The risk of community-acquired pneumonia in children using gastric acid suppressants.

BACKGROUND: With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). METHODS: We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. RESULTS: Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. CONCLUSION: The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.

Exhaled breath profiling in diagnosing wheezy preschool children.

Although wheeze is common in preschool children, the underlying pathophysiology has not yet been disentangled. Volatile organic compounds (VOCs) in exhaled breath may serve as noninvasive markers of early wheeze. We aimed to assess the feasibility of VOC collection in preschool children, and to study whether a VOC profile can differentiate between children with and without recurrent wheeze. We included children (mean (range) age 3.3 (1.9-4.5) yrs) with (n=202) and without (n=50) recurrent wheeze. Exhaled VOCs were analysed by gas chromatography-time-of-flight mass spectrometry. VOC profiles were generated by ANOVA simultaneous component analysis (ASCA) and sparse logistic regression (SLR). Exhaled breath collection was possible in 98% of the children. In total, 913 different VOCs were detected. The signal-to-noise ratio improved after correction for age, sex and season using ASCA pre-processing. An SLR model with 28 VOCs correctly classified 83% of the children (84% sensitivity, 80% specificity). After six-fold cross-validation, 73% were correctly classified (79% sensitivity, 50% specificity). Assessment of VOCs in exhaled breath is feasible in young children. VOC profiles are able to distinguish children with and without recurrent wheeze with a reasonable accuracy. This proof of principle paves the way for additional research on VOCs in preschool wheezing.

Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review.

There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.

Pediatric long-COVID: An overlooked phenomenon?

BACKGROUND: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children. PATIENTS AND METHODS: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail. RESULTS: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2-18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints. CONCLUSION: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.

Evidence for a Cystic Fibrosis Enteropathy.

BACKGROUND: Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. METHODS: Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. RESULTS: Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. CONCLUSION: This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance.