthy lungs has rarely been studied. We investigated the association of accelerometer-based PA with spirometric indices, maximal inspiratory mouth pressure (PImax) and lung diffusion capacity in lung-healthy adults. METHODS: In total, 341 apparently lung-healthy participants from the population-based KORA (Cooperative Health Research in the Region of Augsburg) FF4 cohort study (45% male, aged 48-68 years, 47% never smokers) completed lung function testing and wore ActiGraph accelerometers over a one week period at the hip. In adjusted regression analyses, moderate to vigorous PA (MVPA) was characterized as: sex-specific activity quartiles, achieving ≥ 10 consecutive minutes (yes vs. no), and meeting the WHO PA recommendations (yes vs. no). RESULTS: Positive associations of MVPA-quartiles with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and corresponding Global Lung Function Initiative z-scores were found. Subjects in the most active quartile (> 47 or > 50 min/day for females and males, respectively) had 142 ml [95% CI: 23, 260] higher FEV1 and 155 ml [95% CI: 10, 301] higher FVC than those in the least active quartile (< 17 or < 21 min/day for females and males, respectively); however these associations were stronger among ex-/current smokers. Achieving at least once 10 consecutive minutes of MVPA was only associated with higher PImax [β-estimate: 0.57 kPa; 95% CI: 0.04, 1.10], remaining significant among never smokers. No associations were found with diffusion capacity or for reaching the WHO-recommended 150 min of MVPA/week in 10-min bouts. CONCLUSIONS: Although the effects were small, active subjects showed higher spirometric results. The observed associations were more pronounced among ever smokers suggesting a higher benefit of PA for subjects being at a higher risk for chronic lung diseases.
AU  - Luzak, A.
AU  - Karrasch, S.
AU  - Thorand, B.
AU  - Nowak, D.*
AU  - Holle, R.
AU  - Peters, A.
AU  - Schulz, H.
C1  - 52654
C2  - 44087
CY  - London
TI  - Association of physical activity with lung function in lung-healthy German adults: Results from the KORA FF4 study.
JO  - BMC Pulm. Med.
VL  - 17
IS  - 1
PB  - Biomed Central Ltd
PY  - 2017
ER  - 

TY  - JOUR
AB  - BACKGROUND: Asthma patients are enrolled in multimodal pulmonary rehabilitation (PR) programs. However, available data for the effectiveness of PR in asthma are sparse. Therefore, the primary aim of this randomized control trial (RCT) is to evaluate short-term (end of rehabilitation) and intermediate-term effectiveness (3 months after rehabilitation) of PR for patients with asthma regarding asthma control (primary outcome) and other outcomes. Secondly, moderator effects of gender, age, baseline asthma control, quality of life, and anxiety will be examined. Thirdly, a longitudinal follow-up study will explore the course of the outcomes over one year and the annual costs. METHODS: The EPRA study is a single-center randomized controlled waiting-list trial in the Bad Reichenhall Clinic. Inclusion criteria include a referral diagnosis for uncontrolled asthma, no cognitive impairment and no very severe co-morbidities that indicate significantly greater illness morbidity than asthma alone. In the intervention group (IG), participants will start PR within 4 weeks after randomization; participants of the control group (CG) will start PR 20 weeks after randomization. Data will be assessed at randomization (T0), after 4 weeks (T1; IG: begin of PR), 7 weeks (T2; IG: end of PR), and 20 weeks (T3, CG: begin of PR). The primary outcome is asthma control at T2/T3. Secondary outcomes are health-related quality of life, functional exercise capacity, dyspnea, anxiety, depression, subjective self-management skills, illness perceptions, sick leave and subjective work ability. Outcomes will be analyzed with analysis of covariance, including baseline values of the respective outcomes as covariates. Healthcare costs will be analyzed with a gamma model with a log-link. A longitudinal follow-up study will generate additional data at 3/6/9/12 months after PR for both IG and CG. Latent change models will be used to analyze the course of the primary and secondary outcomes. Annual cost differences before and after rehabilitation will be compared by paired t-test. DISCUSSION: This RCT will determine the effectiveness of a complex inpatient PR for asthma patients concerning asthma control. Furthermore, important medical and economic information regarding the effectiveness of PR as part of the long-term management of patients with uncontrolled asthma will be generated. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00007740 , May 15, 2015). Protocol version: 1.0 (December, 23, 2016).
AU  - Schultz, K.*
AU  - Seidl, H.
AU  - Jelusic, D.*
AU  - Wagner, R.*
AU  - Wittmann, M.*
AU  - Faller, H.*
AU  - Nowak, D.*
AU  - Schüler, M.*
C1  - 50689
C2  - 42676
TI  - Effectiveness of pulmonary rehabilitation for patients with asthma: study protocol of a randomized controlled trial (EPRA).
JO  - BMC Pulm. Med.
VL  - 17
IS  - 1
PY  - 2017
ER  - 

TY  - JOUR
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient's health-related quality of life (HRQL). While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health. This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George's Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments. METHODS: Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions. Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences. RESULTS: In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease. Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions. The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions. For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL. CONCLUSION: All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities. Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.
AU  - Wacker, M.
AU  - Jörres, R.A.*
AU  - Karch, A.*
AU  - Wilke, S.*
AU  - Heinrich, J.
AU  - Karrasch, S.*
AU  - Koch, A.*
AU  - Schulz, H.
AU  - Watz, H.*
AU  - Leidl, R.*
AU  - Vogelmeier, C.*
AU  - Holle, R.
AU  - COSYCONET Consortium (*)
C1  - 48554
C2  - 41174
CY  - London
TI  - Assessing health-related quality of life in COPD: Comparing generic and disease-specific instruments with focus on comorbidities.
JO  - BMC Pulm. Med.
VL  - 16
IS  - 1
PB  - Biomed Central Ltd
PY  - 2016
ER  - 

TY  - JOUR
AB  - BACKGROUND: Dampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health. METHODS: Seven different fungal and bacterial parameters were assessed in mattress dust from 956 adult ECRHS II participants in addition to interview based home characteristics. Associations between microbial parameters and the asthma score and lung function were examined using mixed negative binomial regression and linear mixed models, respectively. RESULTS: Indoor dampness and pet keeping were significant predictors for higher microbial agent concentrations in mattress dust. Current mould and condensation in the bedroom were significantly associated with lung function decline and current mould at home was positively associated with the asthma score. Higher concentrations of muramic acid were associated with higher mean ratios of the asthma score (aMR 1.37, 95%CI 1.17-1.61). There was no evidence for any association between fungal and bacterial components and lung function. CONCLUSION: Indoor dampness was associated with microbial levels in mattress dust which in turn was positively associated with asthma symptoms.
AU  - Tischer, C.G.
AU  - Zock, J.P.*
AU  - Valkonen, M.*
AU  - Doekes, G.*
AU  - Guerra, S.*
AU  - Heederik, D.*
AU  - Jarvis, D.*
AU  - Norbäck, D.*
AU  - Olivieri, M.*
AU  - Sunyer, J.*
AU  - Svanes, C.*
AU  - Täubel, M.*
AU  - Thiering, E.
AU  - Verlato, G.*
AU  - Hyvärinen, A.*
AU  - Heinrich, J.
C1  - 44576
C2  - 37008
CY  - London
TI  - Predictors of microbial agents in dust and respiratory health in the Ecrhs.
JO  - BMC Pulm. Med.
VL  - 15
IS  - 1
PB  - Biomed Central Ltd
PY  - 2015
ER  - 

TY  - JOUR
AB  - BACKGROUND: It is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL. This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities. METHODS: In the population-based KORA F4 study (2006-08) 1,321 participants aged 41-61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities. For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999-2001) and the F4L follow-up study (2010). Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups. RESULTS: 7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1. Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered. Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (-3.5 (p = 0.008) in F4, -3.3 (p = 0.014) in S4 and -4.7 (p = 0.003) in F4L) compared to the group without airflow limitation. The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer. Over ten years, a small decline in PCS-12 was observed in all groups. This decline was larger in participants with COPD grade 2+, but insignificant. Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found. CONCLUSION: Despite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades. Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients.
AU  - Wacker, M.
AU  - Hunger, M.
AU  - Karrasch, S.
AU  - Heinrich, J.
AU  - Peters, A.
AU  - Schulz, H.
AU  - Holle, R.
C1  - 31957
C2  - 34906
CY  - London
TI  - Health-related quality of life and chronic obstructive pulmonary disease in early stages - longitudinal results from the population-based KORA cohort in a working age population.
JO  - BMC Pulm. Med.
VL  - 14
IS  - 1
PB  - Biomed Central Ltd
PY  - 2014
ER  - 

