Formulation of a dry powder for inhalation combining ciclesonide and indacaterol maleate using spray drying.

Dry powders for inhalation are evolving to address the challenge of maximizing lung deposition, with growing interest in carrier-free formulations shaping future therapies. This study focuses on developing an inhalation powder with optimal properties, combining ciclesonide and indacaterol, a combination treatment for asthma not yet available on the market. Using spray-drying technology with cyclodextrins, ultra-flying microparticles aim to be produced to enhance aerosolization and therapeutic efficacy.

Endothelial-driven TGFβ signaling supports lung interstitial macrophage development from monocytes.

Lung interstitial macrophages (IMs) are monocyte-derived parenchymal macrophages whose tissue-supportive functions remain unclear. Despite progress in understanding lung IM diversity and transcriptional regulation, the signals driving their development from monocytes and their functional specification remain unknown. Here, we found that lung endothelial cell-derived Tgfβ1 triggered a core Tgfβ receptor-dependent IM signature in mouse bone marrow-derived monocytes.

In vivo vulnerabilities to GPX4 and HDAC inhibitors in drug-persistent versus drug-resistant BRAF lung adenocarcinoma.

The current targeted therapy for BRAF-mutant lung cancer consists of a dual blockade of RAF/MEK kinases often combining dabrafenib/trametinib (D/T). This regimen extends survival when compared to single-agent treatments, but disease progression is unavoidable. By using whole-genome CRISPR screening and RNA sequencing, we characterize the vulnerabilities of both persister and D/T-resistant cellular models.

[Clinically amyopathic dermatomyositis : a rare entity associated with acute and severe interstitial lung disease].

Dermatomyositis is a rare disease of unknown etiology characterized by a severe inflammatory myopathy associated with a cutaneous syndrome. Dermatomyositis is associated with multisystemic disorders mostly represented by cardiac, pulmonary and articular involvements, which are particularly associated with a bad prognosis. We report a case of a 50-year-old patient suffering from dermatomyositis associated with an interstitial lung disease with a particularly fast and pejorative clinical evolution.

Investigating the rationale for COPD maintenance therapy prescription across Europe, findings from a multi-country study.

This study aims to understand healthcare professionals' thoughts and motivations about optimal management and treatment of patients with chronic obstructive pulmonary disease (COPD). We conducted a DELPHI survey through an online questionnaire distributed to 220 panellists from six European countries and a discrete choice experiment to describe the relationship between selected clinical criteria and the initial COPD treatment of choice. One hundred twenty-seven panellists (general practitioners [GPs] and pulmonologists) completed the survey.

Ly6C monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology.

Gammaherpesviruses (γHVs) have coevolved with their host, leading to a remarkably high infection prevalence and establishment of latency. The lifelong persistence of γHVs in hosts appears to broadly shape host immunity, and we show here that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment of Ly6C monocytes (MOs) into the airway, thereby modulating the host immune response. The absence of Ly6C MOs is associated with severe virus-induced immunopathology and the systemic release of inflammatory mediators.

Local nebulization of 1α,25(OH)D attenuates LPS-induced acute lung inflammation.

Background: Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia.

How to Choose the Right Inhaler Using a Patient-Centric Approach?

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient.

The Budesonide-Hydroxypropyl-β-Cyclodextrin Complex Attenuates ROS Generation, IL-8 Release and Cell Death Induced by Oxidant and Inflammatory Stress. Study on A549 and A-THP-1 Cells.

Synthetic glucocorticoids such as budesonide (BUD) are potent anti-inflammatory drugs commonly used to treat patients suffering from chronic inflammatory diseases. A previous animal study reported a higher anti-inflammatory activity with a 2-hydroxypropyl-β-cyclodextrin (HPβCD)-based formulation of BUD (BUD:HPβCD). This study investigated, on cellular models (A549 and A-THP-1), the effect of BUD:HPβD in comparison with BUD and HPβCD on the effects induced by oxidative and inflammatory stress as well as the role of cholesterol.

Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19.

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis.

ADAM28: Another ambivalent protease in cancer.

Emergence of novel therapeutic options in a perspective of personalized therapy of cancer relies on the discovery of precise molecular mechanisms involved in the switch from a localized tumor to invasive metastasis spread. Pro-tumor functions have been mostly ascribed to proteolytic enzymes from the metalloproteinase family including A Disintegrin And Metalloproteinases (ADAMs). Particularly, when expressed by cancer cells, ADAM28 protease supports cancer cell proliferation, survival and migration as well as metastatic progression.

Severe asthma: oral corticosteroid alternatives and the need for optimal referral pathways.

Objective: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes.

Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation.

Background: Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status.

Objective: Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns.

Locally instructed CXCR4 neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps.

Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps.

Preclinical evaluation of topically-administered PEGylated Fab' lung toxicity.

PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW) polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab' anti-IL17A antibody fragment conjugated to two-armed 40 kDa PEG (PEG40).

Relationship between peak expiratory flow and incidence of frailty, deaths and falls among nursing home residents: Results of the SENIOR cohort.

Objective: To correlate peak expiratory flow (PEF) with the incidence of frailty, deaths and falls among nursing home residents.

Methods: This is a 1-year longitudinal analysis performed on the clinical data of the SENIOR cohort. PEF, measured by peak flow meter, was considered as "low" when the observed value was ≤80% of the theoretical value.

Stromal integrin α11 regulates PDGFR-β signaling and promotes breast cancer progression.

Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors such as breast cancer (BC). Herein, we identify an integrin α11/PDGFRβ+ CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin α11-deficiency led to a drastic reduction of tumor progression and metastasis.

Ozone-primed neutrophils promote early steps of tumour cell metastasis to lungs by enhancing their NET production.

Background: Air pollution, including particulates and gazes such as ozone (O), is detrimental for patient's health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O exposure and metastatic dissemination to lungs.

Objectives: To outline the mechanisms through which pulmonary O exposure modulates metastasis kinetics in an experimental mouse model of O exposure.

ADAM10 mediates malignant pleural mesothelioma invasiveness.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers.