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Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-y and IL-4. The frequency of detectable IFN-y (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE: Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-y and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population. Methods: We evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models. Results: After full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation. Conclusion: High CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function. [ABSTRACT FROM AUTHOR]

The use of electronic cigarettes (e-cigarette) and vaping devices started as a potential aid for cessation and reducing the harmful consequences of cigarette smoking, mainly in the adult population. Today e-cigarette use is highly increasing in vulnerable populations, especially young and pregnant women, due to the misconception of its harmless use. Despite the growing acknowledgment in e-cigarette as a potential harmful device, and due to mixed information found concerning its beneficial aid for smokers, along with an insufficient clinical study done in human models, it is important to further evaluate the possible benefits and risks of non-combusting, vaping nicotine or non-nicotine delivery devices. In this review we tried to summarize the latest updated information found in the literature, concentrating mainly in the variety of adverse effects of e-cigarette use and its contribution for recent and future health concerns. [ABSTRACT FROM AUTHOR]

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19. In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 ("post-infected COVID-19"), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms ("future long-COVID-19"). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-β), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals' presence as an oxidative stress index. We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-β that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents. [ABSTRACT FROM AUTHOR]

Introduction: Laryngeal web is a rare cause of pediatric stridor and respiratory distress. The clinical presentation is variable and symptoms usually correlate with the severity of the airway obstruction. Case Reports: We describe the cases of three children unexpectedly diagnosed with laryngeal web after a severe episode of bronchiolitis and after thirteen and eleven years, respectively, of persistent symptoms despite asthma medications. Conclusion: Even if it is a rare cause of stridor and respiratory distress, congenital subglottic web could be a life threatening condition and clinicians should always consider it in the differential diagnosis of persistent noisy breathing, even in adolescents and young adults. [ABSTRACT FROM AUTHOR]

Background In this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in Italy. Methods We included infants hospitalized for acute bronchiolitis from 2004 to 2014. All infants underwent a nasal washing for virus detection. A regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than 10 µm (PM 10 ) and less than 2.5 µm (PM 2.5 ) in aerodynamic diameter. We obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. Overdispersed Poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (RSV) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive RSV. Results Of the 723 nasal washings from the infants enrolled, 266 (68%) contained RSV, 63 (16.1%) rhinovirus, 26 (6.6%) human bocavirus, 20 (5.1%) human metapneumovirus, and 16 (2.2%) other viruses. The number of RSV-positive infants correlated negatively with temperature (p < 0.001), and positively with relative humidity (p < 0.001). Air pollutant concentrations differed significantly during the peak RSV months and the other months. Benzene concentration was independently associated with RSV incidence (p = 0.0124). Conclusions Seasonal weather conditions and concentration of air pollutants seem to influence RSV-related bronchiolitis epidemics in an Italian urban area. [ABSTRACT FROM AUTHOR]

Background: This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. Methods: Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. Results: After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p < 0.0001) and of FEF25-75 (p = 0.019) were found in NS group. No differences were found in expiratory and inspiratory Rint in both groups. No serious adverse events occurred. Conclusions: Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinically stable conditions. Trial registration: ISRCTN12345678. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Surgery for vascular anomalies can occasionally fail to relieve symptoms, especially when severe tracheobronchial malacia persists. We studied outcomes in children who underwent airway stenting for severe post-surgical airway malacia and tested known clinical and surgical prognostic factors. METHODS: Among 257 children evaluated for tracheobronchial vascular compression, we reviewed the clinical charts for the 59 patients (23%) who underwent surgery. After surgery, children in whom severe malacia and respiratory symptoms persisted underwent airway stenting. RESULTS: Among the 59 patients (boys: 58.1%, median age: 6.4 months, age range: 0.1-182.8 months), 79.7% had major comorbidities, 39% additional upper airway anomalies and 15.2% abnormal bronchial anatomy. Diagnostic imaging identified seven vascular anomalies: innominate artery compression 27.1%, left bronchial compression from the descending aorta and left pulmonary artery 20.3%, lesions associated with right aortic arch 22.0%, double aortic arch 13.6%, bovine arch type 10.2%, aberrant right subclavian artery 5.1% and pulmonary artery sling 1.7%. For severe residual malacia and severe persistent respiratory symptoms, 20 patients (33.9%) had silicone or metallic stents inserted. The most frequent indication for stenting was double aortic arch (P = 0.02 by chi-square test). A clinical prognostic factor for permanent stenting was left bronchial compression from the descending aorta and left pulmonary artery [odds ratio (OR): 14.667, 95% confidence interval (CI): 2.881-74.659], particularly if associated with congenital heart disease (OR: 30.00, 95% CI: 4.349- 206.927). All silicone stents but one were successfully removed; metallic uncovered stents were patent and completely re-epithelialized. CONCLUSIONS: When surgery leaves severe airway obstruction and respiratory symptoms unchanged, children with tracheobronchial malacia can safely undergo airway stenting. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten in genetically predisposed individuals who carry the HLA-DQ2 or -DQ8 alleles. The immune response is abnormal in celiac disease with small intestinal epithelial damage via CD8+CD4- intraepithelial lymphocytes. The etiology is multifactorial involving genetic and environmental factors, an abnormal immune response, and intestinal dysbiosis. The innate and acquired T-cell mediated immunity play important roles in the pathogenesis of this disease, particularly CD4+ Th17 cells, which have been shown to have critical functions in host defense against bacterial pathogens and in the inflammatory responses to deamidated gluten peptides. We review what is known about the interaction between immune system and intestinal microbiota in the pathogenesis of celiac disease. [ABSTRACT FROM AUTHOR]

The titre and epitope specificity of anti-tTG antibodies correlate with duodenal pathology in coeliac diseaseCoeliac disease (CD) is characterized by several markers, including anti-transglutaminase auto-antibodies (tTGAb) directed against multiple epitopes of the gliadin protein. We aimed to investigate the correlation among CD duodenal lesions, tTGAb titres and the immunoreactivity against tTG constructs. A total of 345 CD patients (209 females, 136 males, overall median age: 7.3 years) were tested for full-length (fl) tTGAb with a fluid-phase radioimmunoassay. Out of the total, 231 patients were also tested for immunoreactivity against tTG fragments (F1: a.a. 227–687 and F2: a.a. 473–687). Patients were classified according to diffuse (D), patchy (P) or bulb (B) histological lesions. All sera were found fltTGAb positive. Patients with D, P and B lesions had a mean Ab index of 0.84±0.39, 0.57±0.39 and 0.45±0.24, respectively. Mean tTGAb titre varied between D and localized (P+B) patients (0.84±0.39 versus 0.52±0.34, P < 0.0001). Overall, 86.1% of patients were F1 auto-antibody (F1Ab) positive (D: 89%, P: 75%, B: 40%; D versus P+B: P = 0.004) and 49% of patients were F2 auto-antibody (F2Ab) positive (D: 53%, P: 19%, B: 10%; D versus P+B: P = 0.0006). Of the D patients 50.7% showed combined F1Ab-F2Ab (D versus P+B: P = 0.001), whereas 60% of B patients were negative for both F1Ab and F2Ab (B versus D: P < 0.0001). Coeliac-specific tTGAb immunoreactivity correlates with the grading and extension of histological duodenal lesions in CD patients at diagnosis. The immunoreactivity against single and combined tTG fragments is significantly higher in patients with D lesions. This is the first evidence of a distinct coeliac-specific immunoreactivity in patients with different duodenal involvement. [ABSTRACT FROM AUTHOR]

A 28 year-old caucasian lady, with nine years of uncontrolled bronchial asthma, rhinosinusitis and mild upper limb paresthesia, came to our attention to be followed for coeliac disease (CD). She had a biopsy performed elsewhere which proved the diagnosis five years before. Since there was no clinical improvement on a strict gluten-free diet, we re-evaluated the slides of her duodenal biopsies and we found an overestimation of the duodenal lesions due to the wrong orientation of the specimens. Moreover, she had never had positive CD-related antibodies and she was negative for DQ2/DQ8 MHC Class II heterodimers. Months later, she referred she was suffering from diffuse joint pain, epistaxis and a substantial weight loss. A few days later she was hospitalized because of a sudden onset of dyspnea, peripheral edema and pleural effusion. Her echocardiogram showed global left ventricular hypokenesia with an ejection fraction of 24%. The patient was discharged with a diagnosis of dilated cardiomyopathy and NYHA Class II. After a large spectrum of haematological exams, the diagnosis of Churg Strauss Syndrome (CSS), a rare multisystemic small-vessel necrotizing vasculitis, was confirmed by the presence of four/five out of six diagnostic American College of Rheumatology classification criteria (Asthma, Eosinophilia >10%, Neuropathy, Non-fixed pulmonary infiltrates, Paranasal sinus abnormality and Biopsy containing a blood vessel with extravascular eosinophils). Our patient had been under-diagnosed by pulmonologist and by gastroenterologists although she presented the criteria required for CSS diagnosis. Our case report emphasizes that often seemingly unrelated symptoms can be caused by a single rare clinical complex. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, lung ultrasound (LUS) was widely used to assess SARS-CoV-2 infection. To date, there are patients with persistence of symptoms after acute infection. Therefore, it may be useful to have an objective tool to follow these patients. The aim of our study was to evaluate the presence of LUS artifacts after SARS-CoV-2 infection in children and to analyze the associations between time elapsed since infection and symptomatology during acute infection. We conducted an observational study, enrolling 607 children infected with SARS-CoV-2 in the previous twelve months. All patients performed a LUS and medical history of demographic and clinical data. We observed irregular pleural lines in 27.5%, B-lines in 16.9%, and subpleural consolidations in 8.6% of the cases. These artifacts were more frequently observed in the lower lobe projections. We have observed that the frequency of artifacts decreases with increasing time since infection. In symptomatic patients during COVID infection, B-lines (p = 0.02) were more frequently found. In our sample, some children, even after months of acute infection, have ultrasound artifacts and showed an improvement with the passage of time from the acute episode. Our study provides additional evidence about LUS in children with previous COVID-19 as a support to follow these patients in the months following the infection. [ABSTRACT FROM AUTHOR]

Lung ultrasound has become increasingly used in both adult and pediatric populations, allowing the rapid evaluation of many lung and pleura diseases. This popularity is due to several advantages of the method such as the low cost, rapidity, lack of ionizing radiation, availability of bedside and repeatability of the method. These features are even more important after the outbreak of the SARS-CoV-2 pandemic, given the possibility of recognizing through ultrasound the signs of interstitial lung syndrome typical of pneumonia caused by the virus. The purpose of this paper is to review the available evidence of lung ultrasound (LUS) in children and its main applications in pediatric diseases. [ABSTRACT FROM AUTHOR]

To the editor: We have read with great interest the article by Jaworska et al. [[1]] concerning the role of Lung Ultrasound (LUS) in pneumonia and bronchiolitis in children. Actually, timing in performing LUS was controlled in our recent studies [[2]], in which LUS was performed in children with bronchiolitis or pneumonia, only within the first 24 h from admission in the Emergency department. We also confirmed with a recent study [[3]] the role of LUS in the diagnosis of pneumonia, highlighting the role of LUS especially in finding complications of the disease. [Extracted from the article]

Background: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak.Methods: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR.Results: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm(3), p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm(3), p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants.Conclusions: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment. [ABSTRACT FROM AUTHOR]

Background: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We describe the way we treated 7 children with critical long-term complications after metallic balloon-expandable stenting in the left mainstem bronchus. METHODS: Endoscopic follow-up included a first bronchoscopy 3 weeks after stenting, then monthly for 3 months, every 4-6 months up to 1 year and at scheduled times to calibrate stent diameter up to final calibration. When major complications occurred, patients underwent chest computed tomographic angiography. RESULTS: In 1 of the 7 children (median age 2.8 years), metallic left bronchial stenting served as a bridge to surgery. After a median 4-year follow-up, all 7 children experienced recurrent stent ovalizations with stent breakage in 3 and erosion in 1. In 4 children, computed tomographic angiography showed abundant peribronchial fibrous tissue, in 2 left mediastinal rotation and in 1 displacement along the left bronchus after pulmonary re-expansion as the cause of stent-related complication. Of the 7 children, 6 underwent surgery (5 posterior aortopexy and 1 section of the ligamentum arteriosus) and 3 required nitinol stents placement within the metallic ones. One patient completed the follow-up, and 1 patient was lost to follow-up. All 5 remaining children still have permanent bronchial stents in place, patent and re-epithelialized after a median 10.5-year follow-up. There were no deaths. CONCLUSIONS: Satisfactory anatomical relationships when children have stents placed in the left mainstem bronchus alone do not guarantee the final success. Several mechanisms intervene to cause critical stent-related complications in children during growth. Permanent metallic stents should be used carefully, and only in selected patients. [ABSTRACT FROM AUTHOR]

