Pediatric obesity and severe asthma: Targeting pathways driving inflammation.

Asthma affects more than 300 million people of all ages worldwide, including about 10-15% of school-aged children, and its prevalence is increasing. Severe asthma (SA) is a particular and rare phenotype requiring treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic glucocorticoid courses to achieve symptom control or remaining "uncontrolled" despite this therapy. In SA, other diagnoses have been excluded, and potential exacerbating factors have been addressed. Notably, obese asthmatics are at higher risk of developing SA. Obesity is both a major risk factor and a disease modifier of asthma in children and adults: two main "obese asthma" phenotypes have been described in childhood with high or low levels of Type 2 inflammation biomarkers, respectively, the former characterized by early onset and eosinophilic inflammation and the latter by neutrophilic inflammation and late-onset. Nevertheless, the interplay between obesity and asthma is far more complex and includes obese tissue-driven inflammatory pathways, mechanical factors, comorbidities, and poor response to corticosteroids. This review outlines the most recent findings on SA in obese children, particularly focusing on inflammatory pathways, which are becoming of pivotal importance in order to identify selective targets for specific treatments, such as biological agents.

Eosinophilia and potential antibody cross-reactivity between parasites in a child with pinworm and immune dysregulation: a case report.

BACKGROUND: Intestinal parasitic infections are common in humans, especially among young children. These conditions are often asymptomatic and self-limiting, and diagnosis is mainly based on the search for ova and parasites in the stools since serology may be biased due to cross reactivity between parasites. Pinworm is common in children and is not usually associated with hypereosinophilia; adhesive-tape test is the gold standard testing for the microscopic detection of Enterobious vermicularis (Ev) eggs. CASE PRESENTATION: A 13-year-old boy was referred due to a self-resolving episode of vomiting and palpebral oedema after dinner, together with a history of chronic rhinitis, chronic cough, absolute IgA deficiency and Hashimoto's thyroiditis and hypereosinophilia (higher value = 3140/µl). On evaluation we detected only palpable thyroid and hypertrophic nasal turbinates. Food allergy was excluded, but skin prick tests showed sensitization to house dust mites and cat epithelium and spirometry showed a marked obstructive pattern with positive bronchodilation test prompting the diagnosis of asthma for which maintenance inhaled treatment was started. Chest x-ray and abdomen ultrasound were negative. Further blood testing showed positive IgG anti-Echinococcus spp. and Strongyloides stercoralis and positive IgE for Ascaris, while Ev were detected both by the adhesive tape test and stool examination, so that we made a final diagnosis of pinworm infection. Three months after adequate treatment with pyrantel pamoate the adhesive-tape test turned out negative and blood testing showed a normal eosinophil count. The child later developed also type 1 diabetes. CONCLUSIONS: We suggest the need to investigate for enterobiasis in children with hypereosinophilia and to consider autoimmunity as a potential confounding factor when interpreting serology for helminths.

The Effectiveness of the Buzzy Device in Reducing Pain in Children Undergoing Venipuncture: A Single-Center Experience.

OBJECTIVES: Needle-related procedures are among the most important sources of pain in children in different health care settings. Our study was aimed to evaluate the effectiveness of Buzzy (MMJ Labs, Atlanta, Ga.), a palm-sized bee/ladybug-shaped device combining vibration and cold, as a nonpharmacological strategy to manage needle-related pain in children. METHODS: In this single-center, randomized (1:1) controlled open-label study, we enrolled patients aged from 1 month to 18 years who had to undergo a planned outpatient blood sampling in Pisa University Hospital's Department of Pediatrics and randomly allocated them to either the BUZZY group (intervention group) or NO BUZZY group (control group). Pain was estimated using proper pain scales according to age. RESULTS: Between May 2021 and January 2022, 234 children aged 8.8 ± 5.1 years (50.8% girls) were enrolled and 117 were treated with the Buzzy device. In the study population, pain inversely correlated with age (r = -0.52, P < 0.001); the intervention group showed significantly lower pain (2.5 ± 2.4 vs 4.7 ± 2.8, P < 0.001) and no difference was found between boys and girls. Significant reduction in pain scores was confirmed when stratifying children by age (29 days to <3 years, P = 0.002; ≥3 to ≤8 years, P < 0.001; >8 years, P < 0.001). CONCLUSIONS: The Buzzy device effectively reduces pain caused by percutaneous antecubital venipuncture in children in different age groups and represents a cheap and easy-to-use strategy to manage routine needle-related procedures.

Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?

OBJECTIVES: To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi. METHODS: This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach. RESULTS: From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22-32] vs BDMA, 37 months (95%CI 32-52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48-0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38-0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49-1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56-1.68). CONCLUSIONS: BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.

Neurovisual Manifestations in Children with Mild COVID-19: An Association to Remember.

Neurovisual involvement has been reported in a number of patients with severe SARS-CoV-2 disease (COVID-19), mainly among adult patients. In children, such involvement has been reported in rare cases, often in those presenting with severe forms of COVID-19. The aim of this work is to explore the association between mild COVID-19 and neurovisual manifestations. We report the cases of three previously healthy children who developed neurovisual manifestations following mild acute COVID-19, analysing the clinical phenotype, the latency between the onset of acute COVID-19 and neurovisual involvement, and the kinetic of resolution. Our patients developed different clinical patterns, including visual impairment and ophthalmoplegia. In two cases, these clinical features occurred during acute COVID-19, while in the third patient their development was delayed after 10 days from disease onset. Furthermore, the dynamics of resolution were different, with one patient showing remission after 24 hours, the second after 30 days, and the third showing persistence of the strabismus after 2 months of follow-up. The spreading of COVID-19 among the paediatric population will probably lead to an increase of atypical disease forms, including those presenting with neurovisual involvement. Therefore, a better knowledge of the pathogenic and clinical features of these manifestations is warranted.

Controversies in the treatment of mild asthma. What novelties and practical implications?

Mild asthma is prevalent in childhood and causes as many as 30%-40% asthma exacerbations requiring emergency visits. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Recent updates of the guidelines on the strategies to manage these patients are coming, since the role of inflammation in these asthma phenotypes is crucial, as well as the potential side effect and risks of short-acting beta 2 agonists overuse, prescribed as the only "as-needed" treatments. In this paper, we overview the new (r)evolution regarding intermittent and mild persistent asthma management.

The evolving epidemiology of acute gastroenteritis in hospitalized children in Italy.

Few data are available on the prevalence and features of acute gastroenteritis (AGE) in hospitalized children in Italy, where specific rotavirus vaccines were introduced into the national vaccination plan in 2017. To evaluate vaccination effects on AGE epidemiology, we analysed data from children aged ≤ 18 years admitted for AGE at the University Hospital of Pisa in 2019, comparing them with those recorded in 2012. Demographical, clinical, diagnostic, and treatment data were collected reviewing medical records and were therefore compared. In 2019 and 2012, 86 (median age 2.5 years [IQR 1.4-5.9]) and 85 children (median age 2.3 years [IQR 1.3-5.1]) were respectively admitted with AGE. The most common symptoms were diarrhoea and vomiting; decreased skin turgor was more frequent in 2019 (54% and 34% respectively, p = 0.01). Viral infections were more common than bacterial ones; in 2019, a decrease in rotavirus infections (67% and 22%, p = 0.003) and an increase in adenovirus infections (50% and 10%, p = 0.002) and in the number of patients with negative stool testing (58% and 39%, p = 0.04) were found.Conclusions: Viral infections are the leading cause of AGE in hospitalized children in Italy. The introduction of rotavirus vaccines did not reduce the number of hospitalizations per year. Adenovirus and other non-routinely screened viruses may be undergoing a selection process making them common causative agents for AGE. What is Known: • Rotavirus is the leading cause of acute severe gastroenteritis in children worldwide, especially < 5 years of age. • The introduction of specific vaccines may be changing its epidemiology. • Few data are available on acute gastroenteritis in hospitalized children in Italy. What is New: • Viral infections are the leading cause of acute gastroenteritis in hospitalized children in Italy. • Specific vaccines are reducing rotavirus infections, but adenovirus and other non-routinely screened viruses may be undergoing a selection process making them common causative agents for gastroenteritis.

Use of telemedicine during the COVID-19 pandemic in patients with inflammatory arthritis: a retrospective study on feasibility and impact on patient-reported outcomes in a real-life setting.

Close follow-up is mandatory in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). During the Coronavirus Disease 2019 (COVID-19) pandemic, rheumatological care was rapidly reorganized during the first peak from March 1, 2020 to May 31, 2020, and all patients with RA, PsA, and AS being treated with a subcutaneous biologic disease-modifying anti-rheumatic drug or oral targeted synthetic disease-modifying anti-rheumatic drug were followed remotely. A retrospective database analysis of these 431 patients before and after this period is presented herein. A rheumatologist directly contacted all patients by telephone. Patients could also enter data on patient-reported outcomes remotely using the digital platform iAR Plus. General health (GH) and visual analog scale (VAS) pain were the main outcomes along with FACIT and disease-specific questionnaires (RADAI, ROAD, PROCLARA for RA, and BASDAI, BASGI, BASFI for AS). In all, 449 visits were postponed (69.9% of all scheduled visits); telephone evaluation was deemed inadequate in 193 instances, and patients underwent a standard outpatient visit. Comparing patients on telemedicine to those who underwent hospital visits, we found no statistically significant differences in GH (35.3 vs 39.3; p = 0.24), VAS (33.3 vs 37.1; p = 0.29), or other specific outcome measures in patients with RA, PsA, or AS. These results show that telemedicine has undoubted benefits, and in light of the ongoing COVID-19 pandemic, it is likely that many patients with these diseases may prefer it.

Prevalence of allergic rhinitis with lower airways inflammation: A new endotype with high risk of asthma development?

AIM: Asthma and allergic rhinitis share common pathophysiological mechanisms. However, while asthma phenotypes and endotypes are defined basing on both clinical and immunological features, rhinitis classification is still based on severity and frequency of symptoms. Recently, fractional exhaled nitric oxide (FeNO) has been suggested as a possible biomarker of rhinitis to asthma development. The aim of our study was to define the prevalence of a high FeNO allergic rhinitis endotype in a paediatric population of children with allergic rhinitis in order to quantify the impact of such patients in general practice. METHODS: A total of 159 children (aged 7-16 years) with allergic rhinitis and no asthmatic symptoms were enrolled in our study. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. All patients performed the following assessments: skin prick test (SPT), spirometry and FeNO measurement. RESULTS: FeNO was increased in 54 (33.9%) of 159 patients. No significant correlation with age, severity and frequency of rhinitis was evidenced. Positive SPT for house dust mites was related with a higher prevalence of high FeNO (P = 0.04), with no significant correlation with other sensitisations. All patients showed normal spirometric values. CONCLUSION: A possible new endotype of allergic rhinitis and lower airways inflammation showed to be significantly present in our population. The lack of correlation with allergic rhinitis severity assessment suggests that FeNO could be considered as an independent variable, possibly linked to a higher risk of asthma development in children with no lower airways symptoms and normal spirometry.

Vitamin D in pediatric health and disease.

Several scientific societies established that vitamin D (VD), in its metabolized form 25(OH)D, levels higher than 20 ng/mL are sufficient to ensure optimal bone health, while 25(OH)D levels higher than 30 ng/mL are needed to favor VD extraskeletal actions. However, it has been estimated that approximately 30% of children and 60% of adults worldwide are VD deficient and insufficient, respectively. This is the reason why it is important to provide a practical approach to VD supplementation for infants, children, and adolescents. It is the pediatrician's role to evaluate the modifiable lifestyle risk factors for deficiency, particularly a reduced sun exposure, following an evidence-based approach, and to suggest VD supplementation only when there is a rational reason to support its use.

Sweat chloride assay by inductively coupled plasma mass spectrometry: a confirmation test for cystic fibrosis diagnosis.

The current guidelines for sweat chloride analysis identify the procedures for sweat collection, but not for chloride assay, which is usually performed by methods originally not aiming at the low concentrations of chloride found in sweat. To overcome this limitation, we set up, characterized, and adopted an original inductively coupled plasma mass spectrometry (ICP-MS) method for sweat chloride determination, which was designed for its easy use in a clinical laboratory. The method was linear in the range 8.5E-3 to 272.0E-3 mM, precision exhibited a relative standard deviation < 6%, and accuracy was in the range 99.7-103.8%. Limit of blank, limit of detection, and limit of quantitation were 2.1 mM, 3.2 mM, and 7.0 mM, respectively, which correspond to real concentrations injected into the mass spectrometer of 3.9E-3 mM for LOD and 8.5E-3 mM for LOQ. At first, the method was tested on 50 healthy volunteers who exhibited a mean chloride concentration of 15.7 mM (25-75th percentile 10.1-19.3 mM, range 2.8-37.4 mM); then, it was used to investigate two patients with suspected cystic fibrosis, who exhibited sweat chloride values of 65.6 mM and 81.2 mM, respectively. Moreover, the method was cross-validated by assaying 50 samples with chloride concentration values in the range 10-131 mM, by both ICP-MS and coulometric titration, which is the technology officially used in Tuscany for cystic fibrosis newborn screening. The reference analytical performances and the relatively low cost of ICP-MS, accompanied by the advantageous cost of a single sweat chloride assay, make this technology the best candidate to provide a top reference method for the quantification of chloride in sweat. The method that we propose was optimized and validated for sweat samples ≥ 75 mg, which is the minimum amount requested by the international protocols. However, the method sensitivity and, in addition, the possibility to reduce the sample dilution factor, make possible the quantification of chloride even in samples weighting < 75 mg that are discarded according to the current guidelines. Graphical abstract.

Potential effects of E-cigarettes and vaping on pediatric asthma.

Asthma is the most common chronic disease in childhood and exposure to tobacco smoke has been long recognized as a risk factor for its onset as well as for exacerbations and poor disease control. Since the early 2000s, electronic cigarettes have been marketed worldwide as a non-harmful electronic alternative to combustible cigarettes and as a device likely to help stop smoking, and their use is continuously rising, particularly among adolescents. However, several studies have shown that vape contains many different well-known toxicants, causing significant cytotoxic and pro-inflammatory effects on the airways in-vitro and in animal models. In humans, a variety of harmful lung effects related to vaping, ranging from bronchoconstriction to severe respiratory distress has been already reported. To investigate the potential effects of vaping in pediatric asthma, we searched relevant published studies in the MEDLINE/PubMed database by combining the adequate Medical Subject Headings terms and key words. At the end of our study selection process, five cross-sectional studies focusing on electronic cigarettes use in adolescents and self-reported asthma and/or other respiratory symptoms, one study focusing on the effects of electronic cigarettes second-hand exposure and one case report were retrieved. These preliminary data support a likely detrimental effect of vaping in asthmatic adolescents. Currently available evidence supports that electronic cigarettes are a potential threat to respiratory health, particularly in adolescents with asthma. High-quality studies on larger population assessing the long-term effects of vape exposure, are urgently needed.

Assessing energy performance and critical issues of a large wastewater treatment plant through full-scale data benchmarking.

The wastewater sector accounts for 25% of the global energy demand in the water sector. Since this consumption is expected to increase in the forthcoming years, energy optimization strategies are needed. A truly effective planning of energy improvement measures requires a detailed knowledge of a system, which can only be achieved through energy audit and real-time monitoring. In order to improve the identification of critical issues related to the use of energy resources within a wastewater treatment plant (WWTP), the paper shows the results of a monitoring campaign performed on a large WWTP in southern Italy. Data obtained for the audit cover a 4-year timeframe (2014-2017). Energy-environmental performance has been evaluated through the benchmarking of: system variables, specific consumptions, and operational indicators. Moreover, by using a real-time data measurement and acquisition system it has been possible to evaluate the real performance of the most energy-intensive apparatus of the plant (a turbo-blower), over a period of 8 months. The main results indicate that (a) the plant is mainly affected by a massive capture of infiltrations, working in conditions close to the maximum hydraulic capacity, (b) real-time energy measurements are necessary to accurately characterize plant consumptions and adequately assess their critical aspects.

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.

Lean thinking to improve emergency department throughput at AORN Cardarelli hospital.

BACKGROUND: Throughout the world, emergency departments (ED) are characterized by overcrowding and excessive waiting times. Furthermore, the related delays significantly increase patient mortality and make inefficient use of resources to the detriment of the satisfaction of employees and patients. In this work, lean thinking is applied to the ED of Cardarelli Hospital of Naples with the aim of increasing patient flow, improving the processes that contribute to facilitating the flow of patients through the various stages of medical treatment and eliminating all bottlenecks (queue) as well as all activities that generate waste. METHODS: This project was performed at National Hospital A.O.R.N. A. Cardarelli of Naples. The historical times of access to the ED were analysed from January 2015 to June 2015, for a total of 16,563 records. Subsequently, starting in November 2015, corrective actions were implemented according to the Lean Approach. Data collected after the introduced improvements were collected from April 2016 to June 2016 and compared to those collected during the starting period. RESULTS: The results acquired before application of the Lean Thinking strategy illustrated the as-is process with its drawbacks. An analysis of the non-added value activities was performed to identify the procedures that need to be improved. After implementation of the corrective actions, we observed a positive increase in the performance of the ED, quantified as percentages of hospitalized patients according to triage codes and waiting times. CONCLUSION: This work demonstrates the applicability of Lean Thinking to ED processes and its effectiveness in terms of increasing the efficiency of services and reducing waste (waiting times).

Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy. With the aim to permanently restore gene function and normalise ciliary motility, we used gene editing to replace mutated with wild-type sequence in defective cells. METHODS: The target gene was dynein heavy chain 11 (DNAH11), an essential component of ciliary structure. Airway ciliated cells were collected from two patients with PCD with DNAH11 nonsense mutations and altered ciliary beating and pattern. Repair of the genetic defect was performed ex vivo by site-specific recombination using transcription activator-like effector nucleases (TALENs). RESULTS: In an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. In airway ciliated cells of patients with PCD, site-specific recombination and normalisation of ciliary beating and pattern occurred in 33% and 29% of cells, respectively. CONCLUSION: This study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating PCD.

Ultrasound-guided synovial biopsy of the wrist does not alter subsequent clinical or ultrasound disease activity assessments: a prospective study for incorporation of imaging in clinical trials.

OBJECTIVES: Ultrasound-guided synovial biopsy (UGSB) is a minimally-invasive procedure capable of retrieving good quality tissue from small and large joints. The use of UGSB in prospective clinical trials poses a dilemma as to whether biopsied joints may be later included in core data sets for clinical or imagining response, as the procedure itself may alter disease activity assessment. In this study, we examine the impact of UGSB of the wrist on subsequent clinical and ultrasound (US) assessments in a cohort of rheumatoid arthritis (RA) patients prior to initiation of anti-TNF-alpha therapy. METHODS: Patients had active disease (DAS>5.1) involving their wrist. Both wrists were scanned and the most inflamed one underwent an UGSB. Ultrasonographic and clinical assessments were repeated at the patients' subsequent visit, without any changes in disease-modifying treatment between visits. US images were scored semi-quantitatively and quantitatively for synovial thickness (ST) and power Doppler (PD). Mixed-effects model and paired-Wilcoxon signed rank test were used to assess the effect of UGSB on these scores. RESULTS: Twenty-nine patients were enrolled. No significant difference in mean ST (p=0.32) or PD (p=0.21) was demonstrated pre- and post-biopsy (mean time 14.7 days). Similar results were obtained using quantitative measures. The DAS-28 and its components did not change significantly post-biopsy. CONCLUSIONS: In this population, UGSB of the wrist did not significantly alter subsequent clinical or US assessments, indicating that a wrist joint, which has undergone UGSB, may be incorporated into an US dataset or clinical outcome assessment tools, such as the DAS-28, without prejudice.

Pediatric asthma and altitude: a complex interplay between different environmental factors.

Asthma is one of the most common non-communicable diseases, and its prevalence and morbidity are influenced by a wide array of factors that are only partially understood. In addition to individual predisposition linked to genetic background and early life infections, environmental factors are crucial in determining the impact of asthma both on an individual patient and on a population level.Several studies have examined the role of the environment where asthmatic subjects live in the pathogenesis of asthma. This review aims to investigate the differences in the prevalence and characteristics of asthma between the pediatric population residing at higher altitudes and children living at lower altitudes, trying to define factors that potentially determine such differences. For this purpose, we reviewed articles from the literature concerning observational studies assessing the prevalence of pediatric asthma in these populations and its characteristics, such as spirometric and laboratory parameters and associated sensitization to aeroallergens.Despite the heterogeneity of the environments examined, the hypothesis of a beneficial effect of residing at a higher altitude on the prevalence of pediatric asthma could be confirmed, as well as a good profile on airway inflammation in asthmatic children. However, the possibility of a higher hospitalization risk for asthma in children living at higher altitudes was demonstrated. Moreover, a positive association between residing at a higher altitude and sensitization to pollens and between lower altitude and sensitization to house dust mites could be confirmed in some pediatric patients, even if the results are not homogeneous, probably due to the different geographical and climatic regions considered. Nonetheless, further studies, e.g., extensive and international works, need to be conducted to better understand the complex interplay between different environmental factors, such as altitude, and the pathogenesis of asthma and how its prevalence and characteristics could vary due to climate change.

Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis.

Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN). A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN. 151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results. Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.

Respiratory comorbidities in severe asthma: focus on the pediatric age.

INTRODUCTION: Asthma comorbidities are a frequent cause of adverse outcomes, such as poor asthma control, frequent asthma attacks, reduced quality of life, and higher healthcare costs. Comorbidities are well-known treatable traits whose proper management can help achieve optimal asthma control. Although multimorbidity is frequent among asthmatics, comorbidities are still a potential cause of misdiagnosis and under or over treatments, and little is known about their impact on severe pediatric asthma. AREAS COVERED: We provided a comprehensive, 5-year updated review focusing on the main respiratory comorbidities in severe asthma, particularly in epidemiology, pathogenesis, and current and future therapies. EXPERT OPINION: Respiratory comorbidities have unique characteristics in childhood. Their management must be multidisciplinary, age-specific, and integrated. Further longitudinal studies are needed to understand better the mutual interrelation and synergistic effect between asthma and its respiratory comorbidities, the identification of common, treatable risk factors leading to potential asthma prevention, the effectiveness of actual and future target-therapies, and the correlation between long-lasting respiratory comorbidities and poor lung function trajectories.