Katrin Milger

Inducible NOS Inhibition Reverses Tobacco-Smoke-Induced Emphysema and Pulmonary Hypertension in Mice

Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease. In chimeric mice lacking iNOS in bone marrow (BM)-derived cells, PH was dependent on iNOS from BM-derived cells, whereas emphysema development was dependent on iNOS from non-BM-derived cells. Similar regulatory and structural alterations as seen in mouse lungs were found in lung tissue from humans with end-stage COPD.

Short-term improvement in pulmonary hemodynamics is strongly predictive of long-term survival in patients with pulmonary arterial hypertension

Hemodynamic measurements provide important parameters for determining prognosis and therapy in patients with pulmonary arterial hypertension (PAH). Current guidelines do not incorporate the possible predictive value of individual changes in hemodynamic variables during the disease time course, and there is no consensus about the time point for hemodynamic reevaluation. We aimed to assess the long-term prognostic value of short-term changes in hemodynamic parameters. The study included 122 patients with PAH from the Giessen Pulmonary Hypertension Registry who underwent hemodynamic evaluation at baseline and at 16 weeks (±2.5 standard deviations [SDs]; range: 4–29 weeks) after initial assessment. At baseline, mean pulmonary vascular resistance (PVR) was 1,109 dyn s cm−5, and 82% of patients were in World Health Organization (WHO) functional class III or IV. Fifty patients died, and 2 underwent lung transplantation during long-term observation (≤10 years; mean: 4.7 years). Kaplan-Meier estimates for transplant-free survival were 93.3%, 76.1%, 57.8%, and 53.1% at 1, 3, 5, and 7 years, respectively. When assigned to prognostic groups, improvements in cardiac output of >0.22 L min−1 (hazard ratio [HR]: 2.05; P = 0.015) and a decrease in PVR of >176 dyn s cm−5 (HR: 1.89; P = 0.044) at 4–29 weeks were associated with long-term transplant-free survival. Changes in mean pulmonary arterial pressure did not predict long-term prognosis. Of 2 noninvasive parameters assessed in this selected patient group, change in WHO functional class, but not in 6-minute walk distance, predicted long-term prognosis. Short-term assessment of changes in hemodynamic parameters at 16 weeks ± 2.5 SDs after initial invasive evaluation is useful to determine long-term prognosis in patients with PAH.

Neurosyphilis manifesting with unilateral visual loss and hyponatremia: a case report

BackgroundSyphilis is called the chameleon of the diseases due to its variety of its clinical presentations, potentially affecting every organ of the body. Incidence of this ancient disease is once again on the increase worldwide.Case presentationWe here report an unusual case of neurosyphilis manifesting with unilateral visual loss and hyponatremia. The patient also had primary syphilitic lesions and was concomitantly diagnosed with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Treatment with ceftriaxone and prednisolone, completely resolved the hyponatremia and visual acuity was partially restored.ConclusionAwareness of syphilis as a differential diagnosis is important as previously unreported presentations of neurosyphilis can arise, especially in HIV infected patients.

Cardiovocal Syndrome (Ortner's Syndrome) Associated with Chronic Thromboembolic Pulmonary Hypertension and Giant Pulmonary Artery Aneurysm: Case Report and Review of the Literature.

Cardiovocal syndrome or Ortners syndrome is hoarseness due to left recurrent laryngeal nerve palsy caused by mechanical affection of the nerve from enlarged cardiovascular structures. Chronic thromboembolic pulmonary hypertension is extremely rarely found to cause this syndrome. We describe a case of a 56-year-old patient with sudden onset of hoarseness. The patient had known long standing severe pulmonary hypertension. Fiberoptic laryngoscopy showed left vocal cord palsy. Computed tomography of the neck and chest revealed extensive enlargement of the pulmonary arteries and excluded a malignant tumor. The diagnosis of cardiovocal syndrome was retained. It is important for the radiologist to be aware of this possible etiology causing left recurrent laryngeal nerve palsy and to understand its mechanism.

Development of a Stable Lung Microbiome in Healthy Neonatal Mice

The lower respiratory tract has been previously considered sterile in a healthy state, but advances in culture-independent techniques for microbial identification and characterization have revealed that the lung harbors a diverse microbiome. Although research on the lung microbiome is increasing and important questions were already addressed, longitudinal studies aiming to describe developmental stages of the microbial communities from the early neonatal period to adulthood are lacking. Thus, little is known about the early-life development of the lung microbiome and the impact of external factors during these stages. In this study, we applied a barcoding approach based on high-throughput sequencing of 16S ribosomal RNA gene amplicon libraries to determine age-dependent differences in the bacterial fraction of the murine lung microbiome and to assess potential influences of differing “environmental microbiomes” (simulated by the application of used litter material to the cages). We could clearly show that the diversity of the bacterial community harbored in the murine lung increases with age. Interestingly, bacteria belonging to the genera Delftia and Rhodococcus formed an age-independent core microbiome. The addition of the used litter material influenced the lung microbiota of young mice but did not significantly alter the community composition of adult animals. Our findings elucidate the dynamic nature of the early-life lung microbiota and its stabilization with age. Further, this study indicates that even slight environmental changes modulate the bacterial community composition of the lung microbiome in early life, whereas the lung microbes of adults demonstrate higher resilience towards environmental variations.

Tidal Carbon Dioxide as a Prognostic Feature in Inoperable Chronic Thromboembolic Pulmonary Hypertension

1 Department of Pneumology, Kerckhoff Heart and Thoracic Center, Bad Nauheim, Germany; 2 Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany; 3 Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, member of the German Center for Lung Research (DZL), Munich, Germany; 4 Department of Medicine, Imperial College London, London, United Kingdom