Exogenous lipoid pneumonia in children: A systematic review.

OBJECTIVES: To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP). DESIGN: Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases. RESULTS: Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently. CONCLUSION: Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.

Early onset children's interstitial lung diseases: Discrete entities or manifestations of pulmonary dysmaturity?

Interstitial lung diseases in children (chILD) are rare and diverse. The current classifications include a group of early onset chILD specific to infancy, namely neuro-endocrine cell hyperplasia of infancy (NEHI), pulmonary interstitial glycogenosis (PIG) and the alveolar capillary-congenital acinar dysplasia (ACD-CAD) spectrum, as well as alveolar growth disorders. NEHI and PIG cells are seen in the normal developing foetal lung. We hypothesise that these conditions are in fact overlapping manifestations of pulmonary dysmaturity, respectively of airway, mesenchymal and vascular elements, rather than discrete clinical conditions in their own right. Clinically, these present as respiratory distress in early life. Mild cases rightly never undergo lung biopsy, and for these the clinical description 'persistent tachypnoea of infancy' has been proposed. In terms of pathology, we reviewed current literature, which showed that NEHI cells decline with age, and are not specific to NEHI, which we confirmed by unpublished re-analysis of a second dataset. Furthermore, specific genetic disorders which affect pulmonary maturation lead to a histological picture indistinguishable from NEHI. PIG and ACD-CAD are also associated with pulmonary growth disorders, and manifestations of PIG and NEHI may be present in the same child. We conclude that, contrary to current classifications, NEHI, PIG, and ACD-CAD should be considered as overlapping manifestations of pulmonary dysmaturation, frequently associated with disorders of alveolar growth, rather than as separate conditions. Identification of one of these patterns should be the start, not the end of the diagnostic journey, and underlying in particular genetic causes should be sought.

Persistent Tachypnea of Infancy. Usual and Aberrant.

RATIONALE: Persistent tachypnea of infancy (PTI) is a specific clinical entity of undefined etiology comprising the two diseases neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis. The outcome of typical NEHI is favorable. The outcome may be different for patients without a typical NEHI presentation, and thus a lung biopsy to differentiate the diseases is indicated. OBJECTIVES: To determine whether infants with the characteristic clinical presentation and computed tomographic (CT) imaging of NEHI (referred to as "usual PTI") have long-term outcome and biopsy findings similar to those of infants with an aberrant presentation and/or with additional localized minor CT findings (referred to as "aberrant PTI"). METHODS: In a retrospective cohort study, 89 infants with PTI were diagnosed on the basis of clinical symptoms and, if available, CT scans and lung biopsies. Long-term outcome in childhood was measured on the basis of current status. MEASUREMENTS AND MAIN RESULTS: Infants with usual PTI had the same respiratory and overall outcomes during follow-up of up to 12 years (mean, 3.8 yr) as infants who had some additional localized minor findings (aberrant PTI) visualized on CT images. Both usual and aberrant PTI had a relatively favorable prognosis, with 50% of the subjects fully recovered by age 2.6 years. None of the infants died during the study period. This was independent of the presence or absence of histological examination. CONCLUSIONS: PTI can be diagnosed on the basis of typical history taking, clinical findings, and a high-quality CT scan. Further diagnostic measures, including lung biopsies, may be limited to rare, complicated cases, reducing the need for an invasive and potentially harmful procedure.

Pulmonary function in children with persistent tachypnea of infancy.

