PLAUR polymorphisms and lung function in UK smokers.

BACKGROUND: We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene. In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers. METHODS: 25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992). Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV(1), FEV(1)/FVC) in all smokers. Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression. RESULTS: Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV(1) respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV(1)/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent. Interestingly, several of these associations were driven by male smokers not females. CONCLUSION: This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers. However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers. PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling.

Living with advanced chronic obstructive pulmonary disease: patients concerns regarding death and dying.

Prognosis in COPD is poor and many patients perceive shortcomings in the education they receive about aspects of their condition. This study explores the experiences of patients with COPD, particularly fears surrounding death and dying. Semi-structured interviews were conducted with 21 patients with moderate or severe COPD. Findings revealed that patient understanding of COPD was poor, most patients were unaware of the progressive nature of the condition, and few were aware they could die of COPD. Despite this, patients often expressed concerns that their condition might deteriorate. Patients had particular concerns regarding the manner of their death; the overriding fear was dying of breathlessness or suffocation. None of the patients' had discussed these fears with a health care professional. Improved patient education is needed in order to improve patients understanding of their condition and prognosis. Open communication regarding death, as advocated in a palliative care approach, is also appropriate to alleviate patients fears and to allow them to make decisions regarding the management of their care at the end of life.

Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

Associations between polymorphisms of the high-affinity immunoglobulin E receptor and late-onset airflow obstruction in older populations.

OBJECTIVES: To test the hypothesis that genetic polymorphisms in the beta subunit of the high-affinity immunoglobulin E (IgE) receptor are associated with late-onset airflow obstruction. DESIGN: Case-control candidate gene association study. SETTING: Department of Medicine for the Elderly and Respiratory Medicine in three teaching hospitals in Leicester and Manchester, United Kingdom. PARTICIPANTS: Cases with late-onset airflow obstruction with age-, sex-, and geographically matched controls. MEASUREMENTS: Subjects were genotyped for two polymorphisms of the beta subunit of the high-affinity IgE receptor (RsaI intron 2 and RsaI exon 7). The association between the polymorphisms and phenotypes was examined using contingency tables and linear regression models. RESULTS: Two hundred eighty-three cases and 144 controls were genotyped. RsaI exon 7 AA was associated with eczema (odds ratio (OR)=2.27, 95% confidence interval (CI)=1.17-4.38, P=.015). No other associations were found. Total serum IgE levels were significantly higher in cases than controls (adjusted OR for high/low IgE=2.56, 95% CI=1.53-4.28, P<.001). CONCLUSION: Serum IgE levels, but not the high-affinity IgE receptor polymorphisms, were associated with late-onset airflow obstruction, suggesting that interaction between environmental and genetic factors controlling serum IgE levels and disease pathogenesis may differ between early- and late-onset airflow obstruction phenotypes.

Exploring the care needs of patients with advanced COPD: an overview of the literature.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition worldwide and is associated with significant mortality. This paper gives an overview of the relevant literature regarding care needs in advanced COPD from the perspective of the patient or carer, and aims to explore the appropriateness of a palliative care approach in this group. Publications revealed that patients with COPD have a high symptom burden that impacts on quality of life and social functioning. Information provision in COPD is often lacking and the implications of diagnosis and prognosis are not routinely discussed. The impact on families and carers is considerable, many patients have significant care requirements which can affect family relationships. Although patients with COPD have regular contact with health services, access to specialist services and palliative care is poor. This paper highlights the need for increased provision for palliative care in COPD, alongside dedicated education and training for health professionals, and continued research to identify the most appropriate ways of delivering this care.