Identifying clinical factors associated with invasive pneumococcal disease in Taiwan

Abstract

Risk factors for IPD among all subjects and other subgroups IPD Non‐IPD Adjusted OR (95%CI) Comorbidities n (%) n (%) P‐value Total (n = 4500) 900 3600 Asthma 33 (3.67) 26 (0.72) 3.36 (1.88, 6.01) <0.0001 Non‐asthma COPD 274 (30.44) 509 (14.14) 3.15 (2.51, 3.96) <0.0001 Cardiac disease 270 (30.00) 700 (19.44) 1.72 (1.32, 2.23) <0.0001 Cancer/immunosuppression 122 (12.44) 173 (4.81) 1.65 (1.21, 2.26) 0.0016 Chronic renal/hepatic disease 201 (22.33) 436 (12.11) 1.71 (1.33, 2.21) <0.0001 Diabetes mellitus 153 (17.00) 342 (9.50) 1.52 (1.16, 2.01) 0.0028 Male (n = 2845) Asthma 20 (3.51) 16 (0.70) 3.41 (1.63, 7.14) 0.0011 Non‐asthma COPD 190 (33.39) 373 (16.39) 3.05 (2.32, 4.01) <0.0001 Cardiac disease 190 (33.39) 489 (21.49) 1.86 (1.37, 2.53) <0.0001 Cancer/immunosuppression 81 (14.24) 133 (5.84) 1.66 (1.16, 2.39) 0.0056 Chronic renal/hepatic disease 147 (25.83) 324 (14.24) 1.86 (1.38, 2.50) <0.0001 Diabetes mellitus 103 (18.10) 244 (10.72) 1.33 (0.96, 1.85) 0.0836 Female (n = 1655) Asthma 13 (3.93) 10 (0.76) 3.35 (1.29, 8.69) 0.0130 Non‐asthma COPD 84 (25.38) 136 (10.27) 3.62 (2.39, 5.49) <0.0001 Cardiac disease 80 (24.17) 211 (15.94) 1.37 (0.82, 2.28) 0.2258 Cancer/immunosuppression 31 (9.37) 40 (3.02) 1.62 (0.86, 3.05) 0.1318 Chronic renal/hepatic disease 54 (16.31) 112 (8.46) 1.29 (0.77, 2.16) 0.3293 Diabetes mellitus 50 (15.11) 98 (7.40) 2.35 (1.38, 3.99) 0.0016 Aged 0‐4 years (n = 1665) Asthma 14 (4.20) 11 (0.83) 4.46 (1.83, 10.87) 0.0010 Non‐asthma COPD 23 (6.91) 46 (3.45) 1.68 (0.93, 3.06) 0.0884 Cardiac disease 11 (3.30) 29 (2.18) 0.87 (0.38, 2.00) 0.7393 Cancer/immunosuppression 5 (1.50) 3 (0.23) 2.98 (0.56, 15.85) 0.2002 Chronic renal/hepatic disease 1 (0.30) 2 (0.15) 3.79 (0.34, 42.25) 0.2788 Aged 5‐17 years (n = 570) Asthma 1 (0.88) 3 (0.66) 0.89 (0.06, 13.91) 0.9321 Non‐asthma COPD 11 (9.65) 31 (6.80) 1.70 (0.74, 3.90) 0.2109 Cardiac disease 6 (5.26) 11 (2.41) 2.82 (0.87, 9.11) 0.0831 Chronic renal/hepatic disease 3 (2.63) 2 (0.44) 0.92 (0.03, 26.93) 0.9619 Aged 18‐64 years (n = 1235) Asthma 12 (4.86) 5 (0.51) 7.16 (2.17, 23.69) 0.0013 Non‐asthma COPD 93 (37.65) 105 (10.63) 3.99 (2.72, 5.85) <0.0001 Cardiac disease 88 (35.63) 176 (17.81) 0.97 (0.65, 1.44) 0.8602 Cancer/immunosuppression 51 (20.65) 51 (5.16) 2.05 (1.25, 3.35) 0.0042 Chronic renal/hepatic disease 100 (40.49) 175 (17.71) 1.87 (1.28, 2.72) 0.0011 Diabetes mellitus 74 (29.96) 108 (10.93) 1.85 (1.22, 2.82) 0.0040 Aged 65‐74 years (n = 280) Asthma 2 (3.57) 1 (0.45) 2.43 (0.19, 31.49) 0.4973 Non‐asthma COPD 34 (60.71) 78 (34.82) 2.20 (1.13, 4.27) 0.0205 Cardiac disease 46 (82.14) 107 (47.77) 3.48 (1.59, 7.63) 0.0018 Cancer/immunosuppression 7 (12.50) 22 (9.82) 0.91 (0.33, 2.49) 0.8493 Chronic renal/hepatic disease 28 (50.00) 69 (30.80) 1.46 (0.74, 2.88) 0.2728 Diabetes mellitus 23 (41.07) 61 (27.23) 1.42 (0.72, 2.81) 0.3079 Aged 75 years and above (n = 750) Asthma 4 (2.67) 6 (1.00) 1.10 (0.30, 4.09) 0.8892 Non‐asthma COPD 113 (75.33) 249 (41.50) 3.70 (2.41, 5.68) <0.0001 Cardiac disease 119 (79.33) 377 (62.83) 1.54 (0.97, 2.45) 0.0700 Cancer/immunosuppression 42 (28.00) 97 (16.17) 1.42 (0.90, 2.23) 0.1324 Chronic renal/hepatic disease 69 (46.00) 188 (31.33) 1.47 (0.99, 2.19) 0.0575 Diabetes mellitus 56 (37.33) 173 (28.83) 1.13 (0.75, 1.71) 0.5617 Abbreviations: COPD: chronic obstructive pulmonary disease; IPD, invasive pneumococcal disease. [...]our study has demonstrated that asthma, non‐asthma COPD, cardiac disease, cancer/immunosuppression, chronic renal/hepatic disease, and diabetes mellitus were significantly associated with risk of IPD. Patients who have almost all the above‐mentioned comorbidities are currently recommended for pneumococcal vaccination except those with asthma in Taiwan. [...]the importance of self‐paid pneumococcal vaccination among asthmatic patients aged 18 to 65 without routine immunization should be emphasized.

Dear Editor

Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae has been a notifiable disease in Taiwan since 2007. It results in either long‐term problems, such as brain damage and hearing loss, or a particularly high case‐fatality rate and economic burden. Previous studies reported a variety of underlying medical conditions with increased susceptibility to IPD, but large‐scale indigenous studies regarding these risk factors are limited. We conducted a nationwide study in Taiwan utilizing the national health insurance research database (NHIRD) to identify gender and age‐related risk factors that are associated with IPD.

We used a subset of the database, Longitudinal Health Insurance Database (LHID) 2010 from NHIRD, to identify 903 IPD patients defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) during 2000 to 2013 in Taiwan. The non‐IPD group was matched with the IPD group according to age and gender of the person diagnosed with IPD at a ratio of 4:1. After matching, there were 900 patients in the IPD group and 3600 patients in the non‐IPD group. We identified the potential IPD risk predictors prior to the index date of IPD diagnosis for those with more than two outpatient visits or at least one admission within 12 months, including cases for asthma, non‐asthma chronic obstructive pulmonary disease (COPD), cardiac disease, cancer/ immunosuppression, chronic renal/