Interstitial lung disease in children (chILD) is rare, and most centres will only see a few cases/year. There are numerous possible underlying diagnoses, with specific and non-specific treatment possibilities. The chILD-EU collaboration has brought together centres from across Europe to advance understanding of these considerations, and as part of this process, has created standard operating procedures and protocols for the investigation of chILD. Where established consensus documents exist already, for example, for the performance of bronchoalveolar lavage and processing of lung biopsies, these have been adopted. This manuscript reports our proposals for a staged investigation of chILD, starting from when the condition is suspected to defining the diagnosis, using pathways dependent on the clinical condition and the degree of illness of the child. These include the performance of genetic testing, echocardiography, high-resolution CT, bronchoscopy when appropriate and the definitive investigation of lung biopsy, in order to establish a precise diagnosis. Since no randomised controlled trials of treatment have ever been performed, we also report a Delphi consensus process to try to harmonise treatment protocols such as the use of intravenous and oral corticosteroids, and add-on therapies such as hydroxychloroquine and azithromycin. The aim is not to dictate to clinicians when a therapeutic trial should be performed, but to offer the possibility to collaborators of having a unified approach when a decision to treat has been made

Inflammatory mediators in the exhaled breath are receiving growing medical interest as noninvasive disease markers. Volatile organic compounds have been investigated in this context, but clinical information and methodological standards are limited.The levels of ethane, propane, n-pentane, methanol, ethanol, 2-propanol, acetone, isoprene, benzene, toluene, dimethyl sulphide (DMS) and limonene were measured in repeated breath samples from 20 cystic fibrosis patients and 20 healthy controls (aged 8-29 yrs). Three endexhaled and one ambient air sample were collected per person and analysed on a customised gas chromatography system. Intra-subject coefficients of variation ranged between 9 and 34%, and hydrocarbon breath levels were influenced by their inspired concentrations. The alveolar gradient for pentane was higher in cystic fibrosis patients than in healthy controls (0.36 versus 0.21 ppb) and inversely proportional to forced expiratory volume in one second; highest values were observed in patients with pulmonary exacerbations (0.73 versus 0.24 ppb). Cystic fibrosis patients also exhibited a lower output of DMS (3.9 versus 7.6 ppb). Group differences were not significant for ethane and the remaining substances.It was concluded that chemical breath analysis for volatile organic compounds is feasible and may hold potential for the noninvasive diagnosis and follow-up of inflammatory processes in cystic fibrosis lung disease.

Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.

background children's interstitial lung diseases (chilD) cover many rare entities, frequently not diagnosed or studied in detail. there is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register. Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chilD cases. Methods a web-based chilD management platform with a registry and biobank was successfully designed and implemented. results Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chilD. in 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, london 12%, Hannover 31%, ankara 1% and Paris 5%). in 13%, the diagnosis reached by the referring team was not confirmed by peer review. among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%). the ability of nine expert clinicians to subcategorise the final diagnosis into the chilD-eU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the 'wrong' answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation. Conclusions We have shown that chilD-eU has generated a platform to help the clinical assessment of chilD. Trial registration number results, nct02852928.

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. AbstractRationale: 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.

BackgroundAim of this study was to verify a systematic and practical categorization system that allows dynamic classification of pediatric DPLD irrespective of completeness of patient data.MethodsThe study was based on 2322 children submitted to the kids-lung-register between 1997 and 2012. Of these children 791 were assigned to 12 DPLD categories, more than 2/3 belonged to categories manifesting primarily in infancy. The work-flow of the pediatric DPLD categorization system included (i) the generation of a final working diagnosis, decision on the presence or absence of (ii) DPLD and (iii) a systemic or lung only condition, and (iv) the allocation to a category and subcategory. The validity and inter-observer dependency of this workflow was re-tested using a systematic sample of 100 cases.ResultsTwo blinded raters allocated more than 80 % of the re-categorized cases identically. Non-identical allocation was due to lack of appreciation of all available details, insufficient knowledge of the classification rules by the raters, incomplete patient data, and shortcomings of the classification system itself.ConclusionsThis study provides a suitable workflow and hand-on rules for the categorization of pediatric DPLD. Potential pitfalls were identified and a foundation was laid for the development of consensus-based, international categorization guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0339-1) contains supplementary material, which is available to authorized users.

BackgroundHermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce.MethodsSix children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded.ResultsPulmonary symptoms including dyspnea, coughing, need for oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean age of 8.83 years (range 2-15). All children had recurrent pulmonary infections, 3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of pulmonary complaints increased over time. The leading radiographic pattern was ground-glass opacities with a rapid increase in reticular pattern and traction bronchiectasis between initial and follow-up Computer tomography (CT) in all subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the patients received a lung biopsy for diagnosis; histological patterns were cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like, and desquamative interstitial pneumonia.ConclusionsHPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0780-z) contains supplementary material, which is available to authorized users.

In healthy full-term infants, propranolol (2 mg/kg/day divided in three doses) is well tolerated. No clinically significant hypotension was observed. We conclude that for otherwise healthy infants, BP monitoring during long-term propranolol therapy for CIHs is not necessary.