Background Lower respiratory tract infections (LRTIs) are a leading cause of childhood morbidity and mortality. Potentially pathogenic organisms are present in the respiratory tract in both symptomatic and asymptomatic children, but their presence does not necessarily indicate disease. We aimed to assess the concordance between upper and lower respiratory tract microbiota during LRTIs and the use of nasopharyngeal microbiota to discriminate LRTIs from health.Methods First, we did a prospective study of children aged between 4 weeks and 5 years who were admitted to the paediatric intensive care unit (PICU) at Wilhelmina Children's Hospital (Utrecht, Netherlands) for a WHO-defined LRTI requiring mechanical ventilation. We obtained paired nasopharyngeal swabs and deep endotracheal aspirates from these participants (the so-called PICU cohort) between Sept 10, 2013, and Sept 4, 2016. We also did a matched case-control study (1:2) with the same inclusion criteria in children with LRTIs at three Dutch teaching hospitals and in age-matched, sex-matched, and time-matched healthy children recruited from the community. Nasopharyngeal samples were obtained at admission for cases and during home visits for controls. Data for child characteristics were obtained by questionnaires and from pharmacy printouts and medical charts. We used quantitative PCR and 16S rRNA-based sequencing to establish viral and bacterial microbiota profiles, respectively. We did sparse random forest classifier analyses on the bacterial data, viral data, metadata, and the combination of all three datasets to distinguish cases from controls.Findings 29 patients were enrolled in the PICU cohort. Intra-individual concordance in terms of viral microbiota profiles (96% agreement [95% CI 93-99]) and bacterial microbiota profiles (58 taxa with a median Pearson's r 0·93 [IQR 0·62-0·99]; p<0·05 for all 58 taxa) was high between nasopharyngeal and endotracheal aspirate samples, supporting the use of nasopharyngeal samples as proxy for lung microbiota during LRTIs. 154 cases and 307 matched controls were prospectively recruited to our case-control cohort. Individually, bacterial microbiota (area under the curve 0·77), viral microbiota (0·70), and child characteristics (0·80) poorly distinguished health from disease. However, a classification model based on combined bacterial and viral microbiota plus child characteristics distinguished children with LRTIs from their matched controls with a high degree of accuracy (area under the curve 0·92).Interpretation Our data suggest that the nasopharyngeal microbiota can serve as a valid proxy for lower respiratory tract microbiota in childhood LRTIs, that clinical LRTIs in children result from the interplay between microbiota and host characteristics, rather than a single microorganism, and that microbiota-based diagnostics could improve future diagnostic and treatment protocols.

After an experimental neonatal screening program for cystic fibrosis (CF) from 1973–1979, a follow-up study took place from 1980–1997. Patients were treated at specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1) to determine whether the previously reported benefits from screening persisted with time and after adjustment for confounding variables; and 2) to investigate whether centre treatment was associated with improved prognosis of CF patients.Prognosis of patients detected by screening (S; n=24) was compared with patients detected clinically, born during (non-S; n=29) and after the screening programme (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C patients. Multivariable regression analysis was used to compare survival and mixed-effects model regression analysis was used to compare clinical outcome between patients. The analyses included the variables screening, centre treatment, sex, meconium ileus and genotype.S patients had a significantly smaller decline in forced expiratory volume in one second (FEV1) (difference +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels (difference −473.69 mg·dL−1) than non-S patients until 12 yrs of age. At 12 yrs of age, vital capacity was significantly higher in S patients than in non-S patients (difference +362.79 mL). Survival seemed to be best for S patients compared to both non-S and post-S patients. Post-S patients were significantly heavier (difference in sd weight +0.77), had a significantly smaller decline in FEV1(difference +2.80% pred) and lower IgG levels (difference −453.04 mg·dL−1) than non-S patients until 12 yrs of age. C patients had a significantly improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05–0.57) than non-C patients.Early diagnosis through neonatal screening leads to better preservation of lung function in the long term in cystic fibrosis patients. Management of cystic fibrosis patients in specialized centres improves survival.

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Extended gene analysis in dried blood spots can discriminate CF patients and carriers. If proven equally reliable in larger series, an approach to neonatal screening in which tests are only considered as screen positive when two CF mutations are found is possible. This can increase the specificity of the screening programme, and carrier detection can practically be avoided.

Respiratory tract infections (RTI) in children remain a cause of disease burden worldwide. Nasopharyngeal (NP) & oropharyngeal (OP) swabs are used for respiratory pathogen detection, but hold disadvantages particularly for children, highlighting the importance and preference for a child friendly detection method. We aimed to evaluate the performance and tolerability of a rhinorrhea swab (RS) in detecting viral pathogens when compared to a combined OP(/NP) or mid‐turbinate (MT) nasal swab. This study was conducted between September 2021 and July 2022 in the Netherlands. Children aged 0−5 years, with an upper RTI and nasal discharge, were included and received a combined swab and a RS. Multiplex polymerase chain reaction (PCR) and severe acute respiratory syndrome coronavirus‐2 PCR were used for viral pathogen detection. Tolerability was evaluated with a questionnaire and visual analog scale (VAS) scores. During 11 months 88 children were included, with a median age of 1.00 year [interquartile range 0.00−3.00]. In total 122 viral pathogens were detected in 81 children (92%). Sensitivity and specificity of the RS compared to a combined swab were respectively 97% (95% confidence interval [CI] 91%−100%) and 78% (95% CI 45%−94%). Rhinorrhea samples detected more pathogens than the (combined) nasal samples, 112 versus 108 respectively. Median VAS scores were significantly lower for the RS in both children (2 vs. 6) and their parents (0 vs. 5). A RS can therefore just as effectively/reliably detect viral pathogens as the combined swab in young children and is better tolerated by both children and their parents/caregivers.