From neonatal lung function to lung function and respiratory morbidity at 6-year follow-up.

BACKGROUND: Lung function is traceable from infancy to adulthood. Only a few studies have examined lung function from birth to childhood longitudinally in children born moderate to late preterm. We aimed to investigate how prematurity and lung function in the neonatal period are related to lung function and respiratory morbidity at age 6 in former moderate to late preterm children compared with children born at term. METHODS: Lung function was measured in a cohort of moderately to late preterm (n = 48) and term-born (n = 53) infants in the neonatal period by FeNO, and tidal breathing flow-volume loops (TBFVL) and at age 6 (n = 52) by spirometry, whole-body plethysmograph and impulse oscillation combined with a respiratory symptom questionnaire. RESULTS: Moderate to late preterm children had a higher TPEF /TE ratio neonatally (42.6% vs. 33.7%, p = 0.02) and a lower % predicted orced expiratory volume in the first second at age 6 (94.4% vs. 101.9%, p = 0.01) compared to term-born children. We found a significant association between the variability of neonatal tidal volume and effective airway resistance at age 6 (ß = -0.34, p = 0.03). No association between neonatal FeNO or TBFVL and respiratory morbidity at 6-year follow-up was shown. CONCLUSION: Children born moderate to late preterm had lower lung function at age 6 than term-born children. We did not find evidence for the use of neonatal tidal breathing parameters as a predictor for subsequent respiratory morbidity or lung function, however sample size was small.

Cohort profile: the vitamin A and D and nitric oxide (AD-ON) observational cohort on lung development and symptoms in premature and mature children in North Zealand, Denmark.

PURPOSE: The risk of developing asthma-like symptoms and asthma in childhood is influenced by genetics, environmental exposures, prenatal and early postnatal events, and their interactions. The cohort name refers to vitamins A and D, and nitric oxide (NO) spelt backwards and this cohort profile paper aims to present the data collection and aim of the cohort.The overall aim when establishing this cohort was to investigate if childhood lung function can be traced back to early neonatal lung function and fractional exhaled NO (FeNO) and investigate prenatal and postnatal risk factors including maternal and neonatal vitamin A and D levels in preterm and term born children. PARTICIPANTS: One thousand five hundred women and their babies born at Nordsjaellands Hospital in Denmark from 2013 to 2014 were included in the AD-ON research biobank prior to birth.Neonates from the AD-ON research biobank, admitted to the Neonatal Intensive Care Unit at Nordsjaellands Hospital, were included in the AD-ON neonatal cohort. The neonatal cohort consisted of 149 neonates hereof 63 preterm and 86 term born. The children in the cohort have been invited to follow-up visits at age 1 and 6 years. FINDINGS TO DATE: Published data from this cohort includes a validated and clinically applicable method to measure FeNO in neonates. We found an age-specific pattern of association between respiratory symptoms at age 1 and neonatal FeNO in preterm children. Moreover, we found that the respiratory symptoms risk was associated with postnatal factors (Respiratory Syncytial Virus infection and parental smoking) in preterm infants and prenatal factors (parental asthma and maternal infection during pregnancy) in term born infants. FUTURE PLANS: In the future, the children will be examined continuously with 3-year to 5-year intervals until the age of 18. Lung function, allergy tests, environmental exposure measurements and questionnaires will be collected at each follow-up visit.

National multi-centre study found a low prevalence of severely impaired lung function in children and adolescents.

