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Original Article
a
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical
University, Kaohsiung, Taiwan
b
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University,
Kaohsiung, Taiwan
c
Department of Laboratory Medicine, School of Medicine, College of Medicine, Kaohsiung Medical
University, Kaohsiung, Taiwan
d
Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
e
Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
f
Ta-Kuo Clinic, Kaohsiung, Taiwan
g
Teaching and Research Center of Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
h
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
i
Department of Radiation Oncology, College of Medicine, Kaohsiung Medical University, Kaohsiung,
Taiwan
j
Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan
k
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung,
Taiwan
Received 16 July 2018; received in revised form 8 December 2018; accepted 18 February 2019
Available online - - -
KEYWORDS Abstract Purpose: Early-life antibiotic use may be associated with asthma, yet whether this
Asthma; association also exists in patients with allergic rhinitis (AR) remains unknown. We investigated
Allergic rhinitis; the association between antibiotic exposure and asthma development in AR children.
Antibiotics; Methods: AR patients less than 18 year-old were enrolled from the Taiwan National Health In-
Children surance Database, which reported information from 2005 to 2010. The case group was defined
as having newly developed asthma, and the control group was defined as never having an
asthma diagnosis. The age of first exposure to antibiotic prescriptions and antibiotic exposure
* Corresponding author. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, #100, Tz-You 1st
Road, Kaohsiung, 807, Taiwan. Fax: þ886 7 3213931.
E-mail address: pedhung@gmail.com (C.-H. Hung).
https://doi.org/10.1016/j.jmii.2019.02.003
1684-1182/Copyright ª 2019, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
2 Y.-C. Lin et al.
records preceding 5 years before the first asthma diagnosis were obtained from drug prescrip-
tion records. The odds ratio (OR) was examined after adjusting for age, gender, resident ur-
banization, underlying medical disorders and medications.
Results: A total of 3236 AR patients with newly developed asthma and 9708 AR patients
without asthma were included in this study. Antibiotic exposure before the age of 3 years
was not associated with asthma development. Preceding 5-year antibiotic exposure increased
the risk of asthma development with a dose-response relationship, even for antibiotics with
low cumulative defined daily doses (adjusted OR 1.40, 95% CI 1.12e1.75). Preceding 5-year
exposure to penicillin and macrolide significantly increased the risk of asthma when diagnosed
before age 12 in AR patients, but this was not statistically significant when asthma diagnosed
after age 12.
Conclusion: Preceding 5-year antibiotic exposure, particularly to penicillin group of amoxicillin
and macrolides, is associated with the risk of asthma development before age 12 in AR chil-
dren.
Copyright ª 2019, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
Effect of antibiotics on childhood asthma 3
December 31, 2010 from the NHIRD database. The case Statistical analysis
group was defined as AR patients with newly developed
asthma (ICD-9-CM code 49390-49392), and the control group Pearson’s chi-square test or Fisher’s exact test was per-
was defined as AR patients without any history of asthma. formed to investigate the differences in categorical data
Patients who were diagnosed with asthma had at least two between patients from the case and control groups. An
prescriptions of anti-asthmatic drugs at different times independent t-test was conducted to evaluate the differ-
within a 1-year period. Anti-asthmatic drugs included ences in continuous data between the two groups. Condi-
inhaled selective b2-agonists (ATC code R03AC), inhaled tional logistic regression analysis was applied to determine
corticosteroids (ATC code R03BA), combined inhaled sal- the relationship between asthma and antibiotic exposure.
butamol/sodium cromoglycate (ATC code R03AK04), and The DDD recommended by the World Health Organization
combined inhaled selective b2-agonists/corticosteroids (WHO) was used to quantify antibiotic use. The cumulative
(ATC code R03AK06, R03AK07). The date of asthma diag- DDDs of antibiotics were categorized into low dose, mod-
nosis was defined as the index date in the present study. erate dose, and high dose in the study subjects. Various co-
Three non-asthmatic control children were matched to variables, including age, gender, resident urbanization,
each case child by age, gender, selected comorbid medical comorbidities, and co-medications, were adopted in the
disorders and infections, and the use of non-steroidal anti- statistical analysis model. In the analysis of antibiotic
inflammatory drugs (NSAIDs) by propensity score and was subtypes, we adjusted for the above variables but also for
randomly selected. To avoid any chronological overlap be- other different antibiotics. Odds ratios (ORs) and 95% con-
tween exposure and outcome, children who met our fidence intervals (CIs), using no antibiotic exposure as the
asthma definition, died, received their asthma diagnosis reference, were calculated to determine the risk of asthma
before an allergic rhinitis diagnosis, or were first diagnosed development in antibiotic users and in the dose-response
with asthma before age 2 years old were excluded. analysis. All statistical operations were conducted using the
SAS 9.3 statistical package. All p-values were two-sided,
and p-values < 0.05 were statistically significant.
Exposure to antibiotics
Potential confounders In the present study, antibiotic exposure before 3 years old
was not associated with the development of asthma in AR
patients (adjusted OR 0.98, 95% CI 0.85e1.12; Table 2).
Potential confounders known to be associated with asthma
After age stratification of asthma diagnosis date, antibiotic
were investigated, including resident urbanization, atopic
exposure was no significant difference compared to the
dermatitis (ICD-9-CM code 691.8), chronic rhinitis (ICD-9-CM
controls in AR patients who were first diagnosed with
code 472.0), acute sinusitis (ICD-9-CM code 461.9), acute
asthma at 4e6 years old (adjusted OR 1.16, 95% CI
bronchitis (ICD-9-CM code 466), acute tonsillitis (ICD-9-CM
0.81e1.66), at 7e11 years old (adjusted OR 0.93, 95% CI
code 463), acute pharyngitis (ICD-9-CM code 462), pneu-
0.76e1.14), and more than 12 years (adjusted OR 0.93, 95%
monia (ICD-9-CM code 486), and the use of NSAIDs. NSAIDs
CI 0.66e1.30).
were often being used with antibiotics in the treatment of
infection in children. NSAIDs would induce clinical asthma
by the possibility of hypersensitivity and induction of severe Relationship between the cumulative DDDs of
airways obstruction.13 It has been reported that exposure antibiotics and asthma development in AR patients
of NSAIDs is associated with asthma risk.14,15 Therefore, the
use of NSAIDs was considered as an important covariate in There was a positive relationship between antibiotic
the present study. The use of NSAIDs was defined as NSAIDs exposure and the risk of asthma development (adjusted OR
use during 120 days before the index date. 1.74, 95% CI 1.41e2.17; Table 3). To further evaluate
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
4 Y.-C. Lin et al.
Figure 1. Flowchart of participant recruitment in this study. ICD-9-CM: International Classification of Diseases, Ninth Revision,
Clinical Modification NHIRD: National Health Insurance Research Database.
Table 1 Demographic characteristics between cases and controls in children with allergic rhinitis.
Case group Control group p value
(N Z 3236) (N Z 9708)
number (%) number (%)
Age, mean (standard deviation) 7.53 (3.32) 7.48 (3.30) 0.067
<4 years 511 (15.8) 1584 (16.3) 0.720
4e11 years 2407 (74.4) 7199 (74.2)
>Z12 years 318 (9.8) 925 (9.5)
Gender
Female 1426 (44.1) 4271 (44.0) 0.943
Male 1810 (55.9) 5437 (56.0)
Resident urbanization
Urban 889 (27.5) 2627 (27.1) 0.718
Suburban 1183 (36.6) 3626 (37.4)
Rural 1164 (36.0) 3455 (35.6)
Comorbidities
Atopic dermatitis 678 (21.0) 1926 (19.8) 0.172
Chronic rhinitis 763 (23.6) 2173 (22.4) 0.160
Acute sinusitis 2806 (86.7) 8475 (87.3) 0.387
Acute bronchitis 3143 (97.1) 9468 (97.5) 0.211
Acute tonsillitis 2470 (76.3) 7523 (77.5) 0.172
Acute pharyngitis 2718 (84.0) 8246 (84.9) 0.195
Pneumonia 179 (5.5) 473 (4.9) 0.138
Medication
NSAIDs 896 (27.7) 2661 (27.4) 0.759
NSAIDs: nonsteroidal anti-inflammatory drugs.
whether the relationship was dose-dependent, we divided 1.46e2.29 for overall antibiotics; adjusted OR 1.36, 95% CI
the study subjects into three subgroups based on the cu- 1.20e1.55 for penicillin; adjusted OR 1.65, 95% CI
mulative DDDs of antibiotics. The incidence of newly 1.47e1.84 for macrolides), and high dose (adjusted OR
developed asthma in the cases was significantly increased 2.28, 95% CI 1.82e2.86 for overall antibiotics; adjusted OR
in low dose (adjusted OR 1.40, 95% CI 1.12e1.75 for overall 1.65, 95% CI 1.45e1.88 for penicillin; adjusted OR 2.20, 95%
antibiotics; adjusted OR 1.60, 95% CI 1.43e1.79 for mac- CI 1.95e2.47 for macrolides) patients compared to the
rolides), moderate dose (adjusted OR 1.83, 95% CI controls. Otherwise, there was a significant trend toward
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
Effect of antibiotics on childhood asthma 5
Table 2 Antibiotic exposure before 3-year-old and the risk of asthma development in children with allergic rhinitis.
Age of index date Case group Control group Unadjusted model Adjusted modela
number (%) number (%) OR (95% CI) p value OR (95% CI) p value
(exposure/total) (exposure/total)
Overall 2803/3236 (86.6) 8467/9708 (87.2) 0.95 (0.84e1.07) 0.380 0.98 (0.85e1.12) 0.765
4e6 years 466/511 (91.2) 1435/1584 (90.6) 1.08 (0.76e1.53) 0.684 1.16 (0.81e1.66) 0.422
7e11 years 2258/2407 (93.8) 6792/7199 (94.3) 0.91 (0.75e1.10) 0.329 0.93 (0.76e1.14) 0.489
S12 years 79/318 (24.8) 240/925 (25.9) 0.94 (0.70e1.27) 0.698 0.93 (0.66e1.30) 0.652
a
Adjusted age, gender, resident urbanization, comorbidities and medication. OR: odds ratios; CI: confidence intervals.
p-values < 0.05 were statistically significant.
Table 3 Cumulative DDDs of antibiotics within 5-year preceding index date and the risk of asthma development in allergic
rhinitis children.
Group of antibiotics Case group Control group Unadjusted model Adjusted modela
Exposure number (%) Exposure number (%) OR (95% CI) p value OR (95% CI) p value
Any antibiotics
No 108 (3.3) 527 (5.4) 1.00 1.00
Yes 3128 (96.7) 9181 (94.6) 1.66 (1.35e2.05) <0.001 1.74 (1.41e2.17) <0.001
Cumulative DDDs
<8.08 870 (26.9) 3232 (33.3) 1.31 (1.05e1.64) 0.015 1.40 (1.12e1.75) 0.003
8.08e21.96 1046 (32.3) 3059 (31.5) 1.67 (1.34e2.08) <0.001 1.83 (1.46e2.29) <0.001
>21.96 1212 (37.5) 2890 (29.8) 2.05 (1.65e2.54) <0.001 2.28 (1.82e2.86) <0.001
p for trend <0.001 <0.001
Penicillins
No 682 (15.1) 935 (20.7) 1.00 1.00
Yes 3589 (84.9) 3589 (79.3) 1.38 (1.24e1.54) <0.001 1.31 (1.17e1.47) <0.001
Cumulative DDDs
<5.75 1143 (25.3) 1352 (29.9) 1.07 (0.94e1.21) 0.274 1.07 (0.94e1.22) 0.268
5.75e14.75 1260 (27.9) 1184 (26.2) 1.39 (1.23e1.57) <0.001 1.36 (1.20e1.55) <0.001
>14.75 1439 (31.8) 1053 (23.3) 1.74 (1.55e1.97) <0.001 1.65 (1.45e1.88) <0.001
p for trend <0.001 <0.001
Cephalosporins
No 618 (19.1) 1975 (20.3) 1.00 1.00
Yes 2618 (80.9) 7733 (79.7) 1.08 (0.97e1.19) 0.125 0.95 (0.85e1.06) 0.397
Cumulative DDDs
<2.55 581 (18.0) 1860 (19.2) 0.99 (0.87e1.13) 0.979 0.94 (0.82e1.08) 0.414
2.55e6.68 821 (25.4) 2599 (26.8) 1.01 (0.89e1.13) 0.877 0.91 (0.81e1.04) 0.182
>6.68 1216 (37.6) 3274 (33.7) 1.18 (1.06e1.32) 0.003 0.99 (0.88e1.12) 0.936
p for trend 0.001 0.965
Macrolides
No 1864 (41.2) 2617 (57.8) 1.00 1.00
Yes 2660 (58.8) 1907 (42.2) 1.76 (1.63e1.91) <0.001 1.77 (1.63e1.93) <0.001
Cumulative DDDs
<1.50 902 (19.9) 886 (19.6) 1.57 (1.40e1.75) <0.001 1.60 (1.43e1.79) <0.001
1.50e4.29 948 (21.0) 644 (14.2) 1.64 (1.47e1.83) <0.001 1.65 (1.47e1.84) <0.001
>4.29 810 (17.9) 377 (8.3) 2.20 (1.96e2.47) <0.001 2.20 (1.95e2.47) <0.001
p for trend <0.001 <0.001
Others
No 2527 (78.1) 7681 (79.1) 1.00 1.00
Yes 709 (21.9) 2027 (20.9) 1.06 (0.96e1.17) 0.214 0.97 (0.88e1.07) 0.584
Cumulative DDDs
<2.00 224 (6.9) 721 (7.4) 0.94 (0.80e1.10) 0.473 0.88 (0.75e1.03) 0.122
2.00e6.00 244 (7.5) 631 (6.5) 1.17 (1.00e1.37) 0.040 1.07 (0.91e1.25) 0.375
>6.00 241 (7.4) 675 (7.0) 1.08 (0.93e1.26) 0.297 0.97 (0.83e1.14) 0.767
p for trend 0.093 0.920
a
Adjusted age, gender, resident urbanization, comorbidities, medication and other subtype antibiotics. DDDs: defined daily doses;
OR: odds ratios; CI: confidence intervals. p-values < 0.05 were statistically significant.
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
6 Y.-C. Lin et al.
an increasing risk of asthma development with increasing 1.51e2.64), and erythromycin (adjusted OR 1.35, 95% CI
cumulative DDDs of any antibiotic analyzed (p for 1.23e1.47) was associated with asthma development in the
trend < 0.001). Furthermore, a dose-response relationship group of asthma patients first diagnosed before 12 years
between the occurrence of newly developed asthma and old. Only the preceding 5-year exposure of azithromycin
deciles of cumulative DDDs of antibiotics, including overall was associated with asthma patients diagnosed after 12
antibiotics, penicillins, and macrolides, was found (Fig. 2). years old (adjusted OR 3.46, 95% CI 1.37e8.70) (Table 4).
Figure 2. Cumulative DDDs deciles (rank 1, 2, 3.10) within 5 years preceding index date and the risk of newly developed
asthma in children with allergic rhinitis. Data points were adjusted odds ratio (OR) with 95% confidence intervals (bars). No
antibiotic use as reference.
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
Effect of antibiotics on childhood asthma 7
Table 4 Classifications of antibiotic exposure within 5-year preceding index date and the risk of asthma development in
children with allergic rhinitis.
Age of index date/antibiotic type Case group Control group Unadjusted model Adjusted modela
Exposure number (%) OR (95% CI) p value OR (95% CI) p value
Overall N Z 3236 N Z 9708
Any antibiotics 3128 (96.7) 9181 (94.6) 1.66 (1.34e2.05) <0.001 1.74 (1.40e2.16) <0.001
Penicillins 2713 (83.8) 7659 (78.9) 1.38 (1.24e1.54) <0.001 1.31 (1.17e1.47) <0.001
Amoxicillin 2657 (82.1) 7449 (76.7) 1.39 (1.25e1.54) <0.001 1.32 (1.19e1.47) <0.001
Ampicillin 200 (6.2) 563 (5.8) 1.07 (0.90e1.26) 0.425 1.00 (0.84e1.18) 0.959
Penicillin 35 (1.1) 134 (1.4) 0.78 (0.53e1.13) 0.196 0.70 (0.48e1.03) 0.074
Cephalosporins 2618 (80.9) 7733 (79.7) 1.08 (0.97e1.19) 0.125 0.95 (0.85e1.06) 0.397
Macrolides 1866 (57.7) 4226 (43.5) 1.76 (1.63e1.91) <0.001 1.77 (1.63e1.93) <0.001
Azithromycin 506 (15.6) 576 (5.9) 2.93 (2.58e3.33) <0.001 2.97 (2.61e3.38) <0.001
Clarithromycin 97 (3.0) 147 (1.5) 2.01 (1.55e2.60) <0.001 1.99 (1.53e2.59) <0.001
Erythromycin 1397 (43.2) 3488 (35.9) 1.35 (1.24e1.46) <0.001 1.32 (1.22e1.44) <0.001
Others 709 (21.9) 2027 (20.9) 1.06 (0.96e1.17) 0.214 0.97 (0.88e1.07) 0.584
4e11 years old N Z 2918 N Z 8783
Any antibiotics 2839 (97.3) 8358 (95.2) 1.82 (1.43e2.33) <0.001 1.94 (1.51e2.49) <0.001
Penicillins 2504 (85.8) 7085 (80.7) 1.45 (1.29e1.62) <0.001 1.36 (1.20e1.54) <0.001
Amoxicillin 2455 (84.1) 6892 (78.5) 1.45 (1.30e1.62) <0.001 1.37 (1.22e1.54) <0.001
Ampicillin 177 (6.1) 510 (5.8) 1.04 (0.87e1.25) 0.606 0.98 (0.82e1.17) 0.832
Penicillin 35 (1.2) 123 (1.4) 0.85 (0.58e1.24) 0.416 0.76 (0.52e1.11) 0.163
Cephalosporins 2407 (82.5) 7110 (81.0) 1.10 (0.99e1.23) 0.065 0.96 (0.86e1.08) 0.581
Macrolides 1761 (60.3) 3979 (45.3) 1.83 (1.68e2.00) <0.001 1.83 (1.68e2.00) <0.001
Azithromycin 496 (17.0) 567 (6.5) 2.96 (2.60e3.37) <0.001 2.98 (2.61e3.39) <0.001
Clarithromycin 86 (2.9) 130 (1.5) 2.02 (1.53e2.66) <0.001 2.00 (1.51e2.64) <0.001
Erythromycin 1321 (45.3) 3283 (37.4) 1.38 (1.27e1.50) <0.001 1.35 (1.23e1.47) <0.001
Others 610 (20.9) 1741 (19.8) 1.06 (0.96e1.18) 0.206 0.96 (0.86e1.07) 0.533
12 years old N Z 318 N Z 925
Any antibiotics 289 (90.9) 823 (89.0) 1.23 (0.80e1.90) 0.340 1.20 (0.77e1.88) 0.401
Penicillins 209 (65.7) 574 (62.1) 1.17 (0.89e1.53) 0.243 1.15 (0.86e1.52) 0.326
Amoxicillin 202 (63.5) 557 (60.2) 1.15 (0.88e1.49) 0.297 1.13 (0.85e1.49) 0.383
Ampicillin 23 (7.2) 53 (5.7) 1.28 (0.77e2.13) 0.336 1.21 (0.72e2.03) 0.452
Penicillin 0 (0.0) 11 (1.2) NA NA
Cephalosporins 211 (66.4) 623 (67.4) 0.95 (0.73e1.25) 0.744 0.88 (0.66e1.17) 0.394
Macrolides 105 (33.0) 247 (26.7) 1.35 (1.02e1.78) 0.031 1.30 (0.98e1.73) 0.066
Azithromycin 10 (3.1) 9 (1.0) 3.30 (1.33e8.20) 0.010 3.46 (1.37e8.70) 0.008
Clarithromycin 11 (3.5) 17 (1.8) 1.91 (0.88e4.13) 0.098 1.78 (0.81e3.92) 0.149
Erythromycin 76 (23.9) 205 (22.2) 1.10 (0.81e1.49) 0.523 1.07 (0.78e1.46) 0.654
Others 99 (31.1) 286 (30.9) 1.01 (0.76e1.33) 0.943 0.97 (0.73e1.29) 0.841
a
Adjusted age, gender, resident urbanization, comorbidities, medication and other subtype antibiotics. OR: odds ratios; CI: confi-
dence intervals. NA: not applicable. p-values < 0.05 were statistically significant.
antibiotic increases, the risk of asthma also increases, with these changes. Mounting evidence shows that antibiotics
the highest risk being in children who receive more than influence the function of the immune system and the ability
four courses. Most antibiotics are associated with an to resist infection. The gut microbiota is important in
increased risk of asthma development, except for sulfon- human health, and dysbiosis of the intestinal ecosystem
amides.21 We found that antibiotic exposure before 3-year- contributes to the development of certain illnesses that can
old was not associated with the asthma development in AR be reversed by altering the microbiota via probiotic sup-
patient. However, our data suggested that antibiotic plementation. Commensal bacteria killed by antibiotics
exposure in the previous 5 years is associated with newly influence the epithelial barrier in many ways. Structural
diagnosed asthma in pediatric AR patients. The widespread components and metabolites of the intestinal microbiota
use of antibiotics in the past 80 years has saved millions of act on intestinal epithelial cells and local innate leukocytes
human lives and killed incalculable numbers of microbes, to maintain barrier integrity and regulate immune homeo-
both pathogenic and commensal. Human-associated mi- stasis.22 In the present study, penicillin groups and macro-
crobes perform several important functions and we are only lides were associated with the risk of asthma development
beginning to understand the ways in which antibiotics have in AR chideren. However, in penicillin groups, there was
reshaped their ecology and the functional consequences of only amoxicillin but not ampicillin nor penicillin
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
8 Y.-C. Lin et al.
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003
+ MODEL
Effect of antibiotics on childhood asthma 9
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Appendix A. Supplementary data
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Rhinitis therapy and the prevention of hospital care for Supplementary data to this article can be found online at
asthma. J Allergy Clin Immunol 2004;113:415e9. https://doi.org/10.1016/j.jmii.2019.02.003.
Please cite this article as: Lin Y-C et al., Antibiotic exposure and asthma development in children with allergic rhinitis, Journal of
Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2019.02.003