A Chronic Obstructive Pulmonary Disease Self-Management Intervention for Improving Patient-Reported Outcomes in Primary Care in Greece.

Background and Objectives: Self-management programs are essential for increasing COPD patient participation and autonomy in making appropriate decisions about their chronic condition. The present study aimed to assess the impact of COPD self-management interventions on quality of life, functional status, patient education, depression, and anxiety in primary care. Materials and Methods: We conducted a randomized controlled trial recruiting patients with COPD (GOLD A and B) from four primary care centers in Crete, Greece, with one intervention group (n = 40) receiving self-management educational support and one control group (n = 80) receiving usual care. To measure quality of life, functional status, patient education, depression, and anxiety, we used patient-reported outcome measures (PROMs) at baseline and 6 months post-intervention, including the Short-Form Health survey (SF-12), Clinical COPD Questionnaire (CCQ), mMRC, Beck Anxiety Inventory (BAI), Beck Depression Inventory, Health Education Impact Questionnaire (HeiQ), and Health Literacy Questionnaire (HLQ). Results: At the end of the 6-month intervention, most PROMs improved significantly in the intervention group (p < 0.05) but did not show significant changes in the control group. The greatest improvements at follow-up compared to baseline measurements were observed for dyspnea (mMRC-38.6%), anxiety (BAI-35%), depression (BDI-20.2%), COPD health status (CCQ-34.1%), and the actively managing my health subscale of HLQ (23.5%). Conclusions: Our results suggest that a self-management intervention could be an effective strategy for improving PROMs in primary care. Although more research is needed to identify the long-term effects of such interventional programs, policymakers could implement similar programs to improve the overall health of these patients.

Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF.

BACKGROUND: Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs. METHODS: BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed. RESULTS: Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels. CONCLUSION: Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.

Pirfenidone improves survival in IPF: results from a real-life study.

BACKGROUND: Pirfenidone is an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis (IPF). We present our real-world experience in terms of Pirfenidone's effect on mortality and adverse events profile outside the restrictions of a clinical trial. METHODS: This is a retrospective observational intention to treat study of 82 consecutive IPF patients (UHH cohort). RESULTS: We observed a high 3-years survival rate of 73% without excluding patients who discontinued treatment for different reasons. The survival was compared to the survival of an IPF cohort from a tertiary referral center (RBH cohort). After exclusion of severe cases (DLco< 30%), in unadjusted analysis, the survival in the UHH cohort was better than in the RBH cohort (HR:0.32, 95% CI: 0.19-0.53, p < 0.0001). After adjustment for age, gender and FVC, the survival remained higher in the UHH cohort (HR:0.28, 95% CI: 0.16-0.48, p < 0.0001). We observed a similar safety profile compared to previously published data and a lower rate of drug discontinuation due to photosensitivity reactions. CONCLUSION: Pirfenidone provides a survival benefit in a real-life IPF cohort compared to previously used medications. Counselling patients and proactively managing possible adverse effects can reduce the necessity to discontinue pirfenidone.

Sinus rhythm restoration affects collagen turnover in patients with persistent atrial fibrillation.

AIMS: Collagen turnover and atrial fibrosis have been implicated in the generation and perpetuation of atrial fibrillation (AF). We evaluated the importance of serum markers of collagen turnover in predicting the outcome of electrical cardioversion (CV) of persistent AF and the relationship between AF and fibrosis. METHODS AND RESULTS: Serum C-terminal pro-peptide of collagen type-I (CICP) and C-terminal telopeptide of collagen type-I (CITP) were measured in 164 patients with AF before and 2 months after CV. All the patients were successfully cardioverted to sinus rhythm (SR) although in 38 of them AF recurred. Baseline CICP levels were comparable in patients in SR 60 days after CV and in those who experienced a relapse of AF (85.08 ± 16.99 vs. 87.55 ± 10.43 ng/mL, respectively, P = ns). Baseline CITP levels were significantly higher in patients with AF recurrence compared with those who remained in SR (0.48 ± 0.16 vs. 0.32 ± 0.17 ng/mL, respectively, P < 0.0001). In the 126 patients who maintained the SR, CICP levels were significantly lower at the end of the study as compared with the baseline (63.74 ± 15.92 vs. 85.08 ± 16.99 ng/mL P = 0.003), while there was a mild increase in plasma CITP levels (0.36 ± 0.21 vs. 0.32 ± 0.17 ng/mL, respectively, P = 0.03). CONCLUSION: Atrial fibrillation can result in alterations in atrial structure and architecture that make the atrial myocardium more susceptible to the maintenance of the arrhythmia. Sinus rhythm restoration could affect the fibrotic process occurring or exacerbating during AF course.

Prevalence and Characteristics of Patients with Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease: Overlap Syndrome.

Overlap syndrome (OVS) is a distinct clinical entity that seems to result in potential cardiovascular consequences. We aimed to estimate the prevalence and risk factors for OVS in OSA patients and analyze clinical and PSG characteristics associated with OVS. In this cross-sectional study, 2616 patients evaluated for OSA underwent type-1 polysomnography (PSG). They were grouped as pure OSA (AHI > 15/h) and OVS patients. Demographics, PSG data, pulmonary function tests and arterial blood gases (ABGs) were compared between groups after adjustments for confounders. OSA was diagnosed in 2108 out of 2616 patients. Of those, 398 (19%) had OVS. Independent predictors of OVS were older age [OR: 5.386 (4.153-6.987)], current/former smoking [OR: 11.577 (7.232-18.532)], BMI [OR: 2.901 (2.082-4.044)] and ABG measurements [PaCO2 ≥ 45 OR: 4.648 (3.078-7.019), PO2 [OR: 0.934 (0.920-0.949)], HCO3- [OR: 1.196 (1.133-1.263), all p < 0.001]. OVS was also associated with prevalent hypertension [OR: 1.345 (1.030-1.758), p = 0.03] and cardiovascular disease [OR: 1.617 (1.229-2.126), p < 0.001], depressive symptoms [OR: 1.741 (1.230-2.465), p = 0.002] and nocturia [OR: 1.944 (1.378-2.742), p < 0.001], as well as with indices of OSA severity. Disturbances in sleep architecture were more prominent in OVS expressed by lower %N3 and REM% and higher arousal index. Our data suggest that OVS is prevalent among OSA patients, with distinct clinical and PSG characteristics. These characteristics could be utilized as predictive factors for early identification and further evaluation of these patients towards desirable patient-reported outcomes.

Prevalence of multiple behavioral risk factors for chronic diseases in adults aged 50+, from eleven European countries - the SHARE study (2004).

OBJECTIVE: To estimate the prevalence and the associations between multiple behavioral risk factors (MBRFs) for chronic diseases in European adults. METHOD: Data from 26,743 individuals, aged 50+years, participating in the Survey of Health, Ageing and Retirement in Europe (SHARE) (2004/05) were used. MBRFs included physical inactivity, high body weight, smoking habits and risky alcohol consumption. Estimations were based on weights according to the complex sampling design. RESULTS: In total, 71.2% of individuals were physically inactive, while 59.8% had high body weight. 53.4% had 2+ MBRFs, while males presented higher prevalence of MBRF clusters than females (P < 0.001). Females displayed lower odds of increased alcohol consumption (OR = 0.16, P < 0.001) and higher odds of physical inactivity (OR = 1.47, P < 0.001) than males. Individuals who lived alone, compared to living with a partner and those with more, compared to fewer education years, exhibited a significantly higher and lower, respectively, mean MBRF score (P < 0.001). CONCLUSION: The prevalence of MBRFs was considerably high in this sample of European adults, while not living alone and having higher education may prove protective. These findings could be used for the design of primary healthcare programs by health professionals.

Mathematical Modeling Evaluates How Vaccinations Affected the Course of COVID-19 Disease Progression.

