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.

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.

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.

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.

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.

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.

miR-185 and miR-29a are similarly expressed in the bronchoalveolar lavage cells in IPF and lung cancer but common targets DNMT1 and COL1A1 show disease specific patterns.

Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) constitute two progressively devastating lung diseases with common risk factors including aging and smoking. There is an increasing interest in the investigation of common pathogenic mechanisms between IPF and LC with therapeutic implications. Several oncomirs, microRNAs associated with malignancy, are also linked with IPF. miR­29a and miR­185 downregulation is probably involved both in carcinogenesis and fibrogenesis. We have previously observed miR­29a and miR­185 downregulation in IPF cells from bronchoalveolar lavage (BAL) and in this study we investigated their expression in LC BAL cells. Common targets of miR­29a and miR­185 such as DNA methyltransferase (DNMT)1, DNMT3b, COL1A1, AKT1 and AKT2 were measured. Potential correlations with pulmonary function tests, smoking status and endobronchial findings were investigated. Similar levels of miR­29a and miR­185 were detected in IPF and LC while their common targets AKT1 and DNMT3b were not found to differ, suggesting potential pathogenetic similarities at the level of key epigenetic regulators. By conrast, COL1A1 mRNA levels were increased in IPF suggesting a disease­specific mRNA signature. Notably, DNMT1 was downregulated in the LC group and its expression was further reduced in the presence of increasing malignant burden as it was implied by the endobronchial findings.

Lung cancer and annual mean exposure to outdoor air pollution in Crete, Greece.

The increasing burden of lung cancer (LC) in Crete, Greece, has raised certain concerns about the potential association of environmental risk factors with LC. The aim of this study was to assess outdoor air pollution (OAP) and the risk for LC mortality for the first time in Crete using LC primary data. 5057 LC cases (diagnosed from 1992 to 2013) were obtained from the Cancer Registry of Crete (http://www.crc.uoc.gr) and followed up until 2014. The age-standardized incidence and mortality rates (ASIR) were calculated. Data on OAP indicators [particulate matter (PM)2.5, between 2.5 and 10 µm (PM2.5-10), PM10, PM2.5 absorbance (black carbon measure), nitrogen dioxide (NO2), and nitrogen oxides (NOx)] were collected. Spatial statistics were calculated and the binary logistic regression model was constructed at α=0.05 in IBM SPSS 24 and ArcMap 10.3.1. LC in Crete accounts for 40.2 new cases/100 000/year for both sexes (ASIRmales=73.1 new cases/100 000/year; ASIRfemales=11.8 new cases/100 000/year). Annual median estimates of environmental concentrations in Crete were as follows: PM2.5=20.7 (±1.5) µg/m, PM10=38.9 (±2.5) µg/m, PM2.5-10=59.6 (±3.7) µg/m, PM2.5 absorbance=1.2 (±0.3)×10/m, NO2=15.2 (±3.8) µg/m, and NOx=20.1 (±4.9) µg/m. A statistically significant association was observed between OAP and LC mortality (mean correlation coefficient=0.75; P<0.05). The highest risk for 5-year LC mortality was found in the major urban centers and several south-east and north-west rural regions of Crete (relative risk=3.2, 95% confidence interval=1.6-4.7). OAP seems to be an important determinant of LC mortality. Targeted interventions should be performed in the high-risk areas.

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 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.

Self-eating: friend or foe? The emerging role of autophagy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is the most common and severe form of idiopathic interstitial pneumonias. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the pathogenesis remains elusive, and little therapeutic progress has been made in the last few years. Mortality in 3-5 years is still 50%. Autophagy, a highly conserved homeostatic mechanism necessary for cell survival, has been recently implicated in the pathogenesis of pulmonary disorders. In this paper we aim to highlight some key issues regarding the process of autophagy and its possible association with the pathogenesis of idiopathic pulmonary fibrosis.

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.

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.

Smoke-free hospitals in Greece: Personnel perceptions, compliance and smoking habit.

Smoke-free environments in Greece are scarce. Despite existent legislation that forbids smoking in all health care service centers, smoking is still evident. Using a random sample of hospital personnel from a large university hospital in Greece, we evaluated their smoking habits, perceptions and compliance towards hospital smoking regulations. 57.8% of the nursing personnel and 34.5% of medical/research staff were found to be current smokers (p < 0.05). Although 66% of the staff does not oppose the complete hospital smoking ban, 95% responded that they would prefer it to be partial. The above findings warrant the necessity for nurturing efforts to reduce smoking and increase the health professionals' awareness of their position as a role model to both patients and the society.

Increased apoptosis of neutrophils in induced sputum of COPD patients.

AIM: The aim of the current study was to evaluate apoptosis in induced sputum neutrophils and to investigate the relationship between the number of apoptotic cells and clinical parameters in COPD patients. METHODS: Twenty-four COPD ex-smoker patients and 10 healthy controls were included in the study. All subjects underwent clinical evaluation and sputum induction. Sputum cell in situ apoptosis was identified using white light microscopy and TUNEL assay technique. Apoptosis of neutrophils obtained by sputum induction was expressed as apoptotic rate (AR=percentage of apoptotic neutrophils over the number of neutrophils measured). RESULTS: TUNEL assay revealed statistically significant higher AR in COPD patients than controls (p=0.004). Patients with FEV(1)<50%pred had significantly higher median (IQR) AR (%) compared to patients with FEV(1)>or=50% [26.3 (16-29) vs 13.1 (8.6-21), p=0.01]. No significant association was found between the number of apoptotic cells and age, symptoms or medication used. CONCLUSION: The significantly increased apoptotic rate of neutrophils that were found in COPD patients with advanced disease compared to controls might reflect either a deregulation of apoptosis of neutrophils or, a reduced clearance of apoptotic neutrophils from the airways. The pathophysiologic significance of the observed phenomenon has to be further explored.

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.