Asthma: a modifiable disease on a crossroad No abstract available

Long and winding road: from infant wheeze to adult asthma Purpose of review This review aims to recognize the multifactorial cause of asthma, from the influence of mother until adulthood, highlight the main characteristics of the disease at different ages and summarize the evidence of potential prevention strategies. Recent findings To date, regarding the prenatal period, the presence of specific genes, maternal asthma, drugs, and tobacco exposure are the most relevant predisposing features for an asthmatic offspring. For newborns, preterm, bronchopulmonary dysplasia, and low birth weight has been associated with low lung function. Among young children, atopic dermatitis, lower respiratory tract infections, and increased levels of total Immunoglobulin E (IgE) and allergen-specific IgE are important determinants. Breastfeeding has been demonstrated being protective for the onset of asthma. Allergen immunotherapy has also been shown to have significant preventive effect decreasing asthma development. Inhaled corticosteroids use in early childhood prevents exacerbations but does not alter the natural history of asthma. Other interventions, such as the use of palivizumab, probiotics, vitamin D supplementation, and fish consumption presented controversial results. Summary A good knowledge of risk factors for asthma development, from prenatal period to adulthood, may lead to efficacious preventive strategies. Further data of long-term follow-up in population-based studies according to different phenotypes are needed.

Asthma and air pollution: recent insights in pathogenesis and clinical implications Purpose of review Air pollution has adverse effects on the onset and morbidity of respiratory diseases, including asthma. In this review, we discuss recent insights into the effects of air pollution on the incidence and exacerbation of asthma. We focus on epidemiological studies that describe the association between air pollution exposure and development, mortality, persistence and exacerbations of asthma among different age groups. Moreover, we also provide an update on translational studies describing the mechanisms behind this association. Recent findings Mechanisms linking air pollutants such as particulate matter, nitrogen dioxide (NO2) and ozone to the development and exacerbation of asthma include the induction of both eosinophilic and neutrophilic inflammation driven by stimulation of airway epithelium and increase of pro-inflammatory cytokine production, oxidative stress and DNA methylation changes. Although exposure during foetal development is often reported as a crucial timeframe, exposure to air pollution is detrimental in people of all ages, thus influencing asthma onset as well as increase in asthma prevalence, mortality, persistence and exacerbation. Summary In conclusion, this review highlights the importance of reducing air pollution levels to avert the progressive increase in asthma incidence and morbidity.

Epithelial dysfunction in chronic respiratory diseases, a shared endotype? Purpose of review Epithelial barrier defects are being appreciated in various inflammatory disorders; however, causal underlying mechanisms are lacking. In this review, we describe the disruption of the airway epithelium with regard to upper and lower airway diseases, the role of epigenetic alterations underlying this process, and potential novel ways of interfering with dysfunctional epithelial barriers as a novel therapeutic approach. Recent findings A defective epithelial barrier, impaired innate defence mechanisms or hampered epithelial cell renewal are found in upper and lower airway diseases. Barrier dysfunction might facilitate the entrance of foreign substances, initiating and facilitating the onset of disease. Latest data provided novel insights for possible involvement of epigenetic alterations induced by inflammation or other unknown mechanisms as a potential mechanism responsible for epithelial defects. Additionally, these mechanisms might precede disease development, and represent a novel therapeutic approach for restoring epithelial defects. Summary A better understanding of the role of epigenetics in driving and maintaining epithelial defects in various inflammatory diseases, using state-of-the-art biology tools will be crucial in designing novel therapies to protect or reconstitute a defective airway epithelial barrier.

Ecological interactions in asthma: from environment to microbiota and immune responses Purpose of review Asthma is a heterogeneous condition shaped not only by genetics but also host conditioning by environmental factors. Recognizing the ecological context of microbe-immune interactions across environments and body sites is a necessary step toward better understanding how human microbiota influence or drive the pathogenesis and pathophysiology of asthma in its various presentations. Recent findings There is increasing evidence of a critical role for microbiota in asthma pathogenesis and outcomes across various body compartments, including the upper and lower airways, and gut. We discuss recent studies from this area including: development of a method to quantify microbial farm-effect in nonfarm environments, relationships between environmental microbial exposures and asthma prevalence across different geographies, microbiome-mediated responses to ozone, and microbiome-immune interactions within and across body compartments. Beyond bacteria, recent reports of asthma-associated differences in archaea and fungal organisms also are highlighted. Summary Collective evidence warrants application of an ecological framework to advance mechanistic insights into microbiota-immune interactions in asthma. This is necessary to achieve goals of developing successful therapeutic interventions targeting modification of microbiomes.

Precision medicine and treatable traits in chronic airway diseases - where do we stand? Purpose of review To provide an update on the implementation of precision medicine, based on treatable traits and mechanisms, in the daily clinical management of chronic airways diseases. Recent findings Recent insights into the complex and heterogeneous nature of chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma identified several clinical and inflammatory phenotypes. This shifted the management focus of these diseases away from the prototypic disease labels and paved the way for developing novel targeted therapies. The concept of precision medicine aims to link the right patient to the right treatment, while minimizing the risk of adverse effects. Several treatable features (’treatable traits’) have now been identified for these chronic airway diseases, including pulmonary, extra-pulmonary, and psychological/lifestyle/environmental traits. As the next step, innovative detection techniques should clarify underlying mechanisms and molecular pathways of these treatable traits and novel reliable point-of-care (composite) biomarkers to help predict responders to targeted therapies must be developed. Summary Precision medicine links the right patient to the right treatment. Identification of treatable traits in asthma and COPD will help optimize the treatment approach in these heterogeneous diseases. Furthermore, in-depth identification of underlying molecular pathways and reliable biomarkers in chronic airways diseases to guide targeted treatment in individual patients is in progress.

Lost in transition: biomarkers of remodeling in patients with asthma Purpose of review ‘Biomarkers of remodeling’ represent a loose collection of features referring to several biological adaptations of the lung to cope with stressing factors. In addition, remodel-’ing’ infers a dynamic process that would require a spatiotemporal resolution. This review focuses on different aspects of remodeling in pediatric and adult care. Recent findings This review will cover aspects of pediatric remodeling, adult remodeling and techniques and procedures to adequately assess remodeling across different age spectra. In pediatrics, the onset and first features of remodeling are discussed and the continuation into adolescence is addressed. For adults, this review addresses predominant features of remodeling throughout the adult life span and whether there are currently interventions available to treat or reverse remodeling. Summary The term ‘remodeling’ is often referred to via biomarkers that reflect the endstage of a process, although it rather reflects a continuous process starting in childhood and progressing to all age-levels in patients with asthma. Hence, only few biomarkers or surrogates are able to ‘capture’ its spatiotemporal component, and hardly any are ready for routine use in clinical practice. Given the clinical impact of the remodeling processes, new biomarkers are needed to adequately treat patients with asthma and objectively monitor treatment response beyond symptom control and lung function.

The impact of comorbidities on severe asthma Purpose of review Severe asthma is often associated with numerous comorbidities that complicate disease management and affect patient's outcomes. They contribute to poor disease control and mimic asthma symptoms. Although some comorbidities such as obstructive sleep apnea, bronchiectasis, and chronic obstructive pulmonary disease are generally well recognized, many other may remain undiagnosed but may be detected in an expert specialist setting. The management of comorbidities seems to improve asthma outcomes, and optimizes therapy by avoiding overtreatment. The present review provides recent knowledge regarding the most common comorbidities which are associated with severe asthma. Recent findings Comorbidities are more prevalent in severe asthma than in mild-to-moderate disease or in the general population. They can be grouped into two large domains: the pulmonary domain and the extrapulmonary domain. Pulmonary comorbidities include upper respiratory tract disorders (obstructive sleep apnea, allergic and nonallergic rhinitis, chronic rhinosinusitis, nasal polyposis) and middle/lower respiratory tract disorders (chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis and fungal sensitization, bronchiectasis, dysfunctional breathing). Extrapulmonary comorbidities include anxiety, depression, gastro-esophageal reflux disease, obesity, cardiovascular, and metabolic diseases. Summary The identification of comorbidities via multidimensional approach is needed to initiate appropriate multidisciplinary management of patients with severe asthma.

Can training induce inflammatory control in asthma, or is it symptom control only? Purpose of review Exercise has shown to reduce asthma symptoms; however, the underlying mechanism for this improvement remains unclear. Improvement in inflammatory control could be the reason for this reduction in symptoms. This review discusses recent studies evaluating the effect of exercise on inflammatory control in patients with asthma. Recent findings New studies support that exercise is well tolerated and feasible regardless of intensity. Exercise seems to improve systemic low-grade inflammation, but consistency lacks when it comes to reduction in airway inflammation. Summary Physical exercise as an adjuvant therapy leads to improvement in asthma symptoms and asthma-related quality of life and should be recommended for all patients with asthma.