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Information gathered with built-in software (BIS) on new ventilators allow clinicians to access long-term noninvasive ventilation (LTNIV) data. Nevertheless, few evidence are available in literature that highlight potential strengths and disadvantages of using BIS in pediatrics. We aim to evaluate the use of BIS in a cohort of 90 children on LTNIV in our unit, focusing mainly on adherence, air leaks, and residual sleep events. We found that caregivers' perception of ventilator use is independent from objective adherence (P = .137). Furthermore, we failed to find any predictors of adherence. As regards air leaks, we found that pre-scholars' (0-6 years old) total air leaks are lower than teenagers' (more than 12 years old) (P < .05). Multiple regressive analysis showed that age at the beginning of therapy is a predictor of total air leaks: prescholars are associated with lower values (P < .05), while scholars (6-12 years old) are associated with higher values (P < .05). Finally, we explored the validity of BIS automatic scoring of sleep events (AHIBIS ) as compared with the manual scoring of polygraphy (AHIPG ). AHIBIS is within a range of 3.98 from AHIPG in 95% of cases, with a 64% of sensitivity and a 67% of specificity in identifying a pathological state. The disagreement between the two methods seems to increase for high AHI values. In conclusion, data gathered by BIS are a useful support tool for the clinician in assessing the course of LTNIV. However, clinicians must be aware of the several limitations of built-in software, especially in pediatrics.

Introduction and objectives Patients with neuromuscular disease (NMD) are often exposed to ionizing radiations which could be reduced if a noninvasive and reliable diagnostic method is identified. The major aim of this study was to compare the use of chest X-ray (CXR) with lung ultrasound (LUS) in pediatric patients with NMD, to identify pulmonary atelectasis (PA). Materials and methods A prospective study was conducted on children affected by NMD. In all patients who underwent CXR, a LUS was also performed and results compared for the assessment of PA. Results Forty children affected by NMD were enrolled. Spinal muscular atrophy type 1 was the most common NMD, followed by spinal muscular atrophy type 2 and congenital myopathies. More than half of the subjects presented PA, more prevalent in the lung left lower lobes. LUS agreed with CXR results (negative or positive for atelectasis) in 31 patients (77.5%). In two patients, an agreement evaluation was not possible due to non-conclusive LUS. Conversely, LUS disagreed with CXR in seven patients, four of which were positive for atelectasis. If only complete agreement was considered, the statistical analysis between CXR and LUS showed: LUS sensitivity of 57%, LUS specificity of 82%, positive predictive value 80%, negative predictive value 61%. Conclusions This study suggests that the use of LUS should be recommended to early identify PA and reduce frequent ionizing exposition of these fragile patients. Finally, our study also suggests that LUS can provide relevant information for clinicians and respiratory physiotherapists.

Neuromuscular diseases may involve all major respiratory muscles groups including inspiratory, expiratory, and bulbar muscles. Respiratory complications are the major cause of morbidity and mortality. Pneumonia represents a frequent cause of morbidity in children with neuromuscular disease. The aim of this review is to collect knowledge about pneumonia in children with neuromuscular diseases. Pneumonia usually follows viral respiratory infections of the upper respiratory tract, due to the combination of an increased amount of nasal and oral secretions and an impairment of the cough efficiency and of the clearance of secretions due to the muscle weakness, further compromised by the infection itself. The accumulation of bronchial secretions leads to atelectasis and promote bacterial infection. Moreover, dysfunction of swallowing mechanism exposes these children to the risk of developing aspiration pneumonia. However, etiology of viral and bacterial respiratory infection in these patients is still poorly studied.

Sergio Ghirardo (SG): a 15-year-old girl was first admitted to our unit, with significant dyspnoea and fatigue at rest. Her clinical history was uneventful until she was 14 years old when she was hospitalised twice for respiratory symptoms, interpreted as post viral wheezing. Treatment with intravenous corticosteroids, salbutamol and azithromycin was of little clinical benefit. In the last 6 months, she complained of progressive exercise-induced dyspnoea, and her lung function showed a moderate-to-severe obstructive pattern (forced expiratory volume in one second, FEV1/forced vital capacity, FVC 56.6%), with no response to salbutamol. Her symptoms did not improve with inhaled corticosteroids, long-acting β2 agonists and montelukast treatment. Clinically, she reported moderate swelling of the nasal dorsum as a consequence of a blow with a ball received 5 months before admission. She had a bilateral transmissive mild hypoacusis and a significative weight loss of 18 kg in only 8 months. On initial physical examination she appeared pale and tired with a mild redness of the ear helix sparing the lobe and a mild swelling of the nasal dorsum. She was tachypnoeic (20 breaths/min), with normal levels of oxygen saturation. Mild supraclavicular retractions were present during inspiration. On chest auscultation stridor and mild bilateral wheezing were detected. Heart rate was 109 beats/min. The remaining physical examination was normal. Renato Cutrera (RC): we have a previously healthy female adolescent with a personal history of only partially remitting obstructive dyspnoea suggesting a chronic respiratory infection (like tuberculosis or pulmonary mycosis). However, the fatigue associated with significant weight loss should raise the suspicion of pulmonary hypertension. I suggest performing routine blood tests, chest X-ray, full blood count and cardiological evaluation. At the same time, I would administer oral corticosteroids and antibiotic coverage. Federica Porcaro (FP): blood tests showed a mild rise of C reactive protein (CRP) 7.2 mg/L (normal range 0–5 mg/L); whereas …

Bronchiolitis is the most common acute viral infection of the lower airways in infants and the main cause of hospitalisation and death from viral infections in western countries. The worldwide COVID-19 pandemic has led to most countries adopting social distancing measures and population movement restrictions to reduce transmission of the severe acute respiratory syndrome coronavirus 2 infection. During the 2020-2021 winter season, social distancing and mask use altered the spread of common viral respiratory infections, reducing the incidence of winter epidemics.

Background Noncystic fibrosis bronchiectasis (NCFB) is still considered an "orphan disease" in pediatric age. Objective The study describes the clinical and functional features, the instrumental, and microbial findings of a large cohort of patients with NCFB, followed in a single tertiary level hospital. Methods Children and adolescents diagnosed with NCFB from January 1, 2010 to December 31, 2019 were included. Data from the diagnosis and during the years of follow-up were recorded retrospectively. Results One hundred and thirty-eight patients were enrolled. The most common cause of NCFB was postinfectious (33%), followed by primary ciliary dyskinesia (PCD) (30%), esophageal atresia (EA) (9.5%), and secondary immunodeficiency (9.5%). Chronic cough was the most frequent symptom. The median age of symptoms presentation was 3 years (interquartile age [IQR]: 12-84), with a precocious onset in PCD and EA groups. The median age of CT diagnosis was 9 years for all groups but PCD patients who were diagnosed at older age. Lingula, medium, upper, and lower lobes were more involved in PCD group, while diffuse distribution was observed in the postinfectious one. Microbial exams showed Pseudomonas aeruginosa colonization higher in PCD patients (22%). Despite microbial differences in airways colonization, no difference in respiratory exacerbation rate was recorded among groups. Lung function tests demonstrated the stability of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) over time, except for the secondary immunodeficiency group. Conclusions The role of infections in developed countries should not be underestimated and a major effort to obtain an earlier identification of bronchiectasis should be taken. A prompt diagnosis of NFCB could help to reduce the frequency of exacerbations and improve the stability of lung function over time.

Children with medical complexity (CMC) are patients with one or more complex chronic conditions dependent on medical technologies. In our unit (Pediatric Pulmonology and Respiratory Intermediate Care Unit, Department of Pediatrics, “Bambino Gesù” Children's Hospital and Research Institute), we regularly follow‐up CMC patients, particularly children on long‐term, invasive (IMV) or noninvasive (NIV), ventilation. Children suffering from chronic diseases and with medical complexity have lost the possibility to go to the hospital during the COVID‐19 pandemic. The aim of this article is to describe our experience with telemedicine (teleconsultation [TC] and telemonitoring of ventilator [TM]) in CMC on ventilation. We presented 21 children on long‐term ventilation (NIV or IMV) whose planned hospital admission was postponed due to lockdown. A total of 12 healthcare problems were detected during scheduled TCs. Only one problem was not solved by our remote intervention. Specifically, TM has allowed us to change the ventilator parameters and to monitor patients on ventilation remotely. In conclusion, the use of telemedicine in CMC ventilated patients resulted in a feasible tool to avoid in‐person visits during the pandemic.

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device.Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'—IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone.Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability.Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.

Asthma is the most frequent chronic inflammatory disease of the lower airways affecting children, and it can still be considered a challenge for pediatricians. Although most asthmatic patients are symptom-free with standard treatments, a small percentage of them suffer from uncontrolled persistent asthma. In these children, a multidisciplinary systematic assessment, including comorbidities, treatment-related issues, environmental exposures, and psychosocial factors is needed. The identification of modifiable factors is important to differentiate children with difficult asthma from those with true severe therapy-resistant asthma. Early intervention on modifiable factors for children with difficult asthma allows for better control of asthma without the need for invasive investigation and further escalation of treatment. Otherwise, addressing a correct diagnosis of true severe therapy-resistant asthma avoids diagnostic and therapeutic delays, allowing patients to benefit from using new and advanced biological therapies.

Background Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed. Methods Patients included in the Kids Lung Register diagnosed with PTI as infants and now older than 5 years were identified. Initial presentation, extrapulmonary comorbidities, spirometry and clinical outcome were analyzed. Results Thirty-five children older than 5 years with PTI diagnosed as infants were analyzed. At the age of 5 years, 74% of the patients were reported as asymptomatic and did not develope new symptoms during the observational period at school-age (mean, 3.9 years; range, 0.3-6.3). At the age of about 10 years, none of the symptomatic children had abnormal oxygen saturation during sleep or exercise anymore. Lung function tests and breathing frequency were within normal values throughout the entire observational period. Conclusions PTI is a pulmonary disease that can lead to respiratory insufficiency in infancy. As at school age most of the previously chronically affected children became asymptomatic and did not develop new symptoms. We conclude that the overall clinical course is favorable.

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy leading to chronic suppurative lung disease, chronic rhinosinusitis, middle ear disease, sub-fertility and situs abnormalities. As PCD is rare, it is important that scientists and clinicians foster international collaborations to share expertise in order to provide the best possible diagnostic and management strategies. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a multidisciplinary network funded by EU COST Action (BM1407) to coordinate innovative basic science and clinical research from across the world to drive advances in the field. The fourth and final BEAT-PCD Conference and fifth PCD Training School were held jointly in March 2019 in Poznan, Poland. The varied program of plenaries, workshops, break-out sessions, oral and poster presentations were aimed to enhance the knowledge and skills of delegates, whilst also providing a collaborative platform to exchange ideas. In this final BEAT-PCD conference we were able to build upon programmes developed throughout the lifetime of the COST Action. These proceedings report on the conference, highlighting some of the successes of the BEAT-PCD programme.

Diffuse lung disease in infancy includes a wide range of very rare and peculiar pulmonary conditions usually not seen in older children, in whom diffuse lung disease has much greater overlap with adult disorders. The acronym chILD (childhood Interstitial Lung Disease) commonly defines these disorders, although air spaces, airways, alveolar epithelium, vasculature, pleura, and pleural spaces can also be involved, besides the pulmonary interstitium. chILD can be caused by diffuse developmental disorders, alveolar growth abnormalities, surfactant dysfunction disorders, and other specific conditions of poorly understood etiology. Chest CT imaging studies play a pivotal role in the evaluation of chILD. In some conditions CT findings can be specific, and thus make it possible avoiding further testing. In other disorders, findings are nonspecific, although they may suggest a diagnostic pattern and guide further testing. Nevertheless, chILD disorders often remain unrecognized on imaging studies, as they are very rare. The aim of this article is to review the CT patterns of lung involvement in a series of infants with chILD.

BACKGROUND Tracheobronchomalacia, defined as variable collapse of the airways, has been recognized as an important cause of respiratory morbidity but still widely underdiagnosed. Bronchoscopy is still considered as the gold standard, but numerous limitations are known, especially for fragile sick children. Moreover, information on parenchymal lung disease cannot be described. There is a real need for a reliable, non-invasive test to help detection of airway and parenchymal malformations in children, specifically when bronchoscopy cannot be performed. METHODS AND RESULTS 34 paediatric patients underwent cine multidector CT for ongoing respiratory symptoms and were included. All CT images were of good quality and sedation was never needed. Airway disease such as trachea-broncomalacia with/without stenosis was described in 53% with the first being more frequent. Bronchomalacia alone was described in 10 patients and in 4 patients was associated with tracheomalacia. Moreover, CT allowed identification of parenchymal disease in 10 patients. Airways stenosis alone was detected in seven patients. The majority of patients (85%) underwent also bronchoscopy for clinical decision. The agreement between CT and bronchoscopy was explored. The two examinations did not agree only in two cases. CT dynamic showed an excellent sensitivity of 100% (81.47-100 %), a great specificity of 82% (48.22-97.72 %), NPV 100%, and PPV 90% (72-96.9 %). CONCLUSION Dynamic CT results an effective and highly sensitive diagnostic exam for children with tracheo-bronchomalacia. CT is especially indicated for those small and fragile patients that cannot undergo an invasive investigation. Moreover, CT allows a detailed evaluation both of the airways and the lungs which is useful for the clinical management.

Background: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. Methods: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5–12 months; boys: 55.4%) and 213 children aged Results: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2–3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7–4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1–2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2–2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls ( p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. Conclusions: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures – for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke.

Introduction: chILD conditions are ultrarare and require international coordination to register cases and demonstrate an ability to deliver cohorts for clinical trials. That capacity has not been demonstrated. Methods: COST action 16125 ‘Enter-ChILD’ WG6 assessed the registry-based capacity for identifying ILD in children and young adults across Europe, using a survey of COST chILD specialists, and searches of Pubmed (ILD/IPF/ lung + database/registry + national/international) and Google. Two principle registries holding the largest cohort of patients were searched for 7 chILD conditions to identify cohorts (ChILDEU and RespiRare). Results: COST survey had 30 responses from 15 countries. Pubmed identified 8 novel and Google 6 novel databases. 28 unique databases were identified: 9 local, 19 national, 1 international (ChILDEU). In the two largest databases, there were 232 cases reported for the 7 conditions: surfactant disorders (145), Morbus Nieman Pick (9), interferonopathies (COPA, SAVI) (5), connective tissue disorders with ILD (13), sarcoidosis (27), hypersensitivity pneumonitis (22), pulmonary interstitial glycogenosis (11). Extraction of subpopulations for i.e. surfactant disorders is possible but requires additional interrogation of each database. Conclusion: Databases for chILD are common and can readily be identified. Given disease rarity, many chILD conditions can be aggregated across databases, though some require additional database interrogation to identify subpopulations. Common classification terms would enable a more rapid and accurate estimation of potential cohorts for clinical trials.

Background: Non-cystic-fibrosis bronchiectasis (NCFB) is still one of the most common causes of childhood morbidity. Objective: the study aimed to determine aetiology, clinical presentation, lobar distribution and microbiologic colonization of NCFB in children. Methods: we performed a retrospective review of clinical, laboratory and instrumental data from 132 non-CF patients with diagnosis of bronchiectasis. All the included patients were evaluated from 2010 to 2018. Results: Mean age at respiratory symptoms’ onset and diagnosis were 9.7 years (± 4.6 SD) and 10.6 years (±5.95 SD), respectively. The aetiology was as follows: post-infectious (39%), primary ciliary dyskinesia (30%), esophageal atresia with trachea-esophageal fistula (8%), secondary (7%) and primary immune deficiency (6%), bronchial malformation (3%), isolated asthma (3%), chronic aspiration (2%), pulmonary fibrosis with TBX4 gene mutation (1%), broncorrea in patient with CFTR polymorphism (1%). Chronic cough (45%), recurrent pneumonia (25%), single pneumonia episode (16%), recurrent wheezing (11%), were the commonest respiratory problems. Left and right lower lobes, medium lobe were commonly involved by cilindric bronchiectasis. H. Influenza (35, 31%), S. Aureus (20, 18%), P. Aeruginosa (20, 18%), were the more frequently isolated bacteria. 51 and 13 patients needed prophylactic oral (azithromycin) and inhaled antibiotics (tobramycin or colistin), respectively. Conclusions: this is the largest study in pediatric NCFB. As the management of NCFB affected patients remains problematic, a better definition of clinical, radiological and microbiological features of NCFB is required to improve their management. Reference: 1. BMC Pediatrics 2014;14: 299

Background Long-term mechanical ventilation (LTV) with non-invasive ventilation (NIV) prolongs survival in patients with Neuromuscular Diseases (NMDs). Transition from paediatric to adult healthcare system is an undervalued and challenging issue for children with chronic conditions on mechanical ventilation. Methods this retrospective study aims to compare issues of young adults in age to transition to adult care (≥ 15 years old) affected by NMDs on NIV in two different Paediatric Respiratory Units in two different countries: Bambino Gesù Children’s Hospital, Research Institute, (Rome, Italy) (BGCH) and the Paediatric Respiratory Unit of the Royal Brompton Hospital (London, UK) (RBHT). Results The median (min-max) age at starting ventilation was significantly different in the two groups (16 years old vs 12, p = 0.0006). We found significant difference in terms of median age at the time of observation (18 (15–22) vs 17 (15–19) years, p = 0.0294) and of type of referral (all the patients from the BGCH group were referred to paediatric services (n = 15, 100%), median age 18 (15–22); only 6 patients, in the RBHT group, with a median age 15.50 (15–17) years, were entirely referred to paediatric service). We found different sleep-disordered breathing assessments 6 full Polysomnographies, 7 Cardio-Respiratory Polygraphies and 2 oximetry with capnography (SpO2-tcCO2) studies in the BCGH group, while all patients of RBHT group were assessed with an SpO2-tcCO2 study. All patients from both groups underwent multidisciplinary assessment. Conclusions In conclusion, patients with NMDs on NIV in age to transition to adult require complex multidisciplinary management: significant efforts are needed to achieve the proper transition to adult care.

Bronchiolitis is the most frequent airway infection in the first 2 years of life, and the respiratory syncytial virus (RSV) is the most frequently responsible virus. In selected high-risk groups, RSV may cause severe respiratory disease leading to hospitalization, need for mechanical ventilation, and even death. These high-risk groups include children with congenital heart disease, infants with neuromuscular impairment, cystic fibrosis, Down Syndrome, immunodeficiency syndromes and others specific conditions. In these high-risk populations defined in literature as "special population", a 3- to 10-fold increase in the rate of RSV hospitalization has been observed, justifying RSV specific prophylaxis with palivizumab, a monoclonal antibody that binds a viral glycoprotein epitope and blocks the link between RSV and target cell. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomized clinical trials are not feasible. The purpose of this paper is to give an update from the literature of various conditions at higher risk to develop severe RSV infection, and to offer an overview of the efficacy of palivizumab in preventing RSV infection in these specific populations.

Childhood asthma remains a multifactorial disease with heterogeneous clinical phenotype and complex genetic inheritance. The primary aim of asthma management is to achieve control of symptoms, in order to reduce the risk of future exacerbations and progressive loss of lung function, which results especially challenging in patients with difficult asthma. When asthma does not respond to maintenance treatment, firstly, the correct diagnosis needs to be confirmed and other diagnosis - such as cystic fibrosis, primary ciliary dyskinesia, immunodeficiency conditions or airway and vascular malformations - need to be excluded. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Moreover, all possible risk factors or comorbidities (gastroesophageal reflux, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea and obesity) should be investigated. At the same time, the possible reasons for poor symptom control need to be find in all modifiable factors which need to be carefully assessed. Non-adherence to medication or inadequate inhalation technique, persistent environmental exposures and psychosocial factors are, currently, recognized as the more common modifiable factors. Based on these premises, investigation and management of asthma require specialist multidisciplinary expertise and a systematic approach to characterising patients' asthma phenotypes and delivering individualised care. Moreover, since early wheezers are at higher risk of developing asthma, we speculate that precocious interventions aimed at early diagnosis and prevention of modifiable factors might affect the age at onset of wheezing, reduce the prevalence of persistent later asthma and determine long term benefits for lung health.

Introduction: Neuromuscular diseases are characterized by weakness of voluntary muscles which determines accumulation of secretions and atelectasis. As a consequence, an excess use of imaging exams is common. It is necessary to identify a reproducible, low cost and reliable diagnostic method to avoid the need for multiple imaging exams. Material and Methods: Pediatric patients affected by neuromuscular diseases admitted to our Unit were enrolled. In patients who underwent a chest X-ray for clinical reasons, a pulmonary ultrasound (PU) was also performed. Results: X-ray and PU were performed in 27 patients (mean age: 7.5 years). PU highlighted pulmonary atelectasis in 13/27 cases. In 2 patients PU was not conclusive because of severe scoliosis. Out of the 12 patients with negative PU for atelectasis, in two patients PU described pulmonary thickening, in one of those cases complicated by pleural effusion. X-ray described 13/27 cases positive for atelectasis and, between the negative, 1 patient with pneumonia. Considering X-ray as the gold standard, concordance between the two examinations showed: Sensitivity 100%, Specificity 85,7%; Negative predictive value 100%, Positive predictive value: 86,6%. Moreover, it is important to point out that in 2 cases with atelectasis, the PU also allowed to detect a pleural effusion, not described by X-ray. Conclusions: Our results show that PU has an excellent diagnostic reliability in identifying pulmonary atelectasis in children with neuromuscular diseases. PU could be a useful test in the follow-up and diagnosis of pulmonary atelectasis, allowing a significant reduction in ionizing radiation for young and fragile patients.

Community-acquired pneumonia (CAP) is still the most important cause of death in countries with scarce resources. All children (33 months ± 35 DS) discharged from the Pediatric Unit of Itigi Hospital, Tanzania, with a diagnosis of CAP from August 2014 to April 2015 were enrolled. Clinical data were gathered. Dried blood spot (DBS) samples for quantitative real-time polymerase chain reaction (PCR) for bacterial detection were collected in all 100 children included. Twenty-four percent of patients were identified with severe CAP and 11% died. Surprisingly, 54% of patients were admitted with a wrong diagnosis, which increased complications, the need for antibiotics and chest X-rays, and the length of hospitalization. Comorbidity, found in 32% of children, significantly increased severity, complications, deaths, need for chest X-rays, and oxygen therapy. Malnourished children (29%) required more antibiotics. Microbiologically, Streptococcus pneumonia (S. p.), Haemophilus influenza type b (Hib) and Staphylococcus aureus (S. a.) were the bacteria more frequently isolated. Seventy-five percent of patients had mono-infection. Etiology was not correlated with severity, complications, deaths, oxygen demand, or duration of hospitalization. Our study highlights that difficult diagnoses and comorbidities negatively affect clinical evolution. S. p. and Hib still play a large role; thus, implementation of current vaccine strategies is needed. DBS is a simple and efficient diagnostic method for bacterial identification in countries with scarce resources.

Respiratory diseases account for about 25% of all pediatric consultations, and 10% of these are for asthma. The other main pediatric respiratory diseases, in terms of incidence, are bronchiolitis, acute bronchitis and respiratory infections. Oral corticosteroids, in particular prednisolone, are often used to treat acute respiratory diseases given their anti-inflammatory effects. However, the efficacy of treatment with oral corticosteroids differs among the various types of pediatric respiratory diseases. Notably, also the adverse effects of corticosteroid treatment can differ depending on dosage, duration of treatment and type of corticosteroid administered — a case in point being growth retardation in long-course treatment. A large body of data has accumulated on this topic. In this article, we have reviewed the data and guidelines related to the role of oral corticosteroids in the treatment and management of pediatric bronchiolitis, wheezing, asthma and croup in the attempt to provide guidance for physicians. Also included is a section on the management of acute respiratory failure in children.

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

Non-invasive positive pressure ventilation is increasingly used in children both in acute and in chronic setting. Clinical data supporting safety, efficacy and limitations in children are growing. Technical problems related to the ventilators performance and interfaces selection have not been fully resolved, especially for younger children. Non-invasive ventilation can be applied at home. Its use at home requires appropriate diagnostic procedures, accurate titration of the ventilators, cooperative and educated families and careful, well-organized follow-up programs.

Nocturnal pulse oximetry has a high positive predictive value for polysomnographically diagnosed obstructive sleep apnoea (OSA) in children. When significant adenotonsillar hypertrophy is diagnosed, adenotonsillectomy (TA) represents a common treatment for OSA in children. We investigated the role of pulse oximetry in predicting those patients, referred for suspected OSA, who subsequently needed TA. At-home nocturnal pulse oximetry was performed on 380 children (65.7% males), median age 4.1(IRQ 3.0-5.6) years, referred for suspected OSA, and data were retrospectively analysed. For each recording McGill Oximetry Score (MOS) was categorized. Mean pulse rate (PR) z-score and pulse rate variability (PRV)-corrected (PRSD/meanPR) were significantly higher in children with abnormal MOS. Both parameters were significantly higher in subjects who underwent TA compared with those not surgically treated. Both DIIn our study, children with OSA who subsequently needed TA showed higher PRV compared to those without surgical indication. Children with abnormal MOS were nearly 20 times more likely to undergo TA. What is Known: • Nocturnal pulse oximetry has a high positive predictive value for polysomnographically diagnosed obstructive sleep apnoea in children. • When significant adenotonsillar hypertrophy is diagnosed, adenotonsillectomy represents a common treatment for OSA in children. What is New: • An abnormal pulse oximetry highly predict the indication for adenotonsillectomy. • We suggest the use of at-home pulse oximetry as method to predict prescription of adenotonsillectomy, and this may be useful in contexts where polysomnography is not readily available.

Objective To evaluate whether the proportion of acid and weakly acidic refluxes preceding cough bursts could be different in infants, preschool- and school-aged children with chronic, unexplained cough. Patients and Methods One hundred six children with unexplained chronic cough, not receiving acid suppressive therapy, underwent impedance–pH monitoring. They were divided into Group A: 6 years (44 pts). Reflux was defined as acid (pH 7).Cough episodes were considered temporally associated with gastroesophageal reflux (GER) when occurring within 2 min after a GER episode. Results Impedance–pH detected 55.50 (39.00–76.00) reflux episodes/patient with an acid-to-WA reflux event ratio of 3.31 (1.55–8.33). This parameter was significantly lower in Group A (1.33 [0.41–3.40]) than in Group B (3.06 [2.00–6.50]; P

Necrotizing sarcoid granulomatosis (NSG) is a disorder of unknown etiology, rarely described in childhood, belonging to the heterogeneous group of the pulmonary angiitis and granulomatosis. One of the characteristics of NSG is to have typically a benign clinical course with minimal treatment with systemic steroids or even with no therapy at all. Here, we report the case of a boy with a lung consolidation, with morphological and histological features consistent with a diagnosis of NSG. Good clinical and roentgenographic response to high dose prednisone treatment was followed three times by relapses, when steroid treatment was tapered. New lesions were detected in different areas of the lung and not in initially affected area, never previously described in NSG and only rarely in other pulmonary angiitides. Pediatr Pulmonol. 2012. 47:831–835. © 2012 Wiley Periodicals, Inc.

Summary Background Defining atopy in children with severe, therapy-resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen-specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all-or-none phenomenon. Hypothesis SPTs and sIgE cannot be used interchangeably, and if both tests are not performed, opportunities for intervention will be missed. Furthermore, the severity of atopy will be defined differently by the two tests. Methods Cross-sectional study of 47 children with severe, therapy-resistant asthma, mean age 11.8 years, range 5.3–16.6 years, who underwent SPT, and measurement of total and sIgE as part of their clinical work-up. Results Overall, 42/47 (89%) were atopic (defined as either one positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/200 (20%), the SPT and sIgE results were discordant, most commonly in 25/200 (12.5%), the SPT was negative and the sIgE was positive. House dust mite and cat sensitization were more likely detected by sIgE, but dog sensitization by SPT. When atopy was quantified, the sum of sIgEs compared with the sum of SPT weal diameter showed a moderate correlation (r2=0.44, P

Summary Background Management of children with gastroesophageal reflux disease (GORD) and difficult-to-treat (D-T-T) respiratory symptoms may include double fiberoptic, airway and oesophago-gastro-duodenoscopies (DE). A study was performed to evaluate the usefulness and safety of DE in children with severe GORD and D-T-T respiratory symptoms. Methods A 3-year retrospective review of records of children who underwent DE under general anaesthesia was performed: the relevant clinical information obtained and the occurrence of complications in the 72h following the DE. Results Inflammatory changes of the airways were found at bronchoscopy in 40 out of the 60 children: bronchoalveolar lavage (BAL) demonstrated positive lipid-laden alveolar macrophages (LLAM), neutrophilic inflammation or both, respectively in 9, 12 and 16 patients. BAL bacterial cultures were positive in 2 patients with elevated airway neutrophilia. Structural airway abnormalities, explaining not GOR-related D-T-T respiratory symptoms were identified in 11 patients. Oesophagoscopic findings supporting GORD were detected in 32/60 children and confirmed by consistent histological changes in oesophageal mucosal biopsies (OEB) in 27. The frequency of complications, all minor, was low during the procedure and in the following 72h. They included mild desaturation, stridor or bronchospasm, vomiting, dysphagia and hyperthermia requiring antibiotic treatment in 1 patient. No "new onset" complication was observed after 48h following DE. The time-dependent hazard of complications was significantly higher for patients with a history of onset of respiratory symptoms early in life (≤2 years of age) ( p =0.038). Conclusion DE can be useful in the clinical evaluation of children with D-T-T respiratory symptoms and GORD and is associated with low frequency of mild complications when performed by appropriately trained and experienced personnel.

© 2015 Macmillan Publishers Limited Genetic defects of surfactant metabolism are associated with a broad range of clinical manifestations, from neonatal respiratory distress syndrome to adult interstitial lung disease. Early therapies may improve symptoms but diagnosis is often delayed owing to phenotype and genotype variability. Our objective was to characterize the cellular/ultrastructural correlates of surfactant protein C (SP-C) mutations in children with idiopathic diffuse lung diseases. We sequenced SFTPC – the gene encoding SP-C – SFTPB and ABCA3, and analyzed morphology, ultrastructure and SP expression in lung tissue when available. We identified eight subjects who were heterozygous for SP-C mutations. Median age at onset and clinical course were variable. None of the mutations were located in the mature peptide-encoding region, but were either in the pro-protein BRICHOS or linker C-terminal domains. Although lung morphology was similar to other genetic surfactant metabolism disorders, electron microscopy studies showed specific anomalies, suggesting surfactant homeostasis disruption, plus trafficking defects in the four subjects with linker domain mutation and protein misfolding in the single BRICHOS mutation carrier in whom material was available. Immunolabeling studies showed increased proSP-C staining in all cases. In two cases, amyloid deposits could be identified. Immunochemistry and ultrastructural studies may be useful for diagnostic purposes and for genotype interpretation.European Journal of Human Genetics advance online publication, 18 March 2015; doi:10.1038/ejhg.2015.45.

Summary Double aortic arch is the most common congenital anomaly of the aortic arch system, in which the trachea and esophagus are completely encircled by vascular segments of the aortic arch and its branches, often resulting in variable airway compression. One case of late diagnosis of this congenital malformation and long-term consequences of late surgical treatment with persistent tracheo-broncomalacia and dynamic airway obstruction is reported. This report emphasizes the importance of an early diagnosis to minimise the progressive airways damage and subsequent respiratory symptoms, that need an accurate medical follow-up. Pediatr Pulmonol. 2014; 49:E75–E77. © 2013 Wiley Periodicals, Inc.

A 4-year-old boy was admitted to our department with fever, cough and dyspnoea, unresponsive to salbutamol and antibiotic therapy. He had previously contracted bronchiolitis at 20 days of life, followed by intermittent episodes of wheeze that never required hospitalisation and responded to short inhaled corticosteroid cycles. He had an atopic family history. On examination, he had dyspnoea, persistent cough with bronchospasm but normal oxygen saturations. Bloods showed elevated eosinophils (2004 µL), a slightly elevated C-reactive protein (1.5 mg/dL) and total IgE (326 kU/L), and specific IgE was raised for various inhalant allergens (box). A chest X-ray was performed (figure 1). Box Positive inhalant allergens Anthoxanthum odoratum Cynodon dactylon Dactylis glomerata Dermatophagoides farinae Dermatophagoides pteronissimus Holcus lanatus Poa pratensis Phleum pratense Questions 1. What does the chest X-ray infigure 1show? interstitial pneumonia pneumothorax lung atelectasis with mild mediastinal shift diffuse air trapping enlargement of right hilar lymph nodes 2. Given the clinical picture and the chest X-ray, what would your differential diagnosis include from the following? plastic bronchitis (PB) mycoplasma infection tuberculosis foreign body aspiration lung perforation 3. Are any of these conditions not associated with a specific type of cast/PB? Fontan procedure haemophilia lymphatic abnormalities asthma and other allergic disorders sickle cell disease.

Francesca Petreschi (FP): A 9.8 year–old-girl was first admitted in our unit for a persistent bronchospasm, poorly responsive to salbutamol, and progressive onset of respiratory distress after spontaneous expectoration of a bronchial cast (figure 1A). Her clinical history was uneventful until she was 7 years old, when she suffered from two subsequent bouts of pneumonia, but no admission was required. In the following years, she presented few episodes of bronchospasm, clinically diagnosed, with good response to bronchodilator and no limitation on her daily activities. Her family history was positive for allergic disease. On physical examination at her arrival, she appeared quite unwell with persistent wet cough, bilateral respiratory wheeze but normal levels of saturation. The remaining examination was normal. Figure 1 (A) Bronchial cast. (B) Bronchial fistula secreting milky material under pressure. (C) CT scan of the thorax demonstrating left lower lobe opacity and pleural effusion. (D) Lung biopsy compatible with pulmonary lymphangiectasia. (E) CT scan showing chylopericardium. Renato Cutrera (RC): We have a previously healthy young girl with positive family history for allergies and personal history of few lower respiratory infections and intermittent episodes of wheezing. Patient's history and the spontaneous expectoration of a bronchial cast during an acute episode of bronchospasm, together with her physical examination characterised by intense cough and diffuse wheeze are suggestive of a case of plastic bronchitis (PB), already described as possible complication of allergic asthma. The differential diagnosis, though, should always include more inflammatory diseases of the lung, such as cystic fibrosis, pulmonary infections and acute chest syndrome in sickle-cell anaemia.1 Nicola Ullmann (NU): Patient was afebrile; blood exams were normal, including: haemoglobin, c-reactive protein, immunoglobulins and lipid values. Allergy tests were positive to house dust mites and few pollen, but sweat tests and nasal brushing for ciliary dyskinesia were negative. Spirometry showed mainly …

BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (

Background The inflammatory phenotypes of severe asthma in adults may be reflected in peripheral blood. If this were true in children with severe therapy-resistant asthma (STRA), invasive tests could be avoided. At the moment there is no conclusive evidence in children. Methods All patients underwent blood tests, exhaled nitric oxide (FeNO), sputum induction, bronchoalveolar lavage (BAL) and endobronchial biopsy (EB). Results Sixty-three (71.6%) patients had a normal blood profile and only 1/88 had a combined blood eosinophilia and neutrophilia. 76/88 (86%) had normal blood eosinophils, but of these, 84% had airway eosinophilia in either BAL (n = 43;66%) or EB (n = 41;79%). In children with STRA blood eosinophilia was associated with airway eosinophilia. However, normal blood eosinophil levels did not exclude airway eosinophilic inflammation. Conclusions Peripheral blood counts are not reliable in characterising airway inflammation in severe asthmatic children exposed to high dose steroid therapy, therefore bronchoscopy with BAL should be considered.

Objective To investigate the disease outcomes of a cross-sectional sample of children with longstanding juvenile idiopathic arthritis (JIA) seen between September 2002 and December 2006, and to provide a benchmarking of outcomes obtained with current treatment. Methods All consecutive patients were included if they met the following criteria: diagnosis of JIA, disease duration ≥5 years, and informed consent. Outcome assessments included disease activity, inactive disease, minimal disease activity, pain, physical function, health-related quality of life (HRQOL), auxometric measurements, and articular and extraarticular damage. Results A total of 310 patients were included. At study visit, patients had on average a low level of disease activity. However, only 21.8% met the criteria for inactive disease, and less than 50% met the definition of minimal disease activity. Additionally, 19.2% had moderate to severe Childhood Health Assessment Questionnaire disability and 3.6% were in Steinbrocker class III–IV. Approximately 10% had major impairment in HRQOL. A total of 34.2% had damage in ≥1 joint or joint group and 26.1% showed extraarticular damage. Of the 125 patients who underwent a wrist radiograph, 35.2% had significant structural damage and 8.7% had growth retardation. Conclusion Our patients had on average a low level of disease activity, little or no physical disability, and a satisfactory HRQOL. However, a sizable proportion of patients had persistently active disease, impaired function, and damage. These findings underscore the critical need for treatments and treatment strategies that have the ability to better control disease activity and to reduce the development of disease-related morbidities.

Objective To develop adapted versions of the Sharp/van der Heijde radiographic scoring system for use in juvenile idiopathic arthritis (JIA), and to investigate their validity in JIA patients with polyarticular disease. Methods The study group comprised 177 patients with polyarticular JIA. Radiographs of the wrist/hand of each patient were obtained at baseline (first observation) and then at 1, 3, 5, 7/8, and 10 years and were assessed independently by 2 pediatric rheumatologists according to different adaptations of the Sharp/van der Heijde method. To facilitate score assignment, the radiograph for each patient was compared with a bone age–related standard. Validation procedures included analysis of reliability, construct validity, and score progression over time. Results Interobserver and intraobserver agreement on longitudinal score values and score changes was good for all of the adapted scoring versions (intraclass correlation coefficient >0.85). Score changes over time were moderately to strongly correlated with the clinical indicators of long-term joint damage and with the amount of long-term radiographic damage as measured with the carpo:metacarpal ratio, thereby demonstrating good construct validity. A steady increase in scores over time was observed, with joint space narrowing being the most common form of damage throughout the disease course. The inclusion of 5 new areas appeared to increase the overall construct validity of erosion scores. Conclusion Our results show that the adapted versions of the Sharp/van der Heijde score are reliable and valid for the assessment of radiographic progression in patients with JIA.

Background T H 2 cytokines are not responsible for the ongoing symptoms and pathology in children with severe therapy-resistant asthma (STRA). IL-33 induces airway hyperresponsiveness, but its role in airway remodeling and steroid resistance is unknown. Objective We sought to investigate the relationship between IL-33 and airway remodeling in pediatric patients with STRA. Methods IL-33 levels were quantified in neonatal mice given inhaled house dust mite (HDM), and the effect of blocking IL-13 on remodeling and IL-33 levels was assessed. HDM-induced allergic airways disease (AAD) in neonatal ST2 −/− mice lacking the IL-33 receptor was assessed, together with collagen production after IL-33 administration. The effect of steroid therapy on IL-33 levels in patients with neonatal AAD was explored. IL-33 expression was quantified in endobronchial biopsy (EB) specimens from children with STRA and related to remodeling, and collagen production by airway fibroblasts from pediatric patients stimulated with IL-33 and budesonide was quantified. Results Blocking IL-13 after AAD was established in neonatal mice and did not reduce remodeling or IL-33 levels; airway hyperresponsiveness was only partially reduced. IL-33 promoted collagen synthesis both from asthmatic fibroblasts from pediatric patients and after intranasal administration in mice. Increased cellular expression of IL-33, but not IL-13, was associated with increased reticular basement membrane thickness in EB specimens from children with STRA, whereas remodeling was absent in HDM-exposed ST2 −/− mice. IL-33 levels were maintained, whereas IL-13 levels were abrogated by steroid treatment in neonatal HDM-exposed mice and in EB specimens from children with STRA. Conclusion IL-33 is a relatively steroid-resistant mediator that promotes airway remodeling in patients with STRA and is an important therapeutic target.

Background Increased airway smooth muscle (ASM) is a feature of established asthma in schoolchildren, but nothing is known about ASM in preschool wheezers. Objective We sought to determine endobronchial biopsy specimen ASM area fraction in preschool wheezers and its association with asthma at school age. Methods ASM area, reticular basement membrane thickness, and mucosal eosinophil and ASM mast cell values were quantified in endobronchial biopsy specimens previously obtained from preschool children undergoing clinically indicated bronchoscopy: severe recurrent wheezers (n = 47; median age, 26 months) and nonwheezing control subjects (n = 21; median age, 15 months). Children were followed up, and asthma status was established at age 6 to 11 years. Preschool airway pathology was examined in relation to asthma at school age. Results Forty-two (62%) of 68 children had 1 or more evaluable biopsy specimens for ASM. At school age, 51 of 68 children were followed up, and 15 (40%) of 37 preschool wheezers had asthma. Children who had asthma and an evaluable biopsy specimen had increased preschool ASM area fraction (n = 8; median age, 8.2 years [range, 6-10.4 years]; median ASM, 0.12 [range, 0.08-0.16]) compared with that seen in children without asthma (n = 24; median age, 7.3 years [range, 5.9-11 years]; median ASM, 0.07 [range, 0.02-0.23]; P = .007). However, preschool reticular basement membrane thickness and mucosal eosinophil or ASM mast cell values were not different between those who did or did not have asthma at school age. Conclusion Increased preschool ASM is associated with those children who have asthma at school age. Thus a focus on early changes in ASM might be important in understanding the subsequent development of childhood asthma.

Background Defining atopy in children with severe therapy resistant asthma is complex. There is currently no gold standard test; skin prick testing (SPT) and allergen specific immunoglobulin E (sIgE) are both used. Atopy is increasingly considered to be a spectrum, not an all-or-none phenomenon (Allergy 2007; 62 :1379–86). Hypothesis SPTs and sIgE cannot be used interchangeably, and that if both tests are not performed opportunities for intervention will be missed. Furthermore, severity of atopy will be defined differently by the two tests. Total IgE and fractional exhaled nitric oxide (FeNO 50 ) may also help quantify atopy. Methods Cross-sectional study of 47 children with severe therapy resistant asthma, mean age 11.8 years (range 5.3–16.6 years) who underwent measurement of a standard panel (house dust mite (HDM), dog, cat, weed pollens and grass pollens) of SPTs and sIgEs, total IgE and FeNO 50 as part of their clinical work up. Results Overall 42/47 (89%) were atopic (defined as either a single positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/201 (19.8%) the SPT and sIgE results were discordant (Abstract P73 Figure 1), most commonly, 25/201 (12.4%) the SPT was negative and the sIgE was positive. HDM and cat sensitisation were more likely detected by sIgE, but dog by SPT. When atopy was quantified the sum of sIgEs compared with the sum of SPT wheal diameter showed only moderate correlation (r=0.66, p= 50 and total IgE (r=0.34, p=0.02), but no difference in FeNO 50 when patients were defined as atopic on either SPT or sIgE, and no relationship with increasing numbers of positive SPTs or sIgEs. Conclusions SPT and sIgE identify the group prevalence of atopy equally well; however for some allergens, concordance is poor, and when used to quantify atopy SPT and sIgE show only moderate correlation. If allergen avoidance is contemplated in children with severe therapy resistant asthma, then both tests should be performed in order to detect sensitisation.