Comorbidities of asthma
Most research of treatments for airways diseases has been restricted to patients who meet standard definitions of either chronic obstructive pulmonary disease (COPD) or asthma, yet to distinguish COPD from asthma in adult patients who have clinical features of both can be challenging.96 Asthma‐COPD overlap syndrome (ACOS) is a poorly described condition, which shows a clinically different approach compared to asthma or COPD alone. Wang et al. estimated that among newly diagnosed adult‐onset asthma patients in Southern Finland, the prevalence of ACOS is of 6.6%. Most of the cases with ACOS were older, with lower education, more often men and current or former smokers, when compared to the asthma‐only cases. Interestingly, having additionally other respiratory diseases or allergic diseases were less common among the ACOS cases than among the asthma‐only cases, but familial asthma was associated to an increased risk of ACOS.97
Asthma can come together with the local AR, because of united airways. These patients show seasonal or perennial asthma-like symptoms, negative skin prick test and/or specific IgE, but display positive bronchial and/or nasal allergen provocation test responses triggered by HDM. These features suggests a new phenotype of asthma by the absence of systemic atopy, namely local allergic asthma.98
Sanna et al reported that the incidence of co-existing AR, allergic dermatitis, and allergic conjunctivitis, was positively correlated with the risk of the adult-onset asthma, and this tendency was decreased with the increasing of age.99 In a recent review, Samitas et al.100 discussed the one airway concept which suggests disease mechanisms take place in the upper airway might be reflected by lower events. Additionally, bronchial fibroblasts also have been known with their role in airway remodeling by regulating epithelial cell functions.
Sharma et al.101 reviewed experimental and clinical information for specific mediators of asthma and obesity alone or comorbidity, such as adipokines, cytokines, fatty acids which involve in polarization of macrophages, particularly. M1 and M2 macrophages might co-present in distinct organs and may impact asthma and obesity differently. M1 macrophages are suggested beneficial for asthma, while M2 macrophages contribute to the pathology of both asthma and obesity. Potential therapeutics for obese asthmatics by breaking the macrophage-mediated cycle between obesity and asthma were suggested. Recently, Chen et al. indicated that early pubertal maturation is related to childhood-onset asthma in both genders.102Besides, obesity together with early pubertal maturation can increase the risk of asthma, which implies the importance of the body mass index (BMI) control to prevent early pubertal maturation and asthma onset. Using 26 BMI-associated SNPs, Skaaby et al. evaluated the causal effect of BMI on asthma, hay fever, allergic sensitization, total serum IgE, forced expiratory volume in one-second (FEV1) and forced vital capacity. As a result of genetic analysis of 162124 participants, the authors concluded that increasing BMI is causally related to a higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.103
Future directions in asthma therapy, compromise both the optimization of known treatments and the implementation of novel approaches. As an example of the first option, Tay et al. highlighted the importance of comorbid “treatable traits” in difficult asthma, where they concluded that treatment of most extra-pulmonary comorbidities (e.g. rhinitis, chronic rhinosinusitis, gastroesophageal reflux or obesity) improves asthma outcomes. They suggested a targeted assessment of patients suffering from difficult-to-treat asthma, including questionnaires, specialist assessments and tailored referrals; preferably before initiating phenotype-driven biological treatment.104However, it is noteworthy that some common asthma comorbidities (e.g. chronic rhinosinusitis) might profit from the “biologicals approach” as well.105
An important, yet often neglected aspect of asthma is the high prevalence of anxiety and depression in this patient group. A recent study reported on the mental health of asthma patients and found a positive correlation between the severity of anxiety and depression with less well controlled asthma symptoms.106
Generally, the analysis of comorbidities in asthma patients is extremely relevant, as shown by a study by Lemonnier et al. The authors have identified gene expression patterns in peripheral blood mononuclear cells that are associated with the combined presence of asthma, allergic rhinitis and/or dermatitis in the mechanisms of the Development of Allergy and epigenetic variation and Childhood Asthma in Puerto Ricans cohorts. 8 common genes were overexpressed in multi-morbidities, while no genes were observed to be differentially expressed specific to the presence of asthma.107
In another study in adolescents and adults with asthma and rhinitis (A+R+) multimorbidity evaluating the IgE polysensitization towards various aeroallergen components showed frequent IgE sensitization to pollen and indoor allergens in A+R+ and contrasting with pollen allergens in rhinitis alone.108
Comorbidities also impact mortality in asthma. In a 15-year follow-up cohort of adults with asthma, the development of COPD, malignant respiratory tract neoplasms and cardiovascular diseases were the main reasons for an increased mortality. Allergic rhinitis and/or allergic conjunctivitis were associated with decreased mortality but with increased morbidity.109