Florian Kollert

Alternatively activated alveolar macrophages in pulmonary fibrosis—mediator production and intracellular signal transduction

Activated macrophages have been characterized as M1 and M2 according to their inflammatory response pattern. Here we analyzed the M2 marker expression and intracellular signal transduction in the course of cytokine-driven differentiation. We found elevated spontaneous production of the chemokines CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages from patients with lung fibrosis. Stimulation of normal human AM with Th2 cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation induces a strong activation of STAT3 in AM from fibrosis patients. These results suggest an important role for M2 polarized AM in the pathogenesis of pulmonary fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype shift to M2, as seen in patients with fibrotic interstitial lung diseases.

Long-Term Changes of Sexual Function in Men with Obstructive Sleep Apnea after Initiation of Continuous Positive Airway Pressure

INTRODUCTION Obstructive sleep apnea (OSA), particularly intermittent nocturnal hypoxemia, is associated with erectile dysfunction (ED). AIM We investigated in patients with OSA whether continuous positive airway pressure (CPAP) therapy has a long-term effect on sexual function, including ED, in the presence of other risk factors for ED. METHODS Within a long-term observational design, we reassessed 401 male patients who had been referred for polysomnography, with respect to erectile and overall sexual function. Mean ± standard deviation follow-up time was 36.5 ± 3.7 months. Patients with moderate to severe ED were stratified according to the regular use of CPAP. MAIN OUTCOME MEASURE Changes of sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire, including the domains erectile function (EF), intercourse satisfaction, orgasmic function (OF), sexual desire (SD), and overall satisfaction (OS). RESULTS Of the 401 patients, 91 returned a valid IIEF-15 questionnaire at follow-up. Their baseline characteristics were not different from those of the total study group. OSA (apnea-hypopnea index >5/hour) had been diagnosed in 91.2% of patients. In patients with moderate to severe ED (EF domain <17), CPAP users (N = 21) experienced an improvement in overall sexual function (IIEF-15 summary score; P = 0.014) compared with CPAP non-users (N = 18), as well as in the subdomains OF (P = 0.012), SD (P = 0.007), and OS (P = 0.033). Similar results were obtained in patients with poor overall sexual dysfunction (IIEF-15 summary score <44). In patients with moderate to severe ED and low mean nocturnal oxygen saturation (≤93%, median), also the EF subdomain improved in CPAP users vs. non-users (P = 0.047). CONCLUSIONS These data indicate that long-term CPAP treatment of OSA and the related intermittent hypoxia can improve or preserve sexual function in men with OSA and moderate to severe erectile or sexual dysfunction, suggesting a certain reversibility of OSA-induced sexual dysfunctions.

The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R signaling and controls B cell autoimmunity

The protein tyrosine phosphatase PTP1B regulates co-receptor signaling on B cells and thus controls B cell autoimmunity.

Pulmonary hypertension in obesity-hypoventilation syndrome

BACKGROUND Pulmonary hypertension (PH) is considered a clinically important feature of Obesity-Hypoventilation Syndrome (OHS). We aimed to determine prevalence, characteristics and severity of PH including associations with clinical outcomes after established non-invasive positive pressure ventilation (NPPV). METHODS In a prospective cross-sectional study, clinically stable OHS-patients (NPPV duration ≥ 3 months) were consecutively assessed using echocardiography, serum markers and right-heart catheterization (RHC). NPPV use was quantified via ventilator counters. Blood gases, lung function, Epworth-Sleepiness Scale (ESS), sleep-quality, WHO-functional class (WHO-FC), 6-min walk distance, and health-related quality of life (HRQL) via Severe Respiratory Insufficiency (SRI) questionnaire were assessed. RESULTS Of 177 patients considered, 64 fulfilled inclusion criteria. Among these, 21 patients (10 female/11 male; BMI 45 [40; 53] kg/m(2), PaCO2 39.6 [37.8; 45.5] mmHg (median [quartiles])) gave consent for RHC. Four patients (19%) had normal mean pulmonary artery pressure (mPAP < 20 mmHg), 8 (38.1%) mPAP 20-24 mmHg and 9 (42.9%) manifest PH (mPAP ≥ 25 mmHg), 3 of them with combined pre- and/or postcapillary PH. mPAP was negatively correlated to NPPV use, vital capacity and lung diffusing capacity (p < 0.01 each), and positively to BMI (p < 0.05). NPPV use and vital capacity independently predicted mPAP. In patients with PH, ESS, WHO-FC, and some SRI-items were worse (p < 0.05 each) compared to patients without PH. Multivariate analyses revealed mPAP as the only independent predictor of the SRI-physical functioning domain. CONCLUSIONS Mild to moderate PH is frequent in patients with OHS despite NPPV, mPAP being inversely related to NPPV adherence. PH is associated with impairments in daytime-sleepiness, WHO-FC, HRQL and physical functioning.

