Rationale: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. Objectives: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. Methods: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation (“post-intervention period”) and (i) the 6 months before Dupilumab initiation (“wash-out period”) and (ii) the corresponding 6 months of the prior year (“pre-intervention period”). Main results: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting β2-agonists, inhaled corticosteroids (ICS)/long-acting β2-agonists and ICS alone) when comparing the “pre-intervention” to the “post-intervention” period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the “pre-intervention” and “post-intervention” period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. Conclusions: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

Introduction: Bronchiectasis, characterized by airway dilation, mucus hypersecretion, and recurrent exacerbations, is increasingly recognized in children and adolescents. Recent guidelines from the European Respiratory Society (ERS) and Thoracic Society of Australia and New Zealand (TSANZ) emphasize early diagnosis and optimized management. This review explores therapeutic strategies for pediatric bronchiectasis. Materials and methods: Our review involved a comprehensive search of English-language literature in the PubMed and EMBASE databases until December 2023, focusing on observational studies, interventions, reviews, and guidelines in pediatric bronchiectasis. Results: Management strategies encompass airway clearance techniques, mucoactive agents, pulmonary rehabilitation, bronchodilators and inhaled corticosteroids tailored to individual needs and age-appropriate techniques. Antibiotics play key roles in preventing exacerbations, eradicating pathogens, and managing acute exacerbations, which are guided by culture sensitivities and symptoms. Long-term antibiotic prophylaxis, particularly macrolides, aims to reduce exacerbations, although concerns about antibiotic resistance persist. Vaccinations, including pneumococcal and influenza vaccines, are crucial for preventing infections and complications. Surgery and lung transplantation are reserved to severe, refractory cases after failure of medical therapies. Conclusions: The optimal management of pediatric bronchiectasis requires a multidisciplinary approach, including physiotherapy, pharmacotherapy, and vaccinations, tailored to individual needs and guided by evidence-based guidelines. Further research is needed to refine diagnostic and therapeutic strategies and improve outcomes for affected children and adolescents.

Background and Objective: Approximately 30% of individuals diagnosed with familial pulmonary fibrosis (FPF) exhibit a pathogenic variant upon genetic analysis. We established a genetic Multidisciplinary Discussion (geneMDD) aimed to enhance expertise in diagnosing and managing FPF. This study aimed at prospectively evaluating the impact of geneMDD on diagnosis and treatment in patients referred to geneMDD.Methods: In this prospective study, we enrolled all consecutive patients referred to the geneMDD. At each meeting, the impact of the meeting was questioned on the genetic conclusion, the pulmonary diagnosis, and the treatment.Results: A total of 115 patients were included. Before geneMDD, rare variants were detected in 82 out of 107 patients, among which 65 variants were classified as pathogenic/likely pathogenic. Following geneMDD, 2 pathogenic variants (3%) were reclassified as variants of uncertain significance (VUS) (n = 1) or benign (n = 1). Among the 17 variants initially classified as VUS, 2 (11.8%) were reclassified as likely pathogenic/pathogenic. The pulmonary diagnosis was confirmed for all patients (unclassifiable lung fibrosis was the more frequent diagnosis, n = 38, 33.0%). The therapeutic regimen was changed after geneMDD in 30 patients. Factors associated with therapeutic changes included the pulmonary diagnosis and presence of a pathogenic/likely pathogenic variant. In addition, the French health system allows offering whole genome sequencing (WGS) in patients with a first negative genetic analysis by NGS panel after discussion in geneMDD, but in total, since September 1st, 2021, WGS was negative for the four analysed families.Conclusion: This study suggests that geneMDD could influence the treatment of FPF patients.

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves complex interactions between epithelial, mesenchymal, immune, and endothelial cells, often aggravated by lipid metabolism dysfunction, mitochondrial, and peroxisomal abnormalities. Changes in lipid metabolism may drive fibrotic processes, suggesting the potential of lipid biomarkers for disease monitoring. We compared here the cholesterol metabolism and very-long-chain fatty acid profiles of patients with IPF with healthy controls. The IPF patients’ lipidic profiles were also evaluated according to disease severity and progression rate. This prospective, observational study involved 50 IPF patients at disease diagnosis before antifibrotic treatment initiation and 50 age- and gender-matched healthy controls. Using a serum lipidomic profile, we focused on cholesterol synthesis, mitochondrial and peroxisomal markers, inflammatory lipids, and oxidative stress markers. Disease severity was evaluated using the Gender-Age-Physiology (GAP) index, while the prognosis was assessed by classifying patients as rapid or slow progressors based on a 24-month follow-up. IPF patients exhibited lower levels of cholesterol synthesis precursors (e.g., lathosterol), mitochondrial oxysterols, and inflammatory mediators (e.g., arachidonic acid) compared to controls. Reduced levels of these biomarkers were also associated with higher disease severity and rapid disease progression. Conversely, some peroxisomal markers (e.g., brassidic acid and nervonic acid) showed altered trends depending on disease severity. Our findings indicate that patients with IPF, compared to healthy controls, may show lipidomic alterations, particularly a reduction in cholesterol precursors and docosahexaenoic acids, which are also associated with IPF severity and progression. While preliminary, this study suggests lipidomics to be a promising tool to stratify IPF severity and prognosis.

Extract Acute exacerbation (AE), defined by a sudden worsening of respiratory symptoms accompanied by new lung opacities, can occur at any stage of fibrotic interstitial lung diseases (fILD) [1].