Different greenness exposure in Europe and respiratory outcomes in youths. A systematic review and meta-analysis.

The existing evidence on the association between greenness and respiratory outcomes remains inconclusive. We aimed at systematically summarizing existing literature on greenness exposure and respiratory outcomes in European children and adolescents, with a preliminary attempt to qualify the distribution of dominant tree species across different geographical areas and bioclimatic regions. Overall, 4049 studies were firstly identified by searching PubMed/MEDLINE, EMBASE, Scopus, Web of Science, GreenFile and CAB direct, up to 29 August 2023. Eighteen primary studies were included in the systematic review and six were meta-analyzed. No overall significant association was observed between the Normalized Difference Vegetation Index, assessed within 500-m buffers (i.e. NDVI-500), and the odds of asthma for 0.3-increase in the exposure (OR: 0.97, 95% CI from 0.53 to 1.78). Similarly, an overall exposure to the NDVI-300 highest tertile, as compared to the lowest tertile, was not significantly associated with asthma (OR: 0.65, 95% CI from 0.22 to 1.91): heterogeneity among studies was significant (p = 0.021). We delineated some key elements that might have mostly contributed to the lack of scientific consensus on this topic, starting from the urgent need of harmonized approaches for the operational definition of greenness. Additionally, the complex interplay between greenness and respiratory health may vary across different geographical regions and climatic conditions. At last, the inconsistent findings may reflect the heterogeneity and complexity of this relationship, rather than a lack of scientific consensus itself. Future research should compare geographical areas with similar bioclimatic parameters and dominant or potentially present vegetation species, in order to achieve a higher inter-study comparability.

Reference Equations for Within-Breath Respiratory Oscillometry in White Adults.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Relationship of long-term air pollution exposure with asthma and rhinitis in Italy: an innovative multipollutant approach.

BACKGROUND: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants. AIM: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches. METHODS: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM10, PM2.5, NO2 and mean summer concentrations of O3 (µg/m3) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts. RESULTS: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 µg/m3 for PM2.5, 29.2 ± 7.0 µg/m3 for PM10, 28.0 ± 11.2 µg/m3 for NO2, and 70.9 ± 4.3 µg/m3 for summer O3. Through the multipollutant models the following associations emerged: PM10 and PM2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models. CONCLUSIONS: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses.

Endotyping allergic rhinitis in children: A machine learning approach.

INTRODUCTION: The diversity of allergic rhinitis (AR) phenotypes is particularly evident in childhood, suggesting the need to analyze and identify new approaches to capture such clinical heterogeneity. Nasal cytology (NC) is a very useful diagnostic tool for identifying and quantifying nasal inflammation. Data-driven approaches such as latent class analysis (LCA) assign subjects to classes based on their characteristics. We hypothesized that LCA based on NC, including the assessment of neutrophils, eosinophils, and mast cells, may be helpful for identifying AR endotypes in children. METHODS: A total of 168 children were enrolled. Sociodemographic characteristics and detailed medical history were obtained from their parents. All children performed NC and skin prick tests. LCA was applied for identifying AR endotypes based on NC, using the R package poLCA. All the statistical analyses were performed using R 4.0.5 software. Statistical significance was set at p ≤ .05. RESULTS: LCA identified two classes: Class 1 (n = 126, 75%): higher frequency of children with moderate/large number of neutrophils (31.45%); almost all the children in this class had no mast cells (91.27%) and Class 2 (n = 42, 25%): higher frequency of children with moderate/large number of eosinophils (45.24%) and moderate/large number of mast cells (50%). CONCLUSIONS: The present study used a machine learning approach for endotyping childhood AR, which may contribute to improve the diagnostic accuracy and to deliver personalized health care in the context of precision medicine.

The Dietary Inflammatory Index and asthma burden in children: A latent class analysis.

INTRODUCTION: Unbalanced dietary intake has been increasingly recognized as an important modifiable risk factor for asthma. In this study, we assessed whether a pro-inflammatory diet is associated with higher asthma burden in three steps: (1) identification of asthma latent classes (LC) based on symptoms, indoor exposures, and pulmonary function; (2) identification of risk factors associated with LC membership; and (3) estimation of the probabilities of LC membership with variation in DII. METHODS: A cross-sectional study on 415 children aged 5-14 years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquantitative food frequency questionnaire. Elastic net logistic regression was used to investigate whether increasing DII was associated with worse asthma burden. RESULTS: Two LCs were identified. Children in Class 1, "high burden," had higher symptom burden and worse lung function. Children in Class 2, "low burden," had lower symptom burden and less impaired lung function but were more subject to indoor exposures. DII was the only risk factor significantly associated with Class 1 membership. As the DII increased (from -4.0 to +4.0), the probability of Class 1 membership increased from 32% to 65% when compared with control group, whereas it increased from 41% to 72% when compared with Class 2. CONCLUSIONS: We identified two phenotypes of persistent asthma associated with different disease burden linked to indoor exposures. An increasing DII was associated with high-burden asthma, providing further evidence about the role of a pro-inflammatory diet in asthma morbidity.

