The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Gut-Brain Axis Exploration: Stabilometric Platform Performances in Children Affected by Functional Gastrointestinal Disorders.

OBJECTIVE: The pathophysiology of functional gastrointestinal disorders (FGIDs) is associated with dysfunction at various levels of the gut-brain axis. Hypervigilance can result in an increased tendency to report pain. In the present study, we aimed to explore whether hypervigilance can influence attentional processing in postural control in children with FGIDs. PATIENTS AND METHODS: Fifty-nine participants classified into healthy subjects, those with FGIDs, and those with organic diseases (Org) based on Rome IV criteria were enrolled. Postural control under 6 sensory conditions was evaluated using a stabilometric platform. The mean velocity of the center of pressure (CoP) displacement in the anteroposterior direction and the mediolateral direction, the length of the CoP trajectory, and the sway area were also measured. RESULTS: With visual and somatosensorial normal inputs, participants with FGIDs showed a higher number of anteroposterior (FGIDs: 4[interquartile range [IQR] 3-7], control [Cntl] 3 [IQR 3-4], P  < 0.05) latero-lateral oscillations (FGIDs: 3 [IQR 3-6], Cntl 3 [IQR 2-3], P  < 0.05) and a higher perimeter value (FGIDs: 148 [IQR 121-240], Cntl 124 [IQR 111-140], P  = 0.056) compared to healthy subjects. With normal visual but altered somatosensorial input, subjects with FGIDs showed higher values of all parameters (anteroposterior: FGIDs 6[IQR 5-8], Cntl and Org 5 [IQR 4-6], P  < 0.05; latero-lateral FGIDs 6 [IQR 4-8], Cntl 4 [IQR 4-5], Org 4[IQR 3-5], P  < 0.05; perimeter FGIDs 253 [IQR 167-305], Cntl 185 [IQR 161-217], Org 176 [IQR 142-219], P  < 0.05; area FGIDs 98 [IQR 81-233], Cntl 86 [IQR 59-114], Org 56 [IQR 41-97], P < 0.05). CONCLUSIONS: The higher number of oscillations in subjects with FGIDs who had normal visual input could be expression of alteration in attention and therefore hypervigilance as hypothesized in the context of gut-brain axis alterations.

Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children.

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

Feasibility of structured light plethysmography for the evaluation of lung function in preschool children with asthma.

BACKGROUND: Structured light plethysmography (SLP) is a new noninvasive technology to capture the movement of the thoracic and abdominal wall, and to assess some parameters indicative for lung function. OBJECTIVE: The purpose of the study was to evaluate the feasibility of SLP in children with asthma. METHODS: A total of 52 patients were enrolled: 25 with asthma exacerbation (group 1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3). Every patient underwent SLP evaluation and a lung function test. RESULTS: SLP evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt) to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest wall movement, and flow is taken to be the time derivative of the chest wall movement (IE50) value increased in group 1 compared with groups 2 and 3, with statistical significance (p = 0.018); the data were consistent with the spirometry parameter. A correlation between the IE50 and forced expiratory volume in the first second of expiration was highlighted (r = -0.35, p = 0.019). CONCLUSION: SLP assessed airway obstruction, and its use in clinical practice could be applied in preschool children in future studies.

Correlation between vitamin D serum levels and passive smoking exposure in children with asthma.

OBJECTIVE: To establish the relationship between vitamin D serum levels, pulmonary function, asthma control, and passive smoking exposure in children with asthma. METHODS: We studied the relationship between 25-hydroxy cholecalciferol (25[OH]D) concentrations and baseline spirometry and levels of asthma control, and the effect of parental tobacco smoke exposure in 152 white children (84 boys [55.3%]) with a mean age ± standard deviation of 9.9 ± 2.0 years (range 5-15 years) in a cross-sectional study carried out during the winter and early spring. RESULTS: Only 9.9% of our children had a sufficient serum 25(OH)D level (at least 30-40 ng/mL). A significant positive correlation was found between the force vital capacity % predicted, forced expiratory volume in the first second of expiration % predicted, and serum 25(OH)D level (r = 0.36, p < 0.001 for both). The subjects with controlled asthma had higher serum levels of 25(OH)D than children with partially controlled or noncontrolled asthma, both according to Global Initiative for Asthma parameters and the Test for the control of asthma in childhood (p = 0.011). Children with both nonsmoking parents presented significantly higher serum levels of 25(OH)D than children with both smoking parents (median, 20.5 ng/mL [interquartile range {IQR}, 16.6-24.0 ng/mL] versus median, 14.5 ng/mL [IQR, 11.1-19.1 ng/mL], respectively; p < 0.001), with intermediate values for children exposed to single maternal (median, 20.3 ng/mL [IQR, 13.0-23.2 ng/mL]) or to paternal smoking (median, 17.8 ng/mL [IQR, 14.7-22.1 ng/mL]). CONCLUSION: Our results indicated that hypovitaminosis D was frequent in children with asthma who lived in a Mediterranean country. In these children, lower levels of vitamin D were associated with reduced asthma control and passive smoking exposure.

Covid-19 in cystic fibrosis patients compared to the general population: Severity and virus-host cell interactions.

BACKGROUND: People with cystic fibrosis (pwCF) are considered at risk of developing severe forms of respiratory viral infections. We studied the consequences of COVID-19 and virus-host cell interactions in CF vs. non-CF individuals. METHODS: We enrolled CF and non-CF individuals, with /without COVID-like symptoms, who underwent nasopharyngeal swab for detection of SARS-CoV-2. Gene expression was evaluated by RNA sequencing on the same nasopharyngeal swabs. Criteria for COVID-19 severity were hospitalization and requirement or increased need of oxygen therapy. RESULTS: The study included 171 patients (65 pwCF and 106 non-CF individuals). Among them, 10 pwCF (15.4 %) and 43 people without CF (40.6 %) tested positive at RT-PCR. Symptomatic infections were observed in 8 pwCF (with 2 requiring hospitalization) and in 11 individuals without CF (6 requiring hospitalization). Host transcriptomic analysis revealed that genes involved in protein translation, particularly ribosomal components, were downregulated in CF samples irrespective of SARS-CoV-2 status. In SARS-CoV-2 negative individuals, we found a significant difference in genes involved with motile cilia expression and function, which were upregulated in CF samples. Pathway enrichment analysis indicated that interferon signaling in response to SARS-CoV-2 infection was upregulated in both pwCF and non-CF subjects. CONCLUSIONS: COVID-19 does not seem to be more severe in CF, possibly due to factors intrinsic to this population: the lower expression of ribosomal genes may downregulate the protein translation machinery, thus creating an unfavorable environment for viral replication.

Chronic urticaria and celiac disease: a case report.

We describe a case of a 9-year-old girl who presented chronic urticaria associated with celiac disease. The prevalence of the manifestation of chronic urticaria in celiac disease is unknown but increase in atopic immunologic disorders has been reported in the setting of gluten enteropathy. Relationship between the clinical manifestations is not clear. The present case of subclinical celiac disease diagnosis in an otherwise asymptomatic child with chronic urticaria further reinforces the evidence that differential for celiac disease warrants to be always considered in children with refractory urticaria.

Electronic nose in discrimination of children with uncontrolled asthma.

Measuring biomarkers (e.g. volatile organic compounds [VOCs]) in exhaled breath is an attractive approach to monitor airway inflammation in asthma and other lung diseases. Olfactive technology by electronic nose (e-Nose) has been applied to identify VOCs in exhaled breath. We compared e-Nose respiratory patterns in a pediatric cohort with asthma classificate children with different asthma control. This cross-sectional study involved 38 children: 28 with asthma and 10 healthy controls . The asthmatic patients were categorized as having controlled (AC), partially controlled (APC) or uncontrolled asthma (ANC) based on level of asthma symptom control according to Global Initiative for Asthma (GINA). Clinical exams, exhaled breath collection for generating e-Nose VOC profiles, and spirometry were performed. Exhaled breath samples were obtained using a commercial electronic nose (Cyranose 320; Smith Detections, Pasadena, CA, USA). The discriminative ability of breathprints were investigated by principal component analysis and penalized logistic regression. The e-Nose was able to discriminate between the CON (controls) + AC and the ANC + APC group with an area under the curve [AUC] of 0.85 (95% confidence interval [CI] 0.72 to 0.98) and a cross-validated AUC of 0.80 (95% CI 0.70 to 0.85). Sensitivity and specificity calculated using the Youden index were 0.79 and 0.84, respectively. Exhaled biomarker patterns were easy to obtain with the device and were able to differentiate children with uncontrolled symptomatic asthma from asymptomatic controls.

Ebastine overdose in a child.

The lack of side effects after acute ingestion of a high dose of ebastine in our child aging 44 months suggests an overall safety profile of ebastine; it could suggest less time of hospitalization for children who are subjected to this event.

Utility of Specific IgE to Ara h 2 in Italian Allergic and Tolerant Children Sensitized to Peanut.

Emerging data suggest that measurement of serum IgE to peanut components can be clinically helpful and more accurate than IgE to whole peanut to predict peanut allergy. Not all studies have used prospective samples, multiple components and oral challenges. Currently, there are no data on this topic involving Italian children. 32 patients (23 males; median age 9 years) with reported history for peanut allergy and evidence of peanut sensitization (skin prick test to peanut extract ≥ 3mm) have been analyzed for serum IgE to whole peanut and recombinant allergen components Ara h 1, 2, 3, 8, and 9 with Immuno CAP and completed an open oral food challenge with peanut. 12 (37.5%) children had a positive challenge to peanut and were considered allergic. No differences were seen between the median values of IgE to peanut, Ara h 1, 3, 8 and 9 in allergic and tolerant children to peanut challenge. Noteworthy, 5 of 20 tolerant children had IgE to peanut> 15 kUA/l which is commonly considered a predictive value of peanut allergy. Conversely, a significant difference was seen when comparing the median value of IgE to Ara h 2 in the two groups: 0.75 kUA/l (IQR: 0.22-4.34 kUA/l) in allergic children versus 0.1 kUA/l (IQR: 0.1-0.12 kUA/l) in tolerant ones (P< 0.001). IgE levels to Ara h 2 are significantly higher in children that react to oral peanut challenge. Our findings in Italian children have been in line with recent reports in various populations of Northern Europe, the US and Australia and add confirmatory evidence that analysis of IgE to Ara h 2 could reduce the need for peanut challenge in suspected allergic patients.

The use of inhaled corticosteroid in preschool wheezers: what's the point today?

AMONG THE PRESCHOOL CHILDREN WHO WHEEZE TWO DIFFERENT GROUPS CAN BE IDENTIFY: children who have a viral infection and those who respond to multiple triggers, such as exercise or allergens.To distinguish between these different phenotypes of wheezing, and consequently choose therapy represents a major challenge for pediatricians.Transient wheezers conditions do not improve with maintenance treatment with ICS. On the other hand they are definitely useful in children with wheeze/asthma.Increasing evidence is in favor of the potential role of leukotriene receptor antagonists in preschool children with recurrent wheezing.Oral steroid has been demonstrated not to be indicated to control acute wheezing, unless severe disease is expected in non-atopic children.The early phenotyping of preschool wheezers, upon which the appropriate treatment should be based, represents a challenging issue in the paediatric practice.