The regulation policies implemented, the characteristics of vaccines, and the evolution of the virus continue to play a significant role in the progression of the SARS-CoV-2 pandemic. Numerous research articles have proposed using mathematical models to predict the outcomes of different scenarios, with the aim of improving awareness and informing policy-making. In this work, we propose an expansion to the classical SEIR epidemiological model that is designed to fit the complex epidemiological data of COVID-19. The model includes compartments for vaccinated, asymptomatic, hospitalized, and deceased individuals, splitting the population into two branches based on the severity of progression. In order to investigate the impact of the vaccination program on the spread of COVID-19 in Greece, this study takes into account the realistic vaccination program implemented in Greece, which includes various vaccination rates, different dosages, and the administration of booster shots. It also examines for the first time policy scenarios at crucial time-intervention points for Greece. In particular, we explore how alterations in the vaccination rate, immunity loss, and relaxation of measures regarding the vaccinated individuals affect the dynamics of COVID-19 spread. The modeling parameters revealed an alarming increase in the death rate during the dominance of the delta variant and before the initiation of the booster shot program in Greece. The existing probability of vaccinated people becoming infected and transmitting the virus sets them as catalytic players in COVID-19 progression. Overall, the modeling observations showcase how the criticism of different intervention measures, the vaccination program, and the virus evolution has been present throughout the various stages of the pandemic. As long as immunity declines, new variants emerge, and vaccine protection in reducing transmission remains incompetent; monitoring the complex vaccine and virus evolution is critical to respond proactively in the future.

Evaluation of Drug Interactions in Hospitalized Patients with Respiratory Disorders in Greece.

Background: Patients with respiratory disorders often have additional diseases and are usually treated with more than one medication to manage their respiratory conditions as well as additional comorbidities. Thus, they are frequently exposed to polypharmacy (≥5 drugs), which raises the risk for drug-drug interactions (DDIs) and adverse drug reactions (ADRs). In this work, we present the results regarding the prevalence of DDIs in hospitalized patients with respiratory disorders in Greece. Methods: A 6-month descriptive single-center retrospective observational study enrolled 102 patients with acute or chronic respiratory disorders. Clinical characteristics and medication regimens were recorded upon admission, hospitalization, and discharge. The prevalence of DDIs and their clinical significance was recorded and analyzed. Results: Unspecified acute lower respiratory tract infection (25%), exacerbations of chronic obstructive pulmonary disease (12%) and pneumonia (8%) were the most frequent reasons for admission. Cardiovascular disorders (46%), co-existing respiratory disorders (32%), and diabetes (25%) were the most prevalent comorbidities. Polypharmacy was noted in 61% of patients upon admission, 98% during hospitalization, and 63% upon discharge. Associated DDIs were estimated to be 55% upon admission, 96% throughout hospitalization, and 63% on discharge. Pharmacodynamic (PD) DDIs were the most prevalent cases (81%) and referred mostly to potential risk for QT-prolongation (31.4% of PD-DDIs) or modulation of coagulation process as expressed through the international normalized ratio (INR) (29.0% of DDIs). Pharmacokinetic (PK) DDIs (19% of DDIs) were due to inhibition of Cytochrome P450 mediated metabolism that could lead to elevated systemic drug concentrations. Clinically significant DDIs characterized as "serious-use alternative" related to 7% of cases while 59% of DDIs referred to combinations that could be characterized as "use with caution-monitor". Clinically significant DDIs mostly referred to medication regimens upon admission and discharge and were associated with outpatient prescriptions. Conclusions: Hospitalized patients with respiratory disorders often experience multimorbidity and polypharmacy that raise the risk of DDIs. Clinicians should be conscious especially if any occurring arrhythmias, INR modulations, and prolonged or increased drug action is associated with DDIs.

Long-term omalizumab treatment in severe allergic asthma: the South-Eastern Mediterranean "real-life" experience.

