Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

The CORE syndrome: an overlap of severe asthma, obstructive sleep apnea, rhinosinusitis, and esophageal reflux.

PURPOSE: Asthma, obstructive sleep apnea (OSA), rhinosinusitis, and esophageal reflux are conditions that may overlap, forming a syndrome known as CORE. Whenever clinical remission of severe asthma (SA) is not achieved, it is essential to investigate the presence of comorbidities, in particular the presence of OSA that may lead to the diagnosis of CORE syndrome. METHODS: The study was conducted on naive patients with SA and concomitant rhinosinusitis and esophageal reflux, referred to our institute since 2018. Patients who did not experience clinical remission were investigated for OSA through a home sleep apnea test. Subsequently, for those diagnosed with OSA, continuous positive airway pressure (CPAP) was proposed and was re-evaluated after 12 months. RESULTS: Six patients with CORE syndrome were enrolled. The mean apnea-hypopnea index (AHI) was 33.25 ± 20.13 events/h, oxygen desaturation index (ODI) was 28.95 ± 19.95 events/h, and time in bed with SaO2 < 90% (T90) was 26.40 ± 27.22% for which continuous positive airway pressure (CPAP) treatment was proposed but only 3 out of 6 patients accepted. After 12 months, all CPAP-treated patients manifested a significant reduction in daytime sleepiness (ESS score was 6.33 ± 3.8), an improvement in ACT score (+ 8 (+ 32%), + 9 (+ 36%), and + 14 (+ 56%) points), a discontinuation of oral corticosteroids (OCS), an absence of exacerbations, and an improvement of lung function leading to clinical remission of asthma. CONCLUSION: Whenever facing SA patients, non-responders to therapy, it is important to suspect the presence of CORE syndrome; in particular, the detection and subsequent treatment of OSA would seem to improve the outcome of such patients.

Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Low-intensity rehabilitation in persistent post COVID-19 dyspnoea: the value of Spa health resort as appropriate setting.

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persi-sting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of wor-king age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the asses-sment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

A consumer wearable device for tracking sleep respiratory events.

PURPOSE: The diagnosis of obstructive sleep apnea (OSA) is instrument, operator, and time-dependent and therefore requires long waiting times. In recent decades, technological development has produced useful devices to monitor the health status of the population, including sleep. Therefore, the aim of this study was to evaluate a wearable device (WD) in a group of individuals at high risk of OSA. METHODS: The study was conducted on consecutive subjects with high risk of OSA assessed by sleep questionnaires and clinical evaluation. All subjects performed cardio-respiratory monitoring (CRM) and WD simultaneously on a single night, after which the parameters of the two sleep investigations were compared. RESULTS: Of 20 individuals enrolled, 60% were men and mean age was 57.3 ± 10.7 years. The apnea-hypopnea index (AHI) for the CRM was 23.1 ± 19.6 events·h-1 while it was 10.3 ± 8.3 events·h-1 for the WD. Correlation analysis between the results of the two investigations showed r = 0.19 (p = 0.40) for AHI and r = 0.4076 (p = 0.07) for sO2%. The accuracy for different stages of OSA severity was 70% in OSA cases and 60% in moderate to severe cases with sensitivity and specificity varying a great deal. CONCLUSION: Small and low-cost devices may prove to be a valuable resource to reduce costs and waiting times for a sleep investigation in suspected OSA. However, diagnosis of sleep apnea requires valid and reliable instruments, so validation tests are necessary before a device can be commercialized.

Searching for airways biomarkers useful to identify progressive pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF). METHODS: Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal-Wallis test, based on data normality, was used to compare the differential expression between groups. RESULTS: MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF. CONCLUSIONS: This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis.

Switching Biological Therapies in Severe Asthma.

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.

The Effects of Interstitial Lung Diseases on Alveolar Extracellular Vesicles Profile: A Multicenter Study.

