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This narrative review sums up data from the SARS-CoV-2-pandemia on preexisting disease/underlying conditions/comorbidities and risk factors in children for severe COVID-19 and MIS-C/PIMS-TS as well as hospitalization and mortality. Young infants and adolescents are at highest risk of hospital and PICU admission. Two or more comorbidities rather than single entities pose a risk for more severe courses of SARS-CoV-2 infection in children. Asthma and malignancy do not increase complication rates. MIS-C/PIMS-TS is not associated with any specific underlying disease.
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COVID-19 , Adolescente , COVID-19/complicações , Criança , Cuidados Críticos , Hospitalização , Humanos , Lactente , Fatores de Risco , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.
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COVID-19 , Pneumologia , COVID-19/complicações , Consenso , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
BACKGROUND: Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation. METHODS: pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established. DISCUSSION: Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future.
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Infecções Comunitárias Adquiridas/epidemiologia , Hospitalização , Pneumonia Bacteriana/epidemiologia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Progressão da Doença , Alemanha/epidemiologia , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Sepse/etiologia , Índice de Gravidade de DoençaRESUMO
Individual Motivational Interventions after alcohol-related event treated in Hospital - Effective Option for Secondary Prevention in Adolescence? In a prospective, randomized, single-blind study 48 adolescents between 13 and 17 years answered a standardized questionnaire about their behavior of alcohol-consumption after an alcohol-related event with hospitalization. They were divided in 2 groups by randomization: Group A (n=28) took part in an individual motivational intervention (HaLT-Präventionsprojekt), Group B (n=20) did not get any intervention. Six and 12 weeks after the hospitalization the same questionnaire was answered again by telephone-based interviews. The interviewer did not know to which group the interview-partner belonged. 58% (n=28) of all adolescents drank less alcohol or in a lower frequency than before the alcohol-related event. 17% (n=8) did not drink any alcohol in that period of 12 weeks. 54% (n=26) explained, that they had no events of drunkenness in that period. 38% (n=18) did not change their behavior in consumption of alcohol. 6% (n=3) drank more or in higher frequency than before. We could not find any significant difference in the behavior of alcohol-consumption of both groups: 58% (A) resp. 65% (B) drank less than the time before the alcohol-related event (χ²=0,6269; p=0,4285). An influence of the individual motivational intervention could not be shown. Further studies should include interventions for parents and peers.
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Consumo de Bebidas Alcoólicas/psicologia , Transtornos Relacionados ao Uso de Álcool/prevenção & controle , Aconselhamento Diretivo/métodos , Motivação , Prevenção Secundária , Adolescente , Transtornos Relacionados ao Uso de Álcool/psicologia , Feminino , Alemanha , Humanos , Estudos Prospectivos , Método Simples-Cego , Resultado do TratamentoRESUMO
Stromal interaction molecule 1 (STIM1) deficiency is a rare genetic disorder of store-operated calcium entry, associated with a complex syndrome including immunodeficiency and immune dysregulation. The link from the molecular defect to these clinical manifestations is incompletely understood. We report two patients with a homozygous R429C point mutation in STIM1 completely abolishing store-operated calcium entry in T cells. Immunological analysis of one patient revealed that despite the expected defect of T cell proliferation and cytokine production in vitro, significant antiviral T cell populations were generated in vivo. These T cells proliferated in response to viral Ags and showed normal antiviral cytotoxicity. However, antiviral immunity was insufficient to prevent chronic CMV and EBV infections with a possible contribution of impaired NK cell function and a lack of NKT cells. Furthermore, autoimmune cytopenia, eczema, and intermittent diarrhea suggested impaired immune regulation. FOXP3-positive regulatory T (Treg) cells were present but showed an abnormal phenotype. The suppressive function of STIM1-deficient Treg cells in vitro, however, was normal. Given these partial defects in cytotoxic and Treg cell function, impairment of other immune cell populations probably contributes more to the pathogenesis of immunodeficiency and autoimmunity in STIM1 deficiency than previously appreciated.
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Imunidade/genética , Proteínas de Membrana/deficiência , Proteínas de Neoplasias/deficiência , Humanos , Síndromes de Imunodeficiência/etiologia , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Mutação Puntual , Molécula 1 de Interação Estromal , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Vírus/imunologiaRESUMO
. Allergen immunotherapy (AIT) as a validated, disease-modifying treatment is nowadays a widely recommended therapy option for allergic rhinitis and allergic asthma. The registration of allergen extracts used for AIT is based on allergen standardization, dose finding trials, and phase 3 trials proving their efficacy in high-quality, statistically significant randomized clinical trials. Real-world evidence (RWE) studies confirm the clinical relevance of these findings. The most data are available for the treatment of patients suffering from allergic rhinitis. Due to the similar inflammatory mechanisms, allergic rhinitis is often associated with allergic asthma. AIT, which induces tolerance against individual allergens, is the approach to treat the underlying mechanisms of these two interrelated respiratory diseases. Some trials have been published focusing primarily on the effect of AIT on parameters of allergic asthma. Here we give a summary of the evidence for the efficacy of AIT in the indication of allergic asthma.
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Background: Paediatric community-acquired pneumonia (CAP) is a leading cause of paediatric morbidity. However, particularly for outpatients with paediatric CAP, data on aetiology and management are scarce. Methods: The prospective pedCAPNETZ study multicentrically enrols children and adolescents with outpatient-treated or hospitalised paediatric CAP in Germany. Blood and respiratory specimens were collected systematically, and comprehensive analyses of pathogen spectra were conducted. Follow-up evaluations were performed until day 90 after enrolment. Results: Between December 2014 and August 2020, we enrolled 486 children with paediatric CAP at eight study sites, 437 (89.9%) of whom had radiographic evidence of paediatric CAP. Median (interquartile range) age was 4.5 (1.6-6.6) years, and 345 (78.9%) children were hospitalised. The most prevalent symptoms at enrolment were cough (91.8%), fever (89.2%) and tachypnoea (62.0%). Outpatients were significantly older, displayed significantly lower C-reactive protein levels and were significantly more likely to be symptom-free at follow-up days 14 and 90. Pathogens were detected in 90.3% of all patients (one or more viral pathogens in 68.1%; one or more bacterial strains in 18.7%; combined bacterial/viral pathogens in 4.1%). Parainfluenza virus and Mycoplasma pneumoniae were significantly more frequent in outpatients. The proportion of patients with antibiotic therapy was comparably high in both groups (92.4% of outpatients versus 86.2% of hospitalised patients). Conclusion: We present first data on paediatric CAP with comprehensive analyses in outpatients and hospitalised cases and demonstrate high detection rates of viral pathogens in both groups. Particularly in young paediatric CAP patients with outpatient care, antibiotic therapy needs to be critically debated.
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Background: In cystic fibrosis (CF), acute respiratory exacerbations critically enhance pulmonary destruction. Since these mainly occur outside regular appointments, they remain unexplored. We previously elaborated a protocol for home-based upper airway (UAW) sampling obtaining nasal-lavage fluid (NLF), which, in contrast to sputum, does not require immediate processing. The aim of this study was to compare UAW inflammation and pathogen colonization during stable phases and exacerbations in CF patients and healthy controls. Methods: Initially, we obtained NLF by rinsing 10 ml of isotonic saline/nostril during stable phases. During exacerbations, subjects regularly collected NLF at home. CF patients directly submitted one aliquot for microbiological cultures. The remaining samples were immediately frozen until transfer on ice to our clinic, where PCR analyses were performed and interleukin (IL)-1ß/IL-6/IL-8, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were assessed. Results: Altogether, 49 CF patients and 38 healthy controls (HCs) completed the study, and 214 NLF samples were analyzed. Of the 49 CF patients, 20 were at least intermittently colonized with P. aeruginosa and received azithromycin and/or inhaled antibiotics as standard therapy. At baseline, IL-6 and IL-8 tended to be elevated in CF compared to controls. During infection, inflammatory mediators increased in both cohorts, reaching significance only for IL-6 in controls (p=0.047). Inflammatory responses tended to be higher in controls [1.6-fold (NE) to 4.4-fold (MMP-9)], while in CF, mediators increased only moderately [1.2-1.5-fold (IL-6/IL-8/NE/TIMP-1/MMP-9)]. Patients receiving inhalative antibiotics or azithromycin (n=20 and n=15, respectively) revealed lower levels of IL-1ß/IL-6/IL-8 and NE during exacerbation compared to CF patients not receiving those antibiotics. In addition, CF patients receiving azithromycin showed MMP-9 levels significantly lower than CF patients not receiving azithromycin at stable phase and exacerbation. Altogether, rhinoviruses were the most frequently detected virus, detected at least once in n=24 (49.0%) of the 49 included pwCF and in n=26 (68.4%) of the 38 healthy controls over the 13-month duration of the study. Remarkably, during exacerbation, rhinovirus detection rates were significantly higher in the HC group compared to those in CF patients (65.8% vs. 22.4%; p<0.0001). Conclusion: Non-invasive and partially home-based UAW sampling opens new windows for the assessment of inflammation and pathogen colonization in the unified airway system.
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Fibrose Cística , Humanos , Interleucina-8 , Metaloproteinase 9 da Matriz , Mediadores da Inflamação , Reação em Cadeia da Polimerase Multiplex , Azitromicina/uso terapêutico , Interleucina-6 , Lavagem Nasal , Antibacterianos , InflamaçãoRESUMO
This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.
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Not available.
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BACKGROUND: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty. METHODS: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI). RESULTS: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts. CONCLUSION: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose.
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Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4-2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.