Machine learning: A modern approach to pediatric asthma.

Among modern methods of statistical and computational analysis, the application of machine learning (ML) to healthcare data has been gaining recognition in helping us understand the heterogeneity of asthma and predicting its progression. In pediatric research, ML approaches may provide rapid advances in uncovering asthma phenotypes with potential translational impact in clinical practice. Also, several accurate models to predict asthma and its progression have been developed using ML. Here, we provide a brief overview of ML approaches recently proposed to characterize pediatric asthma.

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract.

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Artificial intelligence in the diagnosis of pediatric allergic diseases.

Artificial intelligence (AI) is a field of data science pertaining to advanced computing machines capable of learning from data and interacting with the human world. Early diagnosis and diagnostics, self-care, prevention and wellness, clinical decision support, care delivery, and chronic care management have been identified within the healthcare areas that could benefit from introducing AI. In pediatric allergy research, the recent developments in AI approach provided new perspectives for characterizing the heterogeneity of allergic diseases among patients. Moreover, the increasing use of electronic health records and personal healthcare records highlighted the relevance of AI in improving data quality and processing and setting-up advanced algorithms to interpret the data. This review aimed to summarize current knowledge about AI and discuss its impact on the diagnostic framework of pediatric allergic diseases such as eczema, food allergy, and respiratory allergy, along with the future opportunities that AI research can offer in this medical area.

Validity and repeatability of the Pediatric Allergy Questionnaire for Athletes (AQUAped) for the screening of atopy.

BACKGROUND: High atopy prevalence has been reported in athletes. Having an age-specific questionnaire for predicting atopy is important for an optimal management of young athletes. The study objectives were as follows: (i) developing a scoring system for the Pediatric Allergy Questionnaire for Athletes (AQUAped); (ii) identifying the optimal age target within the range 7-14 years; (iii) assessing AQUAped validity and repeatability in the identified target population. METHODS: A total of 133 young athletes (age 7-14 years) were recruited. Following a screening visit, the participants filled AQUAped at baseline (T0) and after 7 days (T1), concomitantly undergoing skin prick testing. Using atopy as the gold standard (positivity to ≥1 aeroallergen), the 12 core items were scored based on their likelihood ratios, and a total score was calculated. The optimal cut-off was identified based on the Youden's criterion. The repeatability of AQUAped was assessed through the intra-cluster correlation coefficient (ICC). The optimal age target was identified as the largest age range associated with an acceptable cross-validated area under the receiver operating characteristic curve (AUC ≥ 0.70) and an excellent ICC (≥0.75). RESULTS: Forty (30%) children were atopic; the optimal age target was 10-14 years (cross-validated AUC = 0.70, ICC = 0.81). AQUAped total score ranged from -26 to 75, and only 5% of non-atopic children had AQUAped ≥ 24. AQUAped ≥ 2 had 82% specificity, 60% sensitivity, and 74% overall accuracy. CONCLUSION: Developing and testing a scoring system for AQUAped showed that it is a valid and reliable tool for the screening of atopy in young athletes aged 10-14 years.

Rhinomanometry: point of care test (POCT) for allergic rhinitis in children?

Allergic rhinitis (AR) is a global health problem: its prevalence is 23% in Europe, although it is underestimated because as many as 45% of the cases remain undiagnosed. Globally, almost 500 million people suffer from AR, which shows its increasing incidences. The diagnostic course of AR is based on clinical history, supported by anterior rhinoscopy. This inspects the anterior part of the nasal cavity accompanied by allergic sensitivity tests (cutaneous allergic skin tests or specific immunoglobulin E levels). The availability of standardised diagnostic procedures is able to provide objective evaluations of inflammatory situation, and the degree of nasal obstruction may give an advantage in reducing the risk of underestimating the diagnosis of AR. Diagnostic tests with a high level of accuracy are able to provide immediate results, which can sustain the doctor in diagnostic-therapeutic framework. The development of Point of Care Tests (POCTs) could be a useful tool. Considering that nasal obstruction is the most common symptom in patients with AR, the rhinomanometry (RM) test is the most indicated objective evaluation for nasal obstruction. Several studies have also shown the practicability of such diagnostic techniques applied in children. So far, no study has evaluated whether all the applicable requirements are fulfilled by RM in order to be considered as a POCT. The purpose of this perspective was to assess whether all the POCT requirements are fulfilled by RM by conducting a narrative review of the existing literature in which RM has been used in the diagnosis and management of AR in children. A few but encouraging results of studies on children supported the potential use of RM in the area of POCT. However, costs of instruments and the training of personnel involved remain to be explored. The studies support the potential use of RM in POCTs.

