Neuroendocrine Cell Hyperplasia Of Infancy Research Articles

FREnch National Cohort of neuroendocrine cell Hyperplasia of Infancy (FRENCHI): long-term consequences and risk factors of low body mass index.

FREnch National Cohort of neuroendocrine cell Hyperplasia of Infancy (FRENCHI): long-term consequences and risk factors of low body mass index.

The USnational registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort.

Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

Children’s interstitial lung disease: Multidetector computed tomography patterns and correlations between imaging and histopathology

PurposeChildhood interstitial lung disease (chILD) is an umbrella concept covering a wide range of rare lung diseases, many of which are unique to childhood. The diagnosis is based on clinical presentation, multidetector computed tomography (MDCT), genetic testing, lung-function testing, and lung biopsy. Because knowledge of the usefulness of MDCT pattern recognition in ChILD is at present limited, we examined the occurrence of MDCT patterns in children with histologically confirmed interstitial lung disease. MethodWe searched the biopsy, MDCT, and clinical information database of a single national paediatric referral hospital for 2004–2020. Data were from affected children under age 18. MDCT images we reanalysed while blinded to the identity and referral information. ResultsWe included 90 patients, of whom 63 (70 %) were male. The median age at biopsy was 1.3 years (interquartile range 0.1–16.8). Biopsy findings fell into 26 histological classes covering all nine chILD classification categories. We recognized six distinct MDCT patterns: neuroendocrine cell hyperplasia of infancy (23), organizing pneumonia (5), non-specific interstitial pneumonia (4), bronchiolitis obliterans (3), pulmonary alveolar proteinosis (2), and bronchopulmonary dysplasia (n = 2). Of the total 90, in 51 (57 %) children, none of these six MDCT patterns appeared. Of those 39 children with a recognizable MDCT pattern, in 34 (87 %), that pattern predicted their final diagnosis. ConclusionsAmong cases of chILD, we identified a specific predefined MDCT pattern in only 43 %. However, when such a recognizable pattern occurred, it was predictive of the final chILD diagnosis.

РЕЗУЛЬТАТЫ КАТАМНЕСТИЧЕСКОГО НАБЛЮДЕНИЯ И ОСОБЕННОСТИ ТЕЧЕНИЯ COVID-19 У ПАЦИЕНТОВ С НЕЙРОЭНДОКРИННОЙ КЛЕТОЧНОЙ ГИПЕРПЛАЗИЕЙ МЛАДЕНЦЕВ

Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare interstitial lung disease in children. The clinical features of the disease are characterized by tachypnea, moist rales/crepitus, retraction of compliant chest areas and delayed weight gain. The disease is diagnosed using the NEHI clinical scale coupled with the computed tomography of the chest organs. The clinical manifestations of NEHI regress as the child grows, but may persist up to the age of 10 y/o. The purpose of the research was to characterize the course of NEHI including the features of COVID-19 and the impact of passive smoking in children below the age of 8 y/o. Materials and methods: a single-center longitudinal study with follow-up observation of 29 patients with NEHI in January 2012 - December 2022 aged 8 months to 8 years old, 21 of which had COVID-19. Results: 20 of 29 patients with a known follow-up have undergone the long-term oxygen therapy (LTOT) at home lasting from 2 weeks up to 5.5 years (Me 1 year and 2 months; IQR 6 months - 4.5 years). Bronchial asthma was diagnosed in 2. 8 (28%) were diagnosed with atopic dermatitis, 6 (21%) with mental retardation, 3 (10%) with acute urticaria, and 2 (7%) with allergic rhinitis. Gastroesophageal reflux disease (GERD) was diagnosed in 7, all requiring LTOT. The frequency of episodes of respiratory infection was maximum in the first 2 years of life, amounting to 16 episodes per 2 years (Me 7; IQR 4 to 10), and the maximum frequency of hospitalizations during this age period was 5 (Me 2; IQR 1 to 2). Children-passive smokers were diagnosed with malnutrition more often (75%, p=0.449) and required LTOT more often (75%, p=0.694), were more often hospitalized (42%, p=0.422). Despite the possible need for LTOT patients with NEHI had COVID-19 in the form of nasopharyngitis in the majority of cases (89%). Only 8 out of 14 patients had symptoms of NEHI after 5 years of age, and only 1 out of 5 after 7 years. Malnutrition (body mass index for the age<-2) in the first year of life was diagnosed in 13 (45%) children. Malnutrition persisted in 9 out of 24 (37%) by the second year of life, in 5 out of 19 (26%) by the third year, and in 2 out of 14 (14%) by the fourth year of life. Not a single child died. Conclusion: the course of NEHI is characterized by the absence of lethal outcomes, frequent respiratory infections that led to hospitalizations in the first 2 years of life, mild course of COVID-19, regression of clinical symptoms and malnutrition as the child grows, comorbidity with atopic diseases and GERD. The priority should be given to the prevention of passive smoking in children with NEHI.

A 10-month-old infant with respiratory distress and hypoxemia

A 10-month-old infant with Prader-Willi Syndrome presented with a 7 month history of increased work of breathing, wheeze, inspiratory crepitations, and mild hypoxemia. Subsequent investigations including chest CT suggested the diagnosis to be neuroendocrine cell hyperplasia of infancy (NEHI). NEHI is a rare cause of children’s interstitial lung disease. Childhood interstitial lung disease should be considered in an infant with persistent tachypnea, crepitations, and hypoxemia.

Long-term evolution of neuroendocrine cell hyperplasia of infancy: the FRENCHI findings.

Only few studies report long-term evolution of patients with neuroendocrine cell hyperplasia of infancy (NEHI). We report data from a 54-patient cohort followed up in the French network for rare respiratory diseases (RespiRare). Demographic characteristics and respiratory and nutritional evolution were collected at the time of the patient's last scheduled visit. The mean duration of follow-up was 68months (5months to 18years). Fifteen patients (27.8%) were considered clinically cured. During follow-up, hospitalizations for wheezy exacerbations were reported in 35 patients (55%), and asthma diagnosed in 20 (37%). Chest CT scan improvement was noted in 25/44 (56.8%). Spirometry showed a persistent obstructive syndrome in 8/27 (29.6%). A sleep disorder was rare (2/36, 5.5%). Oxygen weaning occurred in 28 of the 45 patients initially treated (62.2%) and was age-dependent (35.7% under 2years, 70.5% between 2 and 6years, and 100% after 7years). Oxygen duration was linked to a biopsy-proven diagnosis (p = 0.02) and to the use of a nutritional support (p = 0.003). Corticosteroids were largely prescribed at diagnosis, with no evident respiratory or nutritional effect during follow-up. Among 23 patients with an initial failure to thrive, 12 (52.2%) had no weight recovery. Initial enteral feeding (17/54, 31.5%) was stopped at a mean age of 43months (3 to 120), with no effect on cure and oxygen liberation at the last visit. Conclusion: Our results show that NEHI has a globally positive, but unequal, improvement over time. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI. What is Known: • Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose long-term outcome is considered positive from very few studies including heterogeneous populations. What is New: • The 68-month follow-up of our 54-patient cohort showed respiratory/nutritional symptom persistence in 72.2%, oxygen requiring in 34%, and asthma in 37%. When controlled, radiological or functional improvement was noted in 56.8 and 40.7%. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI.

Interstitial Lung Disease in Children: "Specific Conditions of Undefined Etiology" Becoming Clearer.

Children's interstitial lung disease (chILD) is a rare group of pediatric lung diseases affecting the lung interstitium diffusely. In this work, we focused our attention on a specific infant group of chILD, also known as "specific conditions of undefined aetiology", including pulmonary interstitial glycogenosis (PIG) and neuroendocrine cell hyperplasia of infancy (NEHI). PubMed was searched to conduct this narrative review. We searched for articles in English using the following keywords: (1) neuroendocrine cell hyperplasia of infancy; (2) NEHI; (3) pulmonary interstitial glycogenosis; (4) PIG; (5) chILD. An increasing interest and insight into these two conditions have been reported. The updated literature suggests that it is possible to look at these disorders as a continuum of diseases, rather than two different entities, since they share a pulmonary dysmaturity. NEHI and PIG are featured by dysmaturity of airway development and consequent respiratory distress. Understanding the underlying pathogenic mechanisms would lead to identifying new targeted therapies to ameliorate the mortality and morbidity of these rare conditions.

КОМПЬЮТЕРНО-ТОМОГРАФИЧЕСКАЯ СЕМИОТИКА НЕЙРОЭНДОКРИННОЙ КЛЕТОЧНОЙ ГИПЕРПЛАЗИИ МЛАДЕНЦЕВ: КЛИНИКО-РЕНТГЕНОЛОГИЧЕСКИЕ СОПОСТАВЛЕНИЯ

The neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease (ILD) of an unknown etiology that manifests itself in children of the first year of life and is characterized by the presence of persistent tachypnea of infancy (PTI) syndrome and nonspecific changes in lung biopsy in the form of hyperplasia of bombesin-positive neuroendocrine cells of the peripheral respiratory tract diagnosed in typical cases based on computed tomography (CT) of the lungs. The purpose of the study was to characterize the CT picture of NEHI in comparison with the severity of the disease. Materials and methods of the study: a multicenter observational cross-sectional study that was maintained January, 2012 March, 2022 portraying 83 patients with NEHI using the NEHI clinical diagnostic scale, ILD severity scale, pulse oximetry, chest CT and echocardiography. Results: CT-semiotics of NEHI is characterized by ground-glass opacification in 97% of cases with predominant localization in the middle lobe of the right lung (89%), upper lobe of the right lung (74%), in the upper lobe of the left lung (72%) and lingual segments (68%) with a prevalence in most cases not exceeding 25% of the total area of the lung fields on sections in the axial projection; parenchymal changes in the form of linear and reticular shading (4%), consolidation (15%), a symptom of “mosaic pneumatization” (35%); and thickening of the walls of the bronchi (28%). Based on the sum of scores on the clinical scale for diagnosing of NEHI, it is impossible to predict the prevalence of CT changes (Rs=0.12, p=0.5), whilst the severity of NEHI does not statistically significantly depend on the ground glass opacification area (Rs=0 .27, p=0.13). Conclusion: The most common CT-identified symptoms of NEHI are the symptoms of ground glass and “mosaic pneumatization” as well as the thickening of the bronchial walls.

French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management

This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs. •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.

Neuroendocrine cell hyperplasia of infancy: Feasibility of objective evaluation with quantitative CT

ObjectiveTo describe quantitative CT parameters of children with a typical pattern for NEHI and compare them to controls. Materials and methodsEleven patients (7 boys) with NEHI and an available chest CT concordant NEHI were identified. Eleven age-, sex-, height-matched, with CT technique-matching were identified for comparison. An open-source software was used to segment the lung parenchyma into lobes using the fissures. Quantitative parameters such as low attenuation areas, mean lung density, kurtosis, skewness, ventilation heterogeneity, lung mass, and volume were calculated for both controls and cases. ResultsAnalysis of the lung parenchyma showed that patients with NEHI had a lower mean lung density (−615 HU vs −556 HU, p = 0.03) with higher ventilation heterogeneity (0.23 vs 0.19, p = 0.04), lung mass (232 g vs 146 g, p = 0.01) and volume (595 mL vs 339 mL, p = 0.008) compared to controls. Most lobes followed this trend, except the middle lobe that showed only a higher lung mass (32.9 g vs 19.6 g, p = 0.02) and volume (77.4 vs 46.9, p = 0.005) in patients with NEHI compared to controls. ConclusionQuantitative CT is a feasible technique in children with a typical pattern for NEHI and is associated with differences in attenuation, ventilation heterogeneity, and lung volume.

КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ ПАЦИЕНТА С НЕЙРОЭНДОКРИННОЙ КЛЕТОЧНОЙ ГИПЕРПЛАЗИЕЙ МЛАДЕНЦЕВ, ПРЕБЫВАЮЩЕГО НА ДЛИТЕЛЬНОЙ ДОМАШНЕЙ КИСЛОРОДОТЕРАПИИ

Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease of unknown etiology that develops in infancy and manifests as persistent tachypnea syndrome. A highly informative scale for the clinical diagnosis of NEHI and CT of the lungs is used to diagnos the disease. The presence of a typical CT picture allows the diagnosis of NEHI to be made. We present a clinical case of a patient diagnosed on the basis of the scale of clinical diagnostics and a typical CT picture of NEHI, complicated by protein-energy insufficiency, chronic respiratory failure of II degree, who is on long-term home oxygen therapy.

Excess neuropeptides in lung signal through endothelial cells to impair gas exchange.

Although increased neuropeptides are often detected in lungs that exhibit respiratory distress, whether they contribute to the condition is unknown. Here, we show in a mouse model of neuroendocrine cell hyperplasia of infancy, a pediatric disease with increased pulmonary neuroendocrine cells (PNECs), excess PNEC-derived neuropeptides are responsible for pulmonary manifestations including hypoxemia. In mouse postnatal lung, prolonged signaling from elevated neuropeptides such as calcitonin gene-related peptide (CGRP) activate receptors enriched on endothelial cells, leading to reduced cellular junction gene expression, increased endothelium permeability, excess lung fluid, and hypoxemia. Excess fluid and hypoxemia were effectively attenuated by either prevention of PNEC formation, inactivation of CGRP gene, endothelium-specific inactivation of CGRP receptor gene, or treatment with CGRP receptor antagonist. Neuropeptides were increased in human lung diseases with excess fluid such as acute respiratory distress syndrome. Our findings suggest that restricting neuropeptide function may limit fluid and improve gas exchange in these conditions.

The elusive pulmonary neuroendocrine cell: How rare diseases may help solving common diseases.

In this issue of Developmental Cell, Xu etal. (2022) describe a transgenic mouse mimicking neuroendocrine cell hyperplasia of infancy, a rare pediatric disease. The mice have excess lung fluid and increased pulmonary neuroendocrine cells with increased endothelium permeability. Acute respiratory distress syndrome is similar, so this rare disease may provide solutions for common diseases.

ШКАЛА КЛИНИЧЕСКОЙ ДИАГНОСТИКИ НЕЙРОЭНДОКРИННОЙ КЛЕТОЧНОЙ ГИПЕРПЛАЗИИ МЛАДЕНЦЕВ: ИНФОРМАТИВНОСТЬ И ДИФФЕРЕНЦИАЛЬНО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ

Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease of unknown etiology that develops in the first year of life and manifests itself as persistent tachypnea syndrome. The aim of the study was to determine the diagnostic value of the clinical scale for the diagnosis of NEHI in comparison with computed tomography (CT) data of the chest organs and for differential diagnosis with acute bronchiolitis (AB)/community-acquired pneumonia (CAP). Materials and methods of research: a multicenter case-control study of children aged 21 days of life to 12 months was carried out: – 83 children with NEHI and 83 infants with AB or CAP. To determine the sensitivity and specificity of this scale for differential diagnosis with AB/CAP, the results of the assessment according to the proposed scale were compared in patients with NEHI (study group) and patients with AB/CAP (control group) on the day of treatment and after 3 weeks. Results: the sensitivity of the clinical scale for the diagnosis of NEHI when compared with the CT data of the chest organs was 85.5%. In the differential diagnosis of NEHI with AB/CAP on the day of treatment, the sensitivity of the clinical scale for the diagnosis of NEHI was 85.5%, the specificity was 80.7%; when re-evaluated after 3 weeks, the accuracy of the scale increased from 83.1% to 91.6%, the specificity – from 80.7% to 97.6%. Diagnosis on a scale after 3 weeks reduced the possibility of overdiagnosis of NEHI from 19.3% to 2.4%. Conclusions: the clinical scale for the diagnosis of NEHI has a high diagnostic value in comparison with the results of CT scan of the chest organs and for differential diagnosis with AB/CAP, especially when re-evaluating.

Congenital interstitial lung diseases: What the anesthesiologist needs to know.

Congenital interstitial lung diseases can affect both adults and children. Pediatric congenital interstitial lung diseases generally carry high risk for morbidly and mortality and include congenital alveolar capillary dysplasia with misalignment of pulmonary veins, congenital alveolar dysplasia, acinar dysplasia, congenital pulmonary lymphangiectasis, diffuse pulmonary lymphangiomatosis, neuroendocrine cell hyperplasia of infancy, pulmonary hemosiderosis, pulmonary alveolar proteinosis, and pulmonary interstitial glycogenosis. Given their usual non-specific clinical presentation, they are frequently misdiagnosed and recognized late, particularly in children who have been apparently healthy for several years (eg, diffuse pulmonary lymphangiomatosis). Some diseases have a very poor prognosis, whereas others have a benign course with appropriate treatment. The current manuscript reviews congenital interstitial lung diseases that typically affect neonates and young children and may be encountered by the pediatric anesthesiologist.

Neuroendocrine cell hyperplasia of infancy diagnosed by imaging techniques

Neuroendocrine cell hyperplasia of infancy diagnosed by imaging techniques

Incidence and Prevalence of Children's Diffuse Lung Disease in Spain

BackgroundChildren's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain. MethodsMulticentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019. ResultsA total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28–10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81–51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2–18 years of age compared with children 0–2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47). ConclusionsWe found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.

The Use of Infant Pulmonary Function Tests in the Diagnosis of Neuroendocrine Cell Hyperplasia of Infancy

Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping. Can indices from iPFTs be used in the diagnosis of NEHI? This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices. We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRCpleth] was 199%predicted; median ratio of residual volume to total lung capacity was 59%predicted) when compared with results in all evaluated groups of infants (P< .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRCpleth had the best discriminatory ability for NEHI diagnosis, with an FRCpleth≥ 150%predicted demonstrating a ROC of 0.91 (95%CI, 0.82-1.00), sensitivity of 86.7%(95%CI, 59.5%-98.3%), and specificity of 95.5%(95%CI, 93.2%-97.3%). Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRCpleth≥ 150%predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings.

Airway basal stem cells generate distinct subpopulations of PNECs.

SUMMARYPulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.

Clinical, functional, and computed tomography findings in a cohort of patients with neuroendocrine cell hyperplasia of infancy.

Neuroendocrine cell hyperplasia of infancy (NEHI) is one of the most common interstitial lung diseases in children. Both the etiology and pathophysiological mechanisms of the disease are still unknown. Prognosis is usually favorable; however, there are significant morbidities during the early years of life. To describe the clinical course, infant pulmonary function tests and computed tomography (CT) findings in a cohort of patients with NEHI in Argentina. This is a observational multicenter cohort study of children diagnosed with NEHI between 2011 and 2020. Twenty patients participated in this study. The median age of onset of symptoms was 3 months and the median age at diagnosis was 6 months. The most common clinical presentation was tachypnea, retractions and hypoxemia. The chest CT findings showed central ground glass opacities and air trapping. Infant pulmonary function tests revealed an obstructive pattern in 75% of the cases (10/12). Most patients (75%) required home oxygen therapy for 17 months (interquartile range 12-25). In 85% of them, tachypnea and hypoxemia spontaneously resolved between the second and third years of life. In this cohort, the first symptoms appeared during the early months of life. The typical clinical, CT, and functional findings allowed the diagnosis without the need of a lung biopsy. Although most patients required home oxygen therapy, they showed a favorable evolution.