Search

Tobacco smoking is one of the most important risk factors for chronic obstructive pulmonary disease (COPD). However, the most critical genes and proteins remain poorly understood. Therefore, we aimed to investigate these hub genes and proteins in tobacco smoke-induced COPD, together with the potential mechanism(s). Differentially expressed genes (DEGs) were analysed between smokers and patients with COPD. mRNA expression and protein expression of IP3 R were confirmed in patients with COPD and extracted smoke solution (ESS)-treated human bronchial epithelial (HBE) cells. Moreover, expression of oxidative stress, inflammatory cytokines and/or autophagy-related protein was tested when IP3 R was silenced or overexpressed in ESS-treated and/or 3-MA-treated cells. A total of 30 DEGs were obtained between patients with COPD and smoker samples. IP3 R was identified as one of the key targets in tobacco smoke-induced COPD. In addition, IP3 R was significantly decreased in patients with COPD and ESS-treated cells. Loss of IP3 R statistically increased expression of oxidative stress and inflammatory cytokines in ESS-treated HBE cells, and overexpression of IP3 R reversed the above functions. Furthermore, the autophagy-related proteins (Atg5, LC3 and Beclin1) were statistically decreased, and p62 was increased by silencing of IP3 R cells, while overexpression of IP3 R showed contrary results. Additionally, we detected that administration of 3-MA significantly reversed the protective effects of IP3 R overexpression on ESS-induced oxidative stress and inflammatory injury. Our results suggest that IP3 R might exert a protective role against ESS-induced oxidative stress and inflammation damage in HBE cells. These protective effects might be associated with promoting autophagy.

Background: Current evidence suggests an increased prevalence of iron deficiency (ID) and anemia in chronic obstructive pulmonary disease (COPD). ID and subsequent anemia can be due to iron losses via bleeding resulting in absolute ID or inflammation-driven retention of iron within macrophages resulting in functional ID and anemia of inflammation. Methods: This is a retrospective analysis of 204 non-exacerbated COPD patients in outpatient care. Current definitions of absolute and functional ID were applied to determine the prevalence of ID and to analyze associations to disease severity in terms of lung function parameters and clinical symptoms. Results: The studied cohort of COPD patients demonstrated a high prevalence of ID, ranging from 30 to 40% during the observation time. At the initial presentation, absolute or functional ID was found in 9.3% to 12.3% of COPD individuals, whereas combined forms of absolute and functional ID were most prevalent (25.9% of all individuals). The prevalence of ID increased during longitudinal follow-up (37 ± 15 months), and especially combined forms of ID were significantly related to anemia. Anemia prevalence ranged between 14.2% and 20.8% during the observation period and anemia was associated with lower FEV1, DLCOc, and CRP elevation. Accordingly, ID was associated with decreased FEV1, DLCOc, and an elevation in CRP. Conclusion: ID is common in COPD patients, but a uniform definition for accurate diagnosis does not exist. Prevalence of functional ID and anemia increased during follow-up. The associations of ID and anemia with reduced functional lung capacity and elevated inflammation may reflect a more severe COPD phenotype.

Inflammatory bowel diseases (IBD) is an umbrella term that covers both ulcerative colitis (UC) and Crohn's disease (CD), which are chronic inflammatory conditions of the gastrointestinal system. Airway diseases are one of the most commonly studied manifestations of IBD. It is observed that populations with pre-existing obstructive pulmonary conditions are at higher risk of new-onset IBD. This newly documented evidence of increased incidence of IBD among patients with pulmonary diseases and the higher than the estimated prevalence of pulmonary diseases among IBD sufferers support the hypothesis of a two-way association. This review article focuses on summarizing the current knowledge and available evidence regarding the association between IBD and obstructive pulmonary diseases such as chronic obstructive pulmonary disease (COPD), emphysema, bronchiectasis, and asthma. We utilized PubMed as the primary search source and database and included the free full-text articles available on it, published over the past five years. We reviewed literature from multiple regions of the world, such as the US, UK, China, and Canada and compiled this traditional review article utilizing the information collected from 4,966,459 patients. Specifications such as age and gender were not mentioned in all articles. This review will serve to strengthen the existing research database concerning the relationship between IBD and obstructive pulmonary diseases. It will help to highlight the significance of the two-way association between IBD and obstructive pulmonary disease and the importance of treating these two conditions simultaneously. It will also raise awareness about the importance of timely detection of IBD and associated airway complications, leading to decreased disease burden and the treatment cost.

Background COPD is a high prevalence chronic disease that involves large reductions of health-related quality of life (HRQL) of patients. This study aims to describe the HRQL of patients with COPD in Extremadura (Spain). Methods This is a cross-sectional observational study carried out using a representative sample of patients diagnosed with COPD in Extremadura. The inclusion criteria were patients of legal age, diagnosed with COPD at least 12 months prior to the visit, residing in Extremadura, with electronic medical records available for the 12 months prior to the visit and providing informed consent. The intervention aimed to elicit HRQL indicators obtained from two validated questionnaires: EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L), and St. George’s Respiratory Questionnaire-COPD (SGRQ-C). The main outcome measures were general HRQL (utility and visual analogue scale) and specific quality of life of COPD patients (total score and three component scores: Symptoms, Activity, and Impacts). Stepwise multiple regression analysis was applied to evaluate the association of EQ-5D-5L and SGRQ-C with respect to clinical and sociodemographic characteristics of the patients. Results We recruited 386 patients (mean age 71.8 ± 10.3 years, 76.2% males). In the EQ-5D-5L, participants reported greater problems with respect to mobility (56.5%) and pain/discomfort (48.2%). The mean utility was 0.72 ± 0.31, and the SGRQ-C total score was 40.9 ± 25.0. The results of both questionnaires were associated with number of exacerbations in the last 12 months, level of COPD severity, gender, and education level of the patient (p Conclusions The results for both utility and total SGRQ-C score indicate that having suffered exacerbations in the last year, presenting a higher level of severity, being a woman, and having a low education level are related to worse HRQL in patients with COPD.

Background Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there is substantial inter-individual variability in the effect of PR on functional performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis of the skeletal muscle molecular responses to PR in COPD patients and comprehensively characterized their baseline pulmonary and physical function, body composition, blood profile, comorbidities, and medication use. Methods Musculus vastus lateralis biopsies were obtained from 51 COPD patients (age 64 +/- 1 years, sex 73% men, FEV1, 34 (26-41) %pred.) before and after 4 weeks high-intensity supervised in-patient PR. Muscle molecular markers were grouped by network-constrained clustering, and their relative changes in expression values-assessed by qPCR and western blot-were reduced to process scores by principal component analysis. Patients were subsequently clustered based on these process scores. Pre-PR and post-PR functional performance was assessed by incremental cycle ergometry and 6 min walking test (6MWT). Results Eight molecular processes were discerned by network-constrained hierarchical clustering of the skeletal muscle molecular rehabilitation responses. Based on the resulting process scores, four clusters of patients were identified by hierarchical cluster analysis. Two major patient clusters differed in PR-induced autophagy (P

Aim. To study the influence of chronic obstructive pulmonary disease (COPD) on post-operation period course in coronary heart disease (CHD) patients after coronary bypass surgery (CBG). Material and methods. Totally, 92 patients included, with CHD. Two groups were formed: 1st — 50 patients with CHD, 2nd — 42 patients with CHD and COPD. We studied the condition of ventilation via bodypletismography method, and registered oxygen consumption at rest and assessed the effectiveness of pulmonary ventilation — oxygen utilization coefficient (OUC2 , mL/L). Via the method of monofactor logistic regression analysis we calculated independent predictors of cardiovascular and respiratory complications during the nearest period of CBG. Results. After CBG the number of in-hospital complications in the 2nd group was higher than in the 1st. In 2nd group there were more prevalent respiratory failure, atrial fibrillation, cerebral function alteration. As predictor for complications after CBG was COPD (OR 2,1; CI 1,7-2,9; p=0,002). Combination of low values of the forced expiration by 1 s (FEV1) — less than 60% from normal with increase of residual volume (RV) more than 130% is significant predictor for the increase of ventilatory support (VS) (OR 2,5; CI 1,9-3,2; p=0,01). At baseline, decrease of OUC2 less than 20 mL/L is also the predictor for RS prolongation (OR 1,9; CI 1,4-2,8; p=0,003). Conclusion. COPD in CHD increases the chances of complicated clinical course of in-hospital period 2,1 times. Such specifics of baseline disorder in ventilation system as decrease FEV1 less than 60% with increase of RV more 130%, and significant decrease of effectiveness of pulmonary ventilation — OUC2 less than 20 mL/L increase chances for RS duration after CBG 2,5 and 1,9 times, respectively.

