Reviews and feature article
Advances in asthma in 2016: Designing individualized approaches to management

https://doi.org/10.1016/j.jaci.2017.06.015Get rights and content

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management.

Section snippets

Viral infections in asthmatic patients and the promise of therapeutic targets

Respiratory viruses remain a key trigger of asthma exacerbations, providing insight into the evolution and pathophysiology of asthma. In a prospective observational cohort study involving 183 asthmatic children aged 6 to 17 years, Kantor et al2 found that subjects with rhinovirus infection had more severe exacerbations than those participants with virus-negative exacerbations. In this cohort rhinovirus-triggered asthma exacerbations became more severe as the degree of sensitization to dust mite

Characterization of the airway microbiome

Through detailed assessments of the airway microbiome, key differences between asthmatic patients, nonasthmatic subjects, and those at risk for asthma have been characterized. Regarding at-risk populations, the nasopharyngeal microbiota in more than 1000 infants with bronchiolitis was analyzed as part of a large multicenter study.9 In this prospective cohort infants with bronchiolitis caused by RSV had a high abundance of Firmicutes and the genus Streptococcus and a low abundance of

Novel genetic associations with asthma and the biologic effect of known gene variants

Through discovery of new associations and demonstration of the biologic effects of known gene variations, the link between genetic changes and asthma expanded in 2016 (Table I).13, 14, 15, 16 Doublesex and mab-3–related transcription factor 1 (DMRT1) emerged as a novel candidate to potentially explain sex-specific asthma effects during childhood.13 A single nucleotide polymorphism (SNP) on chromosome 8 was associated with early lung function decrease in 2 asthma cohorts and was also associated

Influence of air quality and climate on asthma

Annesi-Maesano20 provided an overview of allergy-specific health issues emerging because of climate change, as well as future directions regarding climate-related health. Worldwide, only 12% of urban populations breath air that complies with World Health Organization Air Quality Guidelines. Citing NASA data, we learn not only that the earth has experienced a 0.8°C/1.4°F average global temperature increase since the 1880s but also that two thirds of this warming has occurred since 1975.

Exposures during different stages of development and long-term sequelae of childhood asthma

Among the well-described risk factors for asthma, recent research is helping to define the level of influence had by these risk factors. The Inner-City Asthma Consortium conducted a causal network analysis on a conceptual model of 8 potential asthma risk factor domains. They found that the model could explain about 50% of the variance in asthma severity. The 2 biggest drivers of asthma severity were an allergy pathway starting with allergic sensitization and an environmental tobacco smoke

Patient-centered outcomes research reflects patient priorities and engages stakeholders

The National Asthma Education and Prevention Program Expert Panel Report,37 which was last updated in 2007, provides guidance for the management of asthma. For the most part, it is informed by efficacy studies. These narrowly defined studies include patients most likely to benefit and who are treated under the most promising conditions. However, a limitation of these well-controlled studies is that the interventions are not always effective when applied in the real world, do not take into

Clinical risk factors

Wells et al44 add support to this patient-centered approach by demonstrating that neither self-reported race-ethnicity nor race defined by genetic ancestry predicted ICS response; rather, baseline lung function and self-reported asthma control do, emphasizing the need to find ways to ensure optimal lung function, asthma control, and elimination of barriers to accessing care. Szentpetery et al45 describe asthma risk factors among Puerto Ricans, including exposure to environmental tobacco,

Precision medicine

In January 2015, President Obama proposed a Precision Medicine Initiative52 considering each patient's uniqueness and the need for tailoring treatment to take into account individual variability in genes, environment, and lifestyle. This initiative aligns with translational and comparative effectiveness research, seeking to understand environmental, clinical, and lifestyle risk factors that characterize phenotypes and identifying the biomarkers to help define the pathophysiologic mechanisms or

