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Pediatric obstructive sleep apnea can negatively affect children’s neurocognitive function and development, hindering academic and adaptive goals. Questionnaires are suitable for assessing neuropsychological symptoms in children with sleep-disordered breathing. The study aimed to evaluate the effectiveness of using the Oxygen Desaturation Index compared to the Obstructive Apnea–Hypopnea Index in predicting long-term consequences of sleep-disordered breathing in children. We conducted a retrospective analysis of respiratory polysomnography recordings from preschool and school-age children (mean age: 5.8 ± 2.8 years) and followed them up after an average of 3.1 ± 0.8 years from the home-based polysomnography. We administered three validated questionnaires to the parents/caregivers of the children by phone. Our results showed that children with an Oxygen Desaturation Index (ODI) greater than one event per hour exhibited symptoms in four domains (physical, school-related, Quality of Life [QoL], and attention deficit hyperactivity disorder [ADHD]) at follow-up, compared to only two symptoms (physical and school-related) found in children with an Obstructive Apnea–Hypopnea Index greater than one event per hour at the time of diagnosis. Our study also found a significant correlation between the minimum SpO2 (%) recorded at diagnosis and several outcomes, including Pediatric Sleep Questionnaire (PSQ) scores, physical, social, and school-related outcomes, and ADHD index at follow-up. These results suggest that the Oxygen Desaturation Index could serve as a valuable predictor of long-term symptoms in children with sleep-disordered breathing, which could inform treatment decisions. Additionally, measuring minimum SpO2 levels may help assess the risk of developing long-term symptoms and monitor treatment outcomes.

Background and Objectives: Exhaled breath condensate (EBC) represents a potential diagnostic tool for Primary Ciliary Diskinesia (PCD). An increased oxidative stress is present in the airways of children affected and many neutrophil chemoattractants and markers of oxidative stress can be involved. The aim of the study is to evaluate leukotriene B4 (LTB-4), interleukin 8 (IL-8), 8-isoprostane (8-IP) concentration in PCD subjects, investigating their potential role as non-invasive markers of inflammation for the diagnosis and management of PCD. Methods: Cross-sectional study. 43 patients were enrolled in the study and divided in two groups: PCD (27) and healthy subjects (16). Physical examination, lung function test, nFeNO measurement and EBC collection were performed in all subjects. Results: PCD subjects showed an EBC 8-IP concentration significantly higher than the control group (median value: 11.9 pg/ml; IQR, 5.5–24.0 vs. median, 6.7 pg/ml; IQR, 2.5–11.3, p-value of Wilcoxon rank-sum test 0.0436). LTB4 EBC concentration did not differ between the two group (median, 4.3 pg/ml; IQR, 3.0–8.8 vs. 7.5 pg/ml; IQR, 3.0–9.5; P=0.4901). No significant correlation was found between FEV1 and EBC 8-IP (r=-0.10, P=0.6314) or LTB4 concentration (r=0.03, P=0.8888) in PCD subjects. No significant correlation was found between nFeNO and EBC 8-IP (r=-0.31, P=0.1385) or LTB4 (r=0.04, P=0.8565) in PCD subjects. Conclusions: EBC 8-IP levels are significantly increased in PCD subjects, highlighting the role of oxidative stress in airway inflammation. It could have a potential role as a non-invasive marker of inflammation for the diagnosis and management of PCD, although a therapeutic application of this evidence seems far.

Severe asthma is a rare disease affecting

Introduction: Children showed a lower prevalence of severe respiratory symptoms in acute COVID-19 infection, differently from adults. A recent study among adult patients affected by COVID-19 revealed lung function abnormality. Until now there has been no report regarding pulmonary function in COVID-19 children. Spirometry is not recommended during acute COVID-19 infection. SLP is a non-contact technology which has been used in children with asthma or neuromuscular disease. It evaluates thoracoabdominal wall movements to measure lung volumes. Aims and Objectives: We aimed to investigate SLP in children with COVID-19 acute respiratory symptoms and to describe their pulmonary function. Methods: 7 COVID-19 children with acute respiratory symptoms admitted to the Pediatric Department of Buzzi Children Hospital, Milan, Italy, were evaluated with SLP from May 2020 to January 2021. T-test was used to compare SLP parameters of COVID-19 group with healthy controls and children affected by pneumonia, before the pandemic. Results: Patients’age ranged from 18 months to 16 years. IE50 median value in COVID-19 children was 1.61± 0.30 with a significant difference from healthy controls (IE50 1.22±0.27; p 0.05). Conclusions: This study shows an increased IE50 value resulting in mild deficiency of lung function among children with acute COVID-19 respiratory symptoms, with a difference from controls. SLP does not require contact with patients and offers a proper solution for obtaining lung function parameters during a pandemic.

A 15 years-old boy came to our attention with a diagnosis of poorly controlled asthma. This case required thorough investigations: CT scan imaging revealed a flat angioma extending from the carina to the left main bronchus. Rigid bronchoscopy confirmed the presence of an angioma showing widespread mucosal diffusion involving most of the posterior tracheal wall and main bronchi, on the left side. We present this case report and these images to readers seeking for other experiences in the diagnosis of wide superficial bronchial angioma in pediatric age.

Introduction Scientific research, diagnostic tools and clinical experience have shown that children suffering from IgE-mediated fish allergy don't need to follow a strict exclusion diet. In fact, they could tolerate some species of fish, which could be reintroduced in the diet by verifying their tolerance with an oral food challenge in a clinical setting. Consequently, it is possible to look a new insight on diagnosis and management of IgE-mediated fish allergy in children, considering the use of canned tuna in clinical settings. Methods Authors performed a systematic literature search through the Cochrane Library and Medline/PubMed databases. All quantitative and qualitative paediatric studies involving diagnosis and management of IgE-mediated fish allergy and the use of canned tuna in clinical settings were considered. Articles related to allergological and nutritional features of fish, and especially canned tuna, were selected. This research was conducted on May 2020. Discussion Canned tuna shows peculiar allergological and nutritional characteristics. Relating to allergy, canning process, characterized by cooking the fish under pressure for a time equal to about 7 hours, can lead a conformational change in parvalbumin, making it less allergenic. In terms of nutrition, canned tuna contains B, D and A vitamins and, above all, omega-3 fatty acids and shows a favourable and significantly sustainable nutritional profile. Conclusions Lower allergenicity, adequate nutritional value and its rich availability in markets at reasonable costs, could make the use of canned tuna as a solution with an excellent risk/benefit ratio in the field of IgE-mediated fish allergy.

Background: VOCs originate from metabolic pathophysiological processes at respiratory and systemic level. VOCs pattern has previously been analysed with E-nose on exhaled air; in CF it distinguished P.aeruginosa and A.fumigatus colonization. Aim: to evaluate exhaled VOCs pattern with E-nose (Cyranose320®)in HC and in CF pts; to compare exhaled VOCs in stable CF pts (StCF) and in pts with respiratory exacerbation (ExCF). Methods: a cross-sectional experimental study was approved by Verona Ethic Committee. Spirometry, N2multiple breath washout (MBW) and exhaled air collection were performed in 29 CF pts (age 12.56 ± 4.08; 23 StCF, 6 ExCF) and 15 HC (age 13.36 ±4.13). VOCs analysis was performed with Cyranose320®. The output data underwent multivariate analysis and Principal Component Analysis (PCA). Results: A number of E-nose sensors (S6-8, S10, S12, S21, S27, S28) significantly distinguished between HC and CF pts; also, StCF could be discriminated from ExCf (S6-8, S10, S12, S21, S27). For sensors distinguishing between HC and CF pts, AUC of ROC was more than accurate for S12 (0.85), good for S6-7, S21, S27 (0.73-0.76). PCA identified PC10, PC1, PC7 and PC2, which proved the best PC in predicting between HC and CF subsets. Spirometry distinguished HC from ExCF, but not from St CF, whereas N2MBW distinguished also StCF from HC. Conclusion: E-nose analysis of exhaled air samples distinguished HC from CF pts, and among CF pts, StCF from ExCF. N2MBW distinguished all 3 subsets, whereas spirometry only distinguished ExCF from HC. E-nose is a promising tool for clinical and research setting.

Interleukin (IL)-5 is a potent mediator of the inflammatory cascade in the allergic response.Its predominant role in atopic reactions makes this cytokine an ideal target for blocking the eosinophilic inflammatory hyper-responsiveness to allergens. The management of allergic diseases in childhood – such as severe asthma, atopic dermatitis, and eosinophilic esophagitis - is a challenge. In particular, there are concerns regarding the use of high-dose corticosteroids. Over the last few years, biologics targeting IL-5 or IL-5 receptor - that are mepolizumab, reslizumab, and benralizumab - represent a new, promising, and more personalized therapeutic option.

Asthmatic children usually reach good control of symptoms with a low-medium dose of inhaled corticosteroids (ICS), but approximately 5% has severe asthma. In this group of patients, when the diagnosis of severe asthma is confirmed, biologic agents have to be considered when there is no control of the symptoms despite conventional treatment with controllers according to guidelines. At present, the only biologic agent available in clinical practice for severe asthma treatment in children (6-18 years) is omalizumab. Mepolizumab has been recently approved by EMA for pediatric use. Reslizumab is a monoclonal antibody anti-IL-5 that has been approved for severe eosinophilic asthma treatment only in patients >12 years. Because of their action on specific molecular targets of the asthma pathophysiology, biologic agents are very promising therapeutic options for severe asthmatic patients based on individual endotypes.

A 14 year old male was diagnosed with asthma but didn´t improve with appropriate inhalation therapy. Rigid bronchoscopy revealed a food fragment, almost completely occluding the lower-left bronchus lumen. Based on the reported history, it had been likely there for several years.

Background: Sleep-disordered breathing (SDB) is a general term encompassing a variety of breathing problems occurring during the sleep and characterized by frequently reported signs such as sleep apneas and snoring. Published studies on this topic are increasing over time, as demonstrated by the number of papers available on on-line databases. Methods: Google Trends is a freely accessible and reliable online portal, which allows to explore internet search data. Due to the focus on of childhood SDB in published research, and because of its impact on health and wellbeing, this original study aims at investigating the worldwide popularity of most common sleep signs (apnea and snoring) from January 1st, 2004 to present time. Results: The trend of interest for ‘sleep’, ‘sleep apneas’ and ‘snoring’ limited to pediatric age was lower than its overall popularity in the general population, thus reflecting a lower interest of these symptoms in children than in adults. Unlike an increasing trend of ongoing research, the popularity of pediatric sleep apnea and snoring was found to be relatively low around the world, and remained fairly stable over time. Conclusions: This is a matter for concern, since the low popularity of SDB in children is counterbalanced by a need for reinforcing educational programs aimed at increasing widespread awareness, diagnosis and management of this condition.

Background: Chronic loss of lung function was described in SCD patients (pts), even if not fully characterized in children. Aim: to explore lung function in children with SCD, through the assessment of resistance measurements and ventilation patterns. Methods: spirometry, FOT, IOS and N2MBW were performed in 15 stable pediatric pts with SCD, F 46.67%, Caucasian 13.33%, aged 12 ±3.8 years, mean HbS 66.36 ±17.44, ICS/LABA therapy in 20%, ICS therapy in 13.33%. Results: A mild restrictive pattern was found (FEV1 86.96 ±15.91 %pred, FVC 75.47 ±26.62%pred, MMEF75-25 86.76 ±21%pred). Lung Clearance Index (LCI) 2.5% was elevated (7.91 ±2.26, 120%pred), as well as normalized acinar slope index Sacin (0.12 ±0.14, 220%pred). IOS measured an increase in resistance (R) at 5 Hz (119.37 [101.68-137.79] %pred) while FOT showed an increase in R at 8 Hz (118.05 [101.87-140.29] %pred) and decrease in reactance(X) at 8 Hz. Expiratory R inversely correlated with MMEF75-25 (r -0.6, p 0.03). Pts Conclusions: IOS and FOT may help to depict and monitor early lung function changes in children with SCD. N2MBW did not correlate here with spirometry, FOT or IOS, thus it may be considered to add a novel and complementary insight in functional status of children with SCD, through the representation of ventilation inhomogeneity.

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.

Childhood obstructive sleep apnea syndrome (OSAS) is characterized by anatomical and functional upper airway abnormalities as pathophysiological determinants, and clinical symptoms are frequently clear. OSAS is widely described in rare genetic disorders, such as achondroplasia, Down syndrome, Prader-Willi syndrome, Pierre Robin sequence, and mucopolysaccharidosis. Craniofacial and upper airway involvement is frequently morbid conditions. In children with genetic diseases, the clinical symptoms of OSAS are often slight or absent, and related morbidities are usually more severe and can be observed at any age. The present review is aimed to updating the discoveries regarding OSAS on Achondroplasia, Down syndrome, Prader-Willi syndrome, Pierre Robin sequence, Sickle cell disease, or encountered in our clinical practice (Ehlers-Danlos syndrome, Ellis-van Creveld syndrome, Noonan syndrome). Two additional groups of genetic disorders will be focused (mucopolysaccharidoses and osteogenesis imperfecta). The flowing items are covered for each disease: (I) what is the pathophysiology of OSAS? (II) What is the incidence/prevalence of OSAS? (III) What result from the management and prognosis? (IV) What are the recommendations? Considering the worries of OSAS, such as inattention and behavioural problems, daytime sleepiness, failure to thrive, cardiological and metabolic complications, the benefit of a widespread screening and the treatment in children with genetic diseases is undoubtful. The goals of the further efforts can be the inclusion of various genetic diseases into guidelines for the screening of OSAS, updating the shreds of evidence based on the research progression.

Objectives: The severity of sleep apneas largely depends on abnormal size of upper airway. Therefore, nasal examination is essential part of clinical evaluation of children with sleep-disordered breathing. Methods: We performed a retrospective survey involving children aged 4 years and older which underwent in-laboratory overnight cardiorespiratory polygraph study between January 2016 and May 2017. Nasal obstruction test was used to score severity. Results: Fifty-three children (62% males) with a median age of 6.1 (IQR 3.1) years were enrolled in this study. Linear regression analysis showed that nasal obstruction score was correlated with apnea-hypopnea index (β=0.345; p < 0.014) and oxygen desaturation index (β=0.328; p < 0.022), whilst no association was found with age, BMI Z-score, snoring and phase angle. Correlation analysis also showed that nasal obstruction score was correlated with apnea-hypopnea index (r=0.364; p = 0.009) and oxygen desaturation index (r=0.350; p = 0.012) after adjustment for age and BMI Z-score., but not with snoring time or phase angle degree.Conclusions: Nasal obstruction test may be a useful, time saving assessment which aid exploring sleep disordered breathing in children. However, this test should not be used alone because it is plagued by objective consideration and at risk of under or overestimation.

Structured Light Plethysmography (SLP) is a non-invasive method to study chest and abdominal movement during breathing and can identify abnormal contributions of the different regions of the chest. M.D hospitalized for pneumonia, underwent SLP and spirometry at admission (T0), after 48 hours (T1), and after one month (T2). SLP parameters showed expiratory flow limitation, information consistent with the spirometric parameters collected, and reduced motion in the area effected by pneumonia, with improvement and normalization at T1 and T2. This method gave useful information about the contribution to the respiratory movement of the lung area affected by pneumonia so we can speculate a possible use in the follow-up of children affected by pneumonia or other respiratory diseases, and who are not able to perform a spirometric test.

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.

Objective: The purpose of this study was to assess the relationship between the thoracoabdominal asynchrony (phase angle), as an index of inspiratory airflow resistance, pulse transit time arousal index (PTT Ar/I), as changes in peripheral vascular resistance and intrathoracic pressure, and obstructive apnea index (OA), Oxygen Desaturation Index (ODI), snoring (% estimated Total Sleep Time - eTST) and apnea-hypopnea index (AHI) in a cohort of exogenous obese children. Material and Methods: Body mass index (BMI) and BMI z-scores were calculated according to age and sex in 36 consecutive obese children. Nasal patency, tonsil size, Friedman palate position scoring were also recorded. An overnight sleep respiratory recording was performed using an polygraphic ambulatory device. Results: Subjects studies had normal to mild sleep respiratory involvement (assessed by respiratory polysomnographic scoring). Phase angle correlated significantly with PTT Ar/I, but not with AHI (n/hr), OA (n/hr), ODI (n/hr) and snoring (% eTST), even adjusting for nasal patency, tonsil hypertrophy, palate position and BMI (z-score). Conclusion: Thoracoabdominal asynchrony (phase angle) is correlated with peripheral vascular resistance changes (PTT Ar/I), suggesting a subclinical upper respiratory airflow anomaly with autonomic activation in obese subjects.

