A comprehensive approach to lung function in bronchiectasis

Background: International guidelines recommend simple spirometry for bronchiectasis patients. However, pulmonary pathophysiology of bronchiectasis is very complex and still poorly understood. Our objective was to characterize lung function in bronchiectasis and identify specific functional sub-groups. Methods: This was a multicenter, prospective, observational study enrolling consecutive adults with bronchiectasis during stable sate. Patients underwent body-plethysmography before and after acute bronchodilation testing, diffusing lung capacity (DLCO) with a 3-year follow up. Air trapping and hyperinflation were a residual volume (RV) > 120%predicted and a total lung capacity>120%predicted. Acute reversibility was: \u394FEV1 6512% and 200 mL from baseline (FEV1rev) and \u394RV 6510% reduction from baseline (RVrev). Sensitivity analyses included different reversibility cutoffs and excluded patients with concomitant asthma or chronic obstructive pulmonary disease. Results: 187 patients were enrolled (median age: 68 years; 29.4% males). Pathophysiological abnormalities often overlapped and were distributed as follows: air trapping (70.2%), impaired DLCO (55.7%), airflow obstruction (41.1%), hyperinflation (15.7%) and restriction (8.0%). 9.7% of patients had normal lung function. RVrev (17.6%) was more frequent than FEV1rev (4.3%). Similar proportions were found after multiple sensitivity analyses. Compared with non-reversible patients, patients with RVrev had more severe obstruction (mean(SD) FEV1%pred: 83.0% (24.4) vs 68.9% (26.2); P = 0.02) and air trapping (RV%pred, 151.9% (26.6) vs 166.2% (39.9); P = 0.028). Conclusions: Spirometry alone does not encompass the variety of pathophysiological characteristics in bronchiectasis. Air trapping and diffusion impairment, not airflow obstruction, represent the most common functional abnormalities. RVrev is related to worse lung function and might be considered in bronchiectasis\u2019 workup and for patients\u2019 functional stratification

Vaccination attitude and communication in early settings: An exploratory study

Background: This study assesses attitudes towards vaccination in mothers of new-born babies and explores its association with different exposures to communication. Methods: Data were collected through questionnaires administered by means of interviews. Results: Data highlighted that 20% of mothers showed an orientation towards vaccine hesitancy. As for the reasons behind the attitude to vaccine hesitancy, data showed that concern is a common feature. As for the different exposures to communication, 49% of mothers did not remember having received or looked for any information about vaccination during pregnancy and post-partum; 25% stated they received information from several healthcare and non-healthcare sources; 26% declared having received or looked for information by means of healthcare and non-healthcare sources, as well as having taken part in a specific meeting during antenatal classes or at birth centres. The attitude towards vaccine hesitancy tends to reduce as exposure to different communication increases. Conclusions: This study supports the hypothesis that participation in interactive meetings in small groups focused on vaccination during the prenatal course or at the birth point may act as an enabling factor contributing to a decrease in the tendency to experience vaccine hesitation

Evaluation of “Caterina assay”: An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification

Abstract: Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February–March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The “Caterina assay” is a SYBR®Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February–March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/µL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resource

Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience

Aim: SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome. Method and Materials: We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies. Results: Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024]. Conclusion: The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection

Background: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. Conclusions: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Vaccination Attitude and Communication in Early Settings: An Exploratory Study

Background: This study assesses attitudes towards vaccination in mothers of new-born babies and explores its association with different exposures to communication. Methods: Data were collected through questionnaires administered by means of interviews. Results: Data highlighted that 20% of mothers showed an orientation towards vaccine hesitancy. As for the reasons behind the attitude to vaccine hesitancy, data showed that concern is a common feature. As for the different exposures to communication, 49% of mothers did not remember having received or looked for any information about vaccination during pregnancy and post-partum; 25% stated they received information from several healthcare and non-healthcare sources; 26% declared having received or looked for information by means of healthcare and non-healthcare sources, as well as having taken part in a specific meeting during antenatal classes or at birth centres. The attitude towards vaccine hesitancy tends to reduce as exposure to different communication increases. Conclusions: This study supports the hypothesis that participation in interactive meetings in small groups focused on vaccination during the prenatal course or at the birth point may act as an enabling factor contributing to a decrease in the tendency to experience vaccine hesitation.</jats:p

Evaluation of “Caterina assay”: An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification

Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February–March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The “Caterina assay” is a SYBR®Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February–March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/μL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resources.</jats:p

Vaccination Attitude and Communication in Early Settings: An Exploratory Study

Background: This study assesses attitudes towards vaccination in mothers of new-born babies and explores its association with different exposures to communication. Methods: Data were collected through questionnaires administered by means of interviews. Results: Data highlighted that 20% of mothers showed an orientation towards vaccine hesitancy. As for the reasons behind the attitude to vaccine hesitancy, data showed that concern is a common feature. As for the different exposures to communication, 49% of mothers did not remember having received or looked for any information about vaccination during pregnancy and post-partum; 25% stated they received information from several healthcare and non-healthcare sources; 26% declared having received or looked for information by means of healthcare and non-healthcare sources, as well as having taken part in a specific meeting during antenatal classes or at birth centres. The attitude towards vaccine hesitancy tends to reduce as exposure to different communication increases. Conclusions: This study supports the hypothesis that participation in interactive meetings in small groups focused on vaccination during the prenatal course or at the birth point may act as an enabling factor contributing to a decrease in the tendency to experience vaccine hesitation

Higher blood eosinophil levels after omalizumab treatment are associated with poorer asthma outcomes

Eosinophilic asthma is characterized by high eosinophil levels in induced sputum and peripheral blood. Elevated airway eosinophil counts can be detected in more than 50% of asthmatics and associated with more symptoms, frequent exacerbations, and greater airflow limitation. Increased blood eosinophils (BEs) also predict a greater response to new biological therapies (mepolizumab, reslizumab). Higher pretreatment BE levels are also related to a better response to omalizumab,3 which reduces BE, fractional exhaled nitric oxide (FENO), serum periostin, and exacerbations. Therefore, a higher effect on eosinophil count reduction may lead to greater clinical improvements. Accordingly, if omalizumab response is eosinophilic dependent, it might be reduced in subjects with persistent high BE counts after anti-IgE therapy