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Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open. Main body Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF. Sustained alveolar epithelial micro-injury and activation has been recognised as the trigger of several biological events of disordered repair occurring in genetically susceptible ageing individuals. Despite multidisciplinary team discussion has demonstrated to increase diagnostic accuracy, patients can still remain unclassified when the current diagnostic criteria are strictly applied, requiring the identification of a Usual Interstitial Pattern either on high-resolution computed tomography scan or lung biopsy. Outstanding achievements have been made in the management of these patients, as nintedanib and pirfenidone consistently proved to reduce the rate of progression of the fibrotic process. However, many uncertainties still lie in the correct use of these drugs, ranging from the initial choice of the drug, the appropriate timing for treatment and the benefit-risk ratio of a combined treatment regimen. Several novel compounds are being developed in the perspective of a more targeted therapeutic approach; in the meantime, the supportive care of these patients and their carers should be appropriately prioritized, and greater efforts should be made toward the prompt identification and management of relevant comorbidities. Conclusions Building on the advances in the understanding of IPF pathobiology, the further investigation of the role of gene variants, epigenetic alterations and other molecular biomarkers reflecting disease activity and behaviour will hopefully enable earlier and more confident diagnosis, improve disease phenotyping and support the development of novel agents for personalized treatment of IPF.

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in cancer immunotherapy which have significantly improved the prognosis of several tumours. ICIs act by restoring the “exhausted” immune system and increasing the number of T cells active against pathogens losing tolerogenic signalling, which has been linked to an increased risk of infectious events. We present the case of a 67-year-old man with locally advanced lung adenocarcinoma treated with the anti-PD-L1 durvalumab. Three months after immunotherapy started, an apparent radiological progression was found with elements suggesting a parenchymal superinfection associated with weight loss, asthenia, and sputum emission. A bronchoalveolar lavage resulted positive for Mycobacterium chimaera , and treatment with amikacin iv (for eight weeks) and daily azithromycin, ethambutol, and rifampicin was started. Thirteen months after treatment started, the patient is alive with a stable lung condition. The case highlights the risk of non-tuberculous mycobacteria lung disease (NTM-LD) in patients receiving ICIs treatment. We hypothesise that durvalumab induced an exaggerated immune response toward the mycobacteria, leading to immunopathology and overt clinical manifestations. Clinicians should be aware of this possibility in patients receiving ICIs developing new signs/symptoms related to the respiratory tract, especially in countries with a high prevalence of NTM-LD.

Introduction Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619–623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce. Main body This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies. Conclusions The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.

Neutrophilic airway inflammation is a key pathogenic driver of bronchiectasis, sustaining a vicious cycle of infection, mucus obstruction, recurrent exacerbations and progressive airway damage. The growing knowledge on the neutrophilic bronchiectasis endotype has led to increasing interest in host-directed approaches targeting neutrophilic mediators. Long-term macrolide therapy currently represents the reference anti-inflammatory treatment for patients with bronchiectasis at high risk of exacerbations and is supported by randomized controlled trials and extensive clinical experience. However, its use is limited by antimicrobial resistance, drug-to-drug interactions, safety concerns in selected populations and uncertainty regarding optimal dosing and duration. More recently, inhibition of Cathepsin C (CatC), an upstream regulator of neutrophil serine protease activation, has emerged as a novel therapeutic strategy aimed at reducing protease-driven airway injury. This manuscript presents a focused review of the literature that critically examines and compares long-term macrolides and CatC inhibitors with respect to their mechanisms of action, clinical evidence, safety profiles and potential roles within future treatment algorithms. We summarize data from Phase II and III trials of CatC inhibitors, particularly brensocatib, highlighting their effects on exacerbation risk, lung function trajectories and biomarkers of neutrophilic inflammation. We also discuss the limitations of the current evidence base, including restricted trial populations, limited long-term data and the lack of validated biomarkers to guide treatment selection in clinical practice. Finally, we discuss future perspectives for integrating these therapies into individualized, biomarker-informed management of bronchiectasis. Together, these developments support a shift towards more mechanism-based and personalized anti-inflammatory treatment strategies in bronchiectasis, in which treatment selection is guided by underlying inflammatory pathways. This review aims to translate current clinical evidence into practical considerations for patient selection and future therapeutic positioning, thereby helping bridge the gap between research and clinical implementation.

Background It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long‐term (2 years) following the endoscopic procedure. Results Sixty‐six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01). Conclusions Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.

Background Chronic, progressive respiratory symptoms are associated with great psychological and emotional impact in patients suffering from interstitial lung disease (ILD). This single-centre pilot study evaluated for the first time the safety, feasibility and efficacy of a Mindfulness Based Stress Reduction Program (MBSR) in a group of patients with ILD. Methods Prospective observational study set in a university hospital ILD outpatient clinic. Nineteen patients with different ILDs were recruited 2 months prior to the start of the 8-week MBSR program and followed up for 12 months. Primary outcomes were program safety and feasibility, while secondary outcomes were changes in moods and stress (assessed by Profile Of Mood State (POMS) and Perceived Stress Scale (PSS) questionnaires), symptoms (Shortness Of Breath (SOB) and Cough And Sputum Assessment (CASA-Q) questionnaires), lung function and exercise tolerance at 12 months. Results Two patients (10.5%) dropped out in the observational period before the start of the MBSR intervention because of non-respiratory causes. All 17 patients who entered the 8-week MBSR program managed to complete it with an adherence average of eight sessions of nine. No adverse events related to the mindfulness training were reported. Statistically significant improvements in the POMS total score and in several individual items of POMS and PSS were observed throughout the study. However, respiratory questionnaire scores, lung function and exercise tolerance did not show a significant difference over time. Conclusions An MBSR program appears to be safe and feasible in patients with ILD, and might affect perceived moods and stress producing a positive and lasting improvement in several stress-related negative domains. These findings pave the way to larger (possibly multicentre), randomised, controlled confirmatory trials.

