Adam Nowinski

Oxidative stress in the external intercostal muscles of patients with obstructive sleep apnoea

Background: The external intercostal muscles are chronically exposed to increased inspiratory loading and to continuous hypoxia-reoxygenation cycles in patients with obstructive sleep apnoea syndrome (OSAS). It was therefore hypothesised that oxidative stress levels would be increased in these muscles, and that treatment with continuous positive airway pressure (CPAP) would modify the oxidative stress levels and improve muscle dysfunction. Methods: A case-control study and a case-case study were conducted on the external intercostal muscles of 12 patients with severe OSAS (before and after 6 months of treatment with CPAP) and 6 control subjects. Reactive carbonyl groups, malondialdehyde (MDA)-protein and hydroxynonenal (HNE)-protein adducts, antioxidant enzyme levels, 3-nitrotyrosine and fibre type proportions were measured using immunoblotting and immunohistochemistry. Results: Compared with controls, the intercostal muscles of patients with OSAS had higher levels of protein carbonylation (median values 3.06 and 2.45, respectively, p = 0.042), nitration (median values 1.64 and 1.05, respectively, p = 0.019) and proportions of type I fibres (median values 57% and 48%, respectively, p = 0.035) and reduced respiratory muscle endurance (median values 3.2 and 9.5 min, respectively, p = 0.001). Positive correlations were found between MDA-protein and HNE-protein adducts (r = 0.641, p = 0.02 and r = 0.594, p = 0.05, respectively) and 3-nitrotyrosine (r = 0.625, p = 0.03) and the apnoea-hypopnoea index (AHI) in all the patients with OSAS. Although treatment with CPAP significantly improved the AHI and oxygen desaturation, muscle oxidative stress levels and respiratory muscle endurance were not affected. Conclusions: This study suggests that inspiratory muscle performance is not completely restored after long-term treatment with CPAP.

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome

Background Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Methods Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. Results We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Conclusion Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

The EvA study: aims and strategy

The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach. 441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1–3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry. QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting “emphysema-dominant”, “airway disease-dominant”, “mixed” disease and “mild” disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2) and carbon dioxide (PCO2) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group. The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease. Standardisation of quantitative CT improves delineation of emphysema and airway phenotypes in a multicentre study http://ow.ly/10zjhV

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis.

Pilot program on distance training in spirometry testing - the technology feasibility study.

INTRODUCTION Office spirometry has been widely used in recent years by general practitioners in primary care setting, thus the need for stricter monitoring of the quality of spirometry has been recognized. MATERIAL AND METHODS A spirometry counseling network of outpatients clinics was created in Poland using portable spirometer Spirotel. The spirometry data were transferred to counseling centre once a week. The tests sent to the counseling centre were analyzed by doctors experienced in the analysis of spirometric data. In justified cases they sent their remarks concerning performed tests to the centres via e-mail. RESULTS We received 878 records of spirometry tests in total. Data transmission via the telephone was 100% effective. The quality of spirometry tests performed by outpatients clinics was variable. CONCLUSIONS The use of spirometers with data transfer for training purposes seems to be advisable. There is a need to proper face-to-face training of spirometry operators before an implementation of any telemedicine technology.

Obstructive sleep apnea and the risk of chronic kidney disease – glomerular filtration rate estimations based on serum cystatin C and creatinine concentrations

Rationale: Some studies have demonstrated an association between chronic kidney disease (CKD) and obstructive sleep apnea (OSA). It was suggested that glomerular filtration rate estimations (eGFR) based on serum creatinine may be influenced by muscle abnormalities observed in OSA patients. Aim: The aim of this study was to compare the prevalence of CKD in OSA pts using eGFR estimations based on both cystatin C and creatinine serum concentrations. Materials and methods: A cohort of 240 pts with newly diagnosed OSA was enrolled into the study. Results: 185 males (77%) and 55 females (23%) with mean age = 56.8 ±9.9 yrs, Apnea-Hypopnea Index (AHI) 38.7±21.7/hour, Epworth sleepiness scale (ESS) 11.2± 5.7 were examined for CKD. Results of eGFR in studied group are listed below. View this table: Table1 View this table: Table2 Weak correlations were observed between eGFR estimated using cystatin C and: proBNP (R -0.24, p=0.0061), total cholesterol (R =0.16, p=0.015) and ESS (R -0.16 p=0.015). Conclusion: We have found a signs of CKD in a significant number of studied OSA pts. eGFR based on cystatin C increased prevalence and severity of CKD in OSA pts. Additional eGFR masurements based on cystatin C should be considered in OSA pts.