Diagnosis of interstitial lung diseases (ILD) is difficult to perform. Extracellular vesicles (EVs) facilitate cell-to-cell communication, and they are released by a variety of cells. Our goal aimed to investigate EV markers in bronchoalveolar lavage (BAL) from idiopathic pulmonary fibrosis (IPF), sarcoidosis and hypersensitivity pneumonitis (HP) cohorts. ILD patients followed at Siena, Barcelona and Foggia University Hospitals were enrolled. BAL supernatants were used to isolate the EVs. They were characterized by flow cytometry assay through MACSPlex Exsome KIT. The majority of alveolar EV markers were related to the fibrotic damage. CD56, CD105, CD142, CD31 and CD49e were exclusively expressed by alveolar samples from IPF patients, while HP showed only CD86 and CD24. Some EV markers were common between HP and sarcoidosis (CD11c, CD1c, CD209, CD4, CD40, CD44, CD8). Principal component analysis distinguished the three groups based on EV markers with total variance of 60.08%. This study has demonstrated the validity of the flow cytometric method to phenotype and characterize EV surface markers in BAL samples. The two granulomatous diseases, sarcoidosis and HP, cohorts shared alveolar EV markers not revealed in IPF patients. Our findings demonstrated the viability of the alveolar compartment allowing identification of lung-specific markers for IPF and HP.

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

BACKGROUND: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. OBJECTIVE: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. METHODS: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1 % predicted, nasal polyposis, bronchiectasis). RESULTS: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). CONCLUSIONS: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management.

Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma?

BACKGROUND: Transthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been systematically described. OBJECTIVE: To explore if TUS examination is a useful imaging method in suggesting the presence of a "small airways disease" in patients with severe uncontrolled asthma. METHODS: Seventy-two consecutive subjects with a diagnosis of severe uncontrolled asthma were enrolled. The presence of a "small airways disease" was assessed through the execution of pulmonary function tests. All the patients underwent a complete TUS examination and a chest high resolution computed tomography (HRCT), which was regarded as the reference standard for comparison with TUS findings. RESULTS: Pulmonary function tests results have confirmed a reduction in expiratory flows relative to the small airways and a condition of hyperinflation in 78% and 82% of our patients, respectively. The main signs observed in the TUS examination were a thickened and/or irregular pleural line and the lack or reduction of the "gliding sign." TUS showed high sensitivity and specificity in suggesting the presence of hyperinflation and distal airways inflammation according to the HRCT scan. K Cohen's coefficients showed substantial agreement between the 2 diagnostic tests. CONCLUSION: TUS in patients with severe uncontrolled asthma can provide useful information on the state of the peripheral lung, suggesting the execution of a second-line HRCT scan for better assessment of eventual alterations that may represent the underlying causes of nonresponse to treatment.

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region.

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.

Usefulness of sleep events detection using a wrist worn peripheral arterial tone signal device (WatchPAT™) in a population at low risk of obstructive sleep apnea.

Due to the high prevalence of obstructive sleep apnea (OSA), it is recommended to use in-laboratory polysomnography (PSG) or a home sleep apnea test (HSAT) in uncomplicated adult subjects at high risk of OSA. The aims of the present study were to compare a HSAT device, a wrist worn peripheral arterial tone signal device (WatchPAT™-200 [WP]) with PSG and respiratory polygraphy (RP) in a low-risk population of OSA. A total of 47 adult subjects at low risk of OSA were simultaneously examined with the three different approaches in a single night. The sleep studies were scored independently and in a blinded fashion, then the results and the parameters (Respiratory Disturbance Index, apnea-hypopnea index [AHI] and oxygen desaturation index of 3%) were compared with several statistical analyses. The agreement between the sleep tools and correlation for the assessed parameters were analysed and compared with Bland and Altman plots and Pearson's coefficient (WP versus PSG, r = 0.86). For the severity of OSA ranked according to PSG, the Cohen's k was 0.60 and 0.82 for WP and RP, respectively. Specificity was higher for RP compared to WP for identifying the presence of OSA (AHIPSG cut-off ≥5 events/hr: 0.85 versus 0.73), while was quite similar in identifying patients who were more likely to be treated (AHIPSG cut-off ≥15 events/hr: 0.94 versus 0.96). Assessing the costs and the simplicity of the examination, the results of our present study demonstrate the usefulness of WP compared to PSG, especially in screening and follow-up for the ability to exclude subjects from treatment with continuous positive airway pressure (AHI <15 events/hr) in a population with a low pre-test risk of moderate-to-severe OSA.

Downregulation of exosomal let-7d and miR-16 in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor prognosis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investigated to better understand the pathological steps that lead to the onset of the disease and, moreover, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. In the complexity of IPF, microRNA (miRNAs) biomarker investigation seems to be promising. METHODS: We analysed the expression of five exosomal miRNAs supposed to have a role in the pathogenesis of the disease from serum of a group of IPF patients (n = 61) and we compared it with the expression of the same miRNAs in a group of healthy controls (n = 15). RESULTS: In the current study what emerged is let-7d down-regulation and, unexpectedly, miR-16 significant down-regulation. Moreover, through a cross-sectional analysis, a clustering of the expression of miR-16, miR-21 and miR-26a was found. CONCLUSIONS: These findings could help the individuation of previously unknown key players in the pathophysiology of IPF and, most interestingly, more specific targets for the development of effective medications.