The recently discovered truncated, non-functional, ACE2 transcript (dACE2), but not the full-length ACE2 (f-lACE2), is induced by IFNs in differentiated airway cells. We measured expression of both ACE2 isoforms in SARS-CoV-2 positive and negative subjects, in relation to Interferon-stimulated genes. A significant activation of dACE2 transcript was found, in SARS-CoV-2 positive adults either hospitalized or not, showing a positive correlation with ISG15; f-lACE2 expression was weakly activated and not ISG-related. We confirmed a specific activation of dACE2 transcript in nasopharyngeal cells, related to the mucosal IFN response. [ABSTRACT FROM AUTHOR]

A highly sensitive electrochemical immunoassay for the initial diagnosis of celiac disease (CD) in saliva samples that overcomes the problems related to its high viscosity and to the low concentration of anti-transglutaminase antigen (tTG) IgA in this medium has been developed for the first time. The system uses magnetic beads (MBs) covered with tTG, which reacts with the anti-tTG IgA antibodies present in positive saliva samples. An anti-human IgA, conjugated with alkaline phosphate (AP) enzyme, was used as the label and a strip of eight magnetized screen-printed electrodes as the electrochemical transducer. In particular, two different immunoassay approaches were optimized and blindly compared to analyze a large number of saliva samples, whose anti-tTG IgA levels were independently determined by the radioimmunoassay (RIA) method. The obtained results, expressed as Ab index, were used to perform a diagnostic test evaluation through the construction of receiver operating characteristic (ROC) curves. The approach, involving a pre-incubation between the anti-human IgA-AP and saliva samples prior to the addition of MBs-tTG, showed a cutoff of 0.022 with 95 % clinical sensitivity and 96 % clinical specificity. The area under the ROC curve is equal to 1, a result that classifies our test as 'perfect.' This study demonstrates that it is possible to perform the screening of CD with a rapid, simple, inexpensive, and sensitive method able to detect anti-tTG antibodies in saliva samples, which are easily obtained by non-invasive techniques. This aspect is of fundamental importance to screen a large number of subjects, especially in the pediatric age. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

• Combined expression of ACE2 isoforms was higher in virus-infected children than in adults. • In patients ACE2 expression level was consistently associated with that of ISG15. • The furin level was not correlated with patient's age nor with ISG15. • Cell lines' stimulation by type I/III Interferons induced only the truncated ACE2 isoform. In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS‐CoV‐2 and other viral infections, although its association with early IFN response has not been evaluated yet. In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs' activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed. In addition, type I and III IFN stimulation experiments were performed to examine the IFN-mediated activation of ACE2 isoforms (full-length and truncated) and furin in epithelial cell lines. Following all the IFNs treatments, only the truncated ACE2 levels, were upregulated significantly in the A549 and Calu3 cells, in particular by type I IFNs. If confirmed in vivo following IFNs' activation, the induction of the truncated ACE2 isoform only would not enhance the risk of SARS‐CoV‐2 infection in the respiratory tract. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis.Research Design and Methods: IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb(+) DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis.Results: A total of 12.8% DM1 sera were IgA-tTGAb(+), with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb(+) DM1 compared with nondiabetic CD patients.Conclusions: Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis. RESEARCH DESIGN ANDMETHODS IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb+ DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were com- pared with those found in 83 screen-detected nondiabetic patients at CD diagnosis. RESULTS A total of 12.8% DM1 serawere IgA-tTGAb+,with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG- tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were signi cantly lower in IgA-tTGAb+ DM1 compared with nondiabetic CD patients. CONCLUSIONS Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis. RESEARCH DESIGN AND METHODS--IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb+ DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis. RESULTS--A total of 12.8% DM1 sera were IgA-tTGAb+, with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged ≤18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb+ DM1 compared with nondiabetic CD patients. CONCLUSIONS--Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis. [ABSTRACT FROM AUTHOR]