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Abstract Background There is growing recognition and understanding of the entities that cause interstitial lung disease (ILD) in infants. These entities are distinct from those that cause ILD in older children and adults. Methods A multidisciplinary panel was convened to develop evidence-based guidelines on the classification, diagnosis, and management of ILD in children, focusing on neonates and infants under 2 years of age. Recommendations were formulated using a systematic approach. Outcomes considered important included the accuracy of the diagnostic evaluation, complications of delayed or incorrect diagnosis, psychosocial complications affecting the patient’s or family’s quality of life, and death. Results No controlled clinical trials were identified. Therefore, observational evidence and clinical experience informed judgments. These guidelines: (1) describe the clinical characteristics of neonates and infants (<2 yr of age) with diffuse lung disease (DLD); (2) list the common causes of DLD that should be eliminated during the evaluation of neonates and infants with DLD; (3) recommend methods for further clinical investigation of the remaining infants, who are regarded as having “childhood ILD syndrome”; (4) describe a new pathologic classification scheme of DLD in infants; (5) outline supportive and continuing care; and (6) suggest areas for future research. Conclusions After common causes of DLD are excluded, neonates and infants with childhood ILD syndrome should be evaluated by a knowledgeable subspecialist. The evaluation may include echocardiography, controlled ventilation high-resolution computed tomography, infant pulmonary function testing, bronchoscopy with bronchoalveolar lavage, genetic testing, and/or lung biopsy. Preventive care, family education, and support are essential.

Culture of bronchoalveolar lavage fluid (BALF) is the gold standard for detection of pathogens in the lower airways in cystic fibrosis (CF). However, current culture results do not explain all clinical observations in CF, including negative culture results during pulmonary exacerbation and inflammation in the absence of pathogens. We hypothesize that organisms not routinely identified by culture occur in the CF airway and may contribute to disease. To test this hypothesis we used a culture-independent molecular approach, based on use of rRNA sequence analysis, to assess the bacterial composition of BALF from children with CF and disease controls (DC). Specimens from 42 subjects (28 CF) were examined, and [almost equal to]6,600 total clones were screened to identify 121 species of bacteria. In general, a single rRNA type dominated clone libraries from CF specimens, but not DC. Thirteen CF subjects contained bacteria that are not routinely assessed by culture. In four CF subjects, candidate pathogens were identified and include the anaerobe Prevotella denticola, a Lysobacter sp., and members of the RICKETTSIALES: The presumptive pathogens Tropheryma whipplei and Granulicatella elegans were identified in cases from the DC group. The presence of unexpected bacteria in CF may explain inflammation without documented pathogens and consequent failure to respond to standard treatment. These results show that molecular techniques provide a broader perspective on airway bacteria than do routine clinical cultures and thus can identify targets for further clinical evaluation.

Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age. This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed. Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality. A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients. In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

Home oxygen therapy is often required in children with chronic respiratory conditions. This document provides an evidence-based clinical practice guideline on the implementation, monitoring, and discontinuation of home oxygen therapy for the pediatric population. A multidisciplinary panel identified pertinent questions regarding home oxygen therapy in children, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the quality of evidence and strength of clinical recommendations. After considering the panel's confidence in the estimated effects, the balance of desirable (benefits) and undesirable (harms and burdens) consequences of treatment, patient values and preferences, cost, and feasibility, recommendations were developed for or against home oxygen therapy specific to pediatric lung and pulmonary vascular diseases. Although home oxygen therapy is commonly required in the care of children, there is a striking lack of empirical evidence regarding implementation, monitoring, and discontinuation of supplemental oxygen therapy. The panel formulated and provided the rationale for clinical recommendations for home oxygen therapy based on scant empirical evidence, expert opinion, and clinical experience to aid clinicians in the management of these complex pediatric patients and identified important areas for future research.

BackgroundChildhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available.Methods and resultsThis review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered.ConclusionsThere is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.

The Earable device is a behind-the-ear wearable originally developed to measure cognitive function. Since Earable measures electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG), it may also have the potential to objectively quantify facial muscle and eye movement activities relevant in the assessment of neuromuscular disorders. As an initial step to developing a digital assessment in neuromuscular disorders, a pilot study was conducted to determine whether the Earable device could be utilized to objectively measure facial muscle and eye movements intended to be representative of Performance Outcome Assessments, (PerfOs) with tasks designed to model clinical PerfOs, referred to as mock-PerfO activities. The specific aims of this study were: To determine whether the Earable raw EMG, EOG, and EEG signals could be processed to extract features describing these waveforms; To determine Earable feature data quality, test re-test reliability, and statistical properties; To determine whether features derived from Earable could be used to determine the difference between various facial muscle and eye movement activities; and, To determine what features and feature types are important for mock-PerfO activity level classification. A total of N = 10 healthy volunteers participated in the study. Each study participant performed 16 mock-PerfOs activities, including talking, chewing, swallowing, eye closure, gazing in different directions, puffing cheeks, chewing an apple, and making various facial expressions. Each activity was repeated four times in the morning and four times at night. A total of 161 summary features were extracted from the EEG, EMG, and EOG bio-sensor data. Feature vectors were used as input to machine learning models to classify the mock-PerfO activities, and model performance was evaluated on a held-out test set. Additionally, a convolutional neural network (CNN) was used to classify low-level representations of the raw bio-sensor data for each task, and model performance was correspondingly evaluated and compared directly to feature classification performance. The model’s prediction accuracy on the Earable device’s classification ability was quantitatively assessed. Study results indicate that Earable can potentially quantify different aspects of facial and eye movements and may be used to differentiate mock-PerfO activities. Specially, Earable was found to differentiate talking, chewing, and swallowing tasks from other tasks with observed F1 scores >0.9. While EMG features contribute to classification accuracy for all tasks, EOG features are important for classifying gaze tasks. Finally, we found that analysis with summary features outperformed a CNN for activity classification. We believe Earable may be used to measure cranial muscle activity relevant for neuromuscular disorder assessment. Classification performance of mock-PerfO activities with summary features enables a strategy for detecting disease-specific signals relative to controls, as well as the monitoring of intra-subject treatment responses. Further testing is needed to evaluate the Earable device in clinical populations and clinical development settings.

Children’s interstitial and diffuse lung disease (chILD) is a term that encompasses a large and diverse group of rare pediatric diseases and disorders. Significant progress has been made over the last 2 decades in classification, clinical care, research, and organizational structure to enhance the care of children with these high-morbidity and -mortality diseases. New diseases have been defined clinically and genetically, classification systems developed and applied, organizations formed such as the chILD Research Network (chILDRN) and chILD Foundation, and basic and translational science expanded to focus on chILD diseases. Multidisciplinary collaborations and efforts to advance understanding and treatment of chILD have been extended worldwide. The future horizon holds great promise to expand scientific discoveries, collaborate more broadly, and bring new treatment to these children. An overview of key historical past developments, major clinical and research updates, and opportunities for the future in chILD is reviewed in this Perspective.