Case report A 77-year-old, non-smoking, Italian female with an allergy to acetylsalicylic acid and who was affected by anxious-depressive syndrome presented with dry cough in June 2006, followed by the onset of exertional dyspnea in October of the same year. Because of worsening of her dyspnea, the patient underwent a chest X-ray that showed a consolidation (compatible with the diagnosis of bronchopneumonia), which was effectively treated with antibiotics and steroids. The following chest X-ray showed clearing of the area of consolidation, but cough and breathlessness persisted. [...]on 28 February 2007 the patient underwent a high-resolution computed tomography scan of the chest, which showed evidence in three different basal lung regions of diffuse interstitial lung disease characterized by predominantly bibasal and peripheral reticular opacities, traction bronchiectasis, honeycomb lung destruction, and irregular areas of consolidation with no ground glass opacities (Figure 1). In March 2012, the PIPF-012 study ended; given the persistent stability of her clinical condition, the patient was admitted to continue receiving pirfenidone under the European Named Patient Program upon approval by the local ethics committee. Since May 2007, the patient did not present any clinically significant impairment in her lung function parameters, with substantial stability in FVC.

Background Enhanced Recovery After Surgery (ERAS) guidelines have been widely promoted and supported largely due to several studies showing decreased post-operative complications and length of stay. The objective of this study was to review the emergency room (ER) visits and readmission rates and reasons for both in patients who were part of the Implementation of an Enhanced Recovery After Surgery (iERAS) program for colorectal surgery. Methods All patients having elective colorectal surgery at 15 academic hospitals were enrolled in the iERAS program. All patients were prospectively followed until 30 days post-discharge. Data were analyzed using descriptive statistics and multivariable analysis. Results A total of 2876 patients (48% female; mean 60 years old) were enrolled. Cancer was the most frequent indication (68.2%) for surgery. Overall, the median length of stay (LOS) was 5 days. Post-discharge, 359 (11.6%) of patients had a visit to the ER not requiring admission. The most common reasons for visiting the ER were surgical site infections (SSI) (34.5%), other wound complications (10.0%), and urinary tract infections (UTI) (8.6%). In addition, a smaller proportion of patients, 260 (8.2%) required readmission. The most common reasons for readmission were ileus and nausea/vomiting (26.1%), intra-abdominal abscess (23.9%), and SSI (11.5%). Patient and disease factors associated with ER visits, on multivariable analysis, included extremes of BMI (RR 1.02, 95%CI 1.01–1.04, p  = 0.002), rectal surgery versus colon surgery (RR 1.34, 95%CI 1.14–1.58, p  < 0.001), and open operative approach (RR 1.63, 95%CI 1.28–2.09, p  < 0.001). Independent factors associated with hospital readmissions included rectal surgery (RR 1.89, 95%CI 1.34–2.77, p  < 0.001), formation of a stoma (RR 1.34, 95%CI 1.04–1.74, p  = 0.026), and reoperation during first admission (RR 4.60, 95%CI 3.50–6.05, p  < 0.001). Length of stay of 5 days or less was not associated with ER visits or readmission (RR 0.99, 95%CI 0.72–1.35 and RR 0.91, 95%CI 0.71–1.18, respectively). Conclusion Following colorectal surgery using an ERAS pathway, shortened length of stay is not associated with an increased return to the ER or hospital readmission. The majority of return visits to the hospital are ER visits not requiring readmission and the predominant reason for return are surgical site infections and wound complications.

Background In mammals, an important source of genomic variation is insertion polymorphism of retrotransposons. These may acquire a functional role when inserted inside genes or in their proximity. The aim of this work was to carry out a genome wide analysis of ERE1 retrotransposons in the horse and to analyze insertion polymorphism in relation to evolution and function. The effect of an ERE1 insertion in the promoter of the myostatin gene, which is involved in muscle development, was also investigated. Results In the horse population, the fraction of ERE1 polymorphic loci is related to the degree of similarity to their consensus sequence. Through the analysis of ERE1 conservation in seven equid species, we established that the level of identity to their consensus is indicative of evolutionary age of insertion. The position of ERE1s relative to genes suggests that some elements have acquired a functional role. Reporter gene assays showed that the ERE1 insertion within the horse myostatin promoter affects gene expression. The frequency of this variant promoter correlates with sport aptitude and racing performance. Conclusions Sequence conservation and insertion polymorphism of ERE1 elements are related to the time of their appearance in the horse lineage, therefore, ERE1s are a useful tool for evolutionary and population studies. Our results suggest that the ERE1 insertion at the myostatin locus has been unwittingly selected by breeders to obtain horses with specific racing abilities. Although a complex combination of environmental and genetic factors contributes to athletic performance, breeding schemes may take into account ERE1 insertion polymorphism at the myostatin promoter.