Childhood asthma after bacterial colonization of the airway in neonates.

BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life. METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age. RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively). CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.

Intermittent inhaled corticosteroids in infants with episodic wheezing.

BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study. RESULTS: We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group (absolute difference, 1 percent; 95 percent confidence interval, -4.8 to 6.9 percent). Twenty-four percent of children in the budesonide group had persistent wheezing, as compared with 21 percent in the placebo group (hazard ratio, 1.22; 95 percent confidence interval, 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis. The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status. Height and bone mineral density were not affected by treatment. CONCLUSIONS: Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. (ClinicalTrials.gov number, NCT00234390.).

Fatty acid composition of human milk in atopic Danish mothers.

BACKGROUND: Atopic dermatitis has been related to a disturbed metabolism of polyunsaturated fatty acids (PUFAs). OBJECTIVE: We tested whether the PUFA composition of breast milk differs significantly between mothers with atopic dermatitis, mothers with other types of atopy, and nonatopic mothers. We also investigated whether differences in diet can explain possible observed differences. DESIGN: Mothers with current or previous asthma (n = 396) were divided into 3 groups according to history of atopic dermatitis and allergic rhinitis. Breast-milk samples were collected from 314 women approximately 3 wk after delivery. The habitual diet of the women was assessed with food-frequency questionnaires in the 25th week of gestation (n = 207). Breast-milk samples and simultaneous dietary data from 14 nonatopic mothers were used for comparison. RESULTS: Compared with the milk of nonatopic mothers, that of atopic mothers had significantly higher concentrations of 22:5n-6 and lower concentrations of 20:5n-3; moreover, 20:4n-6/20:5n-3, 22:5n-6/22:6n-3, and long-chain n-3 PUFA/18:3n-3 were shifted toward n-6 PUFA and 18:3n-3 in nonatopic and atopic mothers, respectively. No differences in breast-milk PUFA composition were evident between the subject groups. The diets of the groups differed only slightly with respect to protein intake. However, the PUFA composition of the breast milk was associated with diet and time of milk sampling, and the above difference in milk PUFAs disappeared when those factors were taken into account. CONCLUSION: Our data do not support the possibility that the fatty acid composition of breast milk is affected by atopic dermatitis or atopy in general, because most differences in breast-milk PUFA composition appear to be explained by the diet.

Sensitivity of bronchial responsiveness measurements in young infants.

OBJECTIVES: There is limited evidence on the preferred methods for evaluating lung function in infancy. The objective of this study was to compare sensitivity and repeatability of indexes of lung function in young infants during induced airway obstruction. METHODS: The study population consisted of 402 infants (median age, 6 weeks). Forced flow-volume measurements were obtained by the raised volume rapid thoracoabdominal compression technique and were compared with indexes of tidal breathing, measurements of transcutaneous oxygen (Ptco(2)), and auscultation during methacholine challenge testing. RESULTS: Ptco(2) was the most sensitive parameter to detect increasing airway obstruction during methacholine challenge, followed by forced expiratory volume at 0.5 s (FEV(0.5)). Both were superior to other indexes of forced spirometry as well as tidal breathing indexes and auscultation. Coefficients of variations for Ptco(2) and FEV(0.5) were 4% and 7%, respectively. CONCLUSIONS: Ptco(2) and FEV(0.5) are the most sensitive parameters for measurement of bronchial responsiveness in young infants. Measurements of baseline lung function should preferably be made using FEV(0.5.) Measurements of bronchial responsiveness are best assessed using Ptco(2), which may be performed in nonsedated infants and improve feasibility of future studies on lung function in infancy.

Development of atopic dermatitis during the first 3 years of life: the Copenhagen prospective study on asthma in childhood cohort study in high-risk children.

OBJECTIVES: To describe the development of atopic dermatitis (AD) during the first 3 years of life and identify the localization of the early skin lesions that predicts the development of AD. DESIGN: Prospective, longitudinal, birth cohort study of children born to mothers with a history of asthma, followed up for 3 years with scheduled visits every 6 months as well as visits for onset or acute exacerbations of skin symptoms. SETTING: The cohort was recruited from greater Copenhagen, Denmark, and followed up at a clinical research unit, which controlled all diagnoses and treatment of skin diseases. PARTICIPANTS: A total of 411 infants were enrolled in the cohort; 55 had incomplete follow-up and were excluded from certain analyses. MAIN OUTCOME MEASURES: Atopic dermatitis was defined based on the criteria of Hanifin and Rajka, and severity was assessed by the SCORAD (Scoring Atopic Dermatitis) index. Predictive odds ratios of early skin lesions for those who developed AD vs those who did not were calculated. RESULTS: The cumulative incidence of AD by age 3 years was 44% (155/356). The prevalence rate peaked at age 2 years for boys and at age 2.5 years for girls, but there were no other sex differences in the proportion of children developing AD. Skin involvement in infants with AD was found to begin at the scalp, forehead, ear, and neck in a balaclava-like pattern and continue to the extensor sides and trunk, finally affecting the flexor sides of the extremities. Early skin lesions of arms and joints best predicted AD at age 3 years. CONCLUSIONS: Atopic dermatitis begins at the scalp, forehead, ear, and neck in a balaclava-like pattern. Eczema at the arms and joints provides the highest predictive value for the development of AD at age 3 years. This may be used for early prediction and intervention of AD.

Cutaneous necrotic ulceration due to BCG re-vaccination.

The case report describes a severe local reaction with large cutaneous necrotic ulcer following bacillus Calmette-Guérin (BCG) re-vaccination. This is a very rare adverse event, and only a few reports have been described in the literature.

[Pancreatic panniculitis is necrosis of adipocytes in the subcutis followed by intense pain]. / Pankreatisk pannikulitis er nekrose af fedtceller i subcutis ledsaget af intense smerter.

We report an unusual history of pain in a young patient in the intensive care unit. A 33 year-old alcoholic male with acute pancreatitis had generalized intense pain and developed erythema on the lower truncus and the lower extremities. Treatment with different antibiotics, antihistamines and topical potent steroid cream were all ineffective. A biopsy showed necrotic adipocytes characteristic for pancreatic panniculitis. We suggest that pancreatic panniculitis should be considered in patients with erythema, pain and known pancreatic disease.

Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population.

BACKGROUND: Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development. OBJECTIVE: To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life. METHOD: The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors. RESULTS: 177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05-1.99 p=0.024). This conclusion was unaffected after adjustment for smoking, mother's education and mother's atopic dermatitis. LIMITATIONS: The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection. CONCLUSION: Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.

Causal direction between respiratory syncytial virus bronchiolitis and asthma studied in monozygotic twins.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis has been associated with later development of asthma, wheezing, abnormal pulmonary function, and sensitization. Our aim was to determine the differential effect within monozygotic (MZ) twin pairs discordant for severe RSV bronchiolitis in infancy on the subsequent development of asthma, pulmonary function, and allergy. METHODS: Thirty-seven MZ twin pairs discordant for RSV hospitalization in infancy (mean age 10.6 months) were compared at the mean age of 7.6 years for lung function, bronchial responsiveness, fractional exhaled nitric oxide (Feno), asthma diagnosis, use of asthma medication, and skin prick test to common inhalant allergens. RESULTS: There were no differences within MZ twin pairs discordant for RSV hospitalization in infancy with respect to pulmonary function, Feno, asthma prevalence, asthma medication use, or sensitization (P > .1 for all comparisons). CONCLUSIONS: We found no differential effect from severity of RSV infection on the development of asthma and allergy in MZ twin pairs discordant for RSV hospitalization in infancy. This argues against a specific effect of severe RSV infection in the development of asthma and allergy. Because of the small sample size, this study must be considered as a hypothesis-generating study.