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Treatment with a sphingosine-1-phosphate analog inhibits airway remodeling following repeated allergen exposure

Sphingosine-1-phosphate (S1P) is an immunomodulatory lipid mediator that plays an important role in lymphocyte trafficking. Elevated levels of S1P are found in bronchoalveolar lavage (BAL) fluid of patients with asthma; however, its role in disease is not known. FTY720, a synthetic analog of S1P, has been shown to abrogate allergic inflammation and airway hyperresponsiveness following acute allergen challenge.

However, its effects on asthmatic airway remodeling induced by repeated allergen exposure are unknown. Ovalbumin (OVA)-sensitized rats were challenged on days 14, 19, and 24 after sensitization. FTY720 or vehicle (PBS) therapy was administered 1 h prior to each challenge. BAL fluid and quantitative histological analysis were performed 48 h after the last challenge. FTY720 inhibited O...

Chloride in airway smooth muscle: the ignored anion no longer?

This Perspectives accompanies an Editorial Focus that summarizes new developments concerning the role of chloride in airway smooth muscle physiology. We provide several observations and mechanistic insights to reconcile recent experimental evidence with existing paradigms concerning chloride channel-mediated effects on airway smooth muscle tone.

In addition, we highlight the potentially complex and dynamic nature that chloride currents and membrane potential have on calcium handling and airway smooth muscle contractility.

Changes in serum cortisol levels during community-acquired pneumonia: The influence of dexamethasone

In community-acquired pneumonia (CAP), the cortisol level on admission can be a useful biomarker for prognosis. Serial cortisol measurements during the clinical course of disease and their association with disease outcome have never been reported. Furthermore, the time to recovery of the hypothalamic-pituitary-adrenal axis after a short course of dexamethasone during infection is unclear.

We analyzed data from 270 hospitalized patients with CAP. Total serum cortisol was measured on presentation, day 1, 2, 4, and on control visit (day 30). Intensive care unit (ICU) admission and mortality were assessed. Additionally, to study the influence of dexamethasone on the kinetics of the cortisol response, we analyzed serial cortisol values of 43 patients treated with a four-day regimen of dexamethasone 5 mg.

During hospital stay, 26/270 patients (9.6%) were admitted to the ICU and 15/270 patients (5.6%) died. Compared to patients with an uneventful recovery, cortisol on presentation was significantly higher in patients with an adverse outcome (360 μg/L, IQR 209-597 vs. 238 μg/L, IQR 151-374) (p:0.01), and also remained significantly higher throughout the course of disease. Dexamethasone treatment resulted in nearly complete suppression of the endogenous cortisol production after the first dose, but cortisol production was fully recovered on control visit.

In conclusion, we showed that an adverse outcome of CAP was associated with persisting higher total serum cortisol throughout the course of disease. Delta-cortisol could be another meaningful biomarker in CAP. Next, our data indicate that a four-day dexamethasone regimen during CAP does not lead to prolonged secondary adrenal insufficiency.

Lymphangiogenesis in COPD: Another link in the pathogenesis of the disease

New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis.

Aim : To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters.

Methods : Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history.

Results : D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R 2 = 0.415, R 2 = 0.605, respectively).

Conclusions : We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.

Pulmonary hypertension in interstitial lung disease: Prevalence, prognosis and 6 min walk test

Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the prevalence and impact of PH on prognosis and exercise capacity in ILD patients.

Methods : 212 ILD patients were screened for PH by echocardiography. Criteria for PH were either a tricuspid pressure regurgitation gradient >40 mmHg, a tricuspid annular plane systolic excursion <1.8 cm or right ventricular dilatation. If possible, PH was confirmed by right heart catheterisation. Pulmonary function tests and 6 min walk tests (6MWT) were performed.

Results : 29 patients (14%) had PH, 16 (8%) had mild and 13 (6%) had severe PH (mean pulmonary artery pressure ≥ 35 mmHg). Compared to patients without PH, lung function parameters were lower in PH patients, a larger proportion had idiopathic pulmonary fibrosis (IPF) (41 vs 21%, p = 0.006), and the hazard ratio for death was 8.5 (95% CI: 4–17). After correction for lung function parameters and the presence of IPF, 6MWT was significantly lower in patients with PH compared to non-PH patients (difference ± SEM: 58 ± 22 m, p = 0.01).

Conclusions : PH occurred in 14% of a cohort of patients with ILD and was associated to IPF and lower lung function parameters. Mortality was markedly higher in PH patients, and the presence of PH reduced 6MWT independently of lung function and the presence of IPF. The present results emphasize the need for intensified treatment of patients with ILD and PH.

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