Dirk Schramm

Early-life determinants of asthma from birth to age 20 years: A German birth cohort study

BACKGROUND The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. OBJECTIVE We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. METHODS In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctors diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). RESULTS Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. CONCLUSION Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS.

The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population‐based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow‐up data from two decades of a birth cohort study.

Prediction and prevention of allergic rhinitis: A birth cohort study of 20 years.

BACKGROUND Allergic rhinitis (AR) is one of the most common chronic diseases, usually starting in the first 2 decades of life. Information on predictors, risk, and protective factors is missing because of a lack of long-term prospective studies. OBJECTIVE Our aim was to examine early-life environmental and lifestyle determinants for AR up to age 20 years. METHODS In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated at 19 time points. A Cox regression model examined the associations between 41 independent early-life factors and onset of AR (as the primary outcome), including sensitization against aeroallergens and the secondary outcomes of nonallergic rhinitis and AR plus asthma. RESULTS Two hundred ninety subjects had AR within 13,179 person years observed. The risk of AR was higher with a parental history of AR (adjusted hazard ratio [aHR], 2.49; 95% CI, 1.93-3.21), urticaria (aHR, 1.32; 95% CI, 1.00-1.74), or asthma (aHR, 1.29; 95% CI, 0.95-1.75). Early allergic sensitization (aHR, 4.53; 95% CI, 3.25-6.32), eczema within the first 3 years of life (aHR, 1.83; 95% CI, 1.38-2.42), male sex (aHR, 1.28; 95% CI, 1.02-1.61), and birthday in summer or autumn (aHR, 1.26; 95% CI, 1.00-1.58) were independent predictors of AR up to age 20 years. None of the other socioeconomic, environmental, lifestyle, pregnancy, and birth-related factors were associated with AR. CONCLUSION Only nonmodifiable factors, particularly early allergic sensitization or eczema and parental AR, predicted AR up to age 20 years. No modifiable aspects of early-life environment or lifestyle were identified as targets for primary prevention.

Rapid detection and immune characterization of Mycobacterium abscessus infection in cystic fibrosis patients.

Cystic fibrosis patients are highly susceptible to infections with non-tuberculous mycobacteria. Especially Mycobacterium abscessus infections are common but reliable diagnosis is hampered by non-specific clinical symptoms and insensitive mycobacterial culture. In the present study we established novel methods for rapid detection and immune characterization of Mycobacterium abscessus infection in cystic fibrosis patients. We performed Mycobacterium abscessus specific DNA-strip- and quantitative PCR-based analyses of non-cultured sputum samples to detect and characterize Mycobacterium abscessus infections. Concomitantly in vitro T-cell reactivation with purified protein derivatives (PPDs) from different mycobacterial species was used to determine Mycobacterium abscessus specific T-cell cytokine expression of infected cystic fibrosis patients. Four of 35 cystic fibrosis patients (11.4%) were Mycobacterium abscessus culture positive and showed concordant DNA-strip-test results. Quantitative PCR revealed marked differences of mycobacterial burden between cystic fibrosis patients and during disease course. Tandem-repeat analysis classified distinct Mycobacterium abscessus strains of infected cystic fibrosis patients and excluded patient-to-patient transmission. Mycobacterium abscessus specific T-cells were detected in the blood of cystic fibrosis patients with confirmed chronic infection and a subgroup of patients without evidence of Mycobacterium abscessus infection. Comparison of cytokine expression and phenotypic markers revealed increased proportions of CD40L positive T-cells that lack Interleukin-2 expression as a marker for chronic Mycobacterium abscessus infections in cystic fibrosis patients. Direct sputum examination enabled rapid diagnosis and quantification of Mycobacterium abscessus in cystic fibrosis patients. T-cell in vitro reactivation and cytokine expression analyses may contribute to diagnosis of chronic Mycobacterium abscessus infection.

What does lung function tell us about respiratory multimorbidity in childhood and early adulthood? Results from the MAS birth cohort study

Interaction between respiratory multimorbidity and lung function has not been examined in longitudinal population studies. We aimed to assess the association of multimorbidity of asthma and rhinitis with lung function and bronchial hyperresponsiveness in comparison with single and no allergies from early school age to young adulthood.

Foreign body removal in children: Recommendations versus real life—A survey of current clinical management in Germany

Task forces of the European Respiratory Society (ERS, 2003) and the American Thoracic Society (ATS, 2015) both recommend rigid bronchoscopy for foreign body removal in children. However, there is an increasing number of publications recommending flexible bronchoscopy as primary method for foreign body removal in children.

Presumed Arterial Gas Embolism After Breath-Hold Diving in Shallow Water

Dive-related injuries are relatively common, but almost exclusively occur in recreational or scuba diving. We report 2 children with acute central nervous system complications after breath-hold diving. A 12-year-old boy presented with unilateral leg weakness and paresthesia after diving beneath the water surface for a distance of ∼25 m. After ascent, he suddenly felt extreme thoracic pain that resolved spontaneously. Neurologic examination revealed right leg weakness and sensory deficits with a sensory level at T5. Spinal MRI revealed a nonenhancing T2-hyperintense lesion in the central cord at the level of T1/T2 suggesting a spinal cord edema. A few weeks later, a 13-year-old girl was admitted with acute dizziness, personality changes, confusion, and headache. Thirty minutes before, she had practiced diving beneath the water surface for a distance of ∼25 m. After stepping out, she felt sudden severe thoracic pain and lost consciousness. Shortly later she reported headache and vertigo, and numbness of the complete left side of her body. Neurologic examination revealed reduced sensibility to all modalities, a positive Romberg test, and vertigo. Cerebral MRI revealed no pathologic findings. Both children experienced a strikingly similar clinical course. The chronology of events strongly suggests that both patients were suffering from arterial gas embolism. This condition has been reported for the first time to occur in children after breath-hold diving beneath the water surface without glossopharyngeal insufflation.

Lung function trajectories using different reference equations in a birth cohort study up to the age of 20 years

New spirometry reference values from the Global Lung Function Initiative (GLI) and the LUNOKID (Lungenfunktions-Normalwerte bei Kindern in Deutschland [Lung function Normal Values of Children in Germany]) study were published in 2012 and 2013, respectively, using a nonlinear model for lung function trajectories [1–3]. There is a lack of empirical testing of these new equations and reference values in longitudinal cohort studies. Lung function trajectories using different reference equations in a birth cohort up to the age of 20 years show a drop in FEV1 and FVC of both asthmatic and nonasthmatic subjects at the age of 13 years regardless of which reference equations were used http://ow.ly/hxGJ30ktUYE