This study investigated the prevalence, risk factors and rate of recognition of anxiety and depression in 50 patients hospitalized for exacerbation of chronic obstructive pulmonary disease (COPD). ...Using the Primary Care Evaluation of Mental Disorders questionnaire, 13 patients were identified as having depression, four had anxiety and eight had a combination of the two. Patients with anxiety and/or depression had a significantly higher partial pressure of oxygen and pH, and a lower partial pressure of carbon dioxide, in arterial blood on admission, more severe dyspnoea after a 6-min walk test and less improvement of dyspnoea from admission to discharge than COPD patients without anxiety and/or depression. Two patients were referred to a mental health specialist during their hospitalization, indicating a low rate of recognition. The results suggest that patients with mental disorders are referred and admitted to hospital earlier in the course of a COPD exacerbation due to earlier and more intense perception of dyspnoea.
Asthma is a heterogeneous disease, and asthmatic patients without rhinitis more commonly have fixed airway obstruction, a feature that is also typical of chronic obstructive pulmonary disease (COPD). ...The Dutch hypothesis suggests that both COPD and asthma have common genetic risk factors. The purpose of this study was to assess the association between the polymorphism rs4795405 in the known asthma candidate gene ORMDL3 and asthma with and without rhinitis. We also analyzed COPD in order to investigate whether, in addition to a clinical overlap, there might also be a genetic overlap between COPD and asthma.
The population of this genetic association study comprised 493 Slovenian adults, distributed as follows: 131 patients with asthma (59 had asthma with rhinitis and 72 asthma without rhinitis), 59 patients with rhinitis only, 133 patients with COPD, and 170 controls. Genotypes for rs4795405 were determined using the TaqMan genotyping assay.
rs4795405 was specifically associated with asthma without rhinitis. Assuming a recessive genetic model, we found the CC genotype in 26% of healthy controls, in 24% of patients with asthma with rhinitis (P = .862), and in 44% of patients with asthma without rhinitis (P = .006). Polymorphism rs4795405 was also associated with COPD, for which the CC genotype was found in 37% of cases (P = .045).
rs4795405 was strongly associated with asthma without rhinitis, a subtype of asthma for which a higher degree of airway obstruction was found. These results show the importance of analyzing different asthma phenotypes in genetic association studies. We also observed a genetic overlap between COPD and asthma without rhinitis.
Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were ...implemented around the globe. The United States and Australia finally approved only non‐adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non‐specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1‐specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene‐based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non‐adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B‐Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1‐induced immunogenicity was good for both vaccines. Our results suggest a pronounced non‐specific T cell response after AS03‐adjuvanted 2009 H1N1 vaccination.
Objectives: We investigated the short-term effects of carbon monoxide on total and cardiovascular mortality in 19 European cities participating in the APHEA-2 (Air Pollution and Health: A European ...Approach) project. Methods: We examined the association using hierarchical models implemented in two stages. In the first stage, data from each city were analyzed separately, whereas in the second stage the city-specific air pollution estimates were regressed on city-specific covariates to obtain overall estimates and to explore sources of possible heterogeneity. We evaluated the sensitivity of our results by applying different degrees of smoothing for seasonality control in the city-specific analysis. Results: We found significant associations of CO with total and cardiovascular mortality. A$1-mg/m^3$increase in the 2-day mean of CO levels was associated with a 1.20% 95% confidence interval (CI), 0.63-1.77% increase in total deaths and a 1.25% (95% CI, 0.30-2.21%) increase in cardiovascular deaths. There was indication of confounding with black smoke and nitrogen dioxide, but the pollutant-adjusted effect of CO on mortality remained at least marginally statistically significant. The effect of CO on total and cardiovascular mortality was observed mainly in western and southern European cities and was larger when the standardized mortality rate was lower. Conclusions: The results of this large study are consistent with an independent effect of CO on mortality. The heterogeneity found in the effect estimates among cities may be explained partly by specific city characteristics.
Treatment failure of venom immunotherapy (VIT) is not rare and the risk and pathogenic factors for those failures are so far poorly understood. For that reason we evaluated allergen-specific basophil ...sensitivity in patients who did not tolerate field re-stings after completed VIT treatment.
Basophil responsiveness was evaluated by flow cytometry analyses of basophil CD63 surface expression induced by different concentrations of bee or wasp venom (1, 0.1 and 0.01 microg/ml) in 14 treated patients who had experienced systemic allergic reactions (Muller grades II-III) and 17 treated patients who had no reactions after the field re-stings. We also included a group of 28 Hymenoptera venom-allergic patients who had not received VIT.
In 14 patients who still reacted to bee or wasp sting, basophil response at a venom concentration of 0.1 microg/ml was significantly higher than in patients who tolerated field re-stings (p = 0.03; t test). Basophil response was also slightly higher at a concentration of 1 microg/ml, but not to statistical significance (p = 0.12; t test). There was no difference in the response to direct cross-linking of the IgE and in venom-specific IgE and IgG4 serum concentrations between those 2 groups (p > 0.8; Fisher's exact test, t test). Patients who tolerated field re-stings have also significantly lower basophil response in comparison to patients who had not received VIT, both at 0.1 and 1 microg/ml of venom concentrations (p < 0.001; t test).
The results suggest that basophil venom-specific sensitivity is associated with the efficiency of VIT.
Studies of animal models have shown that the activation of the complement system could have a role in chronic obstructive pulmonary disease (COPD) and asthma by promoting inflammation and enhancing ...airway hyperresponsiveness. We sought to determine whether the levels of complement factors C3a, C4a, and C5a are elevated at the site of inflammation in patients with COPD and patients with asthma. We analyzed the induced sputum of seven patients with COPD, ten patients with asthma, and twelve healthy nonsmokers. The concentrations of anaphylatoxins in the induced sputum were measured by cytometric bead array. We found significantly increased C5a/C5a desArg concentrations in supernatants of the induced sputum of patients with COPD (P = 0.007) and those with asthma (P = 0.002) compared with the control group. In patients with COPD the C5a/C5a desArg concentrations were significantly negatively correlated with lung diffusion coefficient (r = -0.71, P = 0.035). There was no significant difference in C3a/C3a desArg or C4a/C4a desArg measurements between the three groups of subjects. These in vivo results propose the involvement of complement factor C5a in the pathogenesis of COPD and asthma.
Background The role of basophils in anaphylaxis is unclear. Objective We sought to investigate whether basophils have an important role in human anaphylaxis. Methods In an emergency department study ...we recruited 31 patients with acute anaphylaxis, predominantly to Hymenoptera venom. We measured expression of basophil activation markers (CD63 and CD203c); the absolute number of circulating basophils; whole-blood FCER1A , carboxypeptidase A3 (CPA3) , and L-histidine decarboxylase (HDC) gene expression; and serum markers (CCL2, CCL5, CCL11, IL-3, and thymic stromal lymphopoietin) at 3 time points (ie, during the anaphylactic episode and in convalescent samples 7 and 30 days later). We recruited 134 patients with Hymenoptera allergy and 76 healthy control subjects for comparison. We then investigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge to peanut. Results The number of circulating basophils was significantly lower during anaphylaxis (median, 3.5 cells/μL) than 7 and 30 days later (17.5 and 24.7 cells/μL, P < .0001) and compared with those in patients with venom allergy and healthy control subjects (21 and 23.4 cells/μL, P < .0001). FCER1A expression during anaphylaxis was also significantly lower than in convalescent samples ( P ≤ .002) and control subjects with venom allergy ( P < .0001). CCL2 levels (but not those of other serum markers) were significantly higher during anaphylaxis (median, 658 pg/mL) than in convalescent samples (314 and 311 pg/mL at 7 and 30 days, P < .001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophil counts compared with those in prechallenge samples ( P = .016), a decrease in FCER1A expression ( P = .007), and an increase in CCL2 levels ( P = .003). Conclusions Our findings imply an important and specific role for basophils in the pathophysiology of human anaphylaxis.
Background Change in forced expiratory volume in one second (FEV.sub.1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen ...turnover may predict rate of change in FEV.sub.1. Methods One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV.sub.1 (PD-FEV.sub.1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results Annual change of PD-FEV.sub.1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV.sub.1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV.sub.1. Conclusion We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration NCT00292552, Retrospectively registered, trial registration in February 2006. Keywords: COPD, Lung function change, Prognosis, Serological marker, Extracellular matrix
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