Therapeutic Success in Swiss COPD Patients Receiving Dual Bronchodilation Therapy as COPD Maintenance Treatment.

Health-related quality of life (HRQoL) in patients with moderate to severe chronic obstructive pulmonary disease (COPD) is often reduced by high symptom burden and frequent exacerbations. So far, data on therapeutic success in Swiss COPD patients receiving dual bronchodilation therapy as COPD maintenance treatment are limited. Data from a recently published, non-interventional study on clinical benefit after the start of combined tiotropium-olodaterol treatment were analyzed focusing on Swiss patients compared to the overall cohort including patients from various European countries. Demographic data on the changes in Clinical COPD Questionnaire (CCQ) for the assessment of HRQoL in correlation to symptoms and the number of exacerbations, as well as physician's global assessment (PGE), were evaluated 6 weeks after treatment start. In Switzerland (n = 61), significantly more patients had comorbidities and exacerbations but showed less symptoms compared to the overall cohort (n = 4639). HRQoL improved in both cohorts, with a negative correlation to symptom burden and number of exacerbations in the overall cohort. PGE scores improved after 6 weeks with a better general condition at baseline in Swiss patients (PGE score 4/5: 68.9% [Swiss cohort] vs. 49.0% [overall cohort]. Despite significant differences regarding the presence of symptoms and exacerbations, therapeutic success was similar in both patient groups. Highly symptomatic patients benefited mostly from tiotropium-olodaterol treatment.

Swiss Experience in Therapy With Dual Bronchodilation in Chronic Obstructive Pulmonary Disease in Relation to Self-Reported Physical Functionality.

BACKGROUND: Medical therapy in chronic obstructive pulmonary disease (COPD) usually includes inhaled dual bronchodilation leading not only to an improvement in symptoms but also to an increase in physical performance. However, it remains unknown whether responder rates to dual bronchodilation differ between the Swiss subgroup in comparison to participants of other European countries. METHODS: The non-interventional OTIVACTO trial investigated changes in self-reported physical functioning in COPD patients treated with tiotropium/olodaterol 5/5 µg fixed dose combination for 6 weeks. The cut-off between responder and non-responder was defined as a minimum increase of 10 points using the 10-question physical functioning questionnaire (PF-10) score. We searched for patterns of the responder patient group and compared the results of the whole dataset with the subgroup of Swiss participants. RESULTS: Compared to the total cohort (n = 7,608), the Swiss participants (n = 94) were predominantly > 65 years of age and had significantly more comorbidities. There were no significant differences according to COPD stage, smoking status, exacerbation rate in the last 12 months and modified Medical Research Council questionnaire (mMRC) score between the total cohort and the Swiss collective. There were no significant differences between the Swiss subgroup and the total cohort with regard to response to the medication in the PF-10 score. In the intragroup comparison, patients with high mMRC score showed significantly higher values in the PF-10 in both groups. The number of exacerbations had no influence on the PF-10 score in the Swiss subgroup but in the total cohort. CONCLUSION: In terms of age and number of comorbidities, significant differences were found between the overall patient population and the Swiss participants, having no influence on the success of the medication. The patients suffering from increased dyspnea benefited most from tiotropium/olodaterol treatment (Clinical Trials Registry NCT02720757).

Switching COPD patients from the disposable to the new reusable Respimat soft mist inhaler: a real-world study from Switzerland.

OBJECTIVE: The aims of the survey were to assess first experiences of Swiss COPD patients switching from the disposable to the new reusable Respimat inhaler, and to evaluate physicians´ and patients´ views of the new training material. METHODS: Patients with a confirmed diagnosis of COPD using a disposable Respimat inhaler for at least three months were included. Patients´ demographics, COPD stage, current treatment, and comorbidities relevant for the handling of the device were assessed. Further, patients were trained on the reusable Respimat by placebo inhaler, patient brochure, video cards/demo films and SMS reminder service. After at least one cartridge change, patients gave comprehensive feedback on their satisfaction with the reusable Respimat and physicians evaluated the need for re-training. RESULTS: 235 patients participated in the survey. Of these, 37% suffered from comorbidities restricting the handling of the Respimat. 216 (92%) patients had a better overall satisfaction with the reusable than with the disposable Respimat. Dose counter (86%), monthly preparation (81%) and daily handling (77%) were also assessed as better by most of the patients. In 80% of cases, the user ability was stated as better than for the disposable Respimat. Less than 15% of the patients required further training. Placebo inhaler was the mostly preferred training material by both, physicians (in 86% of the patients) and patients (75%). In patients with comorbidities affecting inhaler handling, overall satisfaction was also better in 86% of the patients. CONCLUSION: The majority of patients were satisfied with the new reusable Respimat device and proper handling could be attained using the provided training material, even in patients with restricting comorbidities.

Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling.

Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within the SVZ stem cell niche controls NSPC fate. However, extracellular factors within the niche that trigger astrogliogenesis over neurogenesis during CNS disease are unclear. Here, we show that blood-derived fibrinogen is enriched in the SVZ niche following distant cortical brain injury in mice. Fibrinogen inhibited neuronal differentiation in SVZ and hippocampal NSPCs while promoting astrogenesis via activation of the BMP receptor signaling pathway. Genetic and pharmacologic depletion of fibrinogen reduced astrocyte formation within the SVZ after cortical injury, reducing the contribution of SVZ-derived reactive astrocytes to lesion scar formation. We propose that fibrinogen is a regulator of NSPC-derived astrogenesis from the SVZ niche via BMP receptor signaling pathway following injury.

The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.

Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation. Here, we show that genetic depletion of the transcriptional regulator Id3 decreased the number of astrocytes generated from SVZ-derived adult NSPCs in the cortical lesion area after traumatic brain injury. Cortical brain injury resulted in rapid BMP-2 and Id3 up-regulation in the SVZ stem cell niche. Id3(-/-) adult NSPCs failed to differentiate into BMP-2-induced astrocytes, while NSPCs deficient for the Id3-controlled transcription factor E47 readily differentiated into astrocytes in the absence of BMP-2. Mechanistically, E47 repressed the expression of several astrocyte-specific genes in adult NSPCs. These results identify Id3 as the BMP-2-induced transcriptional regulator, promoting adult NSPC differentiation into astrocytes upon CNS injury and reveal a molecular link between environmental changes and NSPC differentiation in the CNS after injury.

Isolation and culture of mouse cortical astrocytes.

Astrocytes are an abundant cell type in the mammalian brain, yet much remains to be learned about their molecular and functional characteristics. In vitro astrocyte cell culture systems can be used to study the biological functions of these glial cells in detail. This video protocol shows how to obtain pure astrocytes by isolation and culture of mixed cortical cells of mouse pups. The method is based on the absence of viable neurons and the separation of astrocytes, oligodendrocytes and microglia, the three main glial cell populations of the central nervous system, in culture. Representative images during the first days of culture demonstrate the presence of a mixed cell population and indicate the timepoint, when astrocytes become confluent and should be separated from microglia and oligodendrocytes. Moreover, we demonstrate purity and astrocytic morphology of cultured astrocytes using immunocytochemical stainings for well established and newly described astrocyte markers. This culture system can be easily used to obtain pure mouse astrocytes and astrocyte-conditioned medium for studying various aspects of astrocyte biology.