Prevalence and Characteristics of Self-Reported Adult Asthma in Cyprus: A Population-Based Observational Study.

Purpose: To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. Patients and Methods: This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. Results: The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). Conclusion: This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.

Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience.

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients' isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives on Assessment and Management.

Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.

Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction.

BACKGROUND: Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. RESULTS: Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1  < 0·001; PERBB2  = 0·003; PERBB3  = 0·003) and nonsmokers (PERBB1  = 0·019; PERBB2  = 0·005; PERBB3  = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1  < 0·001). DISCUSSION: These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.

Granule cytotoxic activity and oxidative DNA damage in smoking and nonsmoking patients with asthma.

BACKGROUND: Lung cytotoxic mechanisms trigger the release of perforin and granzymes, causing oxidative DNA damage that ultimately leads to apoptosis. These effects, although demonstrated in COPD, have not been investigated in patients with asthma and in particular in patients with asthma who smoke. Our aim was to measure perforin, granzyme A, granzyme B, and 8-OHdG expression in sputum from smoking and nonsmoking patients with asthma, compared with smoking and nonsmoking control subjects. METHODS: Perforin, granzyme A, granzyme B, and 8-OHdG expression levels were detected by enzyme-linked immunosorbent assays in induced sputum specimens. RESULTS: Perforin expression was increased in 40% of smokers and 45% of smoking patients with asthma and in only 7% of nonsmoking patients with asthma (P = .004), compared with control subjects' values. In contrast, granzymes A and B levels were increased in > 40% of patients in all three groups vs control subjects. Finally, 8-OHdG levels were elevated in 35% of smoking patients with asthma, in 20% of smokers, and in only 10% of nonsmoking patients with asthma. Statistical analysis revealed a positive correlation between granzyme A (P < .001) and granzyme B (P = .006) expression levels and the number of pack-years in smoking patients with asthma. CONCLUSIONS: Asthma cytotoxic immune response is mainly represented by granzymes A and B, whereas in smoking patients with asthma perforin and 8-OHdG are additionally involved, resembling the immune response in COPD.

Detection of exacerbations in asthma based on electronic diary data: results from the 1-year prospective BIOAIR study.

BACKGROUND: Objective measures are required that may be used as a proxy for exacerbations in asthma. The aim was to determine the sensitivity and specificity of electronic diary data to detect severe exacerbations (SEs) of asthma. A secondary aim was to identify phenotypic variables associated with a higher risk of exacerbation. METHODS: In the BIOAIR study, 169 patients with asthma (93 severe (SA); 76 mild to moderate (MA)) recorded lung function, symptoms and medication use in electronic diaries for 1 year. Data were analysed using receiver-operator characteristics curves and related to physician-diagnosed exacerbations. Medical history and baseline clinical data were used to assess risk of exacerbation. RESULTS: Of 122 physician-diagnosed exacerbations, 104 occurred in the SA group (1.1 per patient/year), 18 in the MA group (0.2 per patient/year) and 63 were severe using American Thoracic Society/European Respiratory Society criteria. During exacerbations, peak expiratory flow (PEF) and forced expiratory volume in 1 s significantly decreased, whereas day and night symptoms significantly increased. An algorithm combining a 20% decrease in PEF or a 20% increase in day symptoms on 2 consecutive days was able to detect SEs with 65% sensitivity and 95% specificity. The strongest risk factors for SEs were low Asthma Control Questionnaire score, sputum eosinophils ≥ 3%, body mass index >25 and low quality of life (St George's Respiratory Questionnaire), with ORs between 3.61 and 2.22 (p<0.05). CONCLUSIONS: Regular electronic monitoring of PEF and asthma symptoms provides an acceptable sensitivity and specificity for the detection of SEs and may be suitable for personal internet-based monitoring of asthma control.

Molecular response of the human diaphragm on different modes of mechanical ventilation.

BACKGROUND: The mechanical stress that the human diaphragm is exposed to during mechanical ventilation affects a variety of processes, including signal transduction, gene expression, and angiogenesis. OBJECTIVES: The study aim was to assess the change in the production of major angiogenic regulators [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and after contraction/relaxation cycles during mechanical ventilation. METHODS: This observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2, and TGFB1 in surgical patients receiving general anesthesia with controlled mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV without muscle relaxation (group B, n = 10), and pressure support of spontaneous breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient at two time points: 30 min after the induction of anesthesia (t1) and 90 min after the first specimen collection (t2). RESULTS: No significant changes in the mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C between time points t1 and t2. In contrast, in group B, the mRNA levels of the above angiogenic factors were increased in time point t2 compared to t1, a finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1 = 0.001). CONCLUSIONS: These findings suggest that the molecular response of the human diaphragm before and after application of diverse modes of mechanical ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and TGFB1 was only promoted in CMV without muscle relaxation, and this may have important clinical implications.

Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions.

Genetic, immune and environmental interactions are key elements for the development of COPD. Cigarette smoking is considered the primary risk factor initiating inflammatory cascades in genetically susceptible individuals. The "danger signals" elicited by the injured cells of non-specific immunity induce the downstream activation of proinflammatory cascades and antigen-specific adaptive immune responses. The produced oxidative stress further damages the lung leading to acquired genetic changes (histone deacetylation, microsatellite DNA instability, DNA methylation, telomere shortening, miRNA alterations) due to an inefficient DNA repair machinery. On the other hand, augmented apoptosis, impaired efferocytosis and abnormal tissue remodeling contribute to the chronic inflammatory response and tissue destruction in COPD. This review focuses on the role of genetic, epigenetic and immune mechanisms in the development of COPD in order to put forward possible prognostic and therapeutic targets.

DNA damage due to oxidative stress in Chronic Obstructive Pulmonary Disease (COPD).

According to the American Thorasic Society (ATS)/European Respiratory Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases. The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure. The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes. This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD. In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells. These signals are captured by antigen presenting cells and are transferred to the lymphoid tissue, generating an adaptive immune response and enhancing chronic inflammation.

Downregulation of lung mitochondrial prohibitin in COPD.

Prohibitins (PHB1 and PHB2) are versatile proteins located at the inner mitochondrial membrane, maintaining normal mitochondrial function and morphology. They interact with the NADH dehydrogenase protein complex, which is essential for oxidoreductase activity within cells. However, their expression in lung epithelium, especially in smokers and patients with inflammatory lung diseases associated with increased oxidative stress, such as COPD, is unknown. Lung tissue specimens from 45 male subjects were studied: 20 COPD patients [age: 65.7 ± 5.8 years, smoking: 84.6 ± 33.6 pack-years, FEV(1) (%pred.): 58.7 ± 14.6, FEV(1)/FVC (%): 63.8 ± 9.4], 15 non-COPD smokers [age: 59.0 ± 12.1 years, smoking: 52.5 ± 20.8 pack-years, FEV(1) (%pred.): 85.5 ± 14.2, FEV(1)/FVC (%): 78.5 ± 4.7] and 10 non-smokers. Quantitative real-time PCR experiments were carried out for PHB1 and PHB2, using ß-actin as internal control. Non-COPD smokers exhibited lower PHB1 mRNA levels when compared to non-smokers (0.55 ± 0.06 vs. 0.90 ± 0.06, P = 0.043), while PHB1 expression was even further decreased in COPD patients (0.32 ± 0.02), a statistically significant finding vs. both non-COPD smokers (P = 0.040) and non-smokers (P < 0.001). By contrast, PHB2 levels were similar among the three study groups. Western blot analysis for the PHB1 protein verified the qPCR results (non-smokers: 1.77 ± 0.13; non-COPD smokers: 0.97 ± 0.08; COPD patients: 0.59 ± 0.10, P = 0.007). Further analysis revealed that PHB1 downregulation in COPD patients cannot be attributed solely to smoking, and that PHB1 expression levels are associated with the degree of airway obstruction [FEV(1) (P(mRNA) = 0.004, P(protein) = 0.014)]. The significant downregulation of PHB1 in COPD and non-COPD smokers in comparison to non-smokers possibly reflects a distorted mitochondrial function due to decreased mitochondrial stability, especially in the mitochondria of COPD patients.

Lymphangiogenesis in COPD: another link in the pathogenesis of the disease.

BACKGROUND: New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis. AIM: To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters. METHODS: Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history. RESULTS: D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R(2) = 0.415, R(2) = 0.605, respectively). CONCLUSIONS: We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.

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.

Oxidative DNA damage and somatic mutations: a link to the molecular pathogenesis of chronic inflammatory airway diseases.

BACKGROUND: Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects. METHODS: Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants. RESULTS: None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis (P = .0002), smokers without COPD (P = .0056), and healthy subjects (P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD (P = .04) and smokers without COPD (P = .008), but was not statistically different (P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD (P = .001), but was not statistically significant in smokers without COPD (P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD (P = .009). CONCLUSIONS: There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.

CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does gender play a role?