BACKGROUND: Omalizumab is a recombinant humanized anti-IgE monoclonal antibody indicated as an add-on treatment for severe allergic asthma, inadequately controlled despite high dose of inhaled corticosteroids (ICS) and long-acting b2-agonists. OBJECTIVES: Medical registries were used to evaluate the 4 months, 1 and 4 years effectiveness of omalizumab treatment, in a non-interventional, observational "real-life" study. METHODS: Sixty patients with severe persistent allergic asthma from 5 South-Eastern Mediterranean centres from Crete and Cyprus were evaluated. Effectiveness outcomes included spirometry, severe asthma exacerbations rate, level of asthma control (ACT), and additional asthma medication (inhaled steroids). RESULTS: Outcome variables improved after 4 months and sustained after 1 and 4 years treatment with Omalizumab. FEV1 improved statistically significant at all time points versus baseline [ΔFEV1 (% pred.) = +21 p = 0.008 at 4 months, ΔFEV1 (% pred.) = +24.5 p < 0.0001 at 4 years after treatment]. Similarly, FVC increased statistically significant versus baseline [ΔFVC (% pred.) = +20 p = 0.002 at 4 months, ΔFVC (% pred.) = +22.6 p = 0.0002 at 4 years]. The level of asthma control as evaluated by ACT was significantly improved after treatment (+12% p = 0.001 at 4 months, +24% p < 0.0001 at 4 years). Omalizumab treatment reduced significantly asthma exacerbations rate (-65% p = 0.0002 at 1 year, and -70% p < 0.0001 at 4 years). The use of inhaled steroids decreased statistically significant after 4 months (p = 0.017), 1 year (p = 0.029) and 4 years (p = 0.014) of omalizumab treatment. CONCLUSIONS: This long-term "real-life" study demonstrated significant improvement in lung function and other clinical outcomes after omalizumab treatment, evident at 4 months, and sustained after 1 and 4 years suggesting its efficacy in severe allergic asthma, in the "real-life" practice.

Spatio-Temporal Variation of Lung Cancer in Crete, 1992-2013. Economic or Health Crisis?

(1) Background: This is the first population-based study in Greece, with the aim to measure the changing trends of lung cancer (LC) and the associated risk factors before and after the economic crisis. Among the main objectives were the identification of LC hot spots and high-risk areas; (2) Methods: The study was conducted in Crete, the biggest island in Greece. Data (5057 LC cases) were collected from the Cancer Registry of Crete (CRC). The age-standardized incidence and mortality rates (ASIR, ASMR/100,000/year) were estimated, while additional indexes were used, including the adjusted Charlson's comorbidity index (CCI%), the deprivation index (HPI-2), and the exposure to outdoor air pollution (OAP). The analysis was performed for two time periods (Period A: 1992-2008; Period B: 2009-2013); (3) Results: ASIR presented a significant increase during the economic crisis, while an even higher increase was observed in ASMR (Period A: ASMR = 30.5/100,000/year; Period B: ASMR = 43.8/100,000/year; p < 0.001). After 2009, a significant increase in the observed LC hot spots was identified in several sub-regions in Crete (p = 0.04). The risk of LC mortality increased even more for smokers (RR = 5.7; 95%CI = 5.2-6.3) and those living in highly deprived geographical regions (RR = 5.4; 95%CI = 5.1-5.8) during the austerity period. The multiple effect of LC predictors resulted in adjusted RRs ranging from 0.7 to 5.7 within the island (p < 0.05); (4) Conclusions: The increased LC burden after the onset of the economic crisis, along with a changing pattern of LC predictors stressed the urgent need of geographically oriented interventions and cancer control programs focusing on the most deprived or vulnerable population groups.

Evidence-Based Conceptual Collection of Methods for Spatial Epidemiology and Analysis to Enhance Cancer Surveillance and Public Health.

(1) Background: Although spatial statistics are often used by cancer epidemiologists, there is not yet an established collection of methods to serve their needs. We aimed to develop an evidence-based cancer-oriented conceptual collection of methods for spatial analysis; (2) Methods: A triangulation of approaches was used; literature review, consensus meetings (expert panel), and testing the selected methods on "training" databases. The literature review was conducted in three databases. This approach guided the development of a collection of methods that was subsequently commented on by the expert panel and tested on "training data" of cancer cases obtained from the Cancer Registry of Crete based on three epidemiological scenarios: (a) low prevalence cancers, (b) high prevalence cancers, (c) cancer and risk factors; (3) Results: The final spatial epidemiology conceptual collection of methods covered: data preparation/testing randomness, data protection, mapping/visualizing, geographic correlation studies, clustering/surveillance, integration of cancer data with socio-economic, clinical and environmental factors. Some of the tests/techniques included in the conceptual collection of methods were: buffer and proximity analysis, exploratory spatial analysis and others. All suggested that statistical models were found to fit well (R2 = 0.72-0.96) in "training data"; Conclusions: The proposed conceptual collection of methods provides public health professionals with a useful methodological framework along with recommendations for assessing diverse research questions of global health.

Drug-Drug Interactions among Patients Hospitalized with COVID-19 in Greece.

The modulation of the pharmacological action of drugs due to drug-drug interactions (DDIs) is a critical issue in healthcare. The aim of this study was to evaluate the prevalence and the clinical significance of potential DDIs in patients admitted to the University Hospital of Heraklion in Greece with coronavirus disease 2019 (COVID-19). Cardiovascular disorders (58.4%) and diabetes (types I and II) (29.6%) were the most common comorbidities. A high occurrence of DDIs was observed, and clinically significant DDIs that may hamper response to treatment represented 40.3% of cases on admission, 21% during hospitalization, and 40.7% upon discharge. Polypharmacy and comorbidities were associated with a higher prevalence of DDIs in a statistically significant way (p < 0.05, 95% CI). Clinically significant DDIs and increased C-reactive protein values upon admission were associated with prolonged hospitalization. The results reveal that patients admitted due to COVID-19 in Greece often have an additional burden of DDIs that healthcare teams should approach and resolve.

Prediction of obstructive sleep apnea syndrome in a large Greek population.

PURPOSE: We aimed to evaluate the predictive value of anthropometric measurements and self-reported symptoms of obstructive sleep apnea syndrome (OSAS) in a large number of not yet diagnosed or treated patients. Commonly used clinical indices were used to derive a prediction formula that could identify patients at low and high risk for OSAS. METHODS: Two thousand six hundred ninety patients with suspected OSAS were enrolled. We obtained weight; height; neck, waist, and hip circumference; and a measure of subjective sleepiness (Epworth sleepiness scale--ESS) prior to diagnostic polysomnography. Excessive daytime sleepiness severity (EDS) was coded as follows: 0 for ESS ≤ 3 (normal), 1 for ESS score 4-9 (normal to mild sleepiness), 2 for score 10-16 (moderate to severe sleepiness), and 3 for score >16 (severe sleepiness). Multivariate linear and logistic regression analysis was used to identify independent predictors of apnea-hypopnea index (AHI) and derive a prediction formula. RESULTS: Neck circumference (NC) in centimeters, body mass index (BMI) in kilograms per square meter, sleepiness as a code indicating EDS severity, and gender as a constant were significant predictors for AHI. The derived formula was: AHIpred = NC × 0.84 + EDS × 7.78 + BMI × 0.91 - [8.2 × gender constant (1 or 2) + 37]. The probability that this equation predicts AHI greater than 15 correctly was 78%. CONCLUSIONS: Gender, BMI, NC, and sleepiness were significant clinical predictors of OSAS in Greek subjects. Such a prediction formula can play a role in prioritizing patients for PSG evaluation, diagnosis, and initiation of treatment.

Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality.

Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.

Innate immunity proteins in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) may be caused by epithelial cell injury. Epithelial cells respond to injury by secreting innate immunity proteins. To investigate whether altered levels of innate immunity proteins are observed in COPD and IPF, the authors assessed secretory leukocyte protease inhibitor (SLPI), elafin, CC16, and beta-defensin-2 levels by enzyme-linked immunosorbent assay (ELISA) in sputum supernatants from COPD patients (n = 19), smokers without COPD (n = 21), and never-smokers (n = 10) and in BALF supernatants from patients with IPF (n = 11) and subjects without IPF (n = 11). CC16 levels were decreased, whereas SLPI and elafin levels were increased in COPD patients (0.8 [0-4.2] microg/mL, 2.5 [0.3-10.5] microg/mL, 213 [152-318] pg/mL, respectively) compared to smokers without COPD (1.8 [0.1-21.2] microg/mL, 0.8 [0.2-2.6] microg/mL, 172 [71-473] pg/mL, respectively) and never-smokers (0.5 [0-4.8] microg/mL, 0.1 [0.05-0.6] microg/mL, 188 [129-218] pg/mL, respectively) (CC16: P = .001; SLPI: P <.001; elafin: P = .041). beta-Defensin-2 was detected in smokers without COPD (98 [10-729] pg/mL) and never-smokers (74 [35-410] pg/mL), but not in COPD. SLPI and elafin levels did not differ between IPF patients and controls, but CC16 levels were increased in IPF (0.5 [0-2.3] versus 0.2 [0-0.3] microg/mL; P = .019). beta-Defensin-2 was not detected in BALF. In conclusion, in COPD, secretion of CC16 and beta-defensin-2 might be suppressed, whereas SLPI and elafin secretion is up-regulated. In IPF, only CC16 secretion is up-regulated.

