Markos Minas

COPD prevalence and the differences between newly and previously diagnosed COPD patients in a spirometry program.

AIMS To evaluate the prevalence and severity of COPD in a primary care population participating in a spirometry program. Differences between newly and previously diagnosed COPD patients were identified. METHODS A spirometry program was conducted in 15 primary care centres. Visitors aged over 30 years who were willing to perform spirometry were included in this program. RESULTS A total of 1,526 subjects provided acceptable spirometries. COPD prevalence in our population was 18.4%, of whom 69.0% were newly diagnosed. Most patients were classified as GOLD stages I and II (26.0% and 54.0%, respectively). COPD diagnosis was related to gender (men), age (older subjects), history of repeated respiratory infection in childhood, smoking (>10 pack-years) and presence of symptoms (cough, dyspnoea, wheezing). Variables related to newly diagnosed COPD were younger age and absence of chronic cough. CONCLUSIONS A primary care spirometry program may identify a large proportion of undiagnosed COPD patients especially in the early stages of the disease. Newly diagnosed COPD patients were of younger age and presented with less symptoms. These results support the need for spirometry programs in primary care for early COPD detection.

Exhaled NO and exhaled breath condensate pH in the evaluation of asthma control

BACKGROUND Asthma is a chronic inflammatory airways disorder. However, no biomarker of airways inflammation has been included in the assessment of asthma control. OBJECTIVE To evaluate exhaled NO (FeNO) and exhaled breath condensate (EBC) pH in patients with asthma according to the level of control, and their performance in the identification of not well-controlled patients. METHODS FeNO and EBC pH after Argon deaeration were measured in 274 consecutive patients. Asthma control was evaluated by two asthma specialists blinded to FeNO and pH measurements according to GINA guidelines, as well as by asthma control test (ACT) and asthma control questionnaire (ACQ). RESULTS FeNO was higher and EBC pH was lower in patients with not well-controlled compared to controlled asthma. In ROC analysis, FeNO presented an AUC of 0.790 for the identification of not well-controlled asthma performing better in non-smokers; EBC pH presented an AUC of 0.791 for the identification of not well-controlled asthma, performing better in smokers. The performance of both biomarkers was inferior to that of ACT and ACQ. FeNO values >30 ppb presented positive predictive values (PPV) > 0.85 with the exception of smokers treated with inhaled corticosteroids. EBC pH values ≤7.20 presented PPV >0.80 in all groups. The presence of FeNO >30 ppb and/or EBC pH ≤7.20 was indicative of not well-uncontrolled asthma in 88.3% of the patients. CONCLUSION FeNO and EBC pH levels may identify patients with not well-controlled asthma. However, their performance was inferior to clinical judgment and may be limited to selected subgroups of asthmatic patients.

Prevalence of chronic diseases and morbidity in primary health care in central Greece: An epidemiological study

BackgroundIn Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care.MethodsFour primary health centres were randomly selected. During one year period, 12 visits were performed in each centre, one per month, in random order and all visitors willing to participate in the study were included. Data on morbidity of each subject were recorded after performing an interview with the participant and checking his medical records, medical history and current medication. Diseases were coded using the international classification of primary care (ICPC) system.ResultsIn total 20,299 subjects were recorded. The results revealed significant variations in morbidity between genders and age groups. However, in all age groups, diseases of the circulatory system were most prevalent, followed by endocrine, metabolic, musculoskeletal and respiratory diseases. Osteoporosis was significantly more prevalent in females compared to males, whereas skin and eye disorders were more prevalent in subjects below 65 years old. COPD prevalence was very low compared to worldwide data.ConclusionsThe present study revealed great variations in the prevalence of the diseases between genders and age groups. Our data justify the urgent need for the development of electronic health records that may help in the design of new prevention strategies in primary health care.

Leptin, adiponectin, and ghrelin levels in female patients with asthma during stable and exacerbation periods.

Objective. The mechanisms underlying the relationship between obesity and asthma have not been fully established. Data in the literature suggest that adipose tissue-derived hormones may be implicated. However, no definite conclusions regarding the role of leptin and adiponectin with asthma are available. No studies have examined the role of ghrelin in asthma. Methods. We assessed the circulating concentrations of leptin, adiponectin, and ghrelin in 32 postmenopausal stable asthma patients, 37 female asthmatics during exacerbations and 8 weeks later, and 22 controls. We examined the relationship between the three peptides and indexes of pulmonary function, airway inflammation, and atopy. Results. Stable asthma patients exhibited higher leptin and lower ghrelin concentrations compared with controls. Patients with severe asthma had higher leptin and lower adiponectin levels versus patients with mild to moderate asthma. Both leptin concentrations and leptin/adiponectin ratio served as markers for discriminating asthma patients from controls on the one hand, and severe from mild to moderate asthmatics on the other. Leptin levels were inversely correlated with both FEV1/FVC and FEF25–75 in patients with mild to moderate asthma. Atopic asthma patients had higher leptin concentrations than nonatopic asthma patients. There was a positive correlation between serum leptin and total IgE levels in atopic asthmatics. Finally, serum leptin levels and leptin/adiponectin ratio were significantly increased during asthma exacerbations, while adiponectin and ghrelin levels were significantly decreased. Conclusion. Our findings suggest that leptin, adiponectin, and ghrelin may play a significant role in the pathogenesis of asthma during both stable state and asthma exacerbation, independent of obesity.

Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers

Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (T L R2-R753Q, T L R4-D299G, and T L R4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of T L R4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.

Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.

The Association of Metabolic Syndrome with Adipose Tissue Hormones and Insulin Resistance in Patients with COPD without Co-morbidities

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome represent common causes of morbidity and mortality in ageing populations. The effect of the co-existence of COPD and metabolic syndrome on adipose tissue hormones and insulin resistance as well as the differences between COPD patients with and without metabolic syndrome have not been adequately studied. The prevalence of metabolic syndrome, based on Adult Treatment Panel III (ATP III) criteria, was evaluated in 114 male patients with COPD without significant co-morbidities. Pulmonary functions tests (PFTs), arterial blood gases, quality of life and BODE index were assessed. Blood samples were obtained for the assessment of adipose tissue hormones and insulin resistance. The overall prevalence of metabolic syndrome was 21%, being more prevalent in earlier stages of COPD. Patients with COPD and metabolic syndrome were younger with higher body-mass index (BMI), had better pulmonary function, less static hyperinflation and air-trapping, better diffusing capacity for carbon monoxide and BODE index. These patients had higher levels of leptin, lower levels of adiponectin and increased insulin resistance, as expressed by HOMA index, compared with patients without metabolic syndrome. Metabolic syndrome was more prevalent in younger patients with less severe COPD. These patients may constitute a specific COPD phenotype with greater leptin to adiponectin imbalance and insulin resistance, despite smaller impairment in PFTs. The prognosis and differences of these patients compared with other COPD phenotypes needs to be determined in prospective studies.

Comparison of a network of primary care physicians and an open spirometry programme for COPD diagnosis

BACKGROUND Early diagnosis of Chronic Obstructive Pulmonary Disease (COPD) remains the cornerstone for effective management. In this study we compared an open spirometry programme and a case-finding programme providing spirometry to high-risk subjects selected by primary care physicians. METHODS A network of primary care physicians was created after invitation and all participants received training on COPD and spirometry. The study team visited 12 primary care settings in each programme in a 1-year period. Spirometry was performed in all eligible participants. COPD diagnosis and classification was based on GOLD guidelines and evaluation by a chest physician. RESULTS Patients with acceptable spirometry were evaluated (n = 201 in the case-finding and n = 905 in the open spirometry programme). The proportion of newly diagnosed COPD was 27.9% in the case-finding programme compared to 8.4% in the open spirometry programme (p < 0.0001). The number needed-to-screen (NNS) for a new diagnosis of COPD was 3.6 in the case-finding programme compared to 11.9 in the open spirometry programme. The majority of newly diagnosed patients were classified in GOLD stages I an II. The average cost for a new diagnosis of COPD was 173 € in the open spirometry programme and 102 € in the case-finding programme. CONCLUSIONS A case-finding programme involving primary care physicians was more cost-effective for the identification of new cases of COPD compared to an open spirometry programme. The development of networks of primary care physicians with access to good quality spirometry and specialist consultation for early diagnosis of COPD is justified.

Fetuin-A is Associated with Disease Severity and Exacerbation Frequency in Patients with COPD

Abstract Fetuin-A is a liver protein that may serve as an inhibitor of systemic inflammation in humans. In the present study we assessed the levels of fetuin-A in COPD patients in stable condition and on exacerbation in an attempt to evaluate it as a clinically relevant biomarker that may serve as predictor of exacerbations of COPD (ECOPD). One hundred COPD outpatients (GOLD stage I to IV) were enrolled in a tertiary University hospital and were submitted to a detailed evaluation, including pulmonary function testing, exercise capacity, quality of life and evaluation of the presence of metabolic syndrome and serum CRP. All patients were followed-up for 1 year, and 36 were re-evaluated at the onset of an ECOPD. Forty otherwise healthy smokers served as controls. Serum fetuin-A levels were reproducible at baseline, 6 and 12 months. COPD patients presented lower levels of fetuin compared to controls [394.5 (321.8–419.6) vs. 487.3 (441.0–548.0) mg/L, p < 0.001]. COPD patients with GOLD stage IV had lower fetuin-A levels compared to stages I-II and III (p < 0.05). Fetuin-A was significantly reduced at the onset of an ECOPD compared to baseline (p < 0.001) and the time to the first ECOPD significantly different between patients with high and low levels of fetuin-A [HR 2.163 (95%CI 1.104–4.238), p = 0.024). The results of the present study suggest that fetuin-A is a reproducible and clinically relevant biomarker in patients with COPD that may be useful in the identification of exacerbation-prone patients.

Body Composition in Severe Refractory Asthma: Comparison with COPD Patients and Healthy Smokers

Background Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated. Methodology and Principal Findings 213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3–18.3)–19.5(18.4–21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I–III COPD and comparable to those of stage IV COPD patients [18.0(17.3–18.3)–18.8(17.8–20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used. Conclusions and Significance SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.