Asthma Trajectories Research Articles

Distinct immune phenotypes in infants developing asthma during childhood.

Early exposure to environmental triggers may elicit trajectories to chronic inflammatory disease through deregulated immune responses. To address relations between early immune competence and development of childhood asthma, we performed functional immune profiling of 186 parameters in blood of 541 18-month-old infants and examined links between their response phenotype and development of transient or persistent disease at 6 years of age. An abnormal neutrophil-linked antiviral response was associated with increased risk of transient asthma. Children who exhibited persistent asthma at year 6 showed enhanced interleukin-5 (IL-5) and IL-13 production in stimulated T cells at 18 months of age, which was associated with early life bacterial colonization of the airways. These findings highlight the early appearance of distinct immune characteristics in infants developing different asthma endotypes during childhood.

Lung functional development and asthma trajectories.

Early life environmental risk factors are associated with chronic respiratory morbidity in child- and adulthood. A possible mechanism for this sustained effect is their influence on early life lung functional growth and development, a susceptible phase of rapid lung growth with increased plasticity. We summarize evidence of hereditary and environmental ante-, peri-, and early postnatal factors on lung functional development, such as air pollution, tobacco exposure, nutrition, intrauterine growth retardation, prematurity, early life infections, microbiome, and allergies and their effect on lung functional trajectories. While some of the factors (e.g., prematurity) directly impair lung growth, the influence of many environmental factors is mediated through inflammatory processes (e.g., recurrent infections or oxidative stress). The timing and nature of these influences and their impact result in degrees of impaired maximal lung functional capacity in early adulthood; and they potentially impact future long-term respiratory morbidity such as chronic asthma or chronic obstructive airway disease (COPD). We discuss possibilities to prevent or modify such early abnormal lung functional growth trajectories and the need for future studies and prevention programs.

Continued loss of asthma control following epidemic thunderstorm asthma.

BackgroundEpidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA.ObjectiveA multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals.MethodsWe used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the “current,” “past,” “probable,“ and “no asthma” subgroups defined according to their original 2016 survey responses.ResultsFour hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year.ConclusionsFollowing an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change.

Different seasonal effect on asthma trajectories: A population‐based birth cohort study

Different seasonal effect on asthma trajectories: A population‐based birth cohort study

The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: a longitudinal cohort study

BackgroundAsthma and wheezing disorders in childhood and adulthood are clinically heterogeneous regarding disease presentation, natural course, and response to treatment. Deciphering common disease mechanisms in distinct subgroups requires harmonized molecular (endo-) phenotyping of both children and adult patients with asthma in a prospective, longitudinal setting.MethodsThe ALL Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL) is a prospective, multi-center, observational cohort study with seven recruiting sites across Germany. Data are derived from four sources: (a) patient history from medical records, (b) standardized questionnaires and structured interviews, (c) telephone interviews, and (d) objective measurements. Objective measurements include amongst others lung function and quantitative assessment of airway inflammation and exhaled breath, peripheral blood, skin, nasal, pharyngeal, and nasopharyngeal swabs, nasal secretions, primary nasal epithelial cells, and induced sputum. In cases, objective measurements and biomaterial collection are performed regularly, while control subjects are only examined once at baseline.DiscussionThe standardized and detailed collection of epidemiological and physiological data, and the molecular deep phenotyping of a comprehensive range of biomaterials in a considerable number of study participants across all ages are the outstanding characteristics of this multi-center cohort. Despite extensive biomaterial sampling, and a recruitment strategy that also includes pre-school children as young as 6 months, attrition is low. In children 83.9%, and in adults 90.5% attended the 12-month follow-up. The earliest time-point to include cases, however, is disease manifestation. Therefore, unraveling mechanisms that drive disease onset is limited, as this question can only be answered in a population-based birth cohort. Nonetheless, ALLIANCE offers a unique, integrative and inter-disciplinary framework with a comprehensive molecular approach in a prospective and identical fashion across ages in order to identify biomarkers and predictors for distinct childhood wheeze and asthma trajectories as well as their further course during adulthood. Ultimately, this approach aims to translate its most significant findings into clinical practice, and to improve asthma transition from adolescence to adulthood.Trial registrationNCT02496468 for pediatric arm, NCT02419274 for adult arm.

Long-Term Trajectories of Mild Asthma in Adulthood and Risk Factors of Progression

Most patients with asthma have mild disease. However, the clinical course of mild asthma and risk factors for progression are not well studied. To examine the long-term trajectories of mild asthma and the effects of early-stage risk factors on the subsequent disease course. From the administrative health data of British Columbia, Canada, we identified patients aged 14 to 45 years with newly diagnosed mild asthma between January 1997 and December 2012. For each follow-up year, we categorized a patient's asthma severity into mild/dormant, moderate, orsevere on the basis of the intensity of asthma medications andoccurrence of exacerbations. Ordinal logistic regression was used to estimate the probability of severity or all-cause death in the next year as a function of a patient's severity history in the past 3 years and selected baseline risk factors. The study included 70,829 patients with incident mild asthma (62% women; mean age, 31 years). Over 10 years, 8% of these patients transitioned to moderate or severe asthma. Inappropriate use of rescue medications and older age were the most influential determinants for progression from mild asthma (odds ratios, 1.79; 95% CI, 1.68-1.90; P < .001; 1.24 per 10-year increase in age; 95% CI, 1.22-1.27; P < .001), whereas the presence of allergic rhinitis had no significant effects (odds ratio, 0.95; 95% CI, 0.91-1.00; P= .063). Mild asthma remains largely stable over time. However, potentially modifiable factors such as inappropriate use of rescue medications are associated with a worsened prognosis.

Cat ownership, cat allergen exposure, and trajectories of sensitization and asthma throughout childhood

Summary Exposure to cat and/or cat allergens can confer either an increase in risk, or protection, or will have no effect, depending on the age of the assessment, study design and the choice of study population.

Long‐term future risk of severe exacerbations: Distinct 5‐year trajectories of problematic asthma

BackgroundAssessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short‐ but not long‐term risk. Problematic asthma patients with unfavorable long‐term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment.AimTo identify distinct trajectories of severe exacerbation rates among “problematic asthma” patients and develop a risk score to predict the most unfavorable trajectory.MethodsSevere exacerbation rates over five years for 177 “problematic asthma” patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group‐based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory.ResultsThree distinct trajectories were found: 58.5% had rare intermittent severe exacerbations (“infrequent”), 32.0% had frequent severe exacerbations at baseline but improved subsequently (“nonpersistently frequent”), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near‐fatal asthma (“persistently frequent”). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near‐fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the “persistently frequent” trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort.ConclusionsPatients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.

Asthma Trajectories in a Population-based Birth Cohort. Impacts of Air Pollution and Greenness.

The heterogeneity of asthma phenotypes may explain inconsistencies in observed associations with environmental exposures. To identify trajectories of childhood asthma and to characterize the potential impact of residential greenness and air pollution on asthma trajectory subgroups. Linked administrative databases of medical visits were used to define the occurrence and recurrence of asthma over a 10-year follow-up period within a population-based birth cohort of more than 65,000 children. Group-based trajectory modeling was used to identify unique asthma trajectories. Weighted multinomial regression was used to assess the relationship between asthma trajectories and risk factors, including environmental exposures. Group-based trajectory modeling distinguished four trajectories: one with no asthma representing 88.8% of the cohort, one with transient asthma (5.6% of the cohort), and two trajectories with chronic asthma with early (<1 yr; 1.5%) and late (<3 yr; 4.1%) onset during early childhood. These trajectories differed with respect to socioeconomic markers and modifiable risk factors, including maternal smoking and breastfeeding initiation. After accounting for sex, parity, breastfeeding, term birth weight, household income, maternal education, delivery mode, and smoking, an interquartile increase in nitrogen dioxide exposure increased the risk of membership in the early and late-onset chronic asthma trajectories, relative to subjects without asthma, by 50% and 20%, respectively (weighted risk ratio, 1.5 and 1.2; 95% confidence interval, 1.2-1.9 and 1.0-1.4). Greenness was not associated with any of the asthma trajectories. Traffic-related air pollution increased the probability of a chronic asthma trajectory.

Modifying the trajectory of asthma—are there lessons from the use of biologics in rheumatology?

Modifying the trajectory of asthma—are there lessons from the use of biologics in rheumatology?

The natural history of severe asthma and influences of early risk factors: a population-based cohort study

BackgroundSevere asthma is associated with disproportionately high morbidity, but little is known about its natural history and how risk factors at first year of diagnosis modify its subsequent development.MethodsUsing administrative...

Perceived 10-year change in respiratory health: Reliability and predictive ability

To investigate the usefulness of a self-reported respiratory health transition question over 10 years through reliability, ability to capture long-term asthma trajectory and predictive ability. In two 20-year cohorts (Asthma-E3N, n=16,371, 61-88 years; EGEA, n=1254, 27-82 years), perceived 10-year change in respiratory health ("Overall, in the last 10 years, do you think that your bronchial or respiratory health has changed?" if yes: "Has it improved/deteriorated?") was studied in relation with change in respiratory medication dispensation and lung function, with change in asthma status measured over the same period of time, and with subsequent asthma-related outcomes. Perceived deterioration (14% in Asthma-E3N) was associated with increased dispensations of respiratory medications over time (from 17% with >2 dispensations in 2004 to 26% in 2010). Report of perceived deterioration (13% in EGEA) was related to a lung function decline steeper by 9.3mL/year as compared to perceived improvement. In both cohorts, change (improvement or deterioration) was more often perceived by participants with than without asthma (>45% vs <20%) and was dominant among participants with persistent current asthma (77%). Perceived deterioration was related to poorer asthma control 7 years later and to higher use of oral corticosteroids in the following 18 months. The proposed simple self-reported respiratory health transition question over 10 years allows predicting part of the long-term trajectory of asthma.

Asthma trajectories in early childhood: identifying modifiable factors.

BackgroundThere are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories.Data and MethodsThe Millennium Cohort Study is a large, representative birth cohort of British children born in 2000–2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema) reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity.ResultsOur model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample); a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%); a trajectory with high prevalence of both wheeze and other atopic symptoms (9%); and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%). These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation.ConclusionUsing data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles. We identified correlated intervenable pathways in infancy, including household damp and breastfeeding initiation.

Validation of parental reports of asthma trajectory, burden, and risk by using the pediatric asthma control and communication instrument.

SO Okelo, MN Eakin, KA Riekert. J Allergy Clin Immunol Pract. 2014;2(2):186–192 The goal of this study was to evaluate the utility of assessing direction, bother, and risk domains within the Pediatric Asthma Control and Communication Instrument (PACCI), a validated parent-completed questionnaire assessing 5 dimensions of asthma health, as part of guideline-recommended asthma care. A convenience sample of 317 children diagnosed with asthma (mean age: 8.2 years; 58% boys; 44% African American) was recruited from 2 university-based asthma specialty care …

Validation of Parental Reports of Asthma Trajectory, Burden, and Risk by Using the Pediatric Asthma Control and Communication Instrument

Despite a growing interest, few pediatric asthma questionnaires assess multiple dimensions of asthma morbidity, as recommended by national asthma guidelines, or use patient-reported outcomes. To evaluate a questionnaire that measures multiple dimensions of parent-reported asthma morbidity (Direction, Bother, and Risk). We administered the Pediatric Asthma Control and Communication Instrument (PACCI) and assessed asthma control (PACCI Control), quality of life, and lung function among children who presented for routine asthma care. The PACCI was evaluated for discriminative validity. A total of 317 children participated (mean age, 8.2 years; 58% boys; 44% African American). As parent-reported PACCI Direction changed from "better" to "worse," we observed poorer asthma control (P < .001), mean Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) scores (P < .001), and FEV1% (P= .025). Linear regression showed that, for each change in PACCI Direction, the mean PACQLQ score decreased by-0.6 (95% CI,-0.8 to-0.4). As parent-reported PACCI Bother changed from "not bothered" to "very bothered," we observed poorer asthma control (P < .001) and lower mean PACQLQ scores (P < .001). Linear regression showed that, for each change in PACCI Bother category, the mean PACQLQ score decreased by-1.1 (95% CI,-1.3 to-0.9). Any reported PACCI Risk event (emergency department visit, hospitalization, or use of an oral corticosteroid) was associated with poorer asthma control (P<.05) and PACQLQ scores (P < .01). PACCI Direction, Bother, and Risk are valid measures of parent-reported outcomes and show good discriminative validity. The PACCI is a simple clinical tool to assess multiple dimensions of parent-reported asthma morbidity, in addition to risk and control.

The Pediatric Asthma Control and Communication Instrument for the Emergency Department (PACCI-ED) improves physician assessment of asthma morbidity in pediatric emergency department patients

Objectives: To determine whether the Pediatric Asthma Control and Communication Instrument for the Emergency Department (PACCI-ED), a 12-item questionnaire, can help ED attendings accurately assess a patient’s asthma control and morbidity. Methods: This was a randomized-controlled trial performed at an urban pediatric ED of children aged 1–17 years presenting with an asthma exacerbation. Parents answered PACCI-ED questions about their children’s asthma. Attendings were randomized to view responses to the PACCI-ED (intervention group) or to be blinded to the completed PACCI-ED (control group). The two groups were compared on their empirical clinical assessment of: (1) chronic asthma control categories, (2) asthma trajectory (stable, worsening or improving), (3) patient adherence to controller medications, and (4) burden of disease for the patient’s family. The validated PACCI algorithm was used as the criterion standard for these four outcomes. Accuracy of clinical assessment was compared between intervention and control groups using chi-squared tests and an intention-to-treat approach. Results: Seventeen ED attendings were enrolled in the study and 77 children visits were included in the analysis. There were no significant differences between the intervention and the control groups for child’s gender, age, race, and asthma characteristics. Intervention group attendings were more accurate than control group attendings in assessing the category of chronic asthma control (43% versus 19%; p = 0.03), disease trajectory (72% versus 45%; p = 0.02), and the disease burden for families (74% versus 35%; p = 0.001) over the past 12 months. There was a trend towards more accuracy of intervention versus control attendings for estimating patient adherence to controller medications (72% versus 48%; p = 0.06). Conclusions: The PACCI-ED improves the assessment of asthma control, trajectory, and burden by ED attendings, and may help assessment of asthma medication adherence and prior asthma exacerbations. The PACCI-ED can be used to improve provider assessment of asthma morbidity during pediatric ED visits for asthma exacerbations, and to identify children who may benefit from interventions to reduce asthma morbidity.

Advances in pediatric asthma in 2012: Moving toward asthma prevention

Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.

The developmental trajectory of pediatric asthma in 3- to-10-year-olds

Longitudinal studies have suggested that early childhood asthma follows different temporal trajectories.1-3 Children with early childhood recurrent wheezing frequently have “symptom- or disease-free” periods, followed by “relapse” of disease, or do not have diagnosed asthma for the first time until later childhood. Some children or young adults develop asthma for the first time later in life. However, the childhood trajectory and patterns of disease development and remittance are not well figuratively characterized.

Vascular remodelling in asthma

We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

Asthma Development with Obesity Exposure: Observations from the Cohort of the National Health and Nutrition Evaluation Survey Epidemiologic Follow-up Study (NHEFS)

Results of cross-sectional studies suggest an association between body mass index and asthma. However, it is not clear whether the occurrence of asthma precedes increased body mass index or vice versa. From 1971 to 1975, the First National Health and Nutrition Examination Survey collected height and weight data and information about doctor-diagnosed asthma from 14,407 subjects aged 25–74. In 1982 through 1985, information was again obtained on doctor-diagnosed asthma with a follow-up rate of 84.8%. We took this opportunity to examine the relationship between body mass index (BMI) and asthma in this cohort. Subjects with subnormal BMI and subjects admitting current or history of doctor-diagnosed asthma were excluded from the cohort. Mean follow-up was 10 years (range 6.7–13 years). Analyses were adjusted for race and gender. Logistic regression analysis was conducted with asthma as the dependent variable and BMI modeled as a categorical independent variable (BMI groups). At baseline and at follow-up, increasing BMI was associated with increased prevalence of asthma. During the observation interval, however, no increased incidence of asthma associated with increasing BMI was noted. In comparison with normal BMI, the relative risk (RR) for development of doctor-diagnosed asthma in elevated BMI was 1.0 (95% confidence interval 0.9–1.2), for markedly elevated BMI was 1.0 (0.8–1.3), and for severely elevated BMI was 1.1 (0.8–1.5). Race did not affect this relationship. African Americans had an increased risk of asthma, but the risk was unassociated with increasing BMI. Gender did not affect this relationship. The disease burden of asthma appeared in normal weight and slightly overweight women rather than obese and markedly obese women. These results suggest that asthma development may be a point on the trajectory of chronic obesity disease or asthma appears with obesity as a concurrent disorder.