Dual Bronchodilator in the Era of Triple Therapy.

Pharmacological medications used for the treatment of COPD patients have increased significantly. Long-acting bronchodilators have been recognized as the mainstay of the treatment of stable COPD, while ICS are usually added in patients with COPD who experience exacerbations, despite bronchodilator treatment. In the latest years, several studies have been published showing the beneficial effect of adding ICS on dual bronchodilation in patients suffering from more severe disease comparing triple therapy with several therapeutic regiments including dual bronchodilation and providing a message that this triple therapy might be more appropriate for COPD patients. However, not all COPD patients have a desirable response to ICS treatment while long-term ICS use in COPD is associated with several side effects. In this report, we aimed to provide a review of the current knowledge on the importance of dual bronchodilation on COPD patients and to compare its use with triple therapy, by covering a wide spectrum of topics. Finally, we propose an algorithm on performing treatment step up from dual bronchodilation to triple therapy and step down from triple to double bronchodilation considering the current evidence.

A Real-World Observational Study Examining the Impact of Aclidinium Bromide Therapy on the Quality of Life, Symptoms, and Activity Impairment of Patients with Chronic Obstructive Pulmonary Disease: The Greek ON-AIR Study.

Purpose: This multicenter, prospective, observational study aimed to supplement real-world evidence on the effects of aclidinium bromide on the quality of life (QoL), symptoms, and activity impairment of patients with COPD. Patients and Methods: Eligible patients were ≥40 years of age, newly initiated on aclidinium bromide as monotherapy or add-on therapy according to the product's approved label. Patient-reported COPD assessment test (CAT), the severity of symptoms and their impact on daily activities, and the features of the Genuair® inhaler device were assessed at enrollment and at 12 weeks post-treatment onset. Results: Between 13 March 2015 and 29 January 2016, 285 eligible consenting patients (76.3% males; median age: 69.0 years; 26.0% newly diagnosed with COPD) were enrolled by 15 hospital-based respiratory medicine specialists in Greece. Aclidinium bromide was initiated as add-on therapy to other inhaled maintenance medications in 73.1% of evaluable patients. The median (interquartile range [IQR]) baseline CAT score decreased from 14.0 (9.0-20.0) to 10.0 (6.0-15.0) points (p<0.001) after 12 weeks of treatment, with 76.5% of the patients achieving a ≥2-point decrease. The severity of night-time and early-morning symptoms, assessed using a 5-point Likert-type scale, decreased from a median (IQR) of 1.0 (0.0-2.0) to 0.0 (0.0-1.0), and from 2.0 (1.0-2.0) to 1.0 (1.0-2.0), respectively (p<0.001 for both). In patients with paired data, the prevalence of at least moderate night-time symptoms, early-morning symptoms, and daily activity impairment decreased from 28.2% to 19.1%, from 63.6% to 34.2%, and from 59.5% to 38.7%, respectively (p<0.001 for all). Inhaler device features were assessed as "very good"/"good" by more than 90% of the patients. The adverse drug reaction rate was 1.4%. Conclusion: The study provides real-world evidence on the beneficial effects of aclidinium bromide on the patients' QoL, symptom severity, and daily activity impairment, which are complemented by a favorable safety profile and high patient satisfaction with the inhaler device.

Maintained smoking cessation for 6 months equilibrates the percentage of sputum CD8+ lymphocyte cells with that of nonsmokers.

Little is known about the longitudinal effects of smoking cessation on sputum inflammatory cells. We aimed to investigate the changes in sputum inflammatory cells and T-lymphocyte subpopulations after 6 and 12 months smoking cessation. Induced sputum was obtained from 68 healthy smokers before and after 6 months (n = 21) and 1 year (n = 14) smoking cessation and from ten healthy never-smokers. Inflammatory cells were identified by morphology and T-lymphocyte subpopulations by flow cytometry. Sputum macrophages were decreased after 12 months of smoking cessation in comparison to baseline, while neutrophils increased. Moreover, CD8+ T-cells were decreased in smokers before smoking cessation compared to never-smokers and increased in smokers after 6 months of smoking cessation in comparison to baseline; result that was maintained after 1 year of smoking cessation. These novel findings indicate that smoking cessation can equilibrate certain inflammatory cells of smokers with those of nonsmokers, within 6 months of smoking cessation.

Tc2 response at the onset of COPD exacerbations.

BACKGROUND: T lymphocytes and especially the subpopulations of CD8+ cells are believed to have a key role in COPD pathophysiology, but there are only few data regarding the role of these cells in COPD exacerbation. AIM: We aimed to study prospectively changes of CD8+ T-lymphocyte subpopulations in the sputum of COPD patients at the onset of mild exacerbations and at a stable condition in order to provide further insight in the pathophysiology of the disease. METHODS: Induced-sputum samples were collected from 24 COPD patients with median age of 52 years (interquartile range [IQR], 44 to 58 years) and FEV(1) percentage of predicted of 78.05% (IQR, 75.8 to 80.1%) at the onset of mild exacerbations not requiring hospitalization and when stable. Inflammatory cells and T-lymphocyte subpopulations (CD4+, CD8+, and cells producing interferon [IFN]-gamma or interleukin [IL]-4) were measured using flow cytometry and immunocytochemical methods. RESULTS: A significant increase in sputum CD8+ T lymphocytes (p < 0.0001) and significant decreases in CD4+ T lymphocytes as well as in CD4+/CD8+ (p = 0.0001) and CD8+IFN-gamma+/CD8+IL-4+ (p = 0.001), CD4+IFN-gamma+/CD4+IL-4+ (p = 0.0003) sputum cells ratios were found decreased at the onset of exacerbations compared to stable condition. The changes in T-lymphocyte subpopulations were not associated with smoking history, demographic characteristics, or disease severity. CONCLUSION: The findings of the present study suggest that CD8+ lymphocytes are increased and potentially polarized toward a Tc2 profile in the airways of COPD patients at the onset of COPD exacerbations with respect to stable condition. The clinical impact of the observed phenomenon requires further investigation.

Exhaled breath condensate 8-isoprostane, clinical parameters, radiological indices and airway inflammation in COPD.

BACKGROUND: Exhaled breath condensate (EBC) 8-isoprostane levels were found increased in chronic obstructive pulmonary disease. However, the relation between EBC 8-isoprostane and parameters which have a known predictive value in COPD, remains vastly unknown, and so does subsequently its clinical value. OBJECTIVES: To investigate the relationship between 8-isoprostane level in EBC and clinical parameters, radiological indices and airway inflammation in COPD patients. MATERIALS AND METHODS: We studied 18 COPD patients (all ex-smokers) and 12 healthy controls (5 ex-smokers and 7 never-smokers). All patients underwent clinical evaluation, sputum induction, high-resolution computed tomography (HRCT) of the thorax and EBC 8-isoprostane measurement. 8-Isoprostane levels were correlated with markers that reflect disease severity, such as dyspnea severity, FEV(1) (%pred), emphysema changes and bronchiectasis in HRCT. Emphysema was quantified as the percentage of lung area with attenuation values < -950 Hounsfield units. RESULTS: 8-Isoprostane levels were significantly elevated in EBC of patients with COPD [mean (SE) 18.1 (2) vs. 5.6 (0.7) pg/ml, p = 0.0001], irrespective of lung function impairment. 8-Isoprostane levels were correlated with emphysema score in HRCT (r(2) = 0.43, p = 0.001) as well as with Medical Research Council dyspnea scale score (rho = 0.61, p = 0.005). CONCLUSION: Our findings suggest that EBC 8-isoprostane levels may reflect the extension of lung emphysema in COPD patients. In this respect, further investigation is required in order to evaluate the possible role of EBC 8-isoprostane in assessing disease progress in COPD patients.