Asthma is the most common chronic respiratory disease in childhood. The diagnosis of asthma is based on clinical history, airflow limitation and bronchial reactivity. Asthma treatment focuses on control of the condition; in cases of particular respiratory symptoms, the use of rescue medications, limited daily activity and lung function tests are taken into consideration. However, lung function and symptoms do not always reflect underlying airway inflammation and response to therapy. Consequently, objective parameters of airway inflammation could represent asignificant adjunctive tool for the clinician in tailored management of the disease. In recent years researchhas focused on biomarkers to identify phenotype, inflammation, pathobiological pathways and to guide the clinician in the diagnosis and personalized management of asthma. More feasible tests in the pediatric population are the collection of exhaled breath condensate (EBC) and the measurement of exhaled nitric oxide (FeNO), which are the most popular tests in practice. Other markers that might predict asthma exacerbation are volatile organic compounds (VOCs) that indicate airway inflammation and the level of asthma control. Nowadays, the variability and low reproducibility of exhaled biomarkers due to the lack of methodological standardization of pre-collection, collection, post-collection and interpretation of conditions could represent a drawback in clinical practice. Despite these limitations, several biomarkers have been shown to be helpful in distinguishing patients with asthma from healthy children.

Background: Exposure to environmental pollutants is advocated to be a major risk factor, with increased morbidity and mortality in humans due to acute and chronic airway inflammation. The aim of the present review is to show the literature research regarding the link between the sleep-disordered breathing and exposure to indoor/outdoor pollution in children. We hypothesized that environmental air pollution can play a role in childhood sleep-disordered breathing. Methods: We conducted an electronic search in Medline (with PubMed interface), Scopus and the ISI Web of Science using the keywords “sleep” or “sleep apnea” or “sleep disordered breathing” and “pollution” and “children” in “Title/Abstract/Keywords”, with language restriction (non-English paper) and no date limitation to present. The tobacco smoke pollution is well established linking and is not considered for the present subject. We examined the strength of the evidence according to the Oxford Centre for Evidence-Based Medicine [2011] and the Centre for Evidence-Based Medicine [2009]. Results: A total of 105 articles were identified, but 97 of these had to be excluded after an accurate reading of the title, abstract or full text. In the end, eight studies were selected for our analysis for a total of a total of 5,826 children. The results suggest an involvement (grade C) of environmental (not from voluptuary habits) pollution in the worsening of sleep-disordered breathing in children. Conclusions: To date, some studies reported significant differences between areas with higher and lower pollutants and the interventions on indoor pollution reduced sleep-disordered breathing in children. Therefore, although the relevance of the argument is high, the number of studies and the interest in the subject seems at this time quite limited.

Several factors including ethnicity are known to influence 25(OH)D levels. The purpose of our study was to assess 25(OH)D levels among 1374 pediatric subjects of different ethnicity and to determine the prevalence of vitamin D deficiency and insufficiency among different ethnic groups. The prevalence of 25(OH)D a parts per thousand currency sign20 ng/ml was 44.2, 65.2, 69.2, 54.0, and 44.8 % among Caucasians, Africans, North Africans, Indians, and others, respectively (P < 0.001). The median of 25(OH)D was 21.0 ng/ml (IQR = 14.0-29.6 ng/ml) for the cohort. Season of blood sampling, age, ethnicity, gestational age, birth weight, and z-score BMI were associated with 25(OH)D levels. Caucasians had higher median 25(OH)D levels than sub-Saharan Africans (P < 0.001), North Africans (P < 0.001), and Indians (P < 0.001). There were no significant differences in the median 25(OH)D levels between ethnic groups among infants, whereas for children older than 1 year we found significant differences in 25(OH)D levels in the different ethnic groups, compared to Caucasians.Conclusion: Ethnicity was correlated with 25(OH)D levels among children older than 1 year. We found a high prevalence of vitamin D deficiency and insufficiency after the first year of life, and this was more remarkable in non-Caucasian children.

Wheezing is a common condition in pediatric practice, it can be defined as a musical sound, high-pitched and continuous, emitting from the chest during breath exhalation. Although almost 50% of children experiences wheeze in the first 6 years of life, only 40% of them will report continued wheezing symptoms after childhood. The classification of wheeze in preschool children is more difficult compared to school aged children. It is based on the onset and duration of symptoms and divided children in three categories: transient early wheezing, non-atopic wheezing and atopic wheezing/asthma. History and physical examination, skin prick test, exhaled nitric oxide, lung function test are the parameter to evaluate children with wheezing. The aim of management of wheezing is to finalize the control of symptoms, reduce exacerbations and improve the quality of life. All guidelines underline the complexity in making a diagnosis of asthma under five years and the need to identify phenotypes that may help paediatricians in the therapeutic choices.

