"Antibiotic hypersensitivity reactions in Cystic Fibrosis: A thorough inspection on a stumbling block in patient care".

One hurdle in the management of CF, a disease characterized by progressive endobronchial infection, is the presence of hypersensitivity reactions to antimicrobials due to prolonged and repetitive treatment courses. The aim of this review is to compile existing data and provide insight to medical professionals on a long-debated topic for optimum patient care. Clinical studies were inducted from the last 15 years and filtered based on their relativity to drug hypersensitivity reactions (DHRs), antibiotics and CF. After completing the selection process, 10 clinical studies were thoroughly examined. The most frequent antibiotic group related to DHRs were beta-lactams. Frequency of the most common overall type of reaction (immediate or nonimmediate) differed among clinical studies. Although severe reactions seem rare comparatively, they do occur during and even after completion of treatment regimens. The prevalence of true drug allergies should be confirmed using a variety of tests available, however, should not be confused with overall DHR rates. Genetic mutations, gender and lifetime antibiotic dose were not related with an increased risk for DHR development. On the contrary, the most important factor according to most studies was the cumulative antimicrobial dose in a given period of time, especially when delivered parenterally. DHRs are an indisputable problem in the management of CF patients. Understanding possible risk factors and increased awareness is vital in both hospital and outpatient settings as early detection can decrease the severity of the reactions.

Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Greater fruit and vegetables consumption, and adherence to a Mediterranean type of diet reduces the risk for asthma in children; a systematic review and meta-analysis.

The objective of this study was to explore the relationship between the consumption of fruits, vegetables and adherence to the Mediterranean diet with childhood asthma development and severity. A systematic literature search and synthesis of the results was performed throughout the last two decades. A total of 45 studies were analysed and 392,797 children were included. Greater adherence to a Mediterranean type of diet was inversely associated with asthmatic outcomes (OR:0.71,95% CI:0.54,0.88). Regarding fruits, vegetables consumption, a significant inverse association between increased fruits or vegetable intake and asthma was found (OR:0.82,95% CI:0.77,0.86; 0.84,95% CI:0.77,0.91, respectively). Fruits and vegetables consumption combined was also inversely related to all asthmatic outcomes (OR:0.65,95% CI:0.49,0.78). The level of heterogeneity was moderate-to-high (30%-97%). The present review and meta-analysis show a trend to an inverse association between adherence to the Mediterranean diet or a healthy diet rich in fruits and vegetables and the occurrence of childhood asthma but with a low level of certainty.

Children with cystic fibrosis are still receiving inconclusive diagnosis despite undergoing newborn screening.

AIM: We aimed to familiarise clinicians with the terms cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS) and cystic fibrosis screen positive inconclusive diagnosis (CFSPID). We also sought to highlight the monitoring and outcomes of children that match these designations. METHODS: A literature review was performed by searching PubMed from its inception until 30 November 2022. All relevant articles were included in this narrative review. RESULTS: Despite the implementation of newborn screening programmes for cystic fibrosis (CF), the diagnosis remains uncertain in some newborn infants with elevated immunoreactive trypsinogen. In 2016, a unified definition for CRMS/CFSPID was established to categorise these children. While many of them remain healthy, a portion of these children may develop CF. As a result, it is crucial to monitor them regularly. CONCLUSION: CRMS/CFSPID is a designation and not a diagnosis. Longer longitudinal studies are needed to shed light on the most appropriate follow-up of these children. Paediatricians need to be knowledgeable about this condition in order to administer proper care, and children should be in contact with their local CF centre.

Lung ultrasound systematic review shows its prognostic and diagnostic role in acute viral bronchiolitis.

AIM: Lung ultrasound (LUS) has not been included in the current guidelines for the diagnosis of bronchiolitis so far, even though data concerning its effectiveness have been published. METHODS: A systematic literature review was carried out to determine the role of LUS scores in the diagnosis and prognosis of patients aged 0-2 years with bronchiolitis, using MEDLINE, Scopus and ScienceDirect databases from their inception to December 2021. RESULTS: A total of 18 studies matching our eligibility criteria were analysed for the purposes of this review and 1249 patients with bronchiolitis were included. The sonographic and radiological findings were comparable and chest radiography was found to have a higher sensitivity in ruling out severe complications such as concomitant pneumonia. The LUS scores were correlated to the clinical course of bronchiolitis and it was able to predict the need of admission in paediatric intensive care unit, the duration of hospitalisation and the need for respiratory support. CONCLUSION: This review suggests that LUS could have both a diagnostic and a prognostic role in bronchiolitis during first evaluation in the emergency department and hospitalisation. Physicians could adjust management according to sonographic findings as a useful adjunct to the clinical ones.

