Philipp Eickhoff

Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease.

RATIONALE Impaired vascular reactivity is an important factor in the pathogenesis of cardiovascular disease. OBJECTIVES We sought to assess vascular reactivity in patients with chronic obstructive pulmonary disease (COPD) and respective control subjects, and to investigate the relation between vascular function and airflow obstruction and systemic inflammation. METHODS We studied 60 patients with stable COPD; 20 smokers with normal lung function matched for age, sex, and body weight; and 20 similarly matched nonsmokers. Patients with cardiovascular comorbidities were excluded. The endothelium-dependent and endothelium-independent function of the vasculature was measured using flow-mediated and nitrogen-mediated dilation of the brachial artery, respectively. Systemic inflammatory markers, including C-reactive protein, fibrinogen, and interleukin (IL)-6, were determined in serum. MEASUREMENTS AND MAIN RESULTS Both flow-mediated and nitrogen-mediated dilation of the brachial artery were significantly lower in patients with stable COPD than in smoking and nonsmoking control subjects. Levels of inflammatory mediators such as IL-6 and fibrinogen were higher in patients than they were in control subjects. In patients with COPD, stepwise multiple regression analysis showed that age, sex, baseline brachial artery diameter, C-reactive protein level, leukocyte count, blood glucose level, and percentage of predicted forced expiratory volume in 1 s were independent predictors of flow-mediated dilation. There was no relation between flow-mediated dilation and pack-years of smoking. Baseline brachial artery diameter was the only independent predictor of nitrogen-mediated dilation in patients with COPD. CONCLUSIONS Both endothelium-dependent and endothelium-independent vasodilation is significantly impaired in patients with stable COPD. Airflow obstruction and systemic inflammation may increase the risk of cardiovascular disease in patients with COPD.

Circulating vascular endothelial growth factor and systemic inflammatory markers in patients with stable and exacerbated chronic obstructive pulmonary disease

The aim of the present study was to assess circulating levels of VEGF (vascular endothelial growth factor), a biomarker with prognostic significance in cardiovascular disease, and markers of systemic inflammation in patients with stable and exacerbated COPD (chronic obstructive pulmonary disease). Lung function parameters, arterial blood gas analysis and circulating levels of VEGF, IL-6 (interleukin-6), TNF-alpha (tumour necrosis factor-alpha), CRP (C-reactive protein), fibrinogen and the peripheral blood neutrophil cell count were assessed in 30 patients on admission to the hospital for acute exacerbation of COPD, in 30 age-, gender- and BMI (body mass index)-matched patients with stable COPD, and 30 matched controls with normal lung function. Patients with acute exacerbated COPD had higher circulating concentrations of VEGF (P<0.001), IL-6 (P<0.05) and CRP (P<0.01) and an increased blood neutrophil cell count (P<0.05) compared with patients with stable COPD and healthy controls. VEGF levels in exacerbated COPD correlated with systemic inflammatory markers, such as CRP (r=0.61, P<0.005), IL-6 (r=0.46; P<0.01) and fibrinogen (r=0.39, P<0.05). In patients with stable COPD, there was a significant relationship between circulating VEGF levels and the percentage of the predicted FEV(1) (forced expiratory volume in 1 s) (r=0.47, P<0.01). Recovery from the exacerbation resulted in a significant decrease in both circulating VEGF levels and markers of systemic inflammation. In conclusion, circulating levels of VEGF and markers of systemic inflammation are up-regulated in patients with acute exacerbated COPD and decrease after recovery from the exacerbation.

Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold

BackgroundCommon cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold.MethodsWe have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits.ResultsThe results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo.ConclusionIn this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies.Trial registrationISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

Prevalence and clinical course of viral upper respiratory tract infections in immunocompromised pediatric patients with malignancies or after hematopoietic stem cell transplantation.

Background: Respiratory tract infections (RTI) in immunosuppressed pediatric patients with malignancies or after hematopoietic stem cell transplantation (HSCT) are associated with significant morbidity and mortality. Prospective data on the incidence and clinical role of infections by respiratory viruses in this population have been lacking. Methods: In this prospective study, 191 children between 0 and 18 years of age were investigated by real-time polymerase chain reaction for the presence of 8 common respiratory virus types in transnasal aspirations. The study included 110 children with leukemia, lymphoma, or solid tumors (subgroup 1); 31 children after HSCT (subgroup 2); and 50 immunocompetent control patients. Results: In comparison with the control group, immunocompromised children showed a significantly higher incidence of positive virus tests (subgroup 1: 53%; subgroup 2: 81%; controls: 24%; P<0.0001), and more frequently experienced ensuing viral infections in the lower respiratory tract (subgroup 1: 74%; subgroup 2: 88%; controls: 25%; P<0.0001). Sixteen percent of these children had coinfections by 2 or more viruses and revealed more severe respiratory illness. Conclusions: The present epidemiologic study on viral upper RTI in immunocompromised children revealed a high virus-associated morbidity which was particularly prominent in HSCT recipients. In these children, detection of viral coinfections was identified as a risk factor for a severe course of lower RTI.

Soluble receptor of advanced glycation end-products and endothelial dysfunction in COPD

BACKGROUND Chronic obstructive pulmonary disease (COPD) is accompanied by an increased cardiovascular risk which is aggravated by the incidence of acute exacerbations (AE). Endothelial function, as well as the soluble receptor for advanced glycation end-products (sRAGE), both markers of cardiovascular risk, has been shown to be decreased in stable COPD. OBJECTIVES We aimed to investigate a possible link between sRAGE and endothelial function in AE of COPD. We hypothesize that circulating levels of sRAGE and endothelial function are impaired during AE and improve after clinical recovery, respectively. METHODS We enrolled patients admitted to hospital due to an AE of COPD without overt cardiovascular comorbidities. Study related procedures comprised spirometry, measurement of plasma sRAGE levels and the quantification of endothelial function by means of the flow-mediated dilation technique (FMD). All measurements were scheduled during hospitalization and after confirmed clinical stability. RESULTS We recruited 29 patients (27% female) with moderate to severe COPD. Median sRAGE concentration was 525 pg/mL (371-770, 1st-3rd quartile) and mean FMD 6.7 ± 3.6% at AE. There was a significant increase of sRAGE levels to 876 pg/mL (633-1371, 1st-3rd quartile, p < 0.001) and a simultaneous improvement in FMD (10.0 ± 3.4%, p < 0.001) after clinical recovery. There was a significant positive association between sRAGE and FMD (regression coefficient = 2.43; p = 0.01) in our study sample. CONCLUSION Our results indicate a substantial decrease in sRAGE levels and endothelial function during AE, with evidence of improvements after clinical recovery. sRAGE may contribute to cardiovascular risk in COPD.

Mitral valve endocarditis caused by ulcerative colitis followed by septic embolic occlusion of the superior mesenteric artery

Acute endocarditis is a rare complication of ulcerative colitis. We report on a young woman, who initially presented with fever, elevated inflammatory markers, and symptoms of ulcerative pancolitis but without any cardiac co-morbidity. A few days after total colectomy, the patient complained of acute abdominal pain which led to the suspected diagnosis of mesenteric ischaemia caused by a septic embolus. Transthoracic and transoesophageal echocardiography showed a large vegetation on the anterior leaflet of the mitral valve. The patient was successfully treated by an operative approach including mitral valve replacement.

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Background Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels.

Dornase alpha inhalations as a treatment option for recurrent lower respiratory tract infections in a child with Sotos syndrome

SummaryRecurrent episodes of lower respiratory tract infections (LRTIs) are a rare complication of muscular hypotonia in patients with Sotos syndrome. We report on a male child suffering from repeated LRTIs including bronchitis, pneumonia, and atelectasis during infancy despite inhalations with salbutamol and fluticasone combined with manual chest percussion therapy. After initiation of dornase alpha inhalations in addition to the current treatment, we observed an improvement in the respiratory symptoms as well as a reduction in the rate of hospitalizations and in the occurrence of LRTIs. We assume that dornase alpha inhalations, in combination with airway clearance techniques, reduced the viscosity of airway secretions and by this improved mucociliary clearance and coughing efficiency.ZusammenfassungRezidivierende Infektionen der unteren Atemwege sind eine seltene Komplikation einer muskulären Hypotonie bei Patienten mit einem Sotos Syndrom. Wir berichten über einen Knaben, der während seines ersten Lebensjahres an einer Vielzahl von Bronchitiden, Lungenentzündungen und Atelektasen erkrankt ist, trotz Inhalationen mit Salbutamol und Fluticason kombiniert mit manueller Atemphysiotherapie. Zusätzlich zu der bereits bestehenden Therapie wurde mit Dornase Alpha Inhalationen begonnen, woraufhin es zu einer Verbesserung der respiratorischen Symptomatik, sowie zu einer Reduktion der stationären Aufenthalte und der Infektionen der unteren Atemwegen gekommen ist. Wir vermuten, dass Dornase Alpha Inhalationen die Viskosität der bronchialen Sekrete reduziert. Zusammen mit der manuellen Atemphysiotherapie scheint dies zu einer verbesserten mukozilliären Clearence und einem effizienteren Husten zu führen.