TY  - JOUR
AB  - Protein arginine methylation is a novel posttranslational modification regulating a diversity of cellular processes, including protein-protein interaction, signal transduction, or histone function. It has recently been shown to be dysregulated in chronic renal, vascular, and pulmonary diseases, and metabolic products originating from protein arginine methylation have been suggested to serve as biomarkers in cardiovascular and pulmonary diseases. Protein arginine methylation is performed by a class of enzymes called protein arginine methyltransferases (PRMT), which specifically methylate protein-incorporated arginine residues to generate protein-incorporated monomethylarginine (MMA), symmetric dimethylarginine (SDMA), or asymmetric dimethylarginine (ADMA). Upon proteolytic cleavage of arginine-methylated proteins, free intracellular MMA, SDMA, or ADMA is generated, which, upon secretion into the extracellular space (including plasma), directly affects the methylarginine concentration in the plasma. Free methylarginines are cleared from the body by renal excretion or hepatic metabolism. In addition, MMA and ADMA, but not SDMA, can be degraded via a class of intracellular enzymes called dimethylarginine dimethylaminohydrolases (DDAH). ADMA and MMA are endogenous inhibitors of nitric oxide synthases (NOS) and ADMA has been suggested to serve as a biomarker of endothelial dysfunction in cardiovascular diseases. This view has now been extended to the idea that, in addition to serum ADMA, the amount of free, as well as protein-incorporated, intracellular ADMA influences pulmonary cell function and determines the development of chronic lung diseases, including pulmonary arterial hypertension (PAH) or pulmonary fibrosis. This review will present and discuss the recent findings of dysregulated arginine methylation in chronic lung disease. We will highlight novel directions for future investigations evaluating the functional contribution of arginine methylation in lung homeostasis and disease with the outlook that modifying PRMT or DDAH activity presents a novel therapeutic option for the treatment of chronic lung disease.
AU  - Zakrzewicz, D.*
AU  - Eickelberg, O.
C1  - 254
C2  - 26818
TI  - From arginine methylation to ADMA: A novel mechanism with therapeutic potential in chronic lung diseases.
JO  - BMC Pulm. Med.
VL  - 9
PB  - Biomed Central Ltd
PY  - 2009
ER  - 

TY  - JOUR
AB  - BACKGROUND: Asthma is a complex genetic disease with more than 20 genome-wide scans conducted so far. Regions on almost every chromosome have been linked to asthma and several genes have been associated. However, most of these associations are weak and are still awaiting replication. METHODS: In this study, we conducted a second-stage genome-wide scan with 408 microsatellite markers on 201 asthma-affected sib pair families and defined clinical subgroups to identify phenotype-genotype relations. RESULTS: The lowest P value for asthma in the total sample was 0.003 on chromosome 11, while several of the clinical subsets reached lower significance levels than in the overall sample. Suggestive evidence for linkage (p = 0.0007) was found for total IgE on chromosomes 1, 7 and again on chromosome 11, as well as for HDM asthma on chromosome 12. Weaker linkage signals could be found on chromosomes 4 and 5 for early onset and HDM, and, newly described, on chromosome 2 for severe asthma and on chromosome 9 for hay fever. CONCLUSIONS: This phenotypic dissection underlines the importance of detailed clinical characterisations and the extreme genetic heterogeneity of asthma.
AU  - Altmüller, J.
AU  - Seidel, C.
AU  - Lee, Y.*
AU  - Loesgen, S.*
AU  - Bulle, D.*
AU  - Friedrichs, F.*
AU  - Jellouschek, H.*
AU  - Kelber, J.*
AU  - Keller, A.*
AU  - Schuster, A.*
AU  - Silbermann, M.*
AU  - Wahlen, W.*
AU  - Wolff, P.*
AU  - Schlenvoigt, G.*
AU  - Ruschendorf, F.*
AU  - Nürnberg, P.*
AU  - Wjst, M.
C1  - 2533
C2  - 23505
TI  - Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families.
JO  - BMC Pulm. Med.
VL  - 5
PB  - BioMed Central
PY  - 2005
ER  -