BACKGROUND-AIM: C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6 months after the start of effective CPAP treatment. METHODS: The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period. RESULTS: C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79 ± 0.65 mg/dL versus 0.70 ± 0.52 mg/dL (p < 0.05) after 3 months and 0.30 ± 0.33 mg/dL (p < 0.001) after 6 months of CPAP therapy]. When patients were divided into males and females, the above evolution pattern was changed. At the third month time point, the CRP values showed a statistically significant decrease only in males (from 0.74 ± 0.53 mg/dL to 0.61 ± 0.5 mg/dL, p < 0.01) while females showed only minimal and insignificant changes (from 0.87 ± 0.79 mg/dL to 0.83 ± 0.51 mg/dL, p > 0.05). After 6 months' treatment, CRP decreased significantly in both genders (males from 0.74 ± 0.53 mg/dL to 0.28 ± 0.32 mg/dL, p < 0.001 and females from 0.87 ± 0.79 mg/dL to 0.34 ± 0.36 mg/dL, p < 0.001). CONCLUSION: Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6 months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP's protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.

Asthma in the Elderly: Can We Distinguish It from COPD?

Asthma in older adults affects quality of life and results in a higher hospitalization rate and mortality. In common clinical practice, asthma in the elderly is underdiagnosed and undertreated or overdiagnosed and mistreated. The age-related reduction in perception of shortness of breath and the high incidence of comorbidities make the diagnosis and management more difficult and challenging for the physicians. Chronic obstructive pulmonary disease (COPD) is usually easy to distinguish from asthma, but sometimes the distinction from late-onset asthma in older patients, particularly in cigarette smokers, is difficult and may be impossible. Both diseases are characterized by the presence of airflow obstruction but have distinct pathogenesis, inflammatory pattern, and prognosis. The distinction between Asthma and COPD based simply on spirometric parameters is difficult especially in the elderly asthmatics. The combination of lung function testing, bronchial hyperresponsiveness (BHR) and atopy status, HRCT scans, and the newly developed biological techniques, allowing the assessment of biomarker profiles, could facilitate the distinction between these diseases.

Utility of formulas predicting the optimal nasal continuous positive airway pressure in a Greek population.

BACKGROUND: There have been reports that optimal CPAP pressure can be predicted from a previously derived formula, with the Hoffstein formula being the most accurate and accepted in the literature so far. However, the validation of this predictive model has not been applied in different clinical settings. Our aim was to compare both the Hoffstein prediction formula and a newly derived formula to the CPAP pressure setting assessed during a formal CPAP titration study. METHODS: We prospectively studied 1,111 patients (871 males/240 females) with obstructive sleep apnea hypopnea syndrome (OSAHS) undergoing a CPAP titration procedure. In this large population sample, we tested the Hoffstein formula, utilizing body mass index (BMI), neck circumference and apnea/hypopnea index (AHI), and we compared it with our new formula that included not only AHI and BMI but also smoking history and gender adjustment. RESULTS: We found that using the Hoffstein prediction formula, successful prediction (predicted CPAP pressure within ±2 cm H(2)O compared to the finally assessed optimum CPAP pressure during titration) was accomplished in 873 patients (79%), with significant correlation between CPAP predicted pressure (CPAPpred(1)) and the optimum CPAP pressure (CPAPopt) [r = 0.364, p < 0.001]. With the new formula, including smoking history and gender adjustment, successful prediction was accomplished in 1,057 patients (95%), with significant correlation between CPAP predicted pressure (CPAPpred(2)) and the CPAPopt (r = 0.392, p < 0.001). However, there was a highly significant correlation between the two formulas (r = 0.918, p < 0.001). CONCLUSIONS: We conclude that the level of CPAP necessary to abolish sleep apnea can be successfully predicted from both equations, using common clinical measurements and prediction formulas that may be useful in calculating the starting pressure for initiating CPAP titration. It may also be possible to shorten CPAP titration and perhaps in selected cases to combine it with the initial diagnostic study.

C-reactive protein evolution in obstructive sleep apnoea patients under CPAP therapy.

BACKGROUND: C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. METHODS: Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. RESULTS: A significant reduction in CRP levels was observed after CPAP therapy (0·74±0·62mgdL(-1) vs. 0·31±0·29mgdL(-1) , P<0·001) in the whole patient group. The evolution of CRP values showed a gradual decrease at 3months with a steep decline at 6months, reaching a plateau after this time point. When the patients were divided into those with good and poor compliance with CPAP therapy, the above CRP evolution pattern was observed only in the former group. CONCLUSION: Good CPAP compliance results in a significant CRP reduction. To achieve the best positive impact on cardiovascular morbidity and mortality, a time period of at least 6months of CPAP use is required.