BACKGROUND: Data on the prevalence and type of lung function impairment in preschool and school-aged children previously diagnosed with persistent tachypnea of infancy (PTI) are scarce. Therefore, this study aims to assess pulmonary function in this age group. METHODS: Children diagnosed with PTI over 3 years old were admitted for follow-up visits and healthy controls were enrolled. The study group included children who were able to complete pulmonary function tests (PFTs). Medical history, physical examination, and pulmonary function (spirometry, body plethysmography, impulse oscillometry, nitrogen multiple breath washout test, diffusing capacity for carbon monoxide [DLCO ]) were assessed. RESULTS: Thirty-seven children (26 boys, 11 girls; median age: 5.6 years) diagnosed with PTI and 37 healthy controls were recruited. Forced expiratory volume in 1 s and forced vital capacity were significantly lower (-1.12 vs. 0.48, p = 0.002 and -0.83 vs. 0.31, p = 0.009, respectively); respiratory resistance at 5 Hz (0.06 vs. -0.62, p = 0.003), resonant frequency (1.86 vs. 1.36, p = 0.04), residual volume (RV) (2.34 vs. -1.2, p < 0.0001), RV%TLC (total lung capacity) (2.63 vs. -0.72, p < 0.0001), and specific airway resistance (5.4 vs. 2.59, p = 0.04) were significantly higher in PTI patients as compared with controls (data were presented as median z-score). Air trapping was found in 60.0%, and abnormally high lung clearance index and DLCO  were found in 73.3% and 90.9% of PTI patients, respectively. CONCLUSIONS: This study demonstrated that lung function is affected in most children with PTI. PFTs showed that peripheral airways are the major zone of functional impairment.

Diffuse alveolar hemorrhage in children with interstitial lung disease: Determine etiologies!

OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in children is a rare condition resulting from different underlying diseases. This study aimed at describing characteristics and diagnostic measures in children with ILD (children's interstitial lung disease, chILD) and DAH to improve the diagnostic approach by increasing clinician's awareness of diagnostic shortcomings. PATIENTS AND METHODS: A retrospective data analysis of patients with ILD and DAH treated in our own or collaborating centers between 01/07/1997 and 31/12/2020 was performed. Data on clinical courses and diagnostic measures were systematically retrieved as case-vignettes and investigated. To assess suitability of diagnostic software-algorithms, the Human Phenotype Ontology (HPO) was revised and expanded to optimize conditions of its associated tool the "Phenomizer." RESULTS: For 97 (74%) of 131 patients, etiology of pulmonary hemorrhage was clarified. For 34 patients (26%), no underlying condition was found (termed as idiopathic pulmonary hemorrhage, IPH). Based on laboratory findings or clinical phenotype/comorbidities, 20 of these patients were assigned to descriptive clusters: IPH associated with autoimmune features (9), eosinophilia (5), renal disease (3) or multiorgan involvement (3). For 14 patients, no further differentiation was possible. CONCLUSION: Complete and sometimes repeated diagnostics are essential for establishing the correct diagnosis in children with DAH. We suggest assignment of patients with IPH to descriptive clusters, which may also guide further research. Digital tools such as the Phenomizer/HPO are promising, but need to be extended to increase diagnostic accuracy.

COVID-19 in patients with persistent tachypnea of infancy.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised substantial concern for patients with chronic lung diseases. The aim of this study was to evaluate the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) in children with persistent tachypnea of infancy (PTI). METHODS: Data on the history of COVID-19, including diagnosis and clinical course of the infection, were collected during the regular follow-up visits of children previously diagnosed with PTI. The diagnosis of COVID-19 was based on laboratory criteria recommended by the European Centre for Disease Prevention and Control. RESULTS: Between January 1, 2021, and February 28, 2022, 62 patients with PTI (median age 3.7 years; 42 boys, 20 girls) were evaluated. COVID-19 was diagnosed in 38 patients (61.3%). Sixteen patients (42.1%) were asymptomatic, and 22 (57.9%) were symptomatic. The most common symptoms were rhinorrhea or nasal congestion, cough, and sore throat. Sixteen patients (42.1%) were classified as having a mild course of COVID-19, three children (7.9%) as moderate, and three children (7.9%) as severe. Follow-up performed after a median of 6 months (range 3-12 months) revealed that, after COVID-19, nearly all PTI patients returned to their prior status (32/38, 84.2%); 4 children (10.5%) suffered from exacerbating symptoms of PTI for 1 month. Two children (5.3%) became asymptomatic after COVID-19. CONCLUSION: The course of SARS-CoV-2 infection in children with PTI is usually mild, and the risk of hospitalization is low. The course of PTI did not change after COVID-19 in most children, and only a few patients experienced an exacerbation.

A rare presentation of childhood interstitial lung disease attributed to KDM3B gene mutation: a case report.

Childhood Interstitial Lung Disease (chILD) encompasses various respiratory conditions affecting children's lung airspaces and tissues, with diverse causes. One rare cause involves structural vascular changes. We describe a case of a 10-year-old boy diagnosed with chILD who exhibited specific dysmorphic features, developmental delay, and intellectual disability. He was diagnosed with severe pulmonary arterial hypertension (PAH) due to venous thromboembolic disease, an unusual underlying condition for chILD. A Whole Exome Sequence showed mutations in KDM3B and SIN3A genes, respectively responsible for Diets-Jongmans syndrome (DIJOS) and Witteveen-Kolk syndrome (WITKOS). Both syndromes can explain our patient´s phenotype and KDM3B mutation has been previously described to be associated with PAH. Our case suggests a potential association between KDM3B mutation and PAH leading to chILD. It also enriches the knowledge of genotypic diversity in KDM3B and SIN3A genes as well as the spectrum of clinical associations with DIJOS and WITKOS syndromes.

Learning to make a difference for chILD: Value creation through network collaboration and team science.

Addressing the recognized challenges and inequalities in providing high quality healthcare for rare diseases such as children's interstitial lung disease (chILD) requires collaboration across institutional, geographical, discipline, and system boundaries. The Children's Interstitial Lung Disease Respiratory Network of Australia and New Zealand (chILDRANZ) is an example of a clinical network that brings together multidisciplinary health professionals for collaboration, peer learning, and advocacy with the goal of improving the diagnosis and management of this group of rare and ultra-rare conditions. This narrative review explores the multifaceted benefits arising from social learning spaces within rare disease clinical networks by applying the value creation framework. The operation of the chILDRANZ network is used as an example across the framework to highlight how value is generated, realized, and transferred within such collaborative clinical and research networks. The community of practice formed in the chILDRANZ multidisciplinary meetings provides a strong example of social learning that engages with the uncertainty inherent in rare disease diagnosis and management and pays attention to generate new knowledge and best practice to make a difference for children and families living with chILD. This review underscores international calls for further investment in, and support of, collaborative clinical networks and virtual centers of excellence for rare disease.

Building a pediatric rare lung disease program: It takes a community of villages.

Pediatric rare lung disease programs are increasing in number due to an increase in recognition of the diseases, increased clinical and research interest in children's interstitial lung disease, and the expansion of the children's interstitial lung disease research network. Due to this increased interest newly graduated trainees in pediatric pulmonology and other physicians are often starting new programs, which can be daunting. We provide some guidance for new programs based on our experiences.

Heterogenous Disease Course and Long-Term Outcome of Children's Interstitial Lung Disease Related to Filamin A Gene Variants.