Low Sensitivity of Admission Lung US Compared to Chest CT for Diagnosis of Lung Involvement in a Cohort of 82 Patients with COVID-19 Pneumonia.

Background and Objectives: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). Methods: Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6-12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. Results: Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). Conclusions: As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).

Association between physical activity and risk of hospitalisation in bronchiectasis.

BACKGROUND: Patients with bronchiectasis have a less active lifestyle than healthy peers, but the association with hospital admission has not been explored. The aim of this study was to investigate the association between 1) any physical activity variable; and 2) sedentary time, with hospitalisation due to exacerbation in adults with bronchiectasis. METHODS: In this prospective observational study, baseline lung function, quality of life, exercise tolerance, severity of bronchiectasis and physical activity were recorded. Physical activity was objectively assessed over a week using a SenseWear armband and the results were expressed in steps·day-1 and sedentary time. Number of hospitalisations due to a bronchiectasis exacerbation and time to first event were recorded after 1-year follow-up. RESULTS: Sixty-four patients with bronchiectasis were analysed, of whom 15 (23%) were hospitalised during the follow-up. Hospitalised patients showed poor baseline clinical and severity outcomes, fewer steps walked per day and more sedentary behaviour than the non-hospitalised group. Patients who walked ≤6290 steps·day-1 or spent ≥7.8 h·day-1 in sedentary behaviour had an increased risk of hospital admission due to bronchiectasis exacerbation at 1-year follow-up. Specifically, ≥7.8 h·day-1 of sedentary behaviour was associated with a 5.9-fold higher risk of hospital admission in the following year. CONCLUSIONS: Low levels of physical activity and high sedentary time at baseline were associated with a higher risk of hospitalisation due to bronchiectasis exacerbation. If these findings are validated in future studies, it might be appropriate to include physical activity and sedentary behaviour as an item in severity scores.

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients.

BACKGROUND: Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. METHODS: In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC <80% - VR >100% - FEF 25-75%<60%); 2) non-small airways phenotype (NSAP) group: non-smokers, without air trapping (FVC ≥80% - VR ≤ 100% - FEF 25-75%≥60%). We later proceeded in both groups with a step up in therapy with high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate (BDP/FF) (200/6 µg) in fixed dose to achieve a better control and followed patients for 6 months. RESULTS: Treatment with extrafine BDP/FF(200/6 µg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. CONCLUSIONS: Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 µg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

A survey of fungal microbiota in airways of healthy volunteer subjects from Puglia (Apulia), Italy.

BACKGROUND: The human respiratory tract represents the major portal of entry for numerous microorganisms, primarily those occurring as airborne particles such as viral and bacterial entities, or fungal spores. Microorganism characteristics coupled with the local host immune response will determine whether they will be cleared or adhere and colonize the airways leading to acute or chronic pulmonary disease. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. The lung microbiota is commonly sampled using relatively invasive bronchoscopic procedures. Exhaled breath condensate (EBC) collection offers a potentially less invasive alternative for lung microbiota sampling. This study tries to determine the composition of fungal communities in a cohort of healthy adult volunteer subjects from Puglia (Apulia), Italy. METHODS: Fungi diversity in 27 EBC samples collected from Italian adult volunteers was investigated using conventional microbiological culturing and DNA sequencing approach. RESULTS: Ten tested subjects (37,03%) turned out to present fungi in the EBC. We observed complex fungal communities, in which more than 10% of the isolated species are represented by Aspergillus sydowii (14,8%) and Cladosporium spp (11,11%). Three subjects that showed fungal presence in EBC have been diagnosed with a respiratory disease. CONCLUSIONS: We present a survey of an important scientific field in its early stages that is fungal contamination of airways of healthy subjects in a small geographic area. Furthermore, we interpreted our results to highlight the potential role of fungi in the context of respiratory diseases.

Different dyspnoea perception in COPD patients with frequent and infrequent exacerbations.

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 (P0.1) and ventilatory response to hypercapnia (ΔVE/ΔPETCO2) 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, P0.1 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.