To the Editor:
Chronic inflammatory diseases cause anemia of inflammation (AI). This
causes impaired immune-mediated regulation of hepcidin and several
cytokines, which play a major role in iron homeostasis, accelerates
turnover of red blood cells, and affects the activity of erythropoietin
(EPO), thereby reducing levels of hemoglobin and
iron.1 Asthma is one of common allergic diseases
caused by disturbance of the immune system,2 and this
chronic inflammatory condition could cause systemic
inflammation.3 Several researches have recently shown
that asthma association with the increased prevalence of
anemia.4,5 No studies, however, have been conducted on
whether severe or uncontrolled asthma can more increase the prevalence
of anemia.
We hypothesized that patients with severe asthma were more likely to
have an active inflammatory condition, which may increase the prevalence
of anemia. Therefore, this study aims to evaluate whether the prevalence
of anemia in pediatric asthma patients differs according to asthma
control or severity.
98% of Koreans are enrolled in the universal health insurance system,
and all medical information is reported to the Health Insurance Review
Agency (HIRA). In this study, 10% (~1,100,000) of
patients under the age of 20 provided by HIRA were analyzed using a
dataset constructed by random stratification based on age and sex
(HIRA-PPS-2016).6 We included patients younger than 18
years and patients prescribed asthma medications with diagnosis of
asthma (eTable1, eTable2). Patients diagnosed with anemia other than
iron deficiency anemia (IDA) or AI were excluded. We classified the
severe asthma group who were diagnosed with asthma exacerbation at least
once a year or asthma diagnosis with systemic steroids, and the rest
were defined as the non-severe asthma group. Binary logistic regression
was carried out by applying inverse probability of treatment weighting
(IPTW) using the propensity score. To calculate the predicting
propensity score, we used a multivariable logistic regression model to
estimate the probability of each patient, including confounders
(eTable1). Odds ratio (OR) with 95% confidence interval (CI) are
reported for association anemia and asthma severity.
A total of 236,429 pediatric patients were included in the study. The
flow diagram for the study subject inclusion is shown (Fig. 1) and the
characteristics of the two groups of patients were similarly adjusted
after applying IPTW (eTable3). The increased prevalence of anemia in
patients with severe asthma was expressed OR of 1.56 (95% CI,
1.49-1.64; P < .001) (Table 1). The association between anemia
and asthma severity in children, male, female, or patients under health
insurance was expressed OR of 1.63 (95% CI, 1.55-1.71; P <
.001), 1.59 (95% CI, 1.49-1.70; P <.001), 1.53 (95% CI,
1.42-1.64; P < .001), and 1.56 (95% CI, 1.49-1.64; P
< .001), respectively. There were no associations between
anemia and severe asthma in adolescents and patients under medical aid
(Table 1).
The prevalence of anemia in patients who experienced exacerbation of
asthma or with systemic steroid was analyzed higher than other asthma
patients. This was the same even after adjusting for other confounding
factors in the two patient groups. Previous study suggested that the
correlation between the two diseases in those groups may have been
insignificant since adolescent patients or patients under medical aid
program may have different medical service usage patterns from those of
general patients.5
We do not monitor anemia for asthma patients in general, and the
guidelines do not present it in this regard. However, anemia negatively
affects pediatric patients’ growth, cognitive abnormalities, and poor
quality of life.7,8 In addition, in the case of AI,
treatment or control of the underlying disease takes precedence over the
treatment of anemia rather than simply administering iron or
EPO.9 In addition, it was reported that in patients
with high hepcidin, an index that can distinguish between AI and IDA,
administration of EPO or iron administration was less or non-response to
the treatment of anemia.11-12 Therefore, it might be
recommended to monitor and treat anemia since the prevalence of anemia
may increase in pediatric patients with severe asthma.
This study has some limitations. First, we reported the association
between severe asthma and anemia which is not the causality. Secondly,
since we included patients diagnosed with IDA, the influence of patients
with isolated IDA cannot be ruled out. Nevertheless, our study has
several strengths including a large sample size and statistical
adjustments with propensity weighting.
To our knowledge, this is the first study to show that severe asthma has
a stronger association with anemia compared to non-severe or controlled
asthma. This suggests that it may be necessary to more closely monitor
anemia in patients with severe asthma. Further study is needed to better
understand the etiology that severe asthma causes more AI.