Anaemia in chronic respiratory failure

Background:  In patients with severe chronic obstructive pulmonary disease (COPD), anaemia is common and associated with impaired long‐term survival and quality of life. Whether anaemia is also prevalent in patients with other severe, non‐inflammatory respiratory diseases has not yet been systematically tested.

Predictors of Successful Decannulation Using a Tracheostomy Retainer in Patients with Prolonged Weaning and Persisting Respiratory Failure

Background: For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch to noninvasive ventilation is an important clinical issue. Objectives: We aimed to evaluate the usefulness of a tracheostomy retainer (TR) and the predictors of successful decannulation. Methods: We studied 166 of 384 patients with prolonged weaning in whom a TR was inserted into a tracheostoma. Patients were analyzed with regard to successful decannulation and characterized by blood gas values, the duration of previous spontaneous breathing, Simplified Acute Physiology Score (SAPS) and laboratory parameters. Results: In 47 patients (28.3%) recannulation was necessary, mostly due to respiratory decompensation and aspiration. Overall, 80.6% of the patients could be liberated from a tracheostomy with the help of a TR. The need for recannulation was associated with a shorter duration of spontaneous breathing within the last 24/48 h (p < 0.01 each), lower arterial oxygen tension (p = 0.025), greater age (p = 0.025), and a higher creatinine level (p = 0.003) and SAPS (p < 0.001). The risk for recannulation was 9.5% when patients breathed spontaneously for 19–24 h within the 24 h prior to decannulation, but 75.0% when patients breathed for only 0–6 h without ventilatory support (p < 0.001). According to ROC analysis, the SAPS best predicted successful decannulation [AUC 0.725 (95% CI: 0.634–0.815), p < 0.001]. Recannulated patients had longer durations of intubation (p = 0.046), tracheostomy (p = 0.003) and hospital stay (p < 0.001). Conclusion: In percutaneously tracheostomized patients with prolonged weaning, the use of a TR seems to facilitate and improve the weaning process considerably. The duration of spontaneous breathing prior to decannulation, age and oxygenation describe the risk for recannulation in these patients.

The role of non‐invasive home mechanical ventilation in patients with chronic obstructive pulmonary disease requiring prolonged weaning

Background and objective:  Patients with COPD who require prolonged weaning from invasive mechanical ventilation show poor long‐term survival. Whether non‐invasive home mechanical ventilation (HMV) has a beneficial effect after prolonged weaning has not yet been clearly determined.

CCL18 production is decreased in alveolar macrophages from cigarette smokers.

It is generally known that cigarette smoke alters the activation of alveolar macrophages (AM). CC Chemokine Ligand 18 (CCL18) is a marker of alternatively activated macrophages and is highly expressed in the lung. This study examines the influence of chronic cigarette smoking on the expression of CCL18 by AM. Bronchoalveolar lavage (BAL) and serum were obtained from ten smokers and 14 non-smokers. CCL18 protein concentrations were measured in serum and BAL fluid (BALF) as well as in supernatants from BAL-cells by enzyme-linked immunosorbent assay. In this study we show that the CCL18 production of BAL-cells from smokers was significantly decreased compared to BAL-cells from non-smokers. The BALF CCL18 protein concentration per macrophage cell count was significantly reduced in smokers. Furthermore, we show a decrease in CCL18 production from BAL-cells after stimulation with LPS. This decrease in CCL18 production was only shown in BAL-cells from non-smokers, which is probably due to chronic LPS exposure of smokers, resulting in LPS hypo-responsiveness. No statistically significant difference of CCL18 concentrations was found in BALF or serum of smokers versus non-smokers. CCL18 production by BAL-cells is down-regulated by chronic cigarette smoking and LPS contamination in cigarette smoke might be one factor involved. Thus this article gives further evidence that chronic cigarette smoking alters the phenotype of AM and that the M2 marker CCL18 is down-regulated in smokers macrophages.

The clinical significance of anaemia and disturbed iron homeostasis in chronic respiratory failure

Anaemia is a frequent, clinically relevant condition in various chronic diseases. It seems also to be prevalent in patients with chronic respiratory failure (CRF). We studied the characteristics of anaemia in CRF and its associations with clinical outcome.

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis.

Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH).