Stern, D.A., Morgan, W.J., Halonen, M., Wright, A.L. & Martinez, F.D. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet 372, 1058-1064

Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
The Lancet (Impact Factor: 45.22). 10/2008; 372(9643):1058-64. DOI: 10.1016/S0140-6736(08)61447-6
Source: PubMed


Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults.
1246 healthy newborn babies were enrolled in the Tucson Children's Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years.
Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16-22 years was 12.6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio [M-OR] 2.0, 95% CI 1.2-3.2, p=0.008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7.4, 3.9-14.0) and persistent wheezing (14.0, 6.8-28.0) in early life, sensitisation to A alternata (3.6, 2.1-6.4), low airway function at age 6 years (2.1, 1.1-3.9), and bronchial hyper-responsiveness at 6 years (4.5, 1.9-10.0). Bronchial hyper-responsiveness (6.9, 2.3-21.0), low airway function at 6 years (2.8, 1.1-6.9), and late-onset (4.6, 1.7-12.0) and persistent wheezing (4.0, 1.2-14.0) predicted newly diagnosed asthma at age 22 years.
Asthma with onset in early adulthood has its origins in early childhood.

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    • "A growing body of evidence suggests that early life and childhood factors are important in both adult-onset asthma and COPD.34,35 This concept is based on data that show associations between various adverse perinatal outcomes and harmful environmental stimuli, with slowing of lung function growth for susceptible children and adolescents.36–39 "
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    ABSTRACT: Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene-environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors. Short-acting beta-agonists provide effective symptom relief in airway diseases. Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD. Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling. The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed. Long-acting inhaled anticholinergic medications are particularly useful in COPD. Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care.
    International Journal of COPD 09/2014; 9:945-962. DOI:10.2147/COPD.S46761 · 3.14 Impact Factor
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    • "Although atopic asthma is the more dominant form of asthma during school years and into young adulthood [6]–[8], exacerbation of asthma has been strongly linked to respiratory infection alone, with 44% to 80% of childhood asthma exacerbations being triggered by RV infection [9]. RV is the most common pathogen associated with asthma exacerbations in children [10]. "
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    ABSTRACT: In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation. Primary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways. The presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone. Th2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
    PLoS ONE 04/2014; 9(4):e94010. DOI:10.1371/journal.pone.0094010 · 3.23 Impact Factor
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    • "From a clinical point of view, in infants and preschool children it is not possible to make a diagnosis of asthma and is thus preferable to adopt the term ‘wheezing’ , a condition which encompasses a range of symptoms including breathlessness and whistling sounds [18-21]. Bronchospasm and subsequent wheezing might be triggered by respiratory infections, and this could explain the similar seasonality of asthma and bronchitis in younger children, as suggested by our data. "
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    ABSTRACT: Quality assessment in pediatric care has recently gained momentum. Although many of the approaches to indicator development are similar regardless of the population of interest, few nationwide sets of indicators specifically designed for assessment of primary care of children exist. We performed an empirical analysis of the validity of "Pediatric Asthma Hospitalization Rate" indicator under the assumption that lower admission rates are associated with better performance of primary health care. The validity of "Pediatric Asthma Hospitalization Rate" indicator proposed by the Agency for Healthcare Research and Quality in the Italian context was investigated with a focus on selection of diagnostic codes, hospitalization type, and risk adjustment. Seasonality and regional variability of hospitalization rates for asthma were analyzed for Italian children aged 2-17 years discharged between January 1, 2009, and December 31, 2011 using the hospital discharge records database. Specific rates were computed for age classes: 2-4, 5-9, 10-14, 15-17 years. In the years 2009-2011 the number of pediatric hospitalizations for asthma was 14,389 (average annual rate: 0.52 per 1,000) with a large variability across regions. In children aged 2-4 years, the risk of hospitalization for asthma was 14 times higher than in adolescents, then it dropped to 4 in 5- to 9-year-olds and to 1.1 in 10- to 14-year-olds. The inclusion of diagnoses of bronchitis revealed that asthma and bronchitis are equally represented as causes of hospital admissions and have a similar seasonality in preschool children, while older age groups experience hospital admissions mainly in spring and fall, this pattern being consistent with a diagnosis of atopic asthma. Rates of day hospital admissions for asthma were up to 5 times higher than the national average in Liguria and some Southern regions, and close to zero in some Northern regions. The patterns of hospitalization for pediatric asthma in Italy showed that at least two different indicators are needed to measure accurately the quality of care provided to children. The candidate indicators should also include day hospital admissions to better assess accessibility. Future evaluation by a structured clinical panel review at the national level might be helpful to refine indicator definitions and risk groupings, to determine appropriate application for such measures, and to make recommendations to policy makers.
    Italian Journal of Pediatrics 01/2014; 40(1):7. DOI:10.1186/1824-7288-40-7 · 1.52 Impact Factor
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