Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term “response to bacterium” was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term “response to stress” was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Background: Expiratory pressure relief continuous positive airway pressure (pressure relief CPAP, C-Flex®) is known to be as effective in the treatment of obstructive sleep apnea (OSA) as conventional CPAP while improving overall patients’ adherence. However, the effects of C-Flex on ventilation during sleep have not been studied yet. Objective: This study investigates the effects of pressure relief CPAP on respiratory parameters and possible inspiratory flow limitation with increased difference between inspiratory and expiratory pressure compared with conventional CPAP. Methods: In total, 24 patients were investigated both during conventional CPAP and during three C-Flex pressure relief settings in randomized order during rapid-eye-movement (REM) and non-REM (NREM) sleep. Airflow was monitored with a pneumotachograph; inspiratory flow limitation was assessed by analyzing airflow and esophageal pressure swings. Results: Using higher C-Flex gains, expiratory time decreased in favor of the inspiratory duty cycle while there was no significant change in tidal volume. Analysis of inspiratory flow limitation showed no significant difference between conventional CPAP and the C-Flex gains studied. Conclusions: The increase in the inspiratory duty cycle with C-Flex might either indicate an increase in the work of breathing or a decrease in the work of breathing due to a lower peak end-expiratory pressure and consecutive alleviation of passive expiration. Both treatments appeared equivalent regarding the occurrence of inspiratory flow limitation.

Background: Expiratory pressure relief continuous positive airway pressure (pressure relief CPAP; C-Flex™) causes increases in inspiratory duty cycle and shortening of expiratory time. It has been suggested that these changes are caused by an increase in work of breathing. Objectives: We studied the effects of C-Flex on work of breathing and intrinsic positive end-expiratory pressure as compared to fixed CPAP. Methods: Work of breathing was analyzed in 24 patients with obstructive sleep apnea during treatment with fixed CPAP and C-Flex with 3 different pressure relief settings in a randomized order during rapid-eye-movement (REM) and non-REM sleep. Work of breathing was assessed on a breath-by-breath basis using a piezoelectric esophageal pressure catheter and a pneumotachograph for measuring airflow. Results: We found there was no increase in inspiratory work of breathing observed using C-Flex compared to fixed CPAP. Instead, we found a linear decrease in inspiratory work of breathing with increasing pressure relief, with a mean difference of 1.22 J/min between CPAP and maximum pressure release (C-Flex 3; 90% of the value with nasal CPAP); however, the decrease was not statistically significant. The decrease in inspiratory work of breathing associated with C-Flex has a significant inverse correlation with BMI. Conclusions: The C-Flex technology does not change work of breathing but shows a tendency towards a reduction of inspiratory work of breathing in patients with a lower BMI using higher C-Flex. The effect is probably caused by diminishing airway resistance generated by the positive end-expiratory pressure. Our findings may lead to additional fields of application of the C-Flex technology, such as chronic obstructive pulmonary disease or muscular dystrophy.

The COPD is a very common, chronic, non-contagious disease causing high mortality as well as high socio-economical costs worldwide. Its clinical assessment progressively becomes more comprehensive including the lung function, the rate of exacerbations, the physical capacity, the sensation of dyspnoea, and comorbidities. On the other hand, our therapeutic options are very limited: Although there are several well-tolerated and effective combinable bronchodilators of the group of long-acting beta2-mimetics and anticholinergics, drugs causally affecting pathophysiology are barely available. As anti-inflammatory principles only inhaled glucocorticoids as well as one orally available inhibitor of phosphodiesterase 4 are approved, each improving the course of disease in a subgroup of patients. This lack of effective causative therapeutic principles on the one hand and of biomarkers clearly stratifying patients on the other hand to a large extend are caused by our limited understanding of the pathophysiology. Therefore, this review presents the current progress in clinical and experimental research on COPD with regard to clinical practice.