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Two employees of the National Health Service (NHS) in England developed severe allergic reactions following administration of BNT162b2 vaccine against COVID-19 (coronavirus disease 2019). The British SmPC for the BNT162b2 vaccine already includes reference to a contraindication for use in individuals who have had an allergic reaction to the vaccine or any of its components. As a precautionary measure, the Medicines and Healthcare products Regulatory Agency (MHRA) has issued interim guidance to the NHS not to vaccinate in principle in "patients with severe allergies". Allergic reactions to vaccines are very rare, but vaccine components are known to cause allergic reactions. BNT162b2 is a vaccine based on an mRNA embedded in lipid nanoparticles and blended with other substances to enable its transport into the cells. In the pivotal phase III clinical trial, the BNT162b2 vaccine was generally well tolerated, but this large clinical trial, used to support vaccine approval by the MHRA and US Food and Drug Administration, excluded individuals with a "history of a severe adverse reaction related to the vaccine and/or a severe allergic reaction (e.g., anaphylaxis) to a component of the study medication". Vaccines are recognized as one of the most effective public health interventions. This repeated administration of a foreign protein (antigen) necessitates a careful allergological history before each application and diagnostic clarification and a risk-benefit assessment before each injection. Severe allergic reactions to vaccines are rare but can be life-threatening, and it is prudent to raise awareness of this hazard among vaccination teams and to take adequate precautions while more experience is gained with this new vaccine.
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Persistent lobar atelectasis in pediatric patients on mechanical ventilation results in impaired gas exchange and lung mechanics and contributes to a further need for mechanical ventilation. The most common types of atelectasis in children are resorption atelectasis following airway obstruction, and atelectasis due to surfactant deficiency or dysfunction. We aimed to determine whether bronchoscopic suctioning and surfactant application to atelectatic lung segments would result in improved oxygenation, ventilation, chest X-ray scoring, and early extubation. Five children with heterogeneous lung diseases (aged between 7 months and 15 years) were treated with a diluted surfactant preparation (Curosurf) in a concentration of 5-10 mg/ml (total dose 120-240 mg) which was instilled into the affected segments. Outcome parameters were gas exchange, radiographic resolution of atelectasis and extubation. All mechanically ventilated patients could be extubated within 24 h following the intervention. Bronchoscopic surfactant application could be carried out without adverse effects and brought improvements in oxygenation, respiratory rate, and partial or complete resolution of atelectases without recurrence.
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Broncoscopia/métodos , Pneumonia/complicações , Atelectasia Pulmonar/tratamento farmacológico , Surfactantes Pulmonares/uso terapêutico , Adolescente , Criança , Pré-Escolar , Doença Crônica , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pneumonia/diagnóstico por imagem , Pneumonia/microbiologia , Pneumonia/terapia , Atelectasia Pulmonar/etiologia , Radiografia Torácica , Respiração Artificial , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate regional lung function in lung-healthy children before and after exercise challenge using electrical impedance tomography (EIT). METHODS: Regional lung function was examined using EIT in 100 lung-healthy children (three age subgroups: 74-121, 122-155, 156-195 months) at baseline and 10 min after exercise. Global lung function was assessed by spirometry using Z-Scores of FEV1 , FVC, FEV1 /FVC, and FEF75 . The same lung function measures were determined in 912 EIT image pixels to enable the spatial and temporal ventilation distribution analysis. Coefficients of variation (CV) of these pixel values were calculated and histograms of pixel FEV1 /FVC and times required to exhale 50% and 75% of pixel FVC (t50 and t75 ) generated. Additionally, we compared the findings of the studied population with three cystic fibrosis (CF) children. FINDINGS: Z-Scores corresponded to the worldwide reference values in all studied age groups at baseline. Global lung function was not affected by exercise, only the youngest group exhibited higher FVC and lower FEF75 , FEV1 /FVC attributable to the training effect. The overall degree of ventilation heterogeneity assessed by CV showed no exercise dependency. The histograms of pixel values of FEV1 /FVC, t50 , and t75 revealed a slight modulating effect of exercise on regional ventilation distribution in all subgroups. EIT identified the distinctly higher ventilation heterogeneity in the CF children. CONCLUSION: Global and regional lung functions were not affected by exercise in lung-healthy children. Exercise did not increase ventilation inhomogeneity. The obtained EIT-derived regional lung parameters can serve as reference values for future studies in children with lung diseases.
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Fibrose Cística/diagnóstico por imagem , Fibrose Cística/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiologia , Adolescente , Criança , Impedância Elétrica , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Valores de Referência , Respiração , Testes de Função Respiratória , TomografiaRESUMO
Leukotriene-generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar-capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5-lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurftrade mark) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air-bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B(4) (LTB(4)) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO(2)) (S, 13.8 +/- 4.2 kPa, vs. S + MK, 20 +/- 6.6; P < 0.05), functional residual capacity (S, 15.1 +/- 6.8 ml/kg, vs. S + MK, 18.8 +/- 3.7 ml/kg; P < 0.05), and EVLW (S, 29 +/- 14 ml/kg, vs. S + MK 24 +/- 4 ml/kg; P < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB(4) concentration in BAL (S, 3.5 (1.9-5.4) pg/ml, vs. S + MK, 1.6 (0.7-4.7) pg/ml; P < 0.05) and an increase in IL-8 (S, 2,103 (852-4,243) pg/ml, vs. S + MK, 3,815 (940-26,187) pg/ml; P < 0.05). PMNL counts in BAL were reduced (S, 570 +/- 42 cells/ml, vs. 275 +/- 35 cells/ml; P < 0.05). In conclusion, intrapulmonary application of the 5-lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB(4) reduction.