Rationale: Variable disease course and outcomes have been reported in children's interstitial lung disease associated with FLNA (Filamin A gene) variants. Objectives: To further delineate long-term respiratory outcomes and identify potential contributing factors to severe disease course. Methods: We retrospectively collected longitudinal data from three centers on nine cases (one male) with FLNA variants and early respiratory disease onset (within the first 24 mo of life). Clinical, radiographic, and histopathologic data were analyzed, focusing on cardiorespiratory disease course. Results: All required early respiratory support (three invasive ventilation, three noninvasive ventilation, three supplemental oxygen), and all experienced frequent severe infective respiratory exacerbations. Three died in infancy from refractory respiratory failure and pulmonary hypertension (PH). The six surviving individuals were 3, 10, 11, 15, 18, and 33 years old at time of reporting. The extent of functional respiratory impairment decreased with age; at last follow-up, there were no individuals on home invasive ventilation, one on nocturnal noninvasive ventilation, four on oxygen, and one on no respiratory support. Spirometry consistently demonstrated moderate to severe obstructive defects (forced expiratory volume in 1 s/forced vital capacity [FVC] z-score, -3.76 to -1.77; percent predicted FVC, 31.5% to 92.1%). Seven required PH treatment in early childhood (7/9), and three of the survivors (3/6) still receive treatment. Radiologic and histopathologic findings were consistent among cases. Conclusions: Early mortality was common, but many survivors stabilized even after severe symptoms in infancy. All survivors had persistent obstructive defects on spirometry, and half have persistent or recurrent PH. These typical findings are suggestive of this rare diagnosis and should prompt consideration of genetic testing.

Clinical radiological and pathological staging of children with hypersensitivity pneumonitis.

OBJECTIVE: Hypersensitivity pneumonitis (HP) is rare in the pediatric population. To date, there are no studies defining a correlation between clinical, radiological, and pathological findings in children with HP. The objective of this study is to define the clinical, and radiological characteristics and prognosis of childhood HP and to examine the clinical, radiological, and pathological correlation between HP stages. METHODS: Patients with suspected HP and followed at two tertiary care hospitals between 2000 and 2020 were retrospectively evaluated. Computed tomography (CT) of the chest of patients was evaluated by a single radiologist. The interagreement between clinical and radiological severity of the patients was calculated with the κ test. RESULTS: Fourteen children with suspected HP were identified. The results of 10 patients with the definitive diagnosis were as follows: one patient (10%) had acute, five patients (50%) had subacute, and four patients (40%) had chronic HP. The most prominent findings in chest CT were hilar, or hilar and subcarinal lymphadenopathy (80%), centrilobular nodules (60%), patchy or diffuse ground-glass opacities (50%), and cysts (50%). The interagreement between clinical and radiological severity of the patients was 100% (approximate significance: 0.003). The diagnosis of four patients with suspected HP who were unresponsive to standardized medical treatments or developed multisystem involvement was diagnosed with other diseases. One patient (10%) with definitive chronic HP died due to respiratory failure during follow up. CONCLUSION: Similar to adult HP, the prognosis is worse in children with existing fibrotic equivalents in chest CT. Patients who are not responding to standard medical treatments or develop multisystem involvement should be evaluated for other lung diseases.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pulmonary alveolar proteinosis due to heterozygous mutation in OAS1: Whole lung lavages for long-term bridging to hematopoietic stem cell transplantation.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is defined by increased accumulation of surfactant in the alveolar space. PAP has been reported to be associated with a large number of clinical conditions and diseases. Whole lung lavages (WLLs) can be helpful to stabilize the clinical course of PAP until the underlying condition is identified, which may enable more specific treatment. Recently, heterozygous OAS1 gain-of-function variants were described as cause in patients with infantile-onset PAP combined with hypogammaglobulinemia. CASE PRESENTATION: At age 4 months, a female infant born to term was diagnosed with hypogammaglobulinemia and treated with monthly immunoglobulin injections. At age 15 months, the girl needed supplemental oxygen at night, and at age 18 months, also during the day. At age 2 years, PAP of unknown etiology was diagnosed by computed tomography scan and open lung biopsy. Subsequently, monthly WLLs were started, which stabilized the clinical course for over 2 years until a disease-causing OAS1 variant was diagnosed and the patient was successfully treated by hematopoietic stem cell transplantation (HSCT). CONCLUSION: Here, we describe the successful management of a female patient with severe PAP caused by a heterozygous OAS1 gain-of-function variant until a definitive diagnosis was made and cured by HSCT.

Etiologic Classification of Diffuse Parenchymal (Interstitial) Lung Diseases.

Interstitial lung diseases (ILD) or diffuse parenchymal lung diseases (DPLD) comprise a large number of disorders. Disease definition and classification allow advanced and personalized judgements on clinical disease, risks for genetic or environmental transmissions, and precision medicine treatments. Registers collect specific rare entities and use ontologies for a precise description of complex phenotypes. Here we present a brief history of ILD classification systems from adult and pediatric pneumology. We center on an etiologic classification, with four main categories: lung-only (native parenchymal) disorders, systemic disease-related disorders, exposure-related disorders, and vascular disorders. Splitting diseases into molecularly defined entities is key for precision medicine and the identification of novel entities. Lumping diseases targeted by similar diagnostic or therapeutic principles is key for clinical practice and register work, as our experience with the European children's ILD register (chILD-EU) demonstrates. The etiologic classification favored combines pediatric and adult lung diseases in a single system and considers genomics and other -omics as central steps towards the solution of "idiopathic" lung diseases. Future tasks focus on a systems' medicine approach integrating all data and bringing precision medicine closer to the patients.

Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience.

OBJECTIVE: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old). METHODS: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months. RESULTS: Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups. CONCLUSIONS: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.

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

BACKGROUND: Children'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. METHODS: Multicentre 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. RESULTS: A 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). CONCLUSIONS: We 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 improved clinical course of persistent tachypnea of infancy with inhaled bronchodilators and corticosteroids.

BACKGROUND: Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS: Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS: Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p < 0.001), chest retractions (43.8% of patients, p = 0.04), and crackles (29.2% of patients, p = 0.02). Also, a significant improvement in forced expiratory volume in 1 s (FEV1 ) (median z score: -2.21 vs. -0.47, p = 0.03), residual volume (RV) (median z score 5.28 vs. 1.07, p = 0.007), RV% total lung capacity (TLC) (median z score: 6.05 vs. 1.48, p = 0.01), sRaw (median z score: 6.6 vs. 4.64, p = 0.01), R5 (median z score: 1.27 vs. 0.31, p = 0.009), and R5-R20 (median: 0.58 vs. 0.26 kPa/(l/s), p = 0.002) was demonstrated. CONCLUSIONS: Inhaled bronchodilators and ICS may exert a positive effect on the severity of symptoms and pulmonary function test (PFT) in symptomatic children with PTI. However, a randomized control trial should be conducted to confirm their effectiveness.

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

INTRODUCTION: 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. OBJECTIVE: To describe the clinical course, infant pulmonary function tests and computed tomography (CT) findings in a cohort of patients with NEHI in Argentina. METHODS: This is a observational multicenter cohort study of children diagnosed with NEHI between 2011 and 2020. RESULTS: 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. CONCLUSION: 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.

Children's Interstitial and Diffuse Lung Diseases (ChILD) in 2020.

The term children interstitial lung diseases (chILD) refers to a heterogeneous group of rare diseases that diffusely affect the lung. ChILD specific to children younger than 2 years of age include diffuse developmental disorders, growth abnormalities, specific conditions of undefined etiology (neuroendocrine cell hyperplasia of infancy and pulmonary interstitial glycogenosis) and surfactant protein disorders. Clinical manifestations are highly variable, ranging from the absence of relevant symptoms to a severe onset. Most commonly, chILD presents with nonspecific respiratory signs and symptoms, such as dyspnea, polypnea, dry cough, wheezing, recurrent respiratory infections and exercise intolerance. In the diagnostic approach to a child with suspected ILD, chest high resolution computed tomography and genetic tests play a central role. Then, if the diagnosis remains uncertain, laryngotracheal-bronchoscopy and lung biopsy are needed. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs including corticosteroids, hydroxychloroquine and azithromycin. Despite chILD overall rarity, pediatric pulmonologists must be familiar with these diseases in order to carry out a timely diagnosis and patient treatment.

Persistent tachypnea of infancy: Follow up at school age.

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.