Background The possible association between β-adrenoceptor antagonists (β-blockers) and risk of COPD is controversial. The objective of the present study was to test whether β-blocker use is associated with susceptibility to the disease. Methods A total of 301,542 new users of β-blockers and 1,000,633 new users of any other antihypertensive drugs aged 30–90 years without any history of COPD hospitalizations were included in the present study and followed in the Danish National Patient Registry for incident admissions for COPD and COPD death between 1995 and 2015. Multiple adjusted cox regression models were used to examine the association between use of β-blockers and COPD hospitalization. Additionally, subgroup analyses based on underlying diseases at baseline or duration of treatment were performed. Findings People treated with β-blockers continuously for more than 6 months had a lower risk of COPD hospitalization during follow-up compared to people treated with any other antihypertensive drugs (adjusted hazard ratio [HRadjusted] 0·80, 95% CI 0·79–0·82). Risk of COPD hospitalization was lowered in the groups treated with β-blockers among patients with ischemic heart disease (0·72, 0·69–0·75), cardiac arrhythmias (0·76, 0·72–0·80), asthma (0·69, 0·61–0·79), hypertension (0·91, 0·86–0·96), and diseases of the pulmonary circulation (pulmonary embolism and cor pulmonale) (0·72, 0·59–0·87). All-cause mortality as well as risk of COPD death during follow-up was lower in the group treated with β-blockers compared to the group treated with any other antihypertensive drugs (0·56, 0·53–0·59). Interpretation Treatment with β-blockers seems to reduce risk of COPD hospitalization and mortality compared to treatment with any other antihypertensive drugs. Funding The Danish Council for Independent Research in Denmark (grant no. 4183-00569B), The Research Foundation of Health Science in Region Zealand (grant no. RSSF2017000661 and no. 15-000342), The Research Foundation of Medical Science (A.P. Møller Foundation, grant no. 16-68), The Research Foundation in memory of King Christian 10th (grant no. 142/2017), Aase & Ejnar Danielsen's Research Foundation (grant no. 10-001946), and Lundbeck Foundation (grant no. R252-2017-1690)., Highlights • Users of β-blockers had an overall 19·7% lower risk of COPD hospitalization compared to users of any other antihypertensive drug during follow-up. • Users of β-blockers had an overall 44% lower risk of death from COPD compared to users of any other antihypertensive drug. • Results from this study advocates changes in the present hesitation of treatment with β-blockers in patients at risk of or with concomitant COPD.

SummaryThe Finnish National Prevention and Treatment Programme for Chronic Bronchitis and COPD, launched in 1998, has, to date, been running for 6 years (2003).The goals of this action programme were to reduce the incidence of COPD and the number of moderate and severe cases of the disease, and to reduce both the number of days of hospitalisation and treatment costs.A prevalent implementation of over 250 information and training events started.Health centres and pharmacies appointed a person in charge of COPD patients.In order to improve the cooperation between primary and specialised care, two thirds of hospital districts created local COPD treatment chains.The early diagnosis of COPD by spirometric examination was activated during the programme. Number of health centres with available spirometric services increased to 95%.Before the start of the programme, approximately 5–9% of the adult population had COPD. During the whole programme, the proportion of male and female smokers decreased from 30% to 26% and from 20% to 19%, respectively. The total number of hospitalisation periods and days due to COPD decreased by 15% and 18%, respectively. Both the number of pensioners and daily sickness days due to COPD also decreased by 18%. Registered COPD induced deaths remained at their previous levels during the monitoring period, i.e. around 1000 deaths out of 5.2 millions annually. The measures recommended by the programme have been widely introduced but they need to be still more effective.

Background: Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of the disease that require hospitalization. Current guidelines offer little guidance for identifying patients whose clinical situation is appropriate for admission to the hospital, and properly developed and validated severity scores for COPD exacerbations are lacking. To address these important gaps in clinical care, we created the IRYSS-COPD Appropriateness Study. Methods/Design: The RAND/UCLA Appropriateness Methodology was used to identify appropriate and inappropriate scenarios for hospital admission for patients experiencing COPD exacerbations. These scenarios were then applied to a prospective cohort of patients attending the emergency departments (ED) of 16 participating hospitals. Information was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up after admission or discharge home. While complete data were generally available at the time of ED admission, data were often missing at the time of decision making. Predefined assumptions were used to impute much of the missing data. Discussion: The IRYSS-COPD Appropriateness Study will validate the appropriateness criteria developed by the RAND/UCLA Appropriateness Methodology and thus better delineate the requirements for admission or discharge of patients experiencing exacerbations of COPD. The study will also provide a better understanding of the determinants of outcomes of COPD exacerbations, and evaluate the equity and variability in access and outcomes in these patients. This work was supported in part by grants from the Fondo de Investigacion Sanitaria (PI 061010, PI061017, PI06714, PI060326, PI060664); Department of Health of the Basque Country, Department of Education, Universities and Research of the Basque Government (UE09+/62); the Research Committee of the Hospital Galdakao; and the thematic networks- Red IRYSS (Investigacion en Resultados y Servicios Sanitarios)- of the Instituto de Salud Carlos III (G03/220).

Since inhalation therapy will probably remain the preferred route of treatment for patients with chronic obstructive pulmonary disease (COPD), it is important to provide helpful information that may assist physicians and nurses in selecting the appropriate device(s) for individual patients as well as prescribing the correct medication. In line with the GOLD guidelines, the Aerosol Drug Management Improvement Team (ADMIT) propose a three-part "therapy adjustment strategy", which provides health care professionals with a way to monitor and check the delivery of inhaled medication. The strategy is a summation of the key principles behind the evidence-based management of stable COPD and exacerbations. It offers physicians a rapid and user-friendly overview of the requirements of COPD management starting with making the diagnosis and continuing with optimisation of therapy in follow-up appointments. It includes everything from check lists for disease assessment and recommendations for reducing risk factors to selecting the proper inhalers and continuous checking of compliance and correct inhaler technique. These practical COPD therapy adjustment algorithms have been used as part of an interactive online course developed by the ADMIT group (www.admit-online.info). The COPD "flash" video available at this web site offers suggestions on how to organise a complete doctor-patient consultation.

BACKGROUND: Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. METHODS: Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. RESULTS: Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. CONCLUSIONS: Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. ispartof: Respiratory research vol:11 issue:1 pages:35-35 ispartof: location:England status: published

Background: It has been suggested that the antihypertensive agent nebivolol, a β1-adrenoceptor-blocking agent that modulates the endogenous production of nitric oxide, is preferable to ‘conventional’ β1-blockers in hypertensive patients with airway dysfunction. Objectives: Since β1-blockade by nebivolol is larger after repeated dosing than after a single oral intake, we have explored its effect on pulmonary function after a 2-week treatment in hypertensive patients with mild to moderate COPD. Methods: A single-blind crossover design was used. Twenty patients with COPD as selected above and with a diastolic blood pressure of 95–110 mm Hg after 1 week of placebo run-in were entered into the two 2-week active treatment periods with either 5 mg nebivolol (n = 10) or 30 mg nifedipine gastrointestinal-transport-system (GITS) (n = 10) taken for a period of 2 weeks. After a further 1-week washout, subjects were crossed-over to receive the other drug for 2 additional weeks. At each visit, changes in spirometric indexes and the interaction with the bronchodilator effect of salbutamol were investigated. Moreover, systolic and diastolic blood pressure (BP) together with heart rate were manually measured in order to evaluate the cardiovascular effects of the different treatments. Throughout the study, patients recorded symptoms. Results: Similar and significant reductions in systolic and diastolic BP were observed with both treatments. The impact of nifedipine on FEV1 was not significant (p > 0.05), while that of nebivolol was slight. The maximum response to salbutamol was slightly decreased with either nebivolol or nifedipine GITS. Day-to-day airway obstruction control, interpreted from patient recordings of symptom scores and inhaler use, was similar with both treatments. Conclusions: Our pilot study suggests that the use of nebivolol in hypertensive patients with stable mild to moderate COPD was safe during a 2-week trial. Evaluation of longer time periods, larger patient numbers with more severe COPD or during exacerbations is warranted.

Background Respiratory tract infections (RTIs) may be more severe in those with asthma or COPD and these patients are more frequently in need of health care. The aim of the study was to describe the frequency of RTI symptoms in a general adult population and how care-seeking is associated with the presence of obstructive lung disease. Methods Cross-sectional data including spirometry and self-reported chronic diseases were collected among middle-aged and elderly subjects in the Tromsø population survey (Tromsø 6). Self- reported RTI symptoms, consultations and antibiotic use were the main outcome variables. Possible predictors of RTI symptoms were evaluated by multivariable logistic regression. Results Of the 6414 subjects included, 798 (12.4%) reported RTI symptoms in the previous week. RTI symptoms were reported less frequently by subjects aged 75 years or above, than by those younger than 55 years (OR 0.5). Winter season (OR 1.28), current smoking (OR 1.60), low self-rated health (OR 1.26) and moderate to severe bronchial obstruction (OR 1.51), were also statistically significant independent predictors of RTI symptoms, but these variables did not predict RTI symptoms that had started within the previous seven days. Among subjects with RTI symptoms, 5.1% also reported a consultation with a doctor. In those with bronchial obstruction by spirometry, who did not report asthma or COPD, this frequency was 2.4%. Antibiotic treatment was reported by 7.4% of the participants, among whom one third had consulted a doctor. Antibiotics were taken more frequently when asthma or COPD was reported (13.7%), but not in subjects with bronchial obstruction who did not report these diseases (7.2%). Conclusions RTI symptoms seldom led to consultation with a doctor and not even in subjects with obstructive lung disease. This was in particular the case in subjects who did not know about their obstructive lung disease. Strategies for early diagnosis of COPD and providing health care to subjects with such disease cannot rely on their doctor visits due to respiratory symptoms.

Background The ozone challenge model can be used to assess the efficacy of anti-inflammatory compounds in early phases of clinical drug development. PUR118, a calcium salt based formulation engineered in the iSPERSETM dry powder delivery technology, is a novel anti-inflammatory drug for COPD. Here we evaluated the efficacy and safety of three doses of PUR118 in attenuating ozone-induced airway inflammation in healthy volunteers. Methods In a single-blind, phase 1B proof of concept study, 24 subjects were enrolled to sequentially receive three doses of PUR118 (5.5 mg, n = 18; 11.0 mg, n = 18; 2.8 mg, n = 16). Each dose was inhaled 3 times (1, 13, 25 h, preceded by 2 puffs salbutamol) before the ozone exposure (250 ppb, 3 h intermittent exercise). Sputum was induced 3 h after the end of exposure. Results Sputum neutrophils, sputum CD14+ cells, as well as concentrations of IL1B, IL6, IL8, MMP9, and TNFA in sputum supernatant significantly increased after ozone exposure (n = 24). The percentage of sputum neutrophils (n = 12 who completed all treatments) did not change following treatment with different doses of PUR118. The high dose treatment group (n = 16) showed a decrease in the percentage and number of sputum macrophages (p ≤ 0.05) as well as a decrease in blood neutrophils (p = 0.04), and an increase in blood CD14 + cells (p = 0.04) compared to baseline. All dosages of PUR118 were safe and well tolerated. Conclusion Ozone challenge resulted in the expected and significant increase of sputum inflammatory parameters. Treatment with multiple rising doses of PUR118 was safe and three applications within 25 h prior to the ozone challenge had small effects on ozone-induced airway inflammation. Trial registration ClinicalTrials.gov: NCT01690949. Registered 12 September 2012. Electronic supplementary material The online version of this article (doi:10.1186/s40360-015-0021-1) contains supplementary material, which is available to authorized users.