Are BMI and adipokines associated with asthma, atopy and lung function in young adults previously hospitalized for bronchiolitis?

BACKGROUND: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects. METHODS: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms. RESULTS: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group. CONCLUSION: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism.

Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight.

BACKGROUND: Lifelong pulmonary consequences of being born extremely preterm or with extremely low birth weight remain unknown. We aimed to describe lung function trajectories from 10 to 35 years of age for individuals born extremely preterm, and address potential cohort effects over a period that encompassed major changes in perinatal care. METHODS: We performed repeated spirometry in three population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g during 1982-85, 1991-92 and 1999-2000, referred to as extremely preterm-born, and in term-born controls matched for age and gender. Examinations were performed at 10, 18, 25 and 35 years. Longitudinal data were analysed using mixed models regression, with the extremely preterm-born stratified by bronchopulmonary dysplasia (BPD). RESULTS: We recruited 148/174 (85%) eligible extremely preterm-born and 138 term-born. Compared with term-born, the extremely preterm-born had lower z-scores for forced expiratory volume in 1 s (FEV1) at most assessments, the main exceptions were in the groups without BPD in the two youngest cohorts. FEV1 trajectories were largely parallel for the extremely preterm- and term-born, also during the period 25-35 years that includes the onset of the age-related decline in lung function. Extremely preterm-born had lower peak lung function than term-born, but z-FEV1 values improved for each consecutive decade of birth (p=0.009). More extremely preterm-than term-born fulfilled the spirometry criteria for chronic obstructive pulmonary disease, 44/148 (30%) vs 7/138 (5%), p<0.001. CONCLUSIONS: Lung function after extremely preterm birth tracked in parallel, but significantly below the trajectories of term-born from 10 to 35 years, including the incipient age-related decline from 25 to 35 years. The deficits versus term-born decreased with each decade of birth from 1980 to 2000.

Asthma, atopy and lung function in young adults after hospitalisation for bronchiolitis in infancy: impact of virus and sex.

BACKGROUND: Hospitalisation for bronchiolitis is a risk factor for asthma and impaired lung function during childhood, but outcomes in young adults are poorly described. Our primary aim was to study the prevalence of asthma and atopy, and lung function at 17-20 years of age after bronchiolitis in infancy and, secondarily, the impact of viral aetiology (respiratory syncytial virus (RSV) vs non-RSV) and sex on these outcomes. METHODS: This Norwegian cohort study enrolled 225 young adults hospitalised for bronchiolitis in infancy during 1996-2001 and 167 matched control subjects. The follow-up included questionnaires for asthma and examinations of lung function and atopy. Outcomes were analysed by mixed effects regressions. RESULTS: Current asthma was more frequent in the postbronchiolitis group versus the control group: 25.1% (95% CI 19.0% to 31.2%) vs 13.1% (95% CI 7.9% to 18.2%), but not atopy: 44.3% (95% CI 37.1% to 51.5%) vs 48.2% (95% CI 40.5% to 55.8%), adjusted predicted proportions (95% CIs). Asthma prevalence did not differ between the RSV group and the non-RSV group: 24.0% (95% CI 16.1% to 32.0%) vs 23.8% (95% CI 12.8% to 34.7%) nor between sexes. Forced expiratory volume in 1 s (FEV1), the ratio FEV1/forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC, were lower in the postbronchiolitis group. CONCLUSION: Young adults hospitalised for bronchiolitis had higher prevalence of asthma, but not atopy, and a more obstructive lung function pattern than control subjects. The asthma prevalence was high after both RSV bronchiolitis and non-RSV bronchiolitis, and there was no difference between sexes. Bronchiolitis in infancy is associated with respiratory morbidity persisting into young adulthood.

Early life growth and associations with lung function and bronchial hyperresponsiveness at 11-years of age.

Low birthweight and being born small-for-gestational age (SGA) are linked to asthma and impaired lung function. Particularly, poor intrauterine growth followed by rapid catch-up growth during childhood may predispose for respiratory disease. Bronchial hyperresponsiveness (BHR) is an essential feature of asthma, but how foetal and early childhood growth are associated with BHR is less studied. Our hypothesis was that children born SGA or with accelerated early life growth have increased BHR and altered lung function at 11-years of age. We studied the associations between SGA and early childhood growth with lung function and BHR at 11-years of age in a subgroup of 468 children from the Norwegian Mother, Father and Child Cohort Study (MoBa), and included data from the Medical Birth Registry of Norway (MBRN). Weight at 6 months of age was positively associated with forced vital capacity (adjusted Beta: 0.121; 95% Confidence interval: 0.023, 0.219) and negatively associated with the ratio of forced expiratory flow in first second/forced vital capacity (-0.204; -0.317, -0.091) at 11-years of age. Similar patterns were found for weight at 36 months and for change in weight from birth to 6 months of age. SGA or other various variables of early childhood growth were not associated with BHR at 11-years of age. Early life growth was associated with an obstructive lung function pattern, but not with BHR in 11-year old children. Foetal growth restriction or weight gain during early childhood do not seem to be important risk factors for subsequent BHR in children.

Adipokines in adolescence; the associations with lung function and atopy - A cross-sectional study.

Both inflammatory and mechanical effects have been proposed to explain the increased risk of asthma and reduced lung function observed in obese children and adults. The evidence regarding the potential role of obesity in the aetiology of atopy and allergy is more conflicting. The adipokines leptin and adiponectin are inflammatory markers of fat metabolism which may be involved in explaining the increased risk of asthma and reduced lung function in obese children and adults. In this cross-sectional study, we aimed to study how adiponectin and leptin were associated with lung function and atopic sensitisation in adolescents. The study included 384 children at mean age 12.9 years with measurements of adiponectin, leptin, lung function and atopic sensitisation. Adiponectin and leptin levels were measured in serum, lung function was measured by spirometry and atopic sensitisation was measured by serum specific Immunoglobulin E. In linear regression models, leptin was negatively associated with forced vital capacity (FVC) (Beta: -4.13; 95% Confidence Interval: -5.83, -2.44, P < 0.001) and forced expiratory volume in the first second (FEV1) (-3.74; -5.39, -2.09, P < 0.001) after adjusting for body mass index (BMI) and other covariates. No associations were observed between adiponectin and lung function or between leptin or adiponectin and atopic sensitisation. In this cross-sectional analysis of adolescents in all weight classes, leptin was negatively associated with FEV1 and FVC independent of BMI, but no associations were found between adiponectin and lung function. The results suggest that leptin may have a functional role in the airways of healthy children.

Half of children with recurrent or chronic wet cough before three years of age were symptom-free by age seven.

AIM: We aimed to study the natural course of recurrent episodic and chronic wet cough in preschool children, the proportion and age of resolution, and risk factors for persistent symptoms. METHODS: Parents of children with recurrent or chronic wet cough who had attended the outpatient clinic before the age of three years during 2010-2013 at Stavanger University Hospital, Norway, answered a questionnaire regarding clinical symptoms and current medication at a follow-up in 2017-2018. RESULTS: We invited 840 children to participate, and parents consented for 348 (41.4%) of the children. At the first outpatient visit, 171 children (58.8%) had recurrent episodic and 120 (41.2%) had chronic wet cough. At follow-up at a median age of 82 months, 57.0% in both groups were symptom-free, and 9.4% with episodic cough and 13.3% with chronic cough had more than mild symptoms. During the last 12 months prior to the survey, 27.2% with episodic cough and 18.6% with chronic cough had used inhaled corticosteroids. CONCLUSION: Half of the preschool children with recurrent episodic or chronic wet cough outgrew their symptoms by the median age of seven years, but one in four still used inhaled corticosteroids.

Lung function and bronchial hyper-reactivity from 11 to 18 years in children with bronchiolitis in infancy.

BACKGROUND: Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy. METHODS: Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms. RESULTS: z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV1 ), FEV1 /FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18. CONCLUSION: Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls.

Airway symptoms and atopy in young children prescribed asthma medications: A large-scale cohort study.

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age-intervals (0-6, 6-18, 18-36 months, and 3-7 years). Primary outcomes were dispensed asthma medications (no medication, short-acting ß-2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0-6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups.

Vortex Whistle and Smart Phone Application for Peak Flow Recordings in Asthmatic Children: A Feasibility Study.

Introduction: Variable airflow obstruction that can be confirmed by diurnal variability of peak expiratory flow (PEF) >13% is an important characteristic of asthma. Home monitoring of PEF may be helpful to diagnose and monitor asthma. In this feasibility study, we aimed to study if asthmatic children can measure PEF at home twice daily during a 4-week period using a device designed as a "whistle" and a smart phone software application.Materials and Methods: Twice daily during 4 weeks, children aged 5-12 years with current asthma rated their asthma condition electronically on the smart phone application Blowfish before inhaling deeply then exhaling into the device to produce a high-pitched sound recorded by the application. Through mathematical algorithms, the sound was transferred to PEF, which was uploaded to a server. At inclusion, the Pediatric Asthma Quality of Life Questionnaire and the Childhood Asthma Control Test were answered. At the end, the parents graded the device and application.Results: One child did not manage to upload PEF. For the remaining 21 children, the median (quartiles) days with at least one measurement during the period were 27 (21-29.5), and on median 18 (9-24) days PEF was recorded twice daily. The median parental score (potential score 0-20) of the application was 18 (15-20).Discussion/Conclusion: The study shows promising results for home monitoring of PEF by an electronic device with automatic teletransmission. The high rate of successful recordings and parental satisfaction suggests that the clinical utility of the solution should be further studied.

Prescribing of asthma drugs for children 2004-2015. / Forskrivning av legemidler mot astma til barn i perioden 2004­15.

BAKGRUNN: Astma kan være vanskelig å diagnostisere hos barn. For barn under skolealder finnes det få tilgjengelige objektive diagnostiske undersøkelser, og retningslinjene for diagnose og behandling er basert på sykehistorie og klinisk undersøkelse. Dette kan gi rom for varierende behandlingspraksis. MATERIALE OG METODE: Data fra Reseptregisteret ble brukt til å studere forskrivning av legemidler mot astma til barn i aldersgruppene 0-4 år og 5-9 år fordelt på fylker fra 2004-15. RESULTATER: Det var stor variasjon mellom fylkene i andelen per 1 000 barn som fikk forskrevet legemidler mot astma i perioden 2012-14 (aldersgruppen 0-4 år: median: 104/1 000; ekstremverdier: 64-147, aldersgruppen 5-9 år: 68/1000; 46-86). Inhalasjonssteroider var hyppigst forskrevet, og det var her variasjonen mellom fylkene var størst i begge aldersgruppene (aldersgruppen 0-4 år: 85/1 000; 42-116, aldersgruppen 5-9 år: 51/1 000; 31-70). De fleste fikk kun en eller få forskrivninger med inhalasjonssteroider over en treårsperiode. Endring i forskrivningen av inhalasjonssteroider fra 2004 til 2015 varierte betydelig mellom fylkene, mest for aldersgruppen 0-4 år. FORTOLKNING: Stor forskjell i forskrivning av legemidler mot astma fylkene imellom, høy andel sporadisk bruk og endring over tid, særlig i den yngste aldersgruppen, kan tyde på en unaturlig variasjon i behandlingen som ikke kan forklares av forskjeller i astmaforekomst. Uklare retningslinjer som ikke er tilstrekkelig innarbeidet i klinisk praksis kan være én årsak.

The associations between weight-related anthropometrics during childhood and lung function in late childhood: a retrospective cohort study.

BACKGROUND: An association between body weight in childhood and subsequent lung function and asthma has been suggested, but few longitudinal studies exist. Our aim was to explore whether weight-related anthropometric measurements through childhood were associated with lung function in late childhood. METHODS: From an original nested case-control study, a cohort study was conducted, where lung function was measured in 463 children aged 12.8 years, and anthropometry was measured at several ages from birth through 12.8 years of age. Associations between anthropometrics and lung function were analysed using multiple linear and fractional polynomial regression analysis. RESULTS: Birthweight and body mass index (BMI; kg/m2) at different ages through childhood were positively associated with forced vital capacity in percent of predicted (FVC %) and forced expiratory volume in the first second in percent of predicted (FEV1%) at 12.8 years of age. BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of age and the change in BMI from early to late childhood were positively associated with FVC % and FEV1% and negatively associated with FEV1/FVC and forced expiratory flow at 25-75% of FVC/FVC. Interaction analyses showed that positive associations between anthropometrics other than BMI and lung function were mainly found in girls. Inverse U-shaped associations were found between BMI at the ages of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV1% at 12.8 years of age. CONCLUSIONS: Weight-related anthropometrics through childhood may influence lung function in late childhood. These findings may be physiological or associated with air flow limitation. Inverse U-shaped associations suggest a differential impact on lung function in normal-weight and overweight children. TRIAL REGISTRATION: This study was observational without any health care intervention for the participants. Therefore, no trial registration number is available.

Protracted bacterial bronchitis in children. / Protrahert bakteriell bronkitt hos barn.

Protracted bacterial bronchitis is a common cause of persistent, wet cough in pre-school children. The condition has been described relatively recently, and knowledge of the diagnosis may be an aid to making the correct assessment of children with chronic cough, helping to ensure that the symptoms are not misinterpreted and treated as asthma.

High flow nasal cannula in children: a literature review.

High flow nasal cannula (HFNC) is a relatively new non-invasive ventilation therapy that seems to be well tolerated in children. Recently a marked increase in the use of HFNC has been seen both in paediatric and adult care settings. The aim of this study was to review the current knowledge of HFNC regarding mechanisms of action, safety, clinical effects and tolerance in children beyond the newborn period.We performed a systematic search of the databases PubMed, Medline, EMBASE and Cochrane up to 12th of May 2016. Twenty-six clinical studies including children on HFNC beyond the newborn period with various respiratory diseases hospitalised in an emergency department, paediatric intensive care unit or general ward were included. Five of these studies were interventional studies and 21 were observational studies. Thirteen studies included only children with bronchiolitis, while the other studies included children with various respiratory conditions. Studies including infants hospitalised in a neonatal ward, or adults over 18 years of age, as well as expert reviews, were not systematically evaluated, but discussed if appropriate.The available studies suggest that HFNC is a relatively safe, well-tolerated and feasible method for delivering oxygen to children with few adverse events having been reported. Different mechanisms including washout of nasopharyngeal dead space, increased pulmonary compliance and some degree of distending airway pressure may be responsible for the effect. A positive clinical effect on various respiratory parameters has been observed and studies suggest that HFNC may reduce the work of breathing. Studies including children beyond the newborn period have found that HFNC may reduce the need of continuous positive airway pressure (CPAP) and invasive ventilation, but these studies are observational and have a low level of evidence. There are no international guidelines regarding flow rates and the optimal maximal flow for HFNC is not known, but few studies have used a flow rate higher than 10 L/min for infants.Until more evidence from randomized studies is available, HFNC may be used as a supplementary form of respiratory support in children, but with a critical approach regarding effect and safety, particularly when operated outside of a paediatric intensive care unit.

Prescription patterns of inhaled corticosteroids for preschool children--A Norwegian register study.

BACKGROUND: Although guidelines for treatment of wheeze and asthma in preschool children are available, symptoms are overlapping and it may be difficult to decide which children should be given inhaled corticosteroids (ICS). Previous studies suggest an inappropriate prescription pattern of ICS in this age group. We studied time trends of ICS use in preschool children in Norway during 2004-2013 by age, gender and physician specialty, and the persistence of ICS use during preschool years. METHODS: Data were drawn from the Norwegian Prescription Database. The study population consisted of children ≤5 years who were prescribed ICS (alone or in combination) during 2004-2013. RESULTS: The one-year prevalence of ICS use was generally high, and increased from 2004 to 2010, but decreased thereafter. The prevalence was highest in 2-year-olds (boys 12.9% and girls 9.3% in 2010) and declined by age, and higher among boys in all ages. 40-50% of ICS users received only one prescription per year. The share of children with persistent use of ICS over several preschool years was low, irrespective of the age at the first prescription. The majority of prescriptions were given by general practitioners, increasing during the study period. CONCLUSIONS: The prevalence of ICS prescription for preschool children was high, but with low persistence, suggesting that ICS are frequently given for intermittent asthma-like symptoms. Asthma guidelines suggest a restrictive use of ICS during the first years of life, and the results may call for actions to better implement these guidelines.

Decline in admissions for childhood asthma, a 26-year period population-based study.

BACKGROUND: The prevalence of childhood asthma has increased, although the rate of hospitalization for asthma seems to decrease. In Norway, the rate of hospital admission for childhood asthma from 1984 to 2000 increased. The aim of this study was to assess further trends in hospital admissions for childhood asthma up to 2010. METHODS: A population-based study including children 1-13 yrs of age hospitalized for asthma during six periods from 1984/1985 to 2009/2010 in Rogaland, Norway, was performed. Medical records from 1536 admissions (1050 children) were studied; and gender, age, number of admissions, length of hospital stay, medications and symptoms were recorded. RESULTS: For all age groups, the rate of admissions per 10.000 increased from 20.1 in 1984/85 to 33.7 in 1989/90, but declined to 14.4 in 2009/2010. Rates were highest in boys (OR 1.87; 95% CI: 1.69, 2.09), younger age groups (OR 2.51; 2.38, 2.64) and decreased from 1984 to 2010 (OR 0.92; 0.88, 0.94). The rates of readmissions were higher than for primary admissions (OR 1.33; 1.19, 1.47). From 1984 to 2010, there was an increased use of inhaled corticosteroids prior to admission (6 to 51%) and started at discharge (7 to 37%), and systemic steroids given during admission (19 to 83%). CONCLUSION: There has been a substantial decline in the rate of hospital admissions for childhood asthma after 1989/1990, with major differences between age groups and genders. The decline could be due to improved care of children with asthma or a real reduction in asthma exacerbations.

Acute bronchiolitis in infants, a review.

Acute viral bronchiolitis is one of the most common medical emergency situations in infancy, and physicians caring for acutely ill children will regularly be faced with this condition. In this article we present a summary of the epidemiology, pathophysiology and diagnosis, and focus on guidelines for the treatment of bronchiolitis in infants. The cornerstones of the management of viral bronchiolitis are the administration of oxygen and appropriate fluid therapy, and overall a "minimal handling approach" is recommended. Inhaled adrenaline is commonly used in some countries, but the evidences are sparse. Recently, inhalation with hypertonic saline has been suggested as an optional treatment. When medical treatment fails to stabilize the infants, non-invasive and invasive ventilation may be necessary to prevent and support respiratory failure. It is important that relevant treatment algorithms exist, applicable to all levels of the treatment chain and reflecting local considerations and circumstances.