Extracellular Lipids in the Lung and Their Role in Pulmonary Fibrosis

Lipids are major actors and regulators of physiological processes within the lung. Initial research has described their critical role in tissue homeostasis and in orchestrating cellular communication to allow respiration. Over the past decades, a growing body of research has also emphasized how lipids and their metabolism may be altered, contributing to the development and progression of chronic lung diseases such as pulmonary fibrosis. In this review, we first describe the current working model of the mechanisms of lung fibrogenesis before introducing lipids and their cellular metabolism. We then summarize the evidence of altered lipid homeostasis during pulmonary fibrosis, focusing on their extracellular forms. Finally, we highlight how lipid targeting may open avenues to develop therapeutic options for patients with lung fibrosis

Halo Sign and Eosinophilia: What Is Your Diagnosis?

IF 2.772International audienceBlood eosinophilia associated with transient and migrating nodules with a halo sign on chest computed tomography scan should suggest larva migrans related to toxocariasis or ascaris suum

Measurement of hypoxia in the lung in idiopathic pulmonary fibrosis: a matter of control

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GnRH release into the hypophyseal portal blood of the ewe mirrors both pulsatile and continuous intravenous infusion of kisspeptin: Insight into kisspeptin mechanism of action

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Gonadotrophin-releasing hormone release into the hypophyseal portal blood of the ewe mirrors both pulsatile and continuous intravenous infusion of kisspeptin: an insight into kisspeptin's mechanism of action

Recent studies have demonstrated that kisspeptin (Kp) administration, given as a slow constant infusion of Kp10 (the shortest endogenous form of the Kp molecules which carries biological activity), is able to stimulate gonadotrophin secretion and induce ovulation in anoestrus acyclic ewes. Detailed analysis of peripheral luteinising hormone (LH) concentrations, obtained at 10-min intervals, suggested that this Kp10 treatment induced the continuous release of gonadotrophins. Whether this apparent constant secretion of LH resulted from a continuous elevation of GnRH or discrete high-frequency pulses could not be determined. In the present study, we monitored the patterns of gonadotrophin-releasing homrone (GnRH) secreted into hypophyseal portal blood (HPB) and LH in the peripheral circulation when Kp10 was administered either as discrete pulses or by means of a continuous infusion. Samples of HPB and peripheral blood were obtained at 2 and 10-min intervals, respectively, over a 6-h period, from anoestrous acyclic ewes that received an i.v. bolus injection of Kp10 at 1 h and an infusion of Kp10 between hours 2 and 6. GnRH release following Kp10 administration appeared to be dose-dependent, with larger responses being seen to the 20 μg bolus and 20 μg/h infusion than to the 10 μg bolus and 10 μg/h infusion, with the latter being marginally effective in inducing LH release. Bolus injections of Kp10 (either 20 or 10 μg) induced a sharp GnRH pulse in HPB and a discrete LH pulse in peripheral blood. By contrast, constant infusion of Kp10 (either 20 or 10 μg/h for 4 h) induced a sustained increase in baseline GnRH secretion with no convincing evidence of strictly episodic release. Values remained continuously elevated in HPB. No sign of pituitary desensitisation was observed at either concentration. Finally, i.v. injection of a large bolus (500 μg) of Kp10 produced immediate pharmacological concentrations of Kp10 in the peripheral circulation but were not associated with detectable levels of the peptide in the cerebrospinal fluid. In summary, our results demonstrate that the mode of Kp10 administration (pulsatile versus continuous) is important in shaping the pattern of GnRH secretion and suggests that this regulatory effect is most likely exerted at the level of the terminals of GnRH neurones. Moreover our data also suggest that Kp is involved in, rather than having a permissive role in, the control of endogenous GnRH pulsatility

LSC Abstract – Pleural inflammation is essential in bleomycin-induced lung toxicity

IF 10.569International audienceIntroduction: In patients, the therapeutic use of bleomycin (BLM), a potent anticancerous drug, is strongly restrained because of its lung toxicity with pulmonary fibrosis (PF) being the most devastating form. Toxic and Idiopathic PF start classically in the subpleural area. It is know that 1) Pleural mesothelial cells (PMCs) acquire a TGF-β1-induced myofibroblast phenotype and 2) inflammation plays a significant role in fibrogenesis. The role of mesothelial cells in PF and in BLM lung toxicity has still to be investigated.Methods: C57Bl/6 mice were intravenously (IV) injected with BLM or NaCl. In vitro, human pleural mesothelial cells (Met5A) were treated with BLM.Results: Repeated IV BLM induces a peculiar lung fibrotic response with 1) an histological peripheral distribution, 2) a collagen accumulation in pleural and subpleural area, 3) an overexpression in PMCs of MMP-2, -9, HSP27, all involved in myofibroblast tranformation and 4) a migration of PMCs into the lung. This process was associated with an inflammatory profile with an increase 1) in neutrophils in pleural lavage fluid (PLF) and 2) an enhanced caspase-1 activity (total lung tissue). TGF-β1 was overexpressed in PLF. TGF-β1 and collagen accumulations were hampered after pleural inhibition of IL-1β (Anakinra intrapleural injection). IV administration of BLM triggered cell death in pleural and subpleural area (TUNEL). In vitro, BLM-induced cell death correlated with an increase in caspase-1 activity.Conclusion: IV BLM in rodent induces subpleural PF as observed in toxic and idiopathic PF in human. Our results demonstrate a key role of PMCs and suggest a caspase-1 dependent inflammation in this fibrogenesis process

