How does the changing profile of infants referred for ECMO affect the overall respiratory outcome?

Objective: Extracorporeal Membrane Oxygenation (ECMO) has been shown to be effective in full-term neonates with severe but reversible lung disease within the context of randomized controlled trial. Since this trial, ECMO has been open to a wider population of infants in the UK and other treatments have become available. The population referred for ECMO has therefore changed. The aims of this study were (i) to compare respiratory outcomes of infants receiving ECMO in recent years with those from ten years ago, and (ii) to see if respiratory outcome varied with diagnostic group. Methods: All infants referred to a single ECMO centre below the age of 12 months over a 7-year period were eligible. They attended the laboratory one year after ECMO for measurements of lung volume, airways conductance, maximum expiratory flow, and indices of tidal breathing. Results: One hundred and six (77% of those eligible) were tested and results compared with 51 infants referred for ECMO as part of the original UK ECMO trial. The groups were of comparable weight and length. Lung volume was not different but there was a strong trend for the infants seen in more recent years to have better forced expiratory flow and specific airway conductance. Restricting analysis to the major sub-group (Meconium Aspiration) confirmed these findings. When divided into diagnostic subgroups, those infants requiring ECMO for respiratory distress syndrome or who were over 2 weeks when commencing ECMO had a poorer respiratory outcome than others. Conclusions: The respiratory outcome of infants treated beyond the tightly-regulated criteria of the UK trial remains good and even shows a trend towards improvement. Certain subgroups require ECMO for longer and have poorer pulmonary function when followed up. This is important when providing information to parents and may have implications for workload planning of ECMO units and future healthcare provision

Airway eosinophils in older teenagers with outgrown preschool wheeze: a pilot study.

Preschool wheezing affects one-third of all children growing up in the UK [1]. It varies in clinical presentation and severity, and there is evidence to suggest the co-existence of different wheeze phenotypes [2], some of which have been associated with adult asthma and chronic obstructive pulmonary disease [3]. Using data from the Leicester Respiratory Cohort studies [4], we have previously applied objective data-driven methods to distinguish three distinct preschool wheeze phenotypes: “atopic” and “non-atopic” persistent wheeze (PW) and transient viral wheeze (TVW) [5]. In children with PW, attacks of wheeze with and without colds were observed both at preschool age (0–5 years) and when followed-up at early school-age (4–8 years). Children with TVW, triggered predominantly by colds, had symptoms at age 0–5 years but not at age 4–8 years. Prognosis 5 years later (aged 8–13 years) was markedly better in children with TVW compared to the two PW phenotypes [6]

Breastfeeding and Respiratory Tract Infections during the First 2 Years of Life.

Breastfeeding protects against respiratory tract infections (RTIs) in infants [1–3], but whether its effects persist beyond that age is not well understood. Some studies have reported that protection diminishes soon after weaning [2], while others have found that it extends until the age of 2 years [4] or more [5, 6]. It is noteworthy that many previous studies grouped RTIs broadly into upper or lower tract infections, rather than studying specific diseases [3, 7], and few adjusted adequately for confounding factors [5] or investigated a possible effect modification by sex, which had been suggested by several studies showing a stronger protection in girls [8, 9]. This study aimed to quantify the protective effect of breastfeeding against RTIs during the first 2 years of life, while adjusting for potential confounding factors and testing whether the effect varied by sex. We analysed data from the Leicester Respiratory Cohorts, a population-based random sample of children from Leicestershire, UK, which has been described in detail elsewhere [10]. For this analysis we included only children born between 1996 and 1997 who were aged 1–1.99 years at the date of the first survey in 1998. Parents completed a standardised questionnaire that requested detailed information on breastfeeding and respiratory symptoms. We assessed the duration of breastfeeding (no breastfeeding, ⩽6 months or >6 months), the prevalence of frequent colds (>6 episodes), ear infections and croup within the last 12 months, and any episodes of bronchiolitis or pneumonia. We extracted perinatal data and demographic information from maternity records. The Leicestershire Health Authority Research Ethics Committee approved the study. The survey requested information on a number of RTIs for each child, so we first performed an omnibus logistic regression to determine whether breastfeeding was associated with the occurrence of any RTI. By reforming the data into long format, this omnibus logistic regression also adjusted for the clustering of observations within each child [11]. Following a significant omnibus test, we performed unadjusted and adjusted logistic regressions to determine which RTIs were affected by breastfeeding practice. Adjusted models controlled for sex, ethnicity, socioeconomic status (Townsend deprivation score [12]), perinatal factors (gestational age, birthweight, birth season), environmental factors ( pre- and post-natal maternal smoking, number of older siblings, day care attendance) and parental history of asthma, hay fever and bronchitis. We tested for effect modification by sex by adding interaction terms into adjusted models. Finally, we performed a sensitivity analysis including a subgroup of children with information on exact breastfeeding duration, by using breastfeeding as a continuous exposure, rather than categorical. All analyses were performed in Stata (version 14.2, Stata Corporation, Austin, TX, USA). The survey in 1998 was sent to 5400 families with children aged between 1 and 1.99 years. Questionnaires were returned by 4100 parents (response rate of 76%). After excluding 47 children who had no breastfeeding information and 13 children born extremely prematurely (gestational age of <28 weeks [13]), 4040 children remained in the analysis. Of these, 52% were boys, 81% were white and 19% were of South Asian ethnic origin, 1659 (41%) had never been breastfed, 1639 (41%) had been breastfed for ⩽6 months and 742 (18%) for >6 months. Of the 4040 included children, 769 (19%) were reported by their parents to have had frequent colds, 1685 (42%) ear infections and 293 (7%) croup within the last 12 months. Any episodes of bronchiolitis were reported for 453 children (11%) and pneumonia for 53 (1%

Association between breastfeeding and eczema during childhood and adolescence: A cohort study.