AIM: As no data to our knowledge exist, the aim of the study was to describe the national prevalence and characteristics of Danish children and adolescents with severely impaired lung function. METHODS: We performed a descriptive, cross-sectional Danish multi-centre study. Children and adolescents between 6 and 18 years old demonstrating severely impaired lung function from 2015 to 2018, defined by forced expiratory volume in 1 second (FEV1 ) <60% or who had lung transplantation, were eligible for inclusion. RESULTS: This study included 113 children with a mean age (standard deviation) of 12.9 years (3.5 years). The prevalence of severely impaired lung function was approximately 13 in 100,000. The mean (standard deviation) FEV1 was 46.1% (10.1%) of predicted, and z-score was -4.5 (0.8). The most frequent diagnosis was cystic fibrosis (20.4%), followed by asthma (19.5%) and bronchiolitis obliterans (16.8%), while almost 25% had different elements of airway malformations or non-pulmonary conditions. Two adolescents with cystic fibrosis underwent lung transplantation. CONCLUSION: The estimated prevalence of severely impaired lung function in Danish children and adolescents was low, and extremely, few children underwent lung transplantation. The most frequent diagnosis was cystic fibrosis, while almost 25% had different elements of airway malformations or non-pulmonary conditions, which may require clinical attention.

Neonatal FeNO, risk factors, and respiratory morbidity in infants: A cohort study.

BACKGROUND: Respiratory symptoms in infancy are more common in premature infants. Nitric oxide (NO) is involved in prenatal and neonatal lung development. Measurement of exhaled NO is easy and well-tolerated by neonates. We investigated whether neonatal exhaled NO can be used to predict subsequent respiratory symptoms. Furthermore, we sought to determine prenatal and postnatal factors associated with increased respiratory symptom risk during the first year of life in premature and mature infants. METHODS: Tidal fractional exhaled NO (FeNO) was measured in a birth cohort (n = 135) of premature and mature infants, up to six times during the first month of life. Primary outcomes were troublesome respiratory symptoms (TRS) and doctor-diagnosed asthmatic bronchitis (AB) at 1 year of age. FINDINGS: The correlation between FeNO and TRS changed significantly in an age-dependent pattern in moderately premature infants (p = .02). Moderately premature infants with a low FeNO of 2 ppb on postnatal Day 3 had a 48% (95% confidence interval [CI]: 17%-80%) probability of TRS, compared with a probability of 12% (95% CI: 1%-64%) for otherwise similar infants with a FeNO of 11 ppb. Respiratory syncytial virus infection and parental smoking significantly increased the TRS risk in premature infants. Parental asthma and maternal antibiotic use during pregnancy significantly increased the TRS risk in mature infants. INTERPRETATION: An age-specific association between neonatal FeNO and respiratory symptoms was seen in moderately premature infants. TRS risk was associated with postnatal factors in premature and prenatal factors in mature infants.

Late-onset group B streptococcus infections and severe bronchopulmonary dysplasia in an extremely preterm born infant.

This case report is about a boy born extremely preterm at gestational age of 24 weeks, with extremely low birth weight, developing severe bronchopulmonary dysplasia and in need of mechanical ventilation for 155 days. He also had five recurrent infections with group B streptococcus (GBS) within 4 months from birth, and his respiratory condition clearly deteriorated with every GBS infection. It was difficult to wean him from mechanical ventilation. Finally he was extubated when he was 7 months old and kept out of mechanical ventilation after receiving high-dose methylprednisolone, given according to international recommendations. After GBS was cultured for the fifth time, he received oral rifampicin along with intravenous penicillin and after this treatment, GBS did not occur again. At the age of 22 months, the boy no longer needed any respiratory support and he was about 6 months late in his neurological development.

Pediatric Expression of Mast Cell Activation Disorders.

Mast cell activation disorders is a term proposed to cover diseases and conditions related to activation of mast cells and effects of mast cell mediators. In its broadest sense, the term encompasses a wide range of diseases from allergic asthma to rhinoconjunctivitis, urticaria, food allergy, anaphylaxis, mastocytosis, and other conditions where MC activation is contributing to the pathogenesis. This article focuses on clinical presentations, challenges, and controversies in pediatric mastocytosis and gives an overview of current knowledge and areas in need of further research.

The Danish National Database for Asthma.

AIM OF THE DATABASE: Asthma is the most prevalent chronic disease in children, adolescents, and young adults. In Denmark (with a population of 5.6 million citizens), >400,000 persons are prescribed antiasthmatic medication annually. However, undiagnosed cases, dubious diagnoses, and poor asthma management are probably common. The Danish National Database for Asthma (DNDA) was established in 2015. The aim of the DNDA was to collect the data on all patients treated for asthma in Denmark and to monitor asthma occurrence, the quality of diagnosis, and management. STUDY POPULATION: Persons above the age of 6 years, with a specific focus on 6-44 years, are included. The DNDA links three existing nationwide registries of administrative records in the Danish health care system: the National Patient Register, the National Health Insurance Services Register, and the National Prescription Registry. For each year, the inclusion criteria are a second purchase of asthma prescription medicine within a 2-year period (National Prescription Registry) or a diagnosis of asthma (National Patient Register). Patients with chronic obstructive pulmonary disease are excluded, but smokers are not excluded. DESCRIPTIVE DATA: A total of 366,471 prevalent patients with asthma have been identified (year 2014 - as a preliminary test search). This number is in agreement with the estimates of ~400,000 inhabitants that are available for patients with possible asthma in Denmark. Data encompass the following quality indicators: annual asthma control visits and pharmacological therapy. MAIN VARIABLES: The variables included are spirometry, as well as tools for diagnosis (including allergy testing), smoking status, height, weight, and acute hospital admissions and unscheduled visits. CONCLUSION: DNDA is available from January 1, 2016.

The Danish National Database for Asthma: establishing clinical quality indicators.

Asthma is one of the most common chronic diseases worldwide affecting more than 300 million people. Symptoms are often non-specific and include coughing, wheezing, chest tightness, and shortness of breath. Asthma may be highly variable within the same individual over time. Although asthma results in death only in extreme cases, the disease is associated with significant morbidity, reduced quality of life, increased absenteeism, and large costs for society. Asthma can be diagnosed based on report of characteristic symptoms and/or the use of several different diagnostic tests. However, there is currently no gold standard for making a diagnosis, and some degree of misclassification and inter-observer variation can be expected. This may lead to local and regional differences in the treatment, monitoring, and follow-up of the patients. The Danish National Database for Asthma (DNDA) is slated to be established with the overall aim of collecting data on all patients treated for asthma in Denmark and systematically monitoring the treatment quality and disease management in both primary and secondary care facilities across the country. The DNDA links information from population-based disease registers in Denmark, including the National Patient Register, the National Prescription Registry, and the National Health Insurance Services register, and potentially includes all asthma patients in Denmark. The following quality indicators have been selected to monitor trends: first, conduction of annual asthma control visits, appropriate pharmacological treatment, measurement of lung function, and asthma challenge testing; second, tools used for diagnosis in new cases; and third, annual assessment of smoking status, height, and weight measurements, and the proportion of patients with acute hospital treatment. The DNDA will be launched in 2016 and will initially include patients treated in secondary care facilities in Denmark. In the nearby future, the database aims to include asthma diagnosis codes and clinical data registered by general practitioners and specialised practitioners as well.

A child with mastocytosis and lymphomatoid papulosis.

A change in clinical behavior of a disease should prompt search for differential diagnoses. Here, the appearance of ulcerated skin nodules in a preexisting cutaneous mastocytosis revealed a concurrent lymphomatoid papulosis - a CD30+ lymphoproliferative skin disease with histological features of a malignant lymphoma, but with a benign self-healing course.

[Mastocytosis]. / Mastocytose.

Mastocytosis is a heterogeneous disease with an increased number and activation of mast cells. Subtypes range from benign to rare aggressive forms, and the disease may affect people of all ages. The pathogenesis involves mutations in the KIT gene in both children and adult patients. Estimated prevalence is one per 10,000, but the disease is very likely underdiagnosed. The diagnosis may be challenging and patients may present to several medical specialties. This article presents an overview of clinical signs and symptoms as well as a diagnostic algorithm and treatment options of mastocytosis.

Multidisciplinary Management of Mastocytosis: Nordic Expert Group Consensus.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.