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Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL−1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients’ clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.

COVID-19 is a complex and heterogeneous disease. The pathogenesis and the complications of the disease are not fully elucidated, and increasing evidence shows that SARS-CoV-2 causes a systemic inflammatory disease rather than a pulmonary disease. The management of hospitalized patients in COVID-19 dedicated units is advisable for segregation purpose as well as for infection control. In this article we present the standard operating procedures of our COVID-19 high dependency unit of the Policlinico Hospital, in Milan. Our high dependency unit is based on a multidisciplinary approach. We think that the multidisciplinary involvement of several figures can better identify treatable traits of COVID-19 disease, early identify patients who can quickly deteriorate, particularly patients with multiple comorbidities, and better manage complications related to off-label treatments. Although no generalizable to other hospitals and different healthcare settings, we think that our experience and our point of view can be helpful for countries and hospitals that are now starting to face the COVID-19 outbreak.

Background Type 2 inflammation plays a pivotal role in various allergic and inflammatory diseases, including chronic rhinosinusitis, asthma, atopic dermatitis, and eosinophilic esophagitis. Dupilumab is one of the emerging therapeutic targets that modulate the key mediators and cellular players involved in type 2 inflammation, aiming to improve the immune response and the quality of life of the patient. Objective Here, we describe the experience made on 792 patients enrolled by several specialists of a multidisciplinary team working on inflammatory type 2 diseases. Design Retrospective study. Methods Patients were treated with dupilumab according to the prescribed indications and were evaluated by several exams, tests, and questionnaires at baseline (T0) and after 12 (T1), 18 (T2), and 24 (T3) months. Results Overall, dupilumab exerts beneficial effects as demonstrated both by patients-reported outcomes and by objective assessments. Compared to baseline, all examined efficacy indicators showed an improvement after 12 months, with positive effects sustained through the 2 years of observation. Our results align with several previous trials. Conclusion Understanding the interconnection between different type 2 inflammatory diseases provides insight into potential avenues for precision medicine approaches and targeted therapies.

It is estimated that about 60–70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa ; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min. From the pharmacokinetic point of view, aminoglycosides are dose-dependent antibiotics and therefore once-daily dosing intravenous regimens have shown to be superior to the conventional multiple daily dosing. Therefore, there is no pharmacological reason to prefer the b.i.d administration as it is usually performed in current clinical practice. Should this be confirmed also for inhalatory route, the use of once-daily dosed aerosolized tobramycin could be an important step in making treatment burden easier in CF patients. The aim of this proof of concept study was to explore the effectiveness of treatment with once daily inhaled tobramycin in reducing P. aeruginos a density in sputum of chronically infected patients.

Background Alterations of cardiac autonomic control (CAC) are associated with poor outcomes in patients with infectious and non-infectious diseases. No evaluation of CAC in patients with community-acquired pneumonia (CAP) has been performed so far. The aim of the study was to assess CAC in patients with CAP and evaluate the impact of its alterations on disease severity and clinical outcomes in a multicenter, prospective, observational study. Methods Consecutive patients hospitalized for CAP were enrolled between 2011 and 2013 two university hospitals in Italy. CAC was assessed by linear spectral and non-linear symbolic analysis of heart rate variability. The presence of severe CAP was evaluated on hospital admission. The primary study outcome was time to clinical stability (TCS) during hospitalization. Results Among the 75 patients enrolled (median age: 75 years; 57 % males), a significantly lower total variability and reduction of sympathetic rhythmical component with predominant respiratory modulation was detected in comparison to controls. Among CAP patients affected by a severe CAP on admission, CAC showed a lower sympathetic modulation and predominant parasympathetic oscillatory rhythm. At the multivariate analysis, variables independently correlated with a TCS >7 days were total power, as marker of total variability, [OR (95 % CI): 0.997 (0.994–1.000), p  = 0.0454] and sympathetic modulation [OR (95 % CI): 0.964 (0.932–0.998), p  = 0.0367]. Conclusions Loss of sympathetic rhythmical oscillation is associated with a more severe disease and worse early clinical outcome in hospitalized patients with CAP.

It is estimated that about 60–70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection,with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min. From the pharmacokinetic point of view, aminoglycosides are dose-dependent antibiotics and therefore once-daily dosing intravenous regimens have shown to be superior to the conventional multiple daily dosing. Therefore, there is no pharmacological reason to prefer the b.i.d administration as it is usually performed in current clinical practice. Should this be confirmed also for inhalatory route, the use of once-daily dosed aerosolized tobramycin could be an important step in making treatment burden easier in CF patients. The aim of this proof of concept study was to explore the effectiveness of treatment with once daily inhaled tobramycin in reducing P. aeruginos a density in sputum of chronically infected patients.

Background: Few prospective studies have evaluated the role of endobronchial needle aspiration in diagnosing central airways neoplasms. Rapid on-site evaluation has long been used in transbronchial needle aspiration of adenopathies and peripheral lesions, but its role in sampling central malignancies has not been substantiated yet. Objectives: In this study we evaluated if endobronchial needle aspiration may increase the sensitivity of bronchoscopy for diagnosing central airways neoplasms when added to conventional diagnostic methods (forceps biopsy, brushing and bronchial washing), and if rapid on-site evaluation may be beneficial in patients undergoing endobronchial needle aspiration. Methods: 125 patients (77% males, aged 70 ± 7 years; mean ± SD) with central lung cancers were randomized to undergo bronchoscopy including conventional diagnostic methods and needle aspiration, with or without rapid on-site evaluation, stratifying the patients on the basis of the neoplasm growth pattern (exophytic and submucosal/peribronchial disease). Results: Needle aspiration significantly increased the sensitivity of bronchoscopy when added to conventional methods (from 76 to 91%; p < 0.001), primarily resulting from differences in submucosal/peribronchial diseases (68 vs. 90%; p < 0.001) and independently from the presence of rapid on-site evaluation; needle aspiration guided by rapid on-site evaluation guaranteed a higher improvement in bronchoscopy sensitivity than conventional needle aspiration (98 vs. 84%, respectively; p = 0.004). Needle aspiration guided by rapid on-site evaluation showed a significantly higher sensitivity than the conventional method (97 vs. 76%, respectively; p = 0.001). Conclusions: Needle aspiration increases the sensitivity of bronchoscopy in diagnosing central airways malignancies when added to conventional diagnostic methods, with a further significant improvement when guided by rapid on-site evaluation.

Severe acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown. We evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis. We also assessed the presence of association with inflammatory biomarkers and the 28-day mortality. Lymphocytopenia was present in 51 of 63 (80.9%) patients, with a median value of 720 lymphocytes/µl (IQR 520-1,135). This reduction was mirrored also on CD8+ (128 cells/µl, IQR 55-215), natural killer (67 cells/µl, IQR 35-158) and natural killer T (31 cells/µl, IQR 11-78) cells. Monocytes were preserved in total number but displayed among them a subpopulation with a higher forward and side scatter properties, composed mainly of cells with a reduced expression of both CD14 and HLA-DR. Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (337.4 cells/µl vs 585.9 cells/µl; p=0.028) and CD4+ cells (232.2 cells/µl vs 381.1 cells/µl; p=0.042) and an higher percentage of CD8+/CD38+/HLA-DR+ lymphocytes (13.5% vs 7.6%; p=0.026). The early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2-like lymphocytes and monocytes with altered immune profile, which include atypical mononuclear cells.

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p  < 0.001) and be vaccinated (37% vs. 12.7%, p  < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p  < 0.001) and immune suppressed (66.4% vs. 35.2%, p  < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease.