Height and bone mineral content after inhaled corticosteroid use in the first 6 years of life.

BACKGROUND: Infants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied in long-term prospective studies. METHODS: Children from two Copenhagen Prospective Studies on Asthma in Childhood cohorts were included. ICS use was registered prospectively from birth to age 6 and the cumulative dose was calculated. Primary outcomes were height and BMC from dual-energy X-ray absorptiometry (DXA) scans at age 6. RESULTS: At age 6, a total of 930 children (84%) from the cohorts had a valid height measurement and 792 (71%) had a DXA scan. 291 children (31%) received a cumulated ICS dose equivalent to or above 10 weeks of standard treatment before age 6. We found an inverse association between ICS use and height, -0.26 cm (95% CI: -0.45 to -0.07) per 1 year standard treatment from 0 to 6 years of age, p=0.006. This effect was mainly driven by children with ongoing treatment between age 5 and 6 years (-0.31 cm (95% CI: -0.52 to -0.1), p=0.004), while there was no significant association in children who stopped treatment at least 1 year before age 6 (-0.09 cm (95% CI: -0.46 to 0.28), p=0.64). There was no association between ICS use and BMC at age 6. CONCLUSIONS: ICS use in early childhood was associated with reduced height at age 6 years but only in children with continued treatment in the sixth year of life.

Associations between Inhaled Corticosteroid Use in the First 6 Years of Life and Obesity-related Traits.

Rationale: Infants and young children might be particularly likely to experience the potential clinical side effects of inhaled corticosteroids (ICSs) on body mass index (BMI), adiposity rebound (AR), and body composition, but this has rarely been studied in long-term studies in this age group. Objectives: To determine the association between ICS exposure in the first 6 years of life and the BMI, AR, body composition, and blood lipid concentrations. Methods: Children from the two mother-child cohorts of the COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) were included. ICS use was registered prospectively to age 6 years, and the cumulative dose was calculated. Multiple linear regression models were used for analysis. Measurements and Main Results: A total of 932 (84%) of the 1,111 children from the COPSAC cohorts had BMI data, 786 (71%) had dual-energy X-ray absorptiometry scan data at the age of 6 years, and 815 (73%) had an AR age calculated. Two hundred ninety-one children (31%) received a cumulative ICS dose higher than that from 10 weeks of standard treatment before the age of 6. ICS treatment during 0-6 years of age was associated with an increased BMI z-score (0.05 [95% confidence interval, 0.005 to 0.09] SDs per each year of standard treatment; P = 0.03) an earlier age at AR (-0.18 [95% confidence interval, -0.28 to -0.08] yr; P = 0.0006), and a 2% increased geometric mean android fat percentage (P = 0.05). ICS exposure and dual-energy X-ray absorptiometry scan data were not associated. Conclusions: ICS use in early childhood was associated with an increased BMI z-score at age 6, an earlier AR, and a trend of association with an increased android body fat percentage.

Findings in Danish long-term care facilities in the first year of the SARS-CoV-2 pandemic.

PURPOSE: To describe the occurrence of SARS-CoV-2 infections, deaths and outbreaks among residents in Danish long-term care facilities (LTCFs) from February 2020 to February 2021. METHODS: Danish COVID-19 national register data from a newly implemented automated surveillance system was used to describe incidence rate and deaths (per 1000 residents' years), number of tests, SARS-CoV-2 infections and outbreaks among LTCF residents. A case was defined as a LTCF resident with a positive SARS-CoV-2 PCR test. An outbreak was defined as two or more cases in one LTCF within a 14-day period, and considered closed if no new cases had occurred within 28 days. Death was defined as occurring within 30-days of a positive test. RESULTS: A total of 55,359 residents living in 948 LTCFs were included. The median age of the residents was 85 years and 63% were female. There was a total of 3712 cases found among residents across 43% of all LTCFs. Nearly all (94%) cases were linked to outbreaks. Higher numbers of cases and outbreaks were seen in Denmark's Capital Region compared to other regions. Overall, 22 SARS-CoV-2 deaths and 359 deaths (non-SARS-CoV-2) per 1000 resident years were identified in the study period. CONCLUSION: Less than half of LTCFs identified any cases. The majority of cases were linked to outbreaks, emphasizing the importance of preventing introductions of SARS-CoV-2 into the facilities. Furthermore, it highlights the need to invest efforts into infrastructures, routine procedures and monitoring of SARS-CoV-2 in LTCFs to limit the introduction and the spread of SARS-CoV-2.

Children with Asthma Have Fixed Airway Obstruction through Childhood Unaffected by Exacerbations.

BACKGROUND: Children with asthma may have a disease course with or without exacerbations, but the relationship between exacerbations and lung function development is poorly understood. OBJECTIVE: To compare lung function trajectories from birth till adolescence in asthmatic children with and without exacerbations. METHODS: Children with asthma from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) birth cohort had lung function and bronchial reactivity assessed repeatedly from 1 month to 13 years. Exacerbations were diagnosed at the COPSAC clinic defined as symptoms requiring hospitalization, oral or high-dose inhaled corticosteroid treatment. Mixed models were applied to analyze lung function trajectories. RESULTS: Children with asthma with exacerbations (N = 50) had a trajectory of increased, fixed airway obstruction compared with children without exacerbations (N = 47): z-score difference in airway resistance (sRawz) (95% confidence interval [CI]): +0.34 (+0.03; +0.66), P = .03, and maximal mid-expiratory flow (MMEFz): -0.41 (-0.69; -0.13), P = .004, but no differences in forced expiratory volume (FEVz): -0.14 (-0.41; +0.13), P = .29, or bronchial reactivity to methacholine (PDz): +0.08 (-0.26; +0.42), P = .65. This did not change comparing lung function trajectories before and after exacerbations: z-score difference (95% CI) sRawz: -0.04 (-0.35; 0.27), P = .80; MMEFz: 0.01 (-0.02; 0.04), P = .55; FEVz: 0.02 (-0.02; 0.05), P = .42; and PDz: -0.01 (-0.06; 0.05), P = .88. CONCLUSION: Children with asthma with exacerbations compared with children with asthma without exacerbations are characterized by increased airway obstruction since infancy through childhood. The airway obstruction is a fixed trajectory without progression due to exacerbations, suggesting that exacerbations are a consequence rather than a cause of diminished airway caliber in childhood.

Publisher Correction: Maturation of the gut microbiome and risk of asthma in childhood.

The originally published version of this Article contained an incorrect version of Figure 3 that was introduced following peer review and inadvertently not corrected during the production process. Both versions contain the same set of abundance data, but the incorrect version has the children's asthma status erroneously disconnected from the abundance data, thereby producing the non-representative p values and graphic presentations. These errors have now been rectified, with the correct version of Figure 3 replaced in both the PDF and HTML versions of the Article.

Maturation of the gut microbiome and risk of asthma in childhood.

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.