BACKGROUND: Breastfeeding is said to protect children from eczema (atopic dermatitis), but the available evidence is conflicting and subject to the influences of parental atopy and reverse causation (when mothers extended duration of breastfeeding because their children had eczema). METHODS: In the prospective, population-based Leicester Respiratory Cohort study, we assessed duration of breastfeeding in children aged 1-4 years. Prevalence of eczema was determined by questionnaire surveys that were repeated until the children were 17 years old. We investigated the association between having been breastfed and current eczema using generalized estimating equations, adjusting for potential confounders, and tested for effect modification by parental atopy. We also assessed the association between having been breastfed and incident eczema at ages 2, 4, and 6 years using multivariable logistic regression. RESULTS: Among the 5,676 children in the study, 2,284 (40%) had never been breastfed, while 1,610 (28%), 705 (12%), and 1,077 (19%) had been breastfed for 0-3, 4-6, and >6 months, respectively. Prevalence of current eczema decreased from 36% in 1-year-olds to 18% in children aged 10-17 years. Breastfeeding was not associated with current eczema. Compared with children who had never been breastfed, the adjusted odds ratios for current eczema at any age were 1.02 (95% confidence interval 0.90-1.15) for children who had been breastfed for 0-3 months, 0.97 (0.82-1.13) for children breastfed for 4-6 months, and 0.98 (0.85-1.14) for children breastfed for >6 months. There was no strong evidence for an effect modification by parental atopy (p-value for interaction term was 0.061) and no association between having been breastfed and incident eczema later in childhood. CONCLUSIONS: This population-based cohort study found no evidence for protection of breastfeeding against childhood eczema at any age, from infancy through adolescence

Longitudinal Associations between Respiratory Infections and Asthma in Young Children.

We examined temporal dependencies between repeated assessments of respiratory infections and asthma in children in the Leicester Respiratory Cohort, Leicestershire, UK. Asthma (doctor diagnosis, health care visits, wheeze frequency) and respiratory infections (cold duration and frequency, cough with colds, ear infections) in the previous 12 months were assessed repeatedly at ages 1, 4, and 6 years for children born between April 1996 and April 1997. We determined associations between contemporaneous and lagged measures of asthma and respiratory infections using structural equation modelling. In 1995 children, asthma was positively associated with contemporaneous infections. Asthma at age 6 was positively associated with asthma at age 4 (regression coefficient = 0.87; 95% CI 0.76, 0.97), but not with asthma at age 1 (-0.01; -0.14, 0.11). We found no evidence for direct protective effect of infections at age 1 on asthma either at age 4 (-0.20; -0.51, 0.10) or 6 (0.24; -0.04, 0.52). Adjusting for potential confounders did not qualitatively change those relationships. Our findings suggest that asthma at age 6 is directly influenced by asthma history and only indirectly if, at all, by earlier infection episodes. We found little support for a protective effect of preschool infections on asthma at early school age

Age-related changes in childhood wheezing characteristics: A whole population study

BACKGROUND: Wheezing illnesses are characterized by phenotypic variability, which changes with age, but few studies report on a wide age range of children. We studied how prevalence, severity, and triggers of wheeze vary throughout childhood. METHODS: We analyzed data from a large population-based cohort of children from Leicestershire, UK, who were followed from infancy through late adolescence using postal questionnaires. We used generalized estimating equations to describe age-related changes in prevalence of any wheeze: episodic viral and multiple trigger wheeze; wheeze triggered by exercise, aeroallergens, food/drinks, laughing/crying; and of severe wheeze (frequent attacks, shortness of breath, sleep disturbance, disturbance of daily activities) from age 1-18 years. We analyzed this in the entire cohort (absolute prevalence) and separately among children with wheeze (relative prevalence). RESULTS: This study included 7670 children. Current wheeze was most common in 1-year-olds (36%) and then decreased in prevalence to reach 17% in children aged 14-17 years. Absolute prevalence of episodic viral wheeze (EVW) decreased with age (from 24% to 7%), while multiple trigger wheeze (MTW) remained relatively constant throughout childhood (8-12%). Among children with wheeze, the proportion with EVW decreased, and the proportion with MTW increased with age. In older children, wheeze triggered by exercise or aeroallergens, and wheeze accompanied by shortness of breath became more frequent, while wheeze triggered by food or laughter, and sleep disturbance decreased in prevalence. CONCLUSION: Knowledge of these age-related changes in wheezing illness is informative for health care planning and the design of future research projects and questionnaires

Towards a metabolomic approach to respiratory disease in childhood: Feasibility and acceptability of a novel breath-sampling procedure and initial breath analysis data

Asthma diagnosis and treatment is based mainly on presence of symptoms and response to treatment. This carries the risk of misdiagnosis and under- or overtreatment. The focus in asthma management has shifted to the underlying chronic airway inflammation. We are developing a novel approach in which breath samples are analysed for volatile organic compounds (VOCs) that alone or in combination may be used as biomarkers for airway inflammation. The aims of the current study are (1) to determine the feasibility and acceptability of the sampling procedures for children aged 8-16 years, and (2) to collect preliminary data on potential candidate markers. [Taken from Introduction and Objectives

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children.

BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent