Health-related quality scores in childhood interstitial lung disease: Good agreement between patient and caregiver reports.

INTRODUCTION: Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores. METHODS: This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit. RESULTS: No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4). CONCLUSIONS: We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires.

Serum biomarkers in neuroendocrine cell hyperplasia of infancy.

BACKGROUND: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease of unknown origin associated with hyperplasia of pulmonary neuroendocrine cells (PNECs). Diagnosis is based on the characteristic clinical picture and typical radiological imaging, and, in some cases, on lung biopsies. To date, no biochemical indicators of the disease have been identified. AIM: We aimed to determine biomarkers that could be useful in the management of children diagnosed with NEHI. METHODS: Patients with NEHI and healthy children were enrolled. Concentrations of serum biomarkers secreted by PNECs (calcitonin gene-related peptide and gastrin-releasing peptide) and biomarkers of the destruction of alveolar capillary membrane (surfactant proteins A and D [SP-A and SP-D]; glycoprotein Krebs von den Lungen-6 [KL-6]; metalloproteinases 7 and 9 [MMP-7 and MMP-9]; tissue inhibitor of metalloprotease 1) were measured. RESULTS: Fifty-two children with NEHI and 23 healthy children were included in the study. The median age of children with NEHI was 3.9 years. There were no differences in serum levels of biomarkers secreted by PNECs between groups. KL-6 levels were significantly higher in children with NEHI than in healthy ones (median 119.6 vs. 92.1 U/mL, p = 0.003); however, concentrations of KL-6 were low in both groups. No significant differences existed between groups for the remaining biomarkers associated with the destruction of the alveolar-capillary membrane. CONCLUSIONS: Measurement of serum biomarkers released by PNECs and those associated with the destruction of the alveolar-capillary membrane does not appear to be useful in the management of children with NEHI.

Diagnostic workup of childhood interstitial lung disease.

Childhood interstitial lung diseases (chILDs) are rare and heterogeneous diseases with significant morbidity and mortality. An accurate and quick aetiological diagnosis may contribute to better management and personalised treatment. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review summarises the roles of the general paediatrician, paediatric pulmonologists and expert centres in the complex diagnostic workup. Each patient's aetiological chILD diagnosis must be reached without prolonged delays in a stepwise approach from medical history, signs, symptoms, clinical tests and imaging, to advanced genetic analysis and specialised procedures including bronchoalveolar lavage and biopsy, if necessary. Finally, as medical progress is fast, the need to revisit a diagnosis of "undefined chILD" is stressed.

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.

Characteristics of gastroesophageal reflux disease in children with interstitial lung disease.

BACKGROUND: Childhood interstitial lung disease (chILD) is a rare group of respiratory tract disorders. One of the factors suggested to be associated with its etiopathogenesis is microaspiration related to gastroesophageal reflux disease (GERD). The aim of the present study was to determine the frequency and characteristics of GERD in children with chILD, with a particular focus on proximal GER episodes. METHODS: This was a prospective cross-sectional study. Consecutive patients with chILD underwent 24-h multichannel intraluminal pH-impedance monitoring. Different types of gastroesophageal reflux episodes (GER) were recorded and compared with regard to the GERD diagnosis. RESULTS: Sixty-two children (median age of 1.22 years) were included. GERD was diagnosed in 20 (32.3%) of them. The GERD (+) and GERD (-) subgroups differed mainly in their esophageal exposure to acid content (2.9 vs. 1.0%, p = 0.02) and bolus exposure (3.0 vs. 1.4%, p < 0.0001), as well as total number of GER (72.5 vs. 42.0 p = 0.0004), acid GER (35.5 vs. 15.0 p = 0.004), and acid proximal GER (21.0 vs. 12.0 p = 0.02). There were no differences in the number of proximal GER comparing GERD (+) and GERD (-) subgroups. CONCLUSIONS: The frequency of GERD seems to be relatively high in the population of children with chILD used in this study. However, it has not demonstrated an association between proximal GER and GERD diagnosis in chILD, which casts uncertainty over the microaspiration theory proposed to link the two diseases. The latter conclusion, however, needs to be confirmed using more accurate aspiration assessment methods.

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.

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.

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.

ERS International Congress, Madrid, 2019: highlights from the Paediatric Assembly.

In this article, the Group Chairs and the Early Career Members of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting findings in the field of paediatrics presented at the 2019 ERS International Congress, which was held in Madrid, Spain. The main findings from each group are summarised at the end of each chapter.

Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease characterized by microcephaly, growth retardation, severe immunodeficiency, and predisposition to lymphoid malignancy. In this report, we describe a case of a 9-year-old boy, previously diagnosed with NBS and symptoms of dyspnea, dry cough, and fever. Despite initial recognition of pneumonia, there was no response to broad spectrum antimicrobial treatment, negative results from microbiological tests, and unclear changes in lung imaging were observed. Therefore, further diagnostics were focused on suspected lymphoid malignancy and involved lung biopsy. Unexpectedly, histopathological examination revealed noncaseating granulomas. The introduction of systemic steroids resulted in significant improvement of the patient's clinical condition. This is the first description of primary pulmonary noncaseating granulomas without nodular involvement in a child with NBS.

Natural history of Hymenoptera venom allergy in children not treated with immunotherapy.

BACKGROUND: Differences in treatment approach still exist for children after systemic sting reactions. In addition, there are still some doubts about when systemic reactors should be treated with venom immunotherapy (VIT). OBJECTIVE: To determine the rate of sting recurrence and natural history of Hymenoptera venom allergy (HVA) in children not treated with VIT. METHODS: A total of 219 children diagnosed as having HVA who were not treated with VIT were identified in 3 pediatric allergology centers. Survey by telephone or mail with the use of a standardized questionnaire was conducted. The number of field re-stings, subsequent symptoms, and provided treatment were analyzed. RESULTS: A total of 130 of the 219 patients responded to the survey, for a response rate of 59.4%. During the median follow-up period of 72 months (interquartile range, 52-85 months), 44 children (77% boys) were stung 62 times. Normal reactions were most common, occurring in 27 patients (62%). Severe systemic reactions (SSRs) occurred in 8 (18%) of those who were re-stung. The subsequent reaction was significantly milder (P < 0.001), especially in the case of patients re-stung by the same insect (P < .001). None of the children with prediagnostic large local reactions and negative test results for venom specific IgE developed SSRs after re-sting by the culprit insect (P = .03). In children with SSRs, median time from diagnosis to re-sting was 2 times longer than that in those with large local reactions and normal reactions (P = .007). CONCLUSIONS: Most children with HVA not treated with VIT reported milder reactions after a re-sting. Probability of SSR to re-sting increases along with the severity of initial reaction.