Application of biomarkers to personalized medicine

In 2012, the JACI published a report from the National Institutes of Health (NIH) Asthma Outcomes Task force to summarize relevant outcomes for NIH asthma research. One of the sections was on physiology and listed various physiologic measures as core (should be included in all asthma research), supplementary (applied in selected research), and exploratory (intended to be evaluated for potential application).58 AHR by methacholine challenge was listed as a supplemental measure. Pralong et al59

New information on asthma medications

In 2016, promising new medications as add-on management for poorly controlled asthma were introduced, and the safety of well-established medications, namely LABAs, was revisited. The addition of roflumilast, a selective phosphodiesterase 4 inhibitor, in conjunction with montelukast to the controller regimen of adults with inadequately controlled asthma despite the use of at least medium-dose ICSs with a LABA resulted in a statistically significant increase in prebronchodilator FEV1 from

Management

In 2016, emphasis was placed on assessment of medication adherence and creation of comprehensive school-based asthma support networks (Table V).39, 87, 88, 89, 90 In a population-based cohort study, only 33% of pediatric patients demonstrated high ICS adherence.91 Similarly, by using reimbursement data, only 24% of adults and pediatric patients maintained regular ICS adherence 1 year after a period of regular ICS use.87 The unique barriers for poor medication adherence are age specific,

Summary

As indicated in this summary, there are rapid areas of development related to the natural history of asthma and the effect of the environment (Table VI).2, 7, 9, 23, 29, 35, 40, 51, 56, 64, 91, 94 There has been no previous era in asthma management that has witnessed the introduction of so many new classes of medications. It will be a challenge for clinicians and those contributing to asthma guidelines to select relevant pieces of information that should be incorporated into clinical practice.

References (94)

  • D.R. Denner et al.

    Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

    J Allergy Clin Immunol

    (2016)
  • M. Schieck et al.

    Doublesex and mab-3–related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages

    J Allergy Clin Immunol

    (2016)
  • C. Sarnowski et al.

    Identification of a new locus at 16q12 associated with time to asthma onset

    J Allergy Clin Immunol

    (2016)
  • S. Turner et al.

    Childhood asthma exacerbations and the Arg16 beta2-receptor polymorphism: a meta-analysis stratified by treatment

    J Allergy Clin Immunol

    (2016)
  • C.W. Yang et al.

    Regulation of T cell receptor signaling by DENND1B in TH2 cells and allergic disease

    Cell

    (2016)
  • I. Annesi-Maesano

    United Nations Climate Change Conferences: COP21 a lost opportunity for asthma and allergies and preparing for COP22

    J Allergy Clin Immunol

    (2016)
  • E.S. Schultz et al.

    Early life exposure to traffic-related air pollution and lung function in adolescence assessed with impulse oscillometry

    J Allergy Clin Immunol

    (2016)
  • E.B. Brandt et al.

    A combination of dexamethasone and anti-IL-17A treatment can alleviate diesel exhaust particle-induced steroid insensitive asthma

    J Allergy Clin Immunol

    (2016)
  • A.H. Liu et al.

    Pathways through which asthma risk factors contribute to asthma severity in inner-city children

    J Allergy Clin Immunol

    (2016)
  • L. Owens et al.

    Early sensitization is associated with reduced lung function from birth into adulthood

    J Allergy Clin Immunol

    (2016)
  • A. Lee et al.

    Prenatal and postnatal stress and asthma in children: temporal- and sex-specific associations

    J Allergy Clin Immunol

    (2016)
  • G. Bandoli et al.

    Synergistic effects of air pollution and psychosocial stressors on adolescent lung function

    J Allergy Clin Immunol

    (2016)
  • H. Morita et al.

    Innate lymphoid cells in allergic and nonallergic inflammation

    J Allergy Clin Immunol

    (2016)
  • Q. Yang et al.

    Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice

    J Allergy Clin Immunol

    (2016)
  • H.K. Somineni et al.

    Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution

    J Allergy Clin Immunol

    (2016)
  • K.C. Dannemiller et al.

