Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. OBJECTIVES: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. METHODS: We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. RESULTS: About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFß, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFß and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. CONCLUSIONS: Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

[Emergency Care Plans for the Management of Emergencies in Children on Home Mechanical Ventilation]. / Notfallpläne zum Management von Notfällen bei Kindern mit außerklinischer Beatmung.

In pediatrics chronic respiratory insufficiency is increasingly treated on an outpatient basis with home mechanical ventilation. Nursing and medical teams with different structures take care of the often complex ill children in the outpatient setting. Structured treatment processes, especially emergency plans for the management of respiratory emergencies of home mechanical ventilated children are lacking. This article is a proposal for emergency management of respiratory infections, emergencies of non-invasively ventilated and invasively ventilated, tracheotomized children. In addition to resuscitation measures according to ERC/AHA, the focus is primarily on secretion management, as well as on the handling of ventilators and devices.

Subjective Smell Disturbances in Children with Sars-Cov-2 or Other Viral Infections do not Correspond with Olfactory Test Results.

BACKGROUND: Olfactory dysfunction associated with SARS-CoV-2 infection in children has not been verified by a validated olfactory test. We aimed to determine whether these complaints are objectifiable (test-based hyposmia), how often they occur during acute SARS-CoV-2 infection compared to other upper respiratory tract infections (URTI), as well as in children recovered from COVID-19 compared to children with long COVID. METHODS: Olfactory testing (U-sniff test; hyposmia<8 points) and survey-based symptom assessments were performed in 434 children (5-17 years; 04/2021-06/2022). 186 symptom-free children served as controls. Of the children with symptoms of acute respiratory tract infection, SARS-CoV-2 PCR test results were positive in 45 and negative in 107 children (URTI group). Additionally, 96 children were recruited at least 4 weeks (17.6±15.2 weeks) after COVID-19, of whom 66 had recovered and 30 had developed long COVID. RESULTS: Compared to controls (2.7%), hyposmia frequency was increased in all other groups (11-17%, p<0.05), but no between-group differences were observed. Only 3/41 children with hyposmia reported complaints, whereas 13/16 children with complaints were normosmic, with the largest proportion being in the long-COVID group (23%, p<0.05). CONCLUSION: Questionnaires are unsuitable for assessing hyposmia frequency in children. Olfactory complaints and hyposmia are not specific for SARS-CoV-2 infection. The number of complaints in the long-COVID group could result from aversive olfactory perception, which is undetectable with the U-sniff test.

Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice.

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. "Children are not little adults" - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.

Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD. The current study randomly assigned 50 newborns who were at high risk of developing AD (1:1) to receive general infant skin-care advice (control group), or skin-care advice plus emollient with advice to apply emollient at least once daily until 1 year of age (intervention group). Repeated skin examinations, skin physiology measurements and skin microbiome profiling were performed. Of the children in the intervention and control groups, 28% and 24%, respectively, developed AD (adjusted Relative Risk (RR) 1.19, p = 0.65, adjusted risk difference 0.05). Skin pH decreased and transepidermal water loss and stratum corneum hydration increased over time in both groups with no significant differences. In the intervention group skin microbiome alpha diversity increased earlier, and the abundance of Streptococcus and Staphylococcus species were significantly reduced at month 1. Daily early emollient use in children with high risk of AD was safe, but it did not significantly reduce the risk of developing AD or impact skin physiology development.

Pediatric multi-drug-resistant tuberculosis in Germany - diagnostic and therapeutic challenges of an "orphan disease".

