Nikolaos M. Siafakas

Factors that influence disease-specific quality of life or health status in patients with COPD: a systematic review and meta-analysis of Pearson correlations

BACKGROUND A major goal in the management of chronic obstructive pulmonary disease (COPD) is to ensure that the burden of the disease for patients with COPD is limited and that patients will have the best possible quality of life. AIMS To explore all the possible factors that could influence disease-specific quality of life and health status in patients with COPD. METHODS A systematic review of the literature and a meta-analysis were performed to explore the factors that could have a positive or negative effect on quality of life and/or health status in patients with COPD. RESULTS Quality of life and health status are determined by certain factors included gender, disease severity indices, lung function parameters, body mass index, smoking, symptoms, co-morbidity, depression, anxiety, and exacerbations. Factors such as dyspnoea, depression, anxiety and exercise tolerance were found to be more correlated with health status than the widely used spirometric values. Forced expiratory volume in one second had a weak to modest Pearson weighted correlation coefficient which ranged from -0.110 to -0.510 depending on the questionnaire used. CONCLUSIONS The broad range of determining factors suggests that, in order to reach the management goals, health status should be measured in addition to lung function in patients with COPD.

Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis

Background  Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8‐isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF.

Assessing health status in COPD. A head-to-head comparison between the COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ)

BackgroundHealth status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management. We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St. George Respiratory Questionnaire (SGRQ).MethodsWe administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits. Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits. Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.ResultsWe enrolled 90 COPD patients. Cronbachs alpha for both CAT and CCQ was high (0.86 and 0.89, respectively). Patients with severe COPD reported worse health status compared to milder subgroups. CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01). Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01). Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98). The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ. Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations. More than half of patients preferred CCQ instead of CAT.ConclusionsThe CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients.

Prognostic Value of Serum Tumor Markers in Patients with Lung Cancer

Background: The role of tumor markers in the diagnosis and prognosis of lung cancer is under investigation. Objectives: The aim of this study was to investigate the diagnostic and prognostic significance of pre-therapeutic levels of various serum tumor markers, CYFRA 21-1, neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), CA 125 and squamous cell carcinoma antigen (SCCAg), in patients with lung cancer. Methods: We studied 102 consecutive patients (mean age 65.2 ± 11 years) with newly diagnosed lung cancer (96 males, 94%, with a mean age of 66.3 ± 10.5 years). All patients had a 5-year follow-up. Measurements of the serum tumor markers were performed on initial diagnosis. Results: Eighty-four patients (82%) had non-small-cell lung cancer (NSCLC) and 18 (18%) small-cell lung cancer (SCLC). From the 84 patients with NSCLC, 34 patients (33%) had squamous-cell lung cancer, 23 (22%) adenocarcinoma and 23 (22%) large-cell carcinomas. The overall median survival was 8.5 months. All SCLC patients had extensive disease with a median survival of 10.1 months and NSCLC patients of 8.4 months. Significant differences in the mean values of NSE and CYFRA 21-1 were observed between SCLC and NSCLC. In NSCLC, CYFRA 21-1, TPA, CA 125 and SCCAg serum levels were related to the stage of the disease at diagnosis, and CYFRA 21-1, NSE, TPA and CA-125 were related to a poor outcome. None of the above tumor markers was related to survival in the SCLC group. Conclusion: CYFRA 21-1 and NSE may help to differentiate cell types in lung cancer patients. Also, CYFRA 21-1 with TPA and CA 125 may provide useful information regarding the staging of the disease at diagnosis and the prognosis of patients with NSCLC.

Isolation of myeloid and plasmacytoid dendritic cells from human bronchoalveolar lavage fluid.

Studies of bronchoalveolar lavage fluid (BALF) dendritic cells (DC) have been hampered by the scarcity of DC and the lack of DC‐specific surface markers. Four surface Ag have been recently described as specific markers for distinct subsets of DC and have been used for the isolation and characterization of fresh noncultured DC from lung resection specimens: BDCA‐1 (CD1c) and BDCA‐3 for myeloid DC type 1 and type 2, respectively, and BDCA‐2 and BDCA‐4 for plasmacytoid DC. The aim of this study was to develop a new method for the isolation of BALF DC, using immunomagnetic separation of BDCA+ cells. Mononuclear cells were obtained from BALF after Ficoll‐Paque density gradient centrifugation. Monocytes, T cells and B cells were magnetically labelled and depleted. The unlabelled cell fraction was incubated with BDCA‐1, BDCA‐3 and BDCA‐4 beads and the total BDCA+ DC were retained. The ability of isolated DC to induce T‐cell responses was evaluated by coculturing the isolated DC with immunomagnetically sorted naive T cells. The above procedure resulted in a population of viable DC that showed a strong capacity in induce T‐cell responses. Functionally intact human BALF myeloid DC types 1 and 2 as well as plasmacytoid DC can be easily obtained by immunomagnetic isolation. Considering that bronchoalveolar lavage is a minimally invasive procedure, these cells are optimal candidates with which to elucidate the properties and capabilities of pulmonary DC.

Faster onset of bronchodilation with formoterol than with salmeterol in patients with stable, moderate to severe COPD: Results of a randomized, double-blind clinical study

OBJECTIVES To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h). DESIGN A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study. SETTING Five centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands. PATIENTS Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L). INTERVENTIONS Patients inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of salmeterol (50 and 100 mg) and matching placebo on five separate days. MAIN RESULTS The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1 AUC*0-1 h, showed that formoterol 12 mg was statistically significantly superior to salmeterol 50 mg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol. CONCLUSIONS Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Sleep patterns in patients with acute coronary syndromes

BACKGROUND Little is known about sleep quality in patients with acute coronary syndromes (ACS) admitted to the coronary care unit (CCU). The aim of this study was to assess nocturnal sleep in these patients, away from the CCU environment, and to evaluate potential connections with the disease process. METHODS Twenty-two patients with first ever ACS, who were not on sedation or inotropes, underwent a full-night polysomnography (PSG) in our sleep disorders unit within 3 days of the ACS and follow-up PSGs 1 and 6 months later. RESULTS PSG parameters showed a progressive improvement over the study period. There was a statistically significant increase in total sleep time (TST), sleep efficiency, slow wave sleep (SWS), and rapid eye movement (REM) sleep, while arousal index, wake after sleep onset (WASO) and sleep latency decreased. Six months after the acute event, sleep architecture was within the normal range. CONCLUSIONS Patients with ACS have marked alterations in sleep macro- and micro-architecture, which have a negative influence on sleep quality. The changes tend to disappear over time, suggesting a relationship with the acute phase of the underlying disease.

Health-related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary disease (overlap syndrome).

The association of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD) is not rare as COPD and OSA are both frequent diseases. The aim of this study was to determine the effect of OSA on quality of life (QOL) in patients with overlap syndrome (OVS). Thirty subjects with OVS and 15 control subjects participated. The St Georges Respiratory Questionnaire (SGRQ) was used to determine QOL. The control group included subjects with COPD and no evidence of OSA by overnight polysomnography. All subjects were habitual snorers with normal Epworth Sleepiness Scale scores. Significant differences were found between the groups for the total score and each of the three components of the SGRQ suggesting worse QOL in OVS patients (symptoms 54.9 ± 18.9 vs. 38.2 ± 19.3, p = 0.008; activity 59.2 ± 16.2 vs. 44.4 ± 11.3, p = 0.003; impacts 35.2 ± 23 vs. 20.8 ± 8.7, p = 0.025 and total 45.7 ± 17.7 vs. 30.9 ± 8.7, p = 0.004 in OVS patients and control group, respectively). Obstructive sleep apnoea has a major impact on QOL in patients with OVS and can exist in COPD patients with habitual snoring even in the absence of daytime sleepiness. Further studies are needed to determine the impact of OSA treatment on QOL and morbidity in this population.

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, FEV1 (%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 (r2 = 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.

A Prospective Analysis of 184 Hemoptysis Cases – Diagnostic Impact of Chest X-Ray, Computed Tomography, Bronchoscopy

Background:The clinical presentation of hemoptysis often raises a number of diagnostic possibilities. Objectives:This study was designed to evaluate the relative frequency of different causes of hemoptysis and the value of chest radiography, computed tomography (CT) scanning and fiber-optic bronchoscopy in the evaluation of a Greek cohort population. Methods:We prospectively followed a total of 184 consecutive patients (137 males/47 females, 145 smokers/39 nonsmokers) admitted with hemoptysis between January 2001 and December 2003 to the University Hospital of Heraklion. Follow-up data were collected on August 2005. Results:The main causes of hemoptysis were bronchiectasis (26%), chronic bronchitis (23%), acute bronchitis (15%) and lung cancer (13%). Bronchiectasis was significantly more frequent in nonsmokers (p < 0.02). Among nonsmokers, patients with moderate/severe bleeding or a history of tuberculosis were more likely to have bronchiectasis (OR 8.25; 95% CI 1.9–35.9, p = 0.007 and OR 16.5; 95% CI 1.7–159.1, p = 0.007, respectively). Nonsmokers with normal or abnormal X-rays were equally likely to have bronchiectasis (OR 2.5; 95% CI 0.66–9.39, p = 0.2). Lung cancer was only found in smokers. Smokers with normal X-rays were less likely to have lung cancer compared to smokers with abnormal X-ray (OR 5.4; 95% CI 1.54–19.34, p = 0.004). There were no smokers with normal CT and lung cancer. Follow-up data were collected in 91% of patients. Lung cancer did not develop in any patient assumed to have hemoptysis of another origin than lung cancer on initial evaluation. Conclusions:Bronchiectasis is the main diagnosis in patients admitted with hemoptysis to a Greek University Hospital and it is more frequent among nonsmokers with moderate/severe bleeding and/or previous tuberculosis infection. Nonsmokers with moderate/severe hemoptysis and/or a history of tuberculosis should be evaluated with high-resolution CT. Smokers with hemoptysis are at increased risk for lung cancer and need to be extensively evaluated with chest CT and bronchoscopy.