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