A two-week summer program promoting physical activity: quality of life assessment in Italian children.

Physical activity (PA) can be associated with better health-related quality of life (HRQoL). This study aimed to assess HRQoL before and after a two-week summer program promoting PA in Italian school-aged children. Participants were recruited during the Giocampus summer2017 (Parma, Italy), from June to July. Before (T0) and after (T1) the program, children and one of their parents answered the Kindl questionnaire. For each domain, least-square mean changes (LSmc) at T1 were derived from linear regression models stratified by responder and adjusted for child gender, age group, time spent in PAs and HRQoL score of the responder at T0. 350 children (7-13 years, 52% males) and 342 parents answered the questionnaire at both T0 and T1. At T1, the HRQoL score of the children significantly improved in the emotional (LSmc 2.9, p<0.001), self-esteem (LSmc 3.3, p<0.001), family (LSmc 4.2, p<0.001) and friend (LSmc 3.1, p<0.001) domains. Parents reported significantly more improvement in self-esteem than children (LSmc 6.7 vs 3.3, p=0.012). Children spending more time in PA reported significantly more improvement in self-esteem than those doing less PA (LSmc 4.4 [p<0.001] vs 2.2 [p=0.181]). A short summer program promoting PA may improve HRQoL in the general population of school-aged children.

RAPP-children: A new tool for assessing quality of life in patients with asthma and rhinitis.

BACKGROUND: RhinAsthma Patient Perspective (RAPP) is a short, validated questionnaire for assessing health-related quality of life (HRQoL) in adult patients with comorbid asthma and rhinitis, while a paediatric version is still not available. OBJECTIVE: The current study aimed to develop and validate the RAPP-children questionnaire. METHODS: RAPP-children was derived by combining RhinAsthma-children subscales into five unique items. At baseline (T0) and after 30 days (T1), 150 children (6-11 years) with comorbid asthma (predominantly intermittent or mild persistent) and rhinitis were given the following: RAPP-children, RhinAsthma-children, Paediatric Asthma Quality of Life Questionnaire (PAQLQ, age >6 years), Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Childhood Asthma Control Test (CACT), KiddyKindl® (age 6 years) or KidKindl® (age >6 years), and a Visual Analogue Scale for nasal symptoms (VAS). At the final visit, a Global Rating of Change (GRC) scale was administered. The approved study was registered on the central registration system ClinicalTrials.gov (ID: NCT03276416). RESULTS: RAPP-children fairly reproduced RhinAsthma-children scores (concordance correlation coefficients between 0.91 and 0.95). RAPP-children showed adequate convergent validity (absolute Spearman's rho larger than 0.5 with PAQLQ, PRQLQ, CACT, KiddyKindl/KidKindl, and VAS), internal consistency (Cronbach's alpha > 0.70), repeatability (intra-cluster correlation coefficient between 0.61 and 0.8) in the presence of clinical stability (GRC = 0), discriminant validity (sensitivity to asthma control status and rhinitis severity), and sensitivity to symptom improvements (GRC > 1). The minimal important difference (MID) was -20. Floor and ceiling effects were minimal. RAPP-children showed fair usability also in younger children (6-8 years). CONCLUSION & CLINICAL RELEVANCE: RAPP-children is a valid, five-item questionnaire for assessing HRQoL in children aged 6 to 11 years with concomitant asthma and rhinitis. Although further investigation is required in moderate and severe asthmatics, this tool can be useful in clinical trials and in routine medical practice for improving the management of respiratory allergy in children.

Assessing repeatability and reproducibility of Anterior Active Rhinomanometry (AAR) in children.

BACKGROUND: Repeatability and reproducibility are essential for clinicians for several purposes. Although discouraged, use of the Coefficient of Variation (CV) for assessing repeatability and reproducibility, rather than the Intraclass Correlation Coefficient (ICC), is still widespread. The aim of the present study was to highlight how using inappropriate indices may lead to misleading results, and this is done by simulation study and using real data on Anterior Active Rhinomanometry (AAR) in both healthy children and ones with rhinitis. METHODS: A simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and ICC to assess repeatability and reproducibility of AAR, for which previous studies have given underestimated results. AAR is recommended as the gold standard tool for measuring nasal resistance in clinical practice. RESULTS: A simulation study showed that the ICCs estimated from data generated assuming a true CV yielded results in agreement with estimated CVs; by contrast, if data were generated assuming a true ICC, CVs yielded conflicting results. For AAR, ICCs showed good repeatability, whereas CVs showed unacceptable repeatability. AUC and 95% CI for AAR showed good performance in predicting current symptoms of rhinitis in the overall study population. CONCLUSIONS: The present study focused on the importance of the choice of appropriate indices of repeatability and reproducibility, demonstrating the repeatability of AAR in both healthy children and ones with rhinitis. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03286049; Registration Date: September 15, 2017; Actual Study Start Date: January 10, 2018).