    Indoor microbial communities: Influence on asthma severity in atopic and nonatopic children

    J Allergy Clin Immunol

    (2016)
  • E. von Mutius

    The microbial environment and its influence on asthma prevention in early life

    J Allergy Clin Immunol

    (2016)
  • H.T. den Dekker et al.

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

    J Allergy Clin Immunol

    (2016)
  • R. Granell et al.

    Associations of wheezing phenotypes with late asthma outcomes in the Avon Longitudinal Study of Parents and Children: a population-based birth cohort

    J Allergy Clin Immunol

    (2016)
  • J.A. Krishnan et al.

    A call for action: comparative effectiveness research in asthma

    J Allergy Clin Immunol

    (2011)
  • A. Anise et al.

    Patient-centered outcomes research to improve asthma outcomes

    J Allergy Clin Immunol

    (2016)
  • D.Q. Shelef et al.

    Using stakeholder engagement to develop a patient-centered pediatric asthma intervention

    J Allergy Clin Immunol

    (2016)
  • T. Bryant-Stephens et al.

    Home visits are needed to address asthma health disparities in adults

    J Allergy Clin Immunol

    (2016)
  • M.A. Martin et al.

    Care transition interventions for children with asthma in the emergency department

    J Allergy Clin Immunol

    (2016)
  • C.B. Kramer et al.

    Enrolling African-American and Latino patients with asthma in comparative effectiveness research: lessons learned from 8 patient-centered studies

    J Allergy Clin Immunol

    (2016)
  • K.E. Wells et al.

    Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects

    J Allergy Clin Immunol

    (2016)
  • S.E. Szentpetery et al.

    Asthma in Puerto Ricans: lessons from a high-risk population

    J Allergy Clin Immunol

    (2016)
  • E.M. Zoratti et al.

    Asthma phenotypes in inner-city children

    J Allergy Clin Immunol

    (2016)
  • J.A. Pongracic et al.

    Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents

    J Allergy Clin Immunol

    (2016)
  • L. Perez et al.

    A health care navigation tool assesses asthma self-management and health literacy

    J Allergy Clin Immunol

    (2016)
  • C.A. Akdis et al.

    Precision medicine and precision health: building blocks to foster a revolutionary health care model

    J Allergy Clin Immunol

    (2016)
  • S.J. Galli

    Toward precision medicine and health: Opportunities and challenges in allergic diseases

    J Allergy Clin Immunol

    (2016)
  • R.M. Dunn et al.

    Personalized asthma therapy in blacks-the role of genetic ancestry

    J Allergy Clin Immunol

    (2016)
  • A. Berry et al.

    Biomarkers in asthmatic patients: has their time come to direct treatment?

    J Allergy Clin Immunol

    (2016)
  • A. Muraro et al.

    Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology

    J Allergy Clin Immunol

    (2016)
  • R.S. Tepper et al.

    Asthma outcomes: pulmonary physiology

    J Allergy Clin Immunol

    (2012)
  • J.A. Pralong et al.

    Predictive value of nonspecific bronchial responsiveness in occupational asthma

    J Allergy Clin Immunol

    (2016)
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      Citation Excerpt :

      Each year, the Journal has summarized key literature related to advances in asthma research.29 In the past 2 years, a number of new medications and strategies have been added to our armamentarium for asthma management, including tiotropium; biologics, such as omalizumab and anti–IL-5 agents (mepolizumab, reslizumab, and benralizumab); and bronchial thermoplasty, with varying levels of approval for use in children along with several other medications, such as anti–IL-4/IL-13 (dupilumab) and perhaps anti–thymic stromal lymphopoietin, that await approval for asthma.29-31 It is exciting to see a number of useful tools for managing asthma but discouraging to see that they are not readily applied.

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    Disclosure of potential conflict of interest: S. J. Szefler serves as a consultant for Roche, AstraZeneca, Aerocrine, Daiichi Sankyo, Boehringer Ingelheim, Merck, Genentech, Novartis, and Teva and receives grant support from GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest.

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