Umut Arinir

Association of interleukin-8 receptor |[alpha]| polymorphisms with chronic obstructive pulmonary disease and asthma

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptor α (IL8RA, CXCR1) and β (IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P=0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.

Relevance of human metapneumovirus in exacerbations of COPD

Background and methodsHuman metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.ResultsWe analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.ConclusionHMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.

Soluble Interleukin-5 Receptor Alpha Is Increased in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background: During chronic obstructive pulmonary disease (COPD) exacerbations (AE-COPD), an influx of eosinophils into the bronchial mucosa has been described. Eosinophilic cationic protein (ECP) and soluble interleukin-5 receptor α (sIL5Rα) are secreted by eosinophils and increased in eosinophilic airway diseases. Methods: We studied ECP and sIL5Rα expression in patients with COPD compared to healthy controls and smokers and investigated a possible association to viral exacerbations of COPD. Expression of sIL5Rα in serum was analyzed by ELISA and ECP by the Uni-Cap system. Induced sputum from patients with COPD was analyzed for six different respiratory viruses by nested PCR. Results: ECP and sIL5Rα were significantly elevated in AE-COPD subjects (n = 54) compared to healthy controls (n = 11, p = 0.018). Furthermore, there was a significant increase in sIL5Rα, but not in ECP, in 30 patients with virus-associated AE-COPD compared to smokers without COPD (n = 16) and healthy controls. The increase in FEV1 after resolution of the AE-COPD correlated with the decrease in sIL5Rα (r = 0.269, p = 0.034). Conclusions: sIL5Rα is increased in AE-COPD and not affected by smoking like ECP. sIL5Rα is increased in patients with virus-associated AE-COPD compared to smokers and controls. Concentrations of sIL5Rα mirror changes in the clinical status and lung function. These data support the involvement of eosinophils in acute exacerbations of COPD.

Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

Objective Human bocavirus (HBoV) is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Methods We retrospectively tested 212 COPD patients, 141 (66.5%) with AE-COPD and 71 (33.5%) with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA). The specificity of positive polymerase chain reaction results was confirmed by sequencing. Results Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%). Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8%) and stable COPD (2.9%). HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain. Conclusion HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely.

Variation in the COL29A1 gene in German patients with atopic dermatitis, asthma and chronic obstructive pulmonary disease

Dear Editor, Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, itchy skin lesions that usually presents in early childhood. The prevalence is approximately 5–15% in Western Europe. AD belongs to the group of allergic disorders also including food allergy, allergic rhinitis and asthma. It is supposed to be a multifactorial disorder influenced by environmental as well as genetic factors. A genomewide screen in European families reported linkage to a region on chromosome 3q21. Recently, Söderhäll et al. further investigated this region in a familybased association analysis using microsatellite markers and single nucleotide polymorphisms (SNP). They were able to narrow down the critical region and identified eight SNPs that showed allelic and haplotypic association with AD, with the strongest association results for SNP rs4688761. Subsequently, the findings were replicated in a second independent family cohort. A novel gene was identified in the critical region that contains a collagenous domain and therefore was classified as collagen 29A1 (COL29A1). Expression analysis of COL29A1 showed highest expression in the skin, but also in other epithelial tissues such as lung and gastrointestinal tract, which are the main manifestation sites of allergic disorders. Taken together, the COL29A1 gene represents the first AD gene that was identified by positional cloning. Expression analysis indicated that variation in COL29A1 may not only play a role in AD pathogenesis but also in the pathogenesis of respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma. For replication of these findings, we genotyped four selected SNPs in COL29A1 in a German case–control cohort comprising 465 patients with AD and 350

The role of respiratory infections in chronic obstructive pulmonary disease

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Lung impairment in systemic sclerosis

Scleroderma is a generic term for autoimmunological diseases having thickened sclerotic skin lesions in common. Scleroderma belongs to a group of connective tissue diseases. The systemic form of scleroderma is called progressive systemic sclerosis (PSS) or systemic sclerosis (SSc). Lung impairments, namely interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are one of the most common manifestations in SSc. This article summarises the forms of lung impairment in SSc with special emphasis on interstitial lung diseases and draws attention to the so far identified pathogenetic mechanisms and the presently accepted therapeutic options.

Zur Genetik der chronisch-obstruktiven Lungenerkrankung

COPD is a heterogenous disease caused by the interaction of genetic susceptibility and environmental influences. The best example to support this is tobacco smoke. Although cigarette smoking is the most important aetiological factor, only up to half of chronic smokers develop significant COPD. There are three main themes within the pathogenesis of COPD: 1) imbalance between proteases and anti-proteases, 2) oxidative stress, 3) inflammation. Disparity between levels of exogeneous oxidants, e. g., tobacco smoke, and endogeneous antioxidants leads to oxidative stress which, in turn, causes an inflammatory response involving pro-inflammatory mediators. The activated inflammatory cells release further proteases and oxidants, leading to chronic inflammation and irreversible destruction of connective tissue in the lung. Individual genetic variations influence these processes in many ways. This article summarises the results of recent candidate gene studies for COPD.Definitionsgemäß ist die chronisch obstruktive Lungenerkrankung (COPD) durch eine progre− diente, nicht−reversible Atemwegsobstruktion charakterisiert. Die Prävalenz wird bei der er− wachsenen Bevölkerung in Deutschland auf 10±15 % geschätzt [1]. Weltweit ist die COPD ge− genwärtig die vierthäufigste Todesursache. Bei steigender Prävalenz, Morbidität und Mortalität wird die COPD im Jahre 2020 auf den 3.Platz der weltweit häufigsten Todesursachen vorrücken [2]. Die sozioökonomische Bedeutung der COPD ist unbestritten. Nach Schätzungen betragen die volkswirtschaftlichen Gesamtkosten in Europa 38,7 Mrd. C = [1, 3]. Die durchschnittlichen jährli− chen Kosten in Deutschland pro COPD−Patient aus volkswirtschaftlicher Sicht wurden auf 3027 C = geschätzt, wobei Krankenhausaufenthalte mit 26%, Medikamente mit 23%, die Frührente mit 17 % und die Rehabilitation mit 1,5 % zu die− sen Kosten beitragen [4]. Als Risikofaktoren für die Entwicklung einer COPD werden sowohl genuine als auch erworbe− Zusammenfassung !

Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung@@@The Role of Respiratory Infections in Chronic Obstructive Pulmonary Disease

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.