Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the “safety” of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.

Background and objectives: A new phenotype with overlapping characteristics between asthma and chronic obstructive pulmonary disease (COPD) called asthma–COPD overlap syndrome (ACOS) is emerging among inflammation diseases. To date, there is no agreement on specific criteria to define this syndrome, and the current guidelines are insufficient to classify the analogy and differences between overlap and COPD or asthma phenotypes. It would be necessary to identify new biomarkers able to identify these diseases clearly. Thus, the aim of this study was to identify a serum and supernatant of sputum microRNA (miRNA) expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13), COPD (n=31), and ACOS (n=8) and controls (n=7). Methods: The expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). For statistical analysis, the ANOVA test, Kruskal–Wallis test, Mann–Whitney U-test, and Spearman’s rank correlation were used. Results: The main finding of this work is that the expression of miRNA-338 is higher in the supernatant of different obstructive diseases than in peripheral blood, while miRNA-145 is higher only in the supernatant of asthma patients. The expression of both selected miRNAs is higher in the supernatant of asthma and COPD patients than in controls. Conclusion: Differences in sputum miRNA expression profile were observed between patients with ACOS and asthma or COPD, which underline the potential role of miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and COPD.

Background: Asthma and bronchiectasis are different conditions that frequently coexist. The prevalence of bronchiectasis rises considerably in subjects with severe asthma (25%–51%). Objective: We evaluated the clinical and biological efficacy of mepolizumab on our pilot population of severe uncontrolled asthmatics with bronchiectasis not related to other pathologies. Patients and methods: Four patients with severe uncontrolled asthma and diagnosed as bronchiectasis were recruited and started biological treatment with mepolizumab. Standard investigations were performed in all four patients at baseline (T0), after 3 months (T1) and after 1 year (T2) of treatment. Results: After 1 year (T2) of therapy with mepolizumab, patients showed a significant increment of asthma control test value (12±1.1 vs 24.5±0.3, P<0.01), a reduction of the number of exacerbations/year (5±0.7 vs 0.75±0.75, P<0.01), an increase of pre-bronchodilator FEV1 (1,680±500 vs 1,860±550 mL, P<0.01) and a reduction of eosinophils in blood (0.75±0.14 vs 0.12±0.02 cells/µL, P<0.01), in the sputum (9.6%±2.1% vs 5.6%±2.7%, P<0.05) and in nasal cytology (++ vs +). Conclusion: The efficacy of mepolizumab in terms of reduction of inflammation and increase of control that we observed in our patients might suggest that targeting the IL-5 in severe eosinophilic asthma with bronchiectasis may be a good therapeutic strategy.

Introduction: Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs. Methods: We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV₁%, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months. Results: We included 18 SA patients (mean age 53.3± 12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or anti-IL-5 agents. A significant improvement in ACT score (from 15.7± 5.1 to 18.8± 4.8, p=0.023), OCSs intake [10 (5– 25) mg/day to 0 (0– 5) mg/day, p=0.0333] and FeNO [from 25 (20– 80) ppb to 21 (10.9– 55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0– 3) to 0 (0– 1) (p< 0.0068) and increase in FEV₁% from 73.5± 19.5% to 87.1± 19.2% (p=0.0407) and ACT to a mean value of 22.4± 1.7 (p< 0.0001) and the interruption of OCSs in all the patients (p< 0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect. Conclusion: Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings.

Background Some patients with COPD report frequent acute exacerbations (AECOPD) of the disease (FE), whereas others suffer them infrequently (IE). Because the current diagnosis of exacerbation relies on patient's perception of increased symptoms (mostly dyspnoea), we hypothesised that dyspnoea perception might be different in COPD patients with FE (≥2 exacerbations or 1 hospitalisation due to AECOPD in the previous year) or IE (≤1 exacerbation in the previous year), AECOPD being defined by the institution antibiotics and/or steroids treatment, or hospital admission. Objective To test the hypothesis that dyspnoea perception is increased in FE and/or decreased in IE with COPD. Methods We compared the perception of dyspnoea (Borg scale), mouth occlusion pressure 0.1 s after the onset of inspiration (P_0.1) and ventilatory response to hypercapnia (ΔV_E/ΔP_ETCO₂) in 34 clinically stable COPD patients with FE (n=14) or IE (n=20), with similar age, gender, body mass index and degree of airflow limitation. As a reference, we studied a group of age-matched healthy volunteers (n=10) with normal spirometry. Results At rest, P_0.1 was higher in FE than IE and controls (p<0.01). Compared with controls, the ventilatory response to hypercapnia was equally blunted both in FE and IE (p<0.001). Despite similar spirometry, during rebreathing peak Borg score and ΔBorg were higher (p<0.01) in FE and lower (p<0.01) in IE, than in controls. Conclusions Dyspnoea perception during CO₂ rebreathing is enhanced in FE and blunted in IE. These differences may contribute to the differential rate of reported exacerbations in FE and IE. Trial registration number NCT02113839.

Current availability of several biologic treatments for severe asthma makes it possible to choose the most appropriate for each patient. Sometimes a good percentage of patients with severe asthma may be eligible for biologics that target either the allergic phenotype or the eosinophilic one, but not all respond to that selected as first choice. The aim of our real-life study was to assess whether, for patients with severe eosinophilic allergic asthma, not previously controlled by the anti-IgE omalizumab, the shift to another biologic targeting interleukin-5, such as mepolizumab, may represent a good therapeutic choice. A total of 41 consecutive patients with severe, persistent allergic, eosinophilic asthma, uncontrolled despite treatment with omalizumab, were enrolled in seven certified Clinical Respiratory Units of Southern Italy (Catania, Catanzaro, Foggia, Bari, Palermo, and two University Respiratory Units of Naples) and shifted to mepolizumab without a wash-out period. Data at baseline, after at least 12 months of therapy with omalizumab, and after at least 12 months of treatment with mepolizumab were collected. After at least 12 months of therapy with mepolizumab, patients experienced a significant decrease in the number of exacerbations/year (5.8 ± 1.8 versus 0.7 ± 0.9, p < 0.0001), an increment of asthma control test score (12 ± 2.7 versus 21.9 ± 2.7, p < 0.0001), an increase in pre-bronchodilator forced expiratory volume in 1 s (1.56 ± 0.45 l versus 1.86 ± 0.52 l, p < 0.0001), and a reduction of blood eosinophils (584 ± 196 cells/µl versus 82 ± 56 cells/µl, p < 0.0001). The percentage of patients who were dependent on corticosteroids significantly decreased from 46% at baseline to 5% during treatment with mepolizumab. Results of our real-life multicentric experience confirms that the shift to mepolizumab could be a good therapeutic strategy in severe eosinophilic allergic asthma not previously controlled by omalizumab. The reviews of this paper are available via the supplemental material section.