High-Flow Nasal Cannula Oxygenation in Older Patients with SARS-CoV-2-Related Acute Respiratory Failure

We aimed to compare the mortality and comfort associated with high-flow nasal cannula oxygenation (HFNCO) and high-concentration mask (HCM) in older SARS-CoV-2 infected patients who were hospitalized in non-intensive care units. In this retrospective cohort study, we included all consecutive patients aged 75 years and older who were hospitalized for acute respiratory failure (ARF) in either an acute geriatric unit or an acute pulmonary care unit, and tested positive for SARS-CoV-2. We compared the in-hospital prognosis between patients treated with HFNCO and patients treated with HCM. To account for confounders, we created a propensity score for HFNCO, and stabilizing inverse probability of treatment weighting (SIPTW) was applied. From March 2020 to January 2021, 67 patients (median age 87 years, 41 men) were hospitalized with SARS-CoV-2-related ARF, of whom 41 (61%) received HFNCO and 26 (39%) did not. Age and comorbidities did not significantly differ in the two groups, whereas clinical presentation was more severe in the HFNCO group (NEW2 score: 8 (5–11) vs. 7 (5–8), p = 0.02, and Sp02/Fi02: 88 (98–120) vs. 117 (114–148), p = 0.03). Seven (17%) vs. two (5%) patients survived at 30 days in the HFNCO and HCM group, respectively. Overall, after SIPTW, HFNCO was significantly associated with greater survival (adjusted hazard ratio (AHR) 0.57, 95% CI 0.33–0.99; p = 0.04). HFNCO use was associated with a lower need for morphine (AHR 0.39, 95% CI 0.21–0.71; p = 0.005), but not for midazolam (AHR 0.66, 95% CI 0.37–1.19; p = 0.17). In conclusion, HFNCO use in non-intensive care units may reduce mortality and discomfort in older inpatients with SARS-CoV-2-related ARF

Haemoptysis: a frequent diagnostic challenge

("European Respiratory Journal" vol. 45, n°1)

Pleural inhibition of the caspase-1/IL-1β pathway diminishes profibrotic lung toxicity of bleomycin

IF 3.751International audienceBackground: Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung. It has recently been suggested that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic conditions induced by TGF-beta 1 or bleomycin. The importance and role of inflammation in fibrogenesis are still controversial. In this work, we explored the role of IL-1 beta/caspase-1 signaling in bleomycin lung toxicity and in pleural mesothelial cell transformation.Methods: C57BL/6 mice were intravenously injected with either bleomycin or nigericin or NaCl as control. In vitro, the Met5A cell line was used as a model of human pleural mesothelial cells.Results: Intravenous injections of bleomycin induced lung fibrosis with histologically-proven peripheral distribution, collagen accumulation in the pleural and subpleural area, and overexpression of markers of myofibroblast transformation of pleural cells which migrated into the lung. These events were associated with an inflammatory process with an increase in neutrophil recruitment in pleural lavage fluid and increased caspase-1 activity. TGF-beta 1 was also overexpressed in pleural lavage fluid and was produced by pleural cells following intravenous bleomycin. In this model, local pleural inhibition of IL-1 beta with the IL-1 beta inhibitor anakinra diminished TGF-beta 1 and collagen accumulation. In vitro, caspase-1 inhibition interfered with Met5A cell transformation into the myofibroblast-like phenotype induced by bleomycin or TGF-beta 1. Moreover, nigericin, a caspase-1 activator, triggered transformation of Met5A cells and its intra-pleural delivery induced fibrogenesis in mice.Conclusions: We demonstrated, after intravenous bleomycin injection in mice, the role of the pleura and highlighted the key role of IL-1 beta/caspase-1 axis in this fibrogenesis process

Monitoring of noninvasive ventilation: comparative analysis of different strategies

International audienceBackground Noninvasive ventilation (NIV) represents an effective treatment for chronic respiratory failure. However, empirically determined NIV settings may not achieve optimal ventilatory support. Therefore, the efficacy of NIV should be systematically monitored. The minimal recommended monitoring strategy includes clinical assessment, arterial blood gases (ABG) and nocturnal transcutaneous pulsed oxygen saturation (SpO 2 ). Polysomnography is a theoretical gold standard but is not routinely available in many centers. Simple tools such as transcutaneous capnography (TcPCO 2 ) or ventilator built-in software provide reliable informations but their role in NIV monitoring has yet to be defined. The aim of our work was to compare the accuracy of different combinations of tests to assess NIV efficacy. Methods This retrospective comparative study evaluated the efficacy of NIV in consecutive patients through four strategies (A, B, C and D) using four different tools in various combinations. These tools included morning ABG, nocturnal SpO 2 , TcPCO 2 and data provided by built-in software via a dedicated module. Strategy A (ABG + nocturnal SpO 2 ), B (nocturnal SpO 2 + TcPCO 2 ) and C (TcPCO 2 + builtin software) were compared to strategy D, which combined all four tools (NIV was appropriate if all four tools were normal). Results NIV was appropriate in only 29 of the 100 included patients. Strategy A considered 53 patients as appropriately ventilated. Strategy B considered 48 patients as appropriately ventilated. Strategy C misclassified only 6 patients with daytime hypercapnia. Conclusion Monitoring ABG and nocturnal SpO 2 is not enough to assess NIV efficacy. Combining data from ventilator built-in software and TcPCO 2 seems to represent the best strategy to detect poor NIV efficacy. Trial registration Institutional Review Board of the Société de Pneumologie de Langue Française (CEPRO 2016 Georges