Editorial

A plea to abandon asthma as a disease concept

The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts have provided a foundation of 25 years of research on the origins, prevention, and natural history of childhood asthma and related disorders. COPSAC’s approach is characterized by clinical translational research with longitudinal deep phenotyping and exposure assessments from pregnancy, in combination with multi-omic data layers and embedded randomized controlled trials. One trial showed that fish oil supplementation during pregnancy prevented childhood asthma and identified pregnant women with the highest benefits from supplementation, thereby creating the potential for personalized prevention. COPSAC revealed that airway colonization with pathogenic bacteria in early life is associated with an increased risk of asthma. Further, airway bacteria were shown to be a trigger of acute asthma-like symptoms, with benefit from antibiotic treatment. COPSAC identified an immature gut microbiome in early life as a risk factor for asthma and allergy and further demonstrated that asthma can be predicted by infant lung function. At a molecular level, COPSAC has identified novel susceptibility genes, early immune deviations, and metabolomic alterations associated with childhood asthma. Thus, the COPSAC research program has enhanced our understanding of the processes causing childhood asthma and has suggested means of personalized prevention and treatment.

The meaning of the word “asthma” has evolved greatly from antiquity to the present. Once considered as a single entity, asthma is now recognized as a heterogeneous disease characterized by numerous and various phenotypes, that is, the observable characteristics. However, a study of these phenotypes alone does not offer insight into the underlying pathophysiology of the disease. Despite a similar clinical picture, distinct underlying aetiologies for asthma may confer divergent natural histories and treatment responses. There has been a recent impetus to decipher underlying asthma pathways or endotypes through molecular and omics techniques, due to the advent of precision medicine strategies for the treatment of asthma. This chapter describes the history of asthma and the evolution of the word “asthma” over time. It introduces the current epidemiology of asthma and describes childhood and adult asthma phenotypes and endotypes.

Psychological stress shifts the immune system toward the production of T-helper (Th)-2–mediated cytokines and eosinophilia, increases the risks for both asthma and depression, and can precipitate asthma exacerbations. Th2-mediated inflammation is a characteristic of allergic asthma. We have shown that the levels of CD4⁺ Th2 cells in the peripheral blood of patients with asthma are associated with severity and/or control of the disease. To improve our understanding of the interactions between stress and asthma symptoms, we evaluated the effects of psychological comorbidity on Th2-mediated inflammation in patients with asthma.

Sixty-six asthmatic patients were recruited from the University of Alberta Asthma Clinic after they gave informed consent. Stress-related effects on asthma and psychological morbidity were assessed using the Asthma Control Questionnaire, completed by the patients at recruitment. Venous blood was collected at recruitment and Th2-mediated immunity evaluated by flow cytometry, quantitative real-time reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay.

Patients with stress-triggered asthma (n = 12) had higher percentage of CD4⁺ T cells (P = 0.006) and Th2 cells (CD4⁺CRTh2⁺ T cells; P = 0.002) in peripheral blood compared to patients with asthma who did not experience stress-related worsening of disease (n = 54). The same was true when we analyzed patients with any form of psychological comorbidity (n = 19) compared to those without psychological comorbidities (n = 47). These differences were evident among women, but not among men. Women with psychological comorbidity also required higher doses of inhaled and oral corticosteroids compared to those without psychological comorbidity.

Asthma involving psychological morbidity associates with an elevated level of circulating Th2 cells and increased corticosteroid usage, and may be more prevalent in women. Larger-scale prospective studies are required for assessing whether these women constitute a new endotype of Th2-high asthma responsive to treatments aimed to improve psychological comorbidities.

To elucidate the genetic architecture of asthma continues to be a challenge for molecular biologists and medical researchers. However, powerful genomic technologies are at disposal to help decipher complete human genomes; the genetic variability in asthma hinders the discovery of common molecular markers for this disease. In this context, we purpose to explore genomic mosaicism on asthma cells’ biology as a strategy to discover key mechanisms, which can complement or re-define asthma diagnosis.

Recent evidences showed that genomic mosaicism could be a normal event. In brains, each neuron may harbor hundreds of genetic alterations, which may contribute to neuronal diversity. Thus, can mosaicism be a natural motor of diversity in asthma? Why this genetic event is little described in scientific literature?

To discuss these questions, we perform a critical review about the normality of genomic mosaicism; moreover, we examine the difficulty of current experimental approaches to detect different genotypes in cell populations of one individual.

Pulmonary complications are a major cause of perioperative morbidity in the pediatric population. Although preexisting pulmonary pathologic processes in children can present significant challenges to anesthetic delivery, a thorough assessment of the problem combined with meticulous anesthetic management allows most children to undergo surgical interventions without long-term adverse sequelae. Asthma, cystic fibrosis and sickle cell disease continue to pose challenges during anesthesiology. Consultation with a pediatric pulmonologist is indicated when appropriate for specific problems as outlined in this chapter; a team approach may markedly improve operative and postoperative outcomes.

Pulmonary complications are a major cause of perioperative morbidity in the pediatric population. Although preexisting pulmonary pathologic processes in children can present significant challenges to anesthetic delivery, a thorough assessment of the problem combined with meticulous anesthetic management allows most children to undergo surgical interventions without long-term adverse sequelae. Asthma, cystic fibrosis and sickle cell disease continue to pose challenges during anesthesiology. Consultation with a pediatric pulmonologist is indicated when appropriate for specific problems as outlined in this chapter; a team approach may markedly improve operative and postoperative outcomes.