Assessment and management of asthma exacerbations in an emergency department unit.

BACKGROUND: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild-moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S). METHODS: The study population consisted of children aged 3-16 years with mild-moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4-6 puffs of salbutamol via MDI/S. RESULTS: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42-123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01-0.78, P = 0.032). CONCLUSION: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity.

Technical Factors That May Influence mHealth Adherence in Children With Chronic Pulmonary Diseases: Scoping Review.

PURPOSE: To synthesize the technical factors influencing adherence to nonpharmacological treatment (NPhT) in children with chronic pulmonary diseases (CPDs), using mobile health (mHealth) technology. METHODS: Five electronic databases were searched from inception to October 12, 2022, with terms related to pediatrics, CPDs, adherence, NPhT, and mHealth. The methodological quality was assessed using the Critical Appraisal Skills Programme and the Mixed Methods Appraisal Tool checklist. RESULTS: Eleven articles were included. Six major technical themes were supported by the evidence that may influence adherence to NPhT: design and context, technical support/business model, connectivity, free availability, privacy and security, and cultural readiness. CONCLUSIONS: The design of mHealth applications (apps) should be done according to the needs of pediatric patients. This may mitigate any barriers and potentially foster adherence to the use of the apps. WHAT THIS ADDS TO THE EVIDENCE: Six major technical themes may influence adherence to NPhT in children with chronic respiratory diseases.Video Abstract: Supplemental digital content available at http://links.lww.com/PPT/A487 .

Infection with SARS-CoV-2 among children with asthma: evidence from Global Asthma Network.

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. RESULTS: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

Parental education moderates the association between indoor moisture environment and asthma in adolescents: the Greek Global Asthma Network (GAN) cross-sectional study.

OBJECTIVE: Asthma is a major contributor to childhood morbidity. Several environmental and socioeconomic status (SES) factors have been implicated in its etiopathogeneses such as indoor moisture and parental education level. Our study examined the association between exposure to indoor dampness and/or mould (IDM) with adolescent asthma and how parental education could modify or mediate this relationship. METHOD: A total of 1934 adolescents (boys: 47.5%, mean age (standard variation): 12.7(0.6) years) and their parents were voluntarily enrolled and completed a validated questionnaire on adolescents' asthma status, parental educational level, and adolescents' indoor exposure to IDM during three different lifetime periods, i.e., pregnancy, the first year of life and the current time. RESULTS: There was a significant modification effect of parental education only for the current exposure; higher parental education lowered almost 50% the odds of IDM and asthma (adjusted odds ratio (aOR): 1.96, 95% Confidence Intervals (CI): (1.05-3.68) and aOR:1.55, 95% CI (1.04-2.32), for primary/secondary and tertiary parental education, respectively). CONCLUSION: Adolescents whose parents had a higher education level had lesser odds to have asthma, even if they were exposed to a moisture home environment. This could be attributed to the increased knowledge about asthma risk factors and the improved measures for the amelioration of moisture-home environment that highly educated parents are more likely to take. Further research is needed in order to elucidate the interweaved role of family SES in the aforementioned relation.

A systematic review of using flexible bronchoscopy to remove foreign bodies from paediatric patients.

AIM: Our aim was to summarise the evidence about flexible bronchoscopy for paediatric airway foreign body aspiration cases. METHODS: We searched the PubMed database from 1 January 2001 to 9 October 2021 for peer-review papers published in English on the use, and success rates, of flexible bronchoscopy as the first-line treatment for foreign body aspiration cases. This process identified 243 potential papers. RESULTS: We studied 23 papers comprising 2588 cases of foreign body aspiration and flexible bronchoscopy successfully removed the foreign bodies in 87.1% of cases. Complication rates were low in the 983 patients studied in 18 papers. The foreign bodies were organic materials in 78.3% of 1371 patients and mainly lodged in the right bronchial tree in 50.5% of 1402 patients. General anaesthesia was used before flexible bronchoscopy in 14/23 studies and laryngeal mask airways were mostly used in 10/23 studies to secure the airway during the procedure. Ancillary equipment was used to assist the foreign body removal in 57.3% of 1808 cases and these were usually baskets. CONCLUSION: Flexible bronchoscopy was a feasible and safe therapeutic procedure for selected foreign body aspiration cases. Future studies need to focus on comparing the clinical outcomes of flexible and rigid bronchoscopies.

Hierarchical analysis of Mediterranean Dietary pattern on atopic diseases' prevalence in adolescence: The Greek Global Asthma Network study.

INTRODUCTION: The contribution of dietary patterns in the occurrence of atopic diseases, mainly asthma, allergic rhinits, and eczema is ambiguous. Our study examined the association between the level of adherence to the Mediterranean diet (MedDiet) and the prevalence of atopic diseases in adolescence. METHODS: A total of 1934 adolescents (boys: 47.5%, mean age [standard variation]: 12.7[0.6] years) enrolled voluntarily. Participants completed a validated questionnaire on atopic disease status, dietary habits, and other sociodemographic and lifestyle characteristics. KIDMED score was used for the evaluation of adherence to the MedDiet. Discriminant analysis was applied to the hierarchy of foods and beverages consumed in relation to the presence of atopic diseases. RESULTS: Logistic regression analyses revealed that adolescents with moderate and good adherence to the MedDiet had 34 and 60% lower odds of having any asthma symptoms, respectively, and 20 and 41% lower odds of having any allergic rhinitis symptoms, respectively, adjusted for several confounders. The food group with the most important contribution to the MedDiet was cooked and raw vegetables, followed by fruits (Wilk's λ = 0.881 and λ = 0.957, respectively). CONCLUSION: Our study provided evidence for a strong and inverse association between the level of adherence to the MedDiet and the occurrence of asthma and allergic rhinitis symptoms and signified the importance of contribution of fruits and vegetable consumption in this association. Thus, the promotion of MedDiet could be an efficient lifestyle intervention that can contribute to the reduction of the burden of these atopic diseases in adolescents.

Use of point-of-care molecular tests reduces hospitalization and oseltamivir administration in children presenting with influenza-like illness.

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point-of-care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza-like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0-16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision-making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01-9.82; p = .046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06-20.43; p = .041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs.

Effectiveness of an educational program for children and their families on asthma control treatment adherence.

Objective: Τo investigate the effect of an asthma care educational program for children and adolescents with asthma, on adherence to asthma control treatment and on clinical indices.Methods: Individuals newly diagnosed with asthma, aged 4-16 years, randomized to the intervention and control group. The participants were monitored for 6 weeks. At baseline, before the initiation of inhaled corticosteroids/long-acting beta2-agonist (ICS/LABA), the intervention group attended the educational program; the control group received the usual care. Both groups were equipped with electronic monitoring devices for measuring adherence. Spirometry, exhaled nitric oxide fraction (FeNO), and asthma control test (ACT) score were measured in both groups in the pre and post-ICS/LABA initiation visit.Results: Seventy-eight participants were enrolled in this study (n = 39 to each group). Median percentage of adherence was 73% for the total sample, and 80% and 68% in intervention and control group, respectively (p < 0.001). In multivariate analysis, the program was positively associated with improved adherence (p < 0.001). ICS/LABA had a positive effect on spirometric indices, FeNO, and ACT score, whilst the educational program did not improved significantly the above variables.Conclusions: Establishing and increasing adherence is challenging. An asthma care educational program is associated with greater short-term adherence during a period of active monitoring.

ERS statement on tracheomalacia and bronchomalacia in children.

Tracheomalacia and tracheobronchomalacia may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low-contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions, but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics (as well as treatment of comorbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, continuous positive airway pressure is the most commonly used modality either via a face mask or tracheostomy. Parents of children with tracheobronchomalacia report diagnostic delays and anxieties about how to manage their child's condition, and want more information. There is a need for more research to establish an evidence base for malacia. This European Respiratory Society statement provides a review of the current literature to inform future study.

Effect of the month of birth on the height of young adult males.

OBJECTIVE: To explore a possible association between the month of birth and the final adult height in men and see if this could be described in terms of periodicity. MATERIALS AND METHODS: We used anthropometric data of 15,109 young male conscripts of the Greek Army. The data were collected from May 2006 until May 2010 and included men who had been born over a period of 12 years (1980-1991). The data were grouped in 12 monthly periods and analyzed with the use of a sinusoidal model. RESULTS: There was a statistically significant month-of-birth effect on height variation, which was described by a sinusoidal model with period T = 12 months, amplitude 0.223 cm and, two extremes which corresponded to the end of April/beginning of May (peak) and to the end of October/beginning of November (nadir). DISCUSSION: Our results corroborate previous findings suggesting a seasonality in human height without, however, being able to provide a definitive explanation for this phenomenon.

Retrospective study identified fish and milk as the main culprits in cases of food protein-induced enterocolitis syndrome.

AIM: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated food allergy, which is confined to the gastrointestinal tract and occurs most frequently in the first year of life. Our aim was to examine the clinical features, causative agents and outcomes of Greek children with FPIES. METHODS: This was a five-year (2013-2017) retrospective study, based on chart reviews of 78 children with FPIES from six Greek paediatric allergy centres. RESULTS: Only five children needed an oral food challenge (OFC) for diagnosis, but 54 children (69%) had OFCs to monitor tolerance development. The most common problems were fish and milk, which affected affecting 42 (54%) and 25 (35%) of children, respectively. The median age of tolerance based on the results of the negative OFCs occurred by 34.0 (26.6-58.4) months. Fish and milk were tolerated by 24 (57%) and 13 (52%) of children by 43.8 and 24.3 months, respectively. Coexisting IgE sensitisation to the offending food was related to delayed tolerance. CONCLUSION: Fish and milk were the most common food allergies in our series of Greek children with FPIES. Cases with IgE sensitisation to the food trigger took longer to resolve their allergies.

Adherence to the Mediterranean diet and inflammatory markers in children with asthma.

INTRODUCTION: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. METHODS: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. RESULTS: KIDMED score did not differ between the two groups (P=0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P=0.007; Beta: 0.57, P=0.010; Beta: -0.62, P=0.017, respectively). CONCLUSION: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children.

Asthma and Allergy "Epidemic" and the Role of Vitamin D Deficiency.

The increase in asthma and allergies prevalence that has been recorded in many countries during the last decades, and the reemergence of vitamin D (VD) deficiency in many populations worldwide, renders fairly plausible the assumption of an underlying association between these two conditions and justifies the research effort invented in this issue. Indeed, there is growing body of evidence from epidemiological, laboratory, and clinical studies, suggesting that such an association does exist. The hypothesis of low levels of VD leading to compromised fetal programming and impairment of various immune functions involved in asthma and allergic disorders, stands as the most credible explanation of this presumed association. However, the evidence is not yet definite and there are some conflicting results among studies. As a consequence, no safe conclusions can be drawn yet, and more research is required in order to fully clarify the involvement of VD deficiency in the pathogenesis of asthma and allergies, and decide if VD has a role to play in the prevention and therapy of these disorders.

Cytokine responses in primary and secondary respiratory syncytial virus infections.

BACKGROUND: Primary respiratory syncytial virus (RSV) infections are characterized by high levels of IL-8 and an intense neutrophilia. Little is known about the cytokine responses in secondary infections. Preschool children experiencing RSV secondary infections were recruited from the siblings of infants admitted to hospital with RSV acute bronchiolitis. METHODS: Fifty-one infants with acute bronchiolitis (39 RSV positive, 12 RSV negative) and 20 age-matched control infants were recruited. In addition, seven older siblings of infants from the RSV-positive cohort and confirmed RSV infection were recruited. Samples of nasal secretions were obtained using a flocked swab, and secretions extracted using centrifugation. Cytokine bead array was used to obtain levels of interleukin (IL)-17A, IL-8, IL-6, IL-21, and tumor necrosis factor-α. RESULTS: Levels of IL-8 and IL-6 were significantly lower in the RSV-positive siblings compared with the RSV-positive infants. There were no significant differences between levels of the other cytokines in the primary and secondary infections. CONCLUSION: The very high levels of IL-8 and IL-6 response characteristic of the primary RSV infection was not observed in secondary RSV-positive infections and this did not appear to be due to a global reduction in cytokine production.