4. DISCUSSION
In this study, we compared the overall and respiratory mortality rates
in patients with and without asthma using a large NHIS-NSC sample
cohort. Patients with asthma had higher all-cause and respiratory
mortality rates compared with subjects without asthma. The effects of
asthma on all-cause mortality were more evident in the male subgroup,
patients under medical aid, and subjects with COPD. Asthma had a more
substantial effect on respiratory mortality in male subgroups and the
younger population (age < 60 years). In addition, to the best
of our knowledge, this is the first study in which higher mortality in
asthmatics compared with non-asthmatics was comprehensively shown to be
attributed to respiratory comorbidities other than COPD (e.g.,
bronchiectasis, lung cancer, and pneumonia).
A previous study evaluating 164,845 asthmatic patients and matched
controls showed that all-cause mortality was approximately 1.25-fold
higher in asthmatic patients compared with controls4.
Our study confirmed these findings with a larger number of patients from
a nationally representative database, showing that asthmatic patients
had 1.13-fold higher mortality compared with subjects without asthma.
These findings indicate that asthma management remains unsatisfactory,
and proper asthma management strategies are needed, especially in males
and the younger population. The reasons for high mortality in male
asthmatics might be explained by a large gap in the smoking rate between
Korean males and females16. Smoking is associated with
severe asthmatic symptoms and exacerbations17. Smoking
is also associated with increased risk of COPD and lung cancer in
asthmatic patients8,18, which subsequently can
increase mortality. The reasons why the effects of asthma on respiratory
mortality are higher in the younger population remain unclear. One
hypothesis is that the effects of asthma on mortality gradually decrease
as patients age. Many elderly subjects have multiple comorbidities other
than asthma that can lead to mortality19. Thus, the
effects of asthma on mortality in the elderly might not be as high as in
the younger population.
One of the critical findings of our study is that the higher mortality
in asthmatic patients compared with subjects without asthma was mainly
due to comorbid respiratory diseases. Smoking-related respiratory
comorbidities, such as COPD and lung cancer, were the main risk factors
for increased mortality in asthmatics compared with subjects without
asthma. Similarly, previous studies showed that COPD substantially
increases the burden of symptoms, the rate of acute exacerbations, and
the mortality rate in asthmatic patients4,20-22.
Another explanation for this phenomenon is the recent evidence linking
asthma with risk of lung cancer8. Furthermore, our
results showed that asthmatic patients with lung cancer had an extremely
high risk of mortality compared with subjects without asthma. In
addition, the risk of mortality was highest in asthmatic patients with
lung cancer compared with the presence of other respiratory
comorbidities. Overall, the results indicate the need for strategies to
prevent smoking-related pulmonary diseases, such as smoking cessation,
in management of asthmatic patients.
Bronchiectasis is a common comorbidity of asthma and is associated with
severe symptoms and larger number of exacerbations7.
However, the effects of bronchiectasis on mortality in asthmatic
patients have rarely been reported. A recent Spanish study evaluated the
effects of in-hospital bronchiectasis mortality and found that
in-hospital mortality was higher in asthmatic patients with
bronchiectasis than in those without bronchiectasis (2.1% vs .
1.2%). However, the difference in mortality was not significant after
adjusting for covariables23. In contrast, another
study evaluated the impact of bronchiectasis on mortality in patients
with severe asthma and showed that bronchiectasis was associated with
all-cause mortality24. As the former study evaluated
only in-hospital mortality, and the latter evaluated severe asthma
patients, there are limited data on this issue. Showing the effects of
bronchiectasis on increased all-cause and respiratory mortality in
asthmatic patients using a nationwide large sample data is an important
advantage of the present study. Notably, although coexisting NTM
infection did not increase all-cause mortality in asthmatic patients
compared with subjects without asthma, NTM infection was associated with
increased respiratory mortality. However, because the number of patients
with NTM infection was small, further studies are needed.
There are several limitations to our study. First, the NHIS-NSC database
did not provide data on smoking history and pulmonary function, which
are important predictors of our main outcomes. Thus, we could not adjust
smoking status for the effects of these comorbidities on mortality.
Second, this study was performed in Korea. Although we analyzed a large
number of patients using a nationally representative sample, the data
might not be applicable to other ethnic groups in different countries.
However, using the nationwide representative database is also an
important advantage of the study. To the best of our knowledge, this is
the first study that demonstrated increased mortality and causes of
mortality in asthmatics compared with subjects without asthma using
nationally representative data. Third, we did not adjust for compliance
with medications. However, because different inhalation doses can be
administered by one inhaler according to asthma treatment protocol, it
is complicated to analyze medication usage ratio. In addition, some
medications (e.g., budesonide/formoterol inhaler and oral
corticosteroids) are used as controllers as well as relievers.
In conclusion, the mortality in patients with asthma was higher compared
with subjects without asthma, especially in patients with pulmonary
comorbidities, such as COPD, bronchiectasis, lung cancer, or pneumonia.
Despite the recent advancement in asthma management, strategies to
improve mortality of asthma are still needed, especially in patients
with pulmonary comorbidities.