Background: Recent studies have highlighted the possible involvement of leptin in inflammation. The leptin receptor is also expressed by alveolar macrophages, T lymphocytes and bronchial epitelial cells, suggesting a possible role in the cascade of airway inflammation. Objectives: The aim of the study was to evaluate the levels of leptin in exhaled breath condensate (EBC) from asthmatic, normal- and overweight children, in relationship with airway inflammation. Methods: 15 asthmatic non-obese children, 15 healthy non-asthmatic non-obese children, 11 obese children with asthma (OA) and 20 obese children without asthma (ONA) were enrolled. Body impedance of body weight, EBC collection, FeNO, spirometry and a blood sampling for serum leptin were assessed. Results: Leptin EBC levels were significantly higher (3.9 ng ml−1 ± 1.3) in overweight children than those obese with asthma (3.6 ng ml−1 ± 1.6; p = 0.97), non-owerweight asthmatics (2.2 ng ml−1 ± 1.2; p < 0.0001) and in healthy children (0.9 ng ml−1 ± 0.6; p < 0.001). Leptin EBC levels in asthmatic children were significantly higher than in healthy children (p = 0.05). Leptin serum levels were significantly higher in the overweight children compared with the asthmatics (12.7 ng ml−1 ± 13.2; p < 0.001) and the healthy group (11.1 ng ml−1 ± 11.2; p < 0.001). We observed a significant correlation between EBC-leptin levels and the serum-leptin levels (p = 0.001). No correlations were found between EBC-leptin levels, FeNO and lung function. Conclusions: This study shows that leptin is measurable in EBC in children and that EBC-leptin levels are significantly higher in the obese subjects and in asthmatic ones compared with healthy subjects. Leptin may therefore represent a non-invasive marker of non-specific airway inflammation in children.

Background Asthma is a pathology characterized by chronic inflammation and remodeling of the airways. Objectives To evaluate the effect of montelukast treatment on markers of airway inflammation and remodeling in children with mild asthma and to evaluate if the administration of montelukast to children with mild asthma could inhibit the release of matrix metallopeptidase 9, matrix metallopeptidase 12, tissue inhibitor of metalloproteinase 1, transforming growth factor beta 1, C-peptide terminal procollagen type (PICP), and eosinophils count, which are markers of inflammation and remodeling in induced sputum. Methods Thirty children with mild asthma were recruited. They were randomized into two groups: group A received montelukast and as needed beta-2-agonist for 8 weeks (T0-T1), whereas group B received placebo and as needed beta-2-agonist for 8 weeks. After 2 weeks of washout (T1-T2), they were reallocated for treatment according a crossover design (T2-T3). Tests for lung function, oral exhaled nitric oxide, and hypertonic saline solution-induced sputum level were performed at T0-T1-T2-T3. Results In the placebo group, the PICP mean (standard deviation [SD]) value at baseline was 2279.42 ± 2530.77 pg/mL and 1916.00 ± 2178.75 pg/mL after treatment. Patients treated with montelukast, in contrast, showed a baseline mean (SD) value of 2439.29 ± 2834.51 pg/mL and 1406.72 ± 1508.65 pg/mL after treatment. The difference between the mean pre- and posttreatment decrease of PICP in the two groups was statistically significant (delta -690.21 pg/mL [95% confidence interval, -1220.83 to -159.5844 pg/mL]; p = 0.011). The mean (SD) percentage of the eosinophil count in the placebo group was 3.11 ± 4.03% at baseline and 4.86 ± 5.83% after treatment. Patients treated with montelukast, in contrast, showed a percentage mean (SD) value at baseline of 4.51 ± 5.48% and, after treatment, of 3.06 ± 3.29%. The difference between the mean pre- and posttreatment decrease of the percentage eosinophil count in the two groups was statistically significant (delta -2.76% [95% confidence interval, -4.65 to -0.87%]; p = 0.004). Conclusion This study investigated in vivo effects of montelukast on remodeling markers. The reduction of PICP levels and eosinophil count supported the hypothesis that montelukast can modulate collagen deposition in airways and reduce eosinophilic airway inflammation. Clinical Trials database clinicaltrials.gov (NCT00875082).

Background The effect of allergen avoidance on airway inflammation is similar to that observed with treatment with inhaled steroids, whereas inhaled steroids have no effect on oxidative stress-induced inflammation. Objective The aim of this study was to retrospectively evaluate the potential effect of an antioxidant dietary supplement on exhaled nitric oxide over a month in pediatric patients on stable antiasthma treatment. Methods Forty-seven children with moderate-to-severe asthma were retrospectively evaluated. All the patients were sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae, and they were receiving the minimum inhaled corticosteroid dosage required to maintain adequate control. Within a few weeks of admission at Misurina Hospital in the Alps, the regular treatment was gradually reduced, then some children who were receiving a daily dose of inhaled corticosteroids, ≤200 mcg of fluticasone propionate, were prescribed a nutraceutical dietary supplement for at least 4 weeks. Lung function and fractional exhaled nitric oxide (FeNO) measurements were recorded at the beginning and after 1 month of the dietary supplementation. Results Baseline lung function and FeNO values did not differ between the two groups of patients. After 4 weeks of nutraceutical supplementation, FeNO values decreased, from 19.00 ppb (interquartile range, 14-31 ppb) to 11.00 ppb (interquartile range, 6-23 ppb) (p = 0.03). No significant reduction was observed in the group that did not receive the supplementation, and no significant difference between groups was observed, both at baseline and after 4 weeks of nutraceutical supplementation. Conclusion Supplementation with a nutraceutical of antioxidants and anti-inflammatory compounds, such as curcumin, resveratrol, soy phospholipids, zinc, selenium, and vitamin D, may be associated with reduced airway inflammation, as documented by a fall in FeNO.

Introduction: Structured Light Plethysmography(SLP) is a new non-invasive method that records real-time images of chest wall movement,using a grid of light,tracked by a digital vision system of 2 high-speed cameras. Chest movement is analyzed showing the breathing pattern of the patient,the tidal breathing flow/volume graph to point out inspiratory or expiratory flow limitation,and regional subdivision to assessed abnormal contribution to the tidal volume of the different regions of the chest. It doesn9t require patient collaboration like spirometry;so it could be an alternative to evaluate pre-school children. Aims and objectives: Use SLP to evaluate the degree of expiratory flow limitation in asthmatic children. Methods: We evaluate 27 asthmatic children:10 with well-controlled asthma (GroupA),17 during asthma exacerbation(GroupB): every patient underwent SLP evaluation,and when it was possible also a spirometry was collected. We considered at SLP exam IE50:the ratio of inspiratory flow at 50% of tidal volume (VT) to expiratory flow at 50% of VT;value greater than 1.2 suggest expiratory flow limitation. Results: Group A showed greater value of FEV1 [median(LQ-UQ)% pred] [106.1(103.3-116.8)vs 69.7(57.50-82.35)p=0.0002]at spirometry; similarly IE50 was lower in Group A [1.16(0.99-1.54)vs 1.40(1.25-1.72)p=0.026] Conclusions: IE50 showed expiratory flow limitation in children during asthma exacerbation and a difference with well-controlled asthma children; this data are coherent with spirometric data collected. SLP is non-invasive and doesn9t need collaboration so it could represent a way to study the degree of obstruction in pre-school asthmatic children.

The purpose of the present study was to investigate the possible anti-oxidant effect(s) of Ambroxol on neutrophils activated by ligand-binding of the drug with membrane-associated adhesion integrin CD11a and to estimate dose-response changes in oxygen free radical production. The amount of free radical production by anti-CD11a- and anti-CD4-coated neutrophils stimulated with N-formyl-methionylleucyl-phenylalanine (FMLP) and challenged with increasing concentration of Ambroxol, was evaluated within a time frame of 90 minutes. A significant dose-dependent effect response of Ambroxol on O2− production by cells coated with anti-CD11a antibody was observed. This preliminary study opens a new perspective on the therapeutic role of Ambroxol as an antioxidant drug and for its potential use in controlling oxidative stress, particularly in leukocyte-dependent inflammation.