Associations of greenness, greyness and air pollution exposure with children's health: a cross-sectional study in Southern Italy.

BACKGROUND: Due to the complex interplay among different urban-related exposures, a comprehensive approach is advisable to estimate the health effects. We simultaneously assessed the effect of "green", "grey" and air pollution exposure on respiratory/allergic conditions and general symptoms in schoolchildren. METHODS: This study involved 219 schoolchildren (8-10 years) of the Municipality of Palermo, Italy. Data were collected through questionnaires self-administered by parents and children. Exposures to greenness and greyness at the home addresses were measured using the normalized difference vegetation index (NDVI), residential surrounding greyness (RSG) and the CORINE land-cover classes (CLC). RSG was defined as the percentage of buffer covered by either industrial, commercial and transport units, or dump and construction sites, or urban fabric related features. Two specific categories of CLC, namely "discontinuous urban fabric - DUF" - and "continuous urban fabric - CUF" - areas were found. Exposure to traffic-related nitrogen dioxide (NO2) was assessed using a Land-Use Regression model. A symptom score ranging from 0 to 22 was built by summing affirmative answers to twenty-two questions on symptoms. To avoid multicollinearity, multiple Logistic and Poisson ridge regression models were applied to assess the relationships between environmental factors and self-reported symptoms. RESULTS: A very low exposure to NDVI ≤0.15 (1st quartile) had a higher odds of nasal symptoms (OR = 1.47, 95% CI [1.07-2.03]). Children living in CUF areas had higher odds of ocular symptoms (OR = 1.49, 95% CI [1.10-2.03]) and general symptoms (OR = 1.18, 95% CI [1.00-1.48]) than children living in DUF areas. Children living in proximity (≤200 m) to High Traffic Roads (HTRs) had increased odds of ocular (OR = 1.68, 95% CI [1.31-2.17]) and nasal symptoms (OR = 1.49, 95% CI [1.12-1.98]). A very high exposure to NO2 ≥ 60 µg/m3 (4th quartile) was associated with a higher odds of general symptoms (OR = 1.28, 95% CI [1.10-1.48]). No associations were found with RGS. A Poisson ridge regression model on the symptom score showed that children living in proximity to HTRs (≤200 m) had a higher symptoms score (RR = 1.09, 95% CI [1.02-1.17]) than children living > 200 m from HTRs. Children living in CUF areas had a higher symptoms score (RR = 1.11, 95% CI [1.03-1.19]) than children living in DUF areas. CONCLUSIONS: Multiple exposures related to greenness, greyness (measured by CORINE) and air pollution within the urban environment are associated with respiratory/allergic and general symptoms in schoolchildren. No associations were found when considering the individual exposure to greyness measured using the RSG indicator.

Rapid systematic review shows that using a high-flow nasal cannula is inferior to nasal continuous positive airway pressure as first-line support in preterm neonates.

AIM: We reviewed using a high-flow nasal cannula (HFNC) as first-line support for preterm neonates with, or at risk of, respiratory distress. METHODS: This rapid systematic review covered biomedical databases up to June 2017. We included randomised controlled trials (RCTs) published in English. The reference lists of the studies and relevant reviews we included were also screened. We performed the study selection, data extraction, study quality assessment, meta-analysis and quality of evidence assessment following the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Pooled results from six RCTs covering 1227 neonates showed moderate-quality evidence that HFNC was associated with a higher rate of failure than nasal continuous positive airway pressure (NCPAP) in preterm neonates of at least 28 weeks of gestation, with a risk ratio of 1.57. Low-quality evidence showed no significant differences between HFNC and NCPAP in the need for intubation and bronchopulmonary dysplasia rate. HFNC yielded a lower rate of nasal injury (risk ratio 0.50). When HFNC failed, intubation was avoided in some neonates by switching them to NCPAP. CONCLUSION: HFNC had higher failure rates than NCPAP when used as first-line support. Subsequently switching to NCPAP sometimes avoided intubation. Data on the most immature neonates were lacking.

Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND: Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. METHODS: In this 21-day, open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS delivered through a nasal douche. Efficacy measures were least square mean changes (LSmc) in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: BHS improved the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p < 0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not. Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc -0.57, p = 0.009), whereas the improvement in PSQI score was comparable between the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall, BHS was well tolerated. CONCLUSIONS: In children with SAR, BHS is effective in improving nasal symptoms and NCC, with an associated beneficial effect on quality of life.