Delay in diagnosing multidrug-resistant tuberculosis (MDR-pTB) in children prolongs time to effective treatment. Data on risk factors for pediatric MDR from low-incidence countries are scarce. Retrospective nationwide case-control study to analyze MDR-pTB cases in Germany between 2010 and 2020 in comparison to a drug-susceptible (DS)-pTB group. We included 52 MDR cases (24 tuberculosis (TB), 28 TB infection (TBI); mean age 7.3 years) and 56 DS cases (31 TB, 26 TBI; mean age 7.9 years). Groups were similar for sex, household size, and migration background. Compared to the DS group, more children with MDR were born in the Commonwealth of Independent States (CIS) (22% MDR-pTB vs. 13% DS-pTB, n.s.) and had more MDR index cases (94% MDR-pTB, 5% DS-pTB, p < 0.001). The interval between first healthcare contact and initiation of effective therapy was significantly longer in MDR-pTB (47 days) than in DS-pTB (11 days, p < 0.001), correlating with disease progression. Treatment for MDR-pTB was successful in 74%, but 22% experienced long-term adverse effects (e.g., hepatopathy, hearing loss). CONCLUSIONS: Close contact to MDR cases or birth in MDR-TB-high-incidence countries are risk factors for MDR-pTB. Early identification of potential MDR index cases by contact investigation, and susceptibility testing in children from high-burden MDR-TB countries are essential for timely diagnosis and treatment, reducing the severity of disease and treatment side effects. TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023817 ), DRKS00023817, 2020-09-08. WHAT IS KNOWN: •Management of children with MDR-TB remains challenging due to difficulties in diagnosing MDR-TB (lack of information on MDR index case, lack of microbiological confirmation in paucibacillary disease). •Choice of treatment regimen and monitoring of side effects. WHAT IS NEW: •Children with an MDR-TB index or born in a MDR-TB-high-incidence country are at higher risk of developing MDR-TB in a low incidence country. •The time lag to initiate treatment in MDR-TB is longer than in DS-TB and MDR-TB treatment involves a higher risk of adverse effects in longer treatment regimens especially with injectables.

Button Battery Ingestions cause the Majority of Severe Complications.

BACKGROUND: Foreign body ingestion in children is a clinically important reason for presentation to the emergency department. The individual outcome ranges from benign spontaneous courses to severe complications. Fatal outcomes occur rarely and complications are related to patient's age as well as type and location of the foreign body. The aim of our present study was to evaluate the outcome of children and adolescents with foreign body ingestion with a focus on complications, which mainly occurred after button battery ingestion. METHODS: We reviewed medical records of patients between 0 and 18 years of age who had presented to the paediatric emergency department of our hospital with suspected foreign body ingestion between January 2011 and March 2021 (123 months). Clinical, imaging, and endoscopic data as well as treatment modalities were analysed. RESULTS: In the ten10 year period under review, a total of 1,162 children and adolescents (6 months - 18 years) presented to our emergency room with suspected foreign body ingestion. Among those, 398 ingestions (34%) could be verified radiologically and/or endoscopically, while in the remaining 764 cases (66%) the suspicion could not be confirmed. The majority of patients with verified ingestion (n=324; 81%) presented with ingestion of a metallic foreign body. We observed 55 cases with verified ingestion of a button battery. Five of these cases had severe complications, with a near-fatal course in two patients who developed an oesophageal-tracheal fistula. CONCLUSION: In contrast to all other ingestions of foreign bodies in children, button battery ingestions lead to mucosal damage and severe complications in a significant number of children.

Maternal knowledge of recommendations for safe infant sleep and intentions for implementation - a cross sectional analysis of data from the KUNO-Kids birth cohort study.

OBJECTIVES: Despite major advances in prevention, sudden infant death syndrome (SIDS) remains an important cause of infant mortality. The aim of our study was to determine actual knowledge and intentions to implement SIDS prevention measures among new mothers and to identify potential knowledge gaps for improved postpartum counselling strategies. METHODS: Data was collected in a standardized interview from participants of the KUNO-Kids birth cohort study before discharge from maternity ward. The mothers did not receive any specific teaching prior to the interview. RESULTS: The majority of 2,526 interviewed mothers were able to actively report important recommendations for safe infant sleep, including the exclusive face-up position. However, 154 mothers (9%) intended to position the newborn face-down sometimes or often. The most frequently envisaged sleeping furniture was a bedside sleeper (n=1,144, 47%), but 2.2% of mothers indicated that the intended default sleeping place for the newborn would be the parents' bed (which is discouraged by the recommendations). For 43% of the infants (n=1,079), mothers planned to have loose objects in the bed and 189 mothers (7%) intended to use a loose blanket. 22% of infants (n=554) will live in a household with a smoker. Multivariate regression showed a significant association of "good knowledge" with maternal age and with not being a single parent, whereas the household size was negatively associated. CONCLUSION: Although the majority of mothers in our birth cohort were aware of many recommendations for safe infant sleep, our data also uncovered weaknesses in SIDS prevention knowledge and point to specific areas with potential for improved counselling.

Time course of nocturnal cough and wheezing in children with acute bronchitis monitored by lung sound analysis.

Cough and wheezing are the predominant symptoms of acute bronchitis. Hitherto, the evaluation of respiratory symptoms was limited to subjective methods such as questionnaires. The main objective of this study was to objectively determine the time course of cough and wheezing in children with acute bronchitis. The impact of nocturnal cough on parent's quality of life was assessed as secondary outcome. In 36 children (2-8 years), the frequency of nocturnal cough and wheezing was recorded during three nights by automated lung sound monitoring. Additionally, parents completed symptom logs, i.e., the Bronchitis Severity Score (BSS), as well as the Parent-proxy Children's Acute Cough-specific Quality of Life Questionnaire (PAC-QoL). During the first night, patients had 34.4 ± 52.3 (mean ± SD) cough epochs, which were significantly reduced in night 5 (13.5 ± 26.5; p < 0.001) and night 9 (12.8 ± 28.1; p < 0.001). Twenty-two patients had concomitant wheezing, which declined within the observation period as well. All subjective parameters (BSS, Cough log and PAC-QoL) were found to be significantly correlated with the objectively assessed cough parameters.Conclusion: Long-term recording of cough and wheezing offers a useful opportunity to objectively evaluate the time course of respiratory symptoms in children with acute bronchitis. To assess putative effects of pharmacotherapy on nocturnal bronchitis symptoms, future studies in more homogeneous patient groups are needed. What is Known: • Cough and wheezing are the predominant symptoms of acute bronchitis. • There is a diagnostic gap in long-term assessment of these respiratory symptoms, which needs to be closed to optimize individual therapies. What is New: • Long-term recording of nocturnal cough and wheezing allows for objective evaluation of respiratory symptoms in children with acute bronchitis and provides a tool to validate the efficacy of symptomatic bronchitis therapies.

Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation.

The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis.

IgG4 and IgE transcripts in childhood allergic asthma reflect divergent antigen-driven selection.

The physiologic function of the "odd" Ab IgG4 remains enigmatic. IgG4 mediates immunotolerance, as, for example, during specific immunotherapy of allergies, but it mediates tissue damage in autoimmune pemphigus vulgaris and "IgG4-related disease." Approximately half of the circulating IgG4 molecules are bispecific owing to their unique ability to exchange half-molecules. Better understanding of the interrelation between IgG4 and IgE repertoires may yield insight into the pathogenesis of allergies and into potential novel therapies that modulate IgG4 responses. We aimed to compare the selective forces that forge the IgG4 and IgE repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified, cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were unique. Compared with previously published unique IgE transcripts from the same blood samples, the somatic mutation rate was significantly enhanced in IgG4 transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed statistical evidence of Ag-driven selection (p < 0.001). On average, the hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE transcripts (p < 0.001). IgG4 transcripts in the circulation of children with allergic asthma reflect some characteristics of classical Ag-driven B2 immune responses but display less indication of Ag selection than do IgE transcripts. Although allergen-specific IgG4 can block IgE-mediated allergen presentation and degranulation of mast cells, key factors that influence the Ag-binding properties of the Ab differ between the overall repertoires of circulating IgG4- and IgE-expressing cells.

IgA response in preterm neonates shows little evidence of antigen-driven selection.

After birth, contact to environmental Ags induces the production of IgA, which represents a first line of defense for the neonate. We sought to characterize the maturation of the repertoire of IgA H chain transcripts in circulating blood B cells during human ontogeny. We found that IgA H chain transcripts were present in cord blood as early as 27 wk of gestation and that the restrictions of the primary Ab repertoire (IgM) persisted in the IgA repertoire. Thus, B cells harboring more "mature" V(H) regions were not preferred for class switch to IgA. Preterm and term neonates expressed a unique IgA repertoire, which was characterized by short CDR-H3 regions, preference of the J(H) proximal D(H)7-27 gene segment, and very few somatic mutations. During the first postnatal months, these restrictions were slowly released. Preterm birth did not measurably accelerate the maturation of the IgA repertoire. At a postconceptional age of 60 wk, somatic mutation frequency of IgA H chain transcripts reached 25% of the adult values but still showed little evidence of Ag-driven selection. These results indicate that similar to IgG, the IgA repertoire expands in a controlled manner after birth. Thus, the IgA repertoire of the newborn has distinctive characteristics that differ from the adult IgA repertoire. These observations might explain the lower affinity and specificity of neonatal IgA Abs, which could contribute to a higher susceptibility to infections and altered responses to vaccinations, but might also prevent the development of autoimmune and allergic diseases.

"Delabeling" by direct provocation testing in children and adolescents with a suspected history of a delayed reaction to ß-lactam antibiotics: Consensus paper of Gesellschaft für pädiatrische Allergologie und Umweltmedizin (GPAU), Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), and Ärzteverband deutscher Allergologen (ÄDA).

BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. RESULTS: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.

Implementation of safe infant sleep recommendations during night-time sleep in the first year of life in a German birth cohort.

The aim of our study was to assess the extent to which families followed recommendations, issued by the German society for sleep medicine, for the prevention of sudden infant death syndrome (SIDS) during night-time sleep. Analyzing longitudinal data from a birth cohort located at the University Children's Hospital Regensburg in Bavaria (Germany), we determined data regarding the infant's sleep location, sleep settings and body position, and exposure to environmental factors. Data were collected in a structured interview after birth and by standardized questionnaires at 4 weeks, 6 months, and 1 year of life, respectively. The majority of 1,400 surveyed infants (94% at 4 weeks) were reported to sleep in the parents' sleeping room during the first months of life. While the most common furniture was a bedside sleeper (used by 48%), we also observed a considerable proportion of families who regularly practiced bed-sharing and, for 16% of infants, the parents' bed was the default sleeping place. 12% of infants were still put regularly in the prone position. The vast majority (87%) of the infants were breastfed at some timepoint and 17% lived in a household with one or more smokers. Although most parents implemented many SIDS recommendations, our analysis illustrates a considerable gap between recommendations and intentions after birth on the one hand and actual implementation in real life on the other. The number-one deviation from the current SIDS guidelines during night-time sleep was bed-sharing with an adult.

Th17 cell frequency in peripheral blood from children with allergic asthma correlates with the level of asthma control.

Here we show that the frequency of T(H)17 cells (CD3(+)CD4(+)CD161(+)CCR6(+) lymphocytes) is increased in peripheral blood of children with allergic asthma. Moreover, we found a significant relationship between the frequency of T(H)17 cells and level of asthma control, with reduced asthma control correlated with a higher proportion of T(H)17 cells.

IgE transcripts in the circulation of allergic children reflect a classical antigen-driven B cell response and not a superantigen-like activation.

Allergic asthma is the most frequent chronic disorder in childhood. Although IgE is a central effector molecule in allergic diseases, the nature of the IgE response is still under debate. The objective of our study was to clarify whether the IgE repertoire in the circulation of allergic children represents a classical Ag-driven and oligoclonal B cell response, a superantigen-like activation of a subset of B cells, or a polyclonal B-1 cell expansion. Using a highly sensitive RT-PCR method, we amplified, cloned, and sequenced IgE H chain transcripts from 13 children with allergic asthma. We gained 1366 functional IgE sequences, which currently represent the most extensive collection of human IgE transcripts. Compared to IgM transcripts from the same children, the somatic mutation rate was significantly enhanced in IgE transcripts (21 per thousand versus 72 per thousand; p < 0.001), which renders a polyclonal B-1 response unlikely. Moreover, IgE sequences displayed significantly enhanced Ag selection and hence were indicative of a classical Ag-driven immune response with affinity maturation (p < 0.001). In contrast to several recent studies, the usage pattern of variable gene segment of the H Ig chain in IgE transcripts followed the germline complexity, arguing against a superantigen-like interaction. We conclude that IgE transcripts in the circulation of children with allergic asthma reflect a classical adaptive B-2 cell response. This study provides reference data for a better characterization of the IgE response under immunomodulating therapies, such as anti-IgE therapy or allergen-specific immunotherapy.

Plasma cells and nonplasma B cells express differing IgE repertoires in allergic sensitization.

The selection of allergen-specific B cells into the plasma cell (PC) pool is a critical step in the immune dysregulation that leads to the production of IgE in allergic diseases. We sought to characterize the murine IgE repertoire. In particular, we questioned whether the IgE repertoire of plasmablasts (PBs)/PCs differs from the IgE repertoire of non-PCs. Therefore, we sorted splenocytes from OVA-sensitized BALB/c mice into CD138(pos) (PBs/PCs) and CD19(pos)/CD138(neg) (non-PCs) B cell fractions. Using reverse transcription PCR, we amplified, cloned, and sequenced IgE mRNA transcripts and analyzed the Ig H chain repertoire. As a reference, we characterized the IgM repertoire of the same animals. Compared to IgM, the IgE sequences contained a significantly higher level of somatic mutations and displayed an oligoclonal expansion with clonotype restriction. Interestingly, we found two phenotypically distinct IgE-producing B cell subpopulations that differed in their repertoire of H chain transcripts; IgE transcripts from PBs/PCs showed significantly more signs of Ag-driven selection than transcripts from non-PCs, including 1) a higher number of somatic mutations, 2) increased clustering of replacement mutations in the CDRs, and 3) biased third CDR of the heavy Ig chain composition. In conclusion, PBs/PCs and non-PCs from OVA-sensitized mice express distinct IgE repertoires, suggesting that 1) the repertoire of IgE-expressing PBs/PCs represents a highly biased selection from the global B cell repertoire and 2) Ag-driven affinity maturation is a major force that selects IgE-producing B cells into the CD138(pos) PC pool.

Validation of the LEOSound® monitor for standardized detection of wheezing and cough in children.

BACKGROUND: A hallmark of many respiratory conditions is the presence of nocturnal symptoms. Nevertheless, especially in children there is currently still a huge diagnostic gap in detecting nighttime symptoms, which leads to an underestimation of the frequency in clinical practise. METHODS: We evaluated the clinical applicability and determined the formal test characteristics of the LEOSound ® system, a device for digital long-time recording and automated detection of acoustic airway events. Airway sounds were recorded overnight in 115 children and adolescents (1-17 years) with and without respiratory conditions. The automated classification for "cough" and "wheezing" was subsequently validated against the manual acoustic reassessment by an expert physician. RESULTS: The general acceptance was good across all age groups and a technically successful recording was obtained in 98 children, corresponding to 92,976 sound epochs (à 30 s) or a total of 774 h of lung sounds. We found a sensitivity of 89% and a specificity of 99% for the automated detection of cough. For detection of wheezing, sensitivity and specificity were both 98%. The cough index and the wheeze index (events per hour) of individual patients showed a strong positive correlation (cough: rS = 0.85, wheeze: rS = 0.95) and a sufficient agreement of the two assessment methods in the Bland-Altman analysis. CONCLUSION: Our data show that the LEOSound® is a suitable device for standardized detection of cough and wheezing and hence a promising diagnostic tool to detect nocturnal respiratory symptoms, especially in children. However, a validation process to reduce false positive classifications is essential in clinical routine use.

Different Patterns of Foods Triggering FPIES in Germany.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy mainly affecting infants and young children. Allergic FPIES reactions differ from IgE-mediated food allergies, for example, regarding elicitors and clinical course. OBJECTIVE: The aim of our study was to describe causative agents and development of tolerance in German children with FPIES. METHODS: We conducted a retrospective survey on children with FPIES from 14 centers in Germany assessing a 6-year period. RESULTS: We analyzed 142 patients with 190 FPIES reactions, 130 of which met acute FPIES criteria and 60 were defined as chronic FPIES. The most frequent eliciting food for acute FPIES was cow's milk, followed by fish, vegetables (eg, potato, pumpkin), meats (eg, beef), and grains. A total of 119 children reacted to 1 food only, 16 children to 2 or 3 foods, and 7 children to ≥4 foods. In chronic FPIES, all but 4 exclusively breastfed infants reacted to cow's milk feeding. IgE sensitization to the triggering food was found in 21 of 152 (14%) cases. Two children developed additional IgE-mediated symptoms upon a food challenge. Time to proof of tolerance was shortest in cow's milk-induced FPIES, and it was shorter in chronic than in acute FPIES. CONCLUSION: In our national survey, we identified triggers for acute FPIES that partially differ from those reported internationally. Mainly foods introduced early in infant nutrition triggered acute reactions. Time to proven tolerance was shown to be contingent on FPIES symptomatology and on the triggering food. These data should be considered regarding nutritional advice for infants with FPIES.