Effects of volatile anaesthetic agents on enhanced airway tone in sensitized guinea pigs

Background. Although volatile anaesthetics afford protection against bronchospasm, their potential to reverse a sustained constriction of hyperreactive airways has not been characterized. Accordingly, we investigated the ability of halothane, isoflurane, sevoflurane and desflurane to reverse lung constriction induced by prolonged stimulation of the muscarinic receptors in guinea pigs sensitized to ovalbumin. Methods. Pulmonary input impedance (ZL) was measured using forced oscillations in five groups of ovalbumin‐sensitized, mechanically ventilated guinea pigs. ZL was measured under baseline conditions, during steady‐state bronchoconstriction induced by an i.v. infusion of methacholine (MCh), and after administration of one of the volatile agents at 1 MAC after the induction of a steady‐state bronchoconstriction. Airway resistance (Raw), and parenchymal tissue resistive and elastic coefficients were extracted from ZL by model fitting. Results. All four volatile agents exhibited an initial relaxation of the MCh‐induced airway constriction followed by gradual increases in Raw. The bronchodilatory effect of isoflurane was the most potent (-28.9 (se 5.5)% at 2 min, P<0.05) and lasted longest (7 min); sevoflurane and halothane had shorter and more moderate effects (-21.1 (3.9)%, P<0.05, and -6.1 (1.7)%, P<0.05, respectively, at 1 min). Desflurane caused highly variable changes in Raw, with a tendency to enhance airway tone. Conclusions. Volatile agents can reverse sustained MCh‐induced airway constriction only transiently in sensitized guinea pigs. Isoflurane proved most beneficial in temporally improving lung function in the presence of a severe constriction of allergic inflamed airways. Desflurane displayed potential to induce further airway constriction. Br J Anaesth 2004; 92: 254-6

BARD1 mediates TGF-β signaling in pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro-proliferative disorder with poor prognosis similar to lung cancer. The pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast proliferation are thought to be central processes. Previous reports have shown that BARD1 expression is upregulated in response to hypoxia and associated with TGF-β signaling, both recognized factors driving lung fibrosis. Differentially spliced BARD1 isoforms, in particular BARD1β, are oncogenic drivers of proliferation in cancers of various origins. We therefore hypothesized that BARD1 and/or its isoforms might play a role in lung fibrosis. Methods We investigated BARD1 expression as a function of TGF-β in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients. Results FL BARD1 and BARD1β were upregulated in response to TGF-β in epithelial cells and fibroblasts in vitro and in vivo. Protein and mRNA expression studies showed very low expression in healthy lung tissues, but upregulated expression of full length (FL) BARD1 and BARD1β in fibrotic tissues. Conclusion Our data suggest that FL BARD1 and BARD1β might be mediators of pleiotropic effects of TGF-β. In particular BARD1β might be a driver of proliferation and of pulmonary fibrosis pathogenesis and progression and represent a target for treatment

Airspace Diameter Map-A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases.

(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (βENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD

The role of leptin in the respiratory system: an overview

Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system

[Cigarette smoke and nicotine during pregnancy : where are we today?]

In Switzerland, about 13 % of pregnant women smoke, giving birth to more than 11'000 infants per year exposed to tobacco in utero. Although this proportion is stable since the 2000's, the users of nicotine with new devices (electronic cigarettes, inhaled heated tobacco, sniffed or chewed tobacco) are increasing. The literature is unanimous about deleterious effects of prenatal exposure to tobacco smoke on the fetus, with multiple short- and long-term consequences. Available data suggest that in utero exposure to e-cigarette could also expose the fetus to a similar profile of adverse effects. In this article, we review briefly the known epidemiological and mechanistic data on the short- and long-term effects of prenatal cigarette smoke and nicotine consumption

Erratum to: Chest physiotherapy using passive expiratory techniques does not reduce bronchiolitis severity: a randomised controlled trial

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children &lt;1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties (P = 0.044). Complications were rare but occurred more frequently, although not significantly (P = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients

Early blood exchange transfusion in malignant pertussis: A case report.

OBJECTIVE:: To report early blood exchange transfusion in malignant pertussis and a favorable clinical outcome. SETTING:: A pediatric intensive care unit in a tertiary hospital in Geneva, Switzerland. DESIGN:: A descriptive case report. PATIENT:: An 8-wk-old girl was diagnosed with malignant pertussis (extreme leukocytosis, seizures, pneumonia, and secondary severe hypoxic respiratory failure associated with pulmonary hypertension). After administration of a one-volume blood exchange transfusion, a rapid decrease in white blood cell count (from 119,000/mm to 36,500/mm) was observed and followed by clinical improvement and favorable outcome despite the initial presence of all described risk factors associated with a high mortality. CONCLUSION:: The use of exchange blood transfusion early in the course of the disease might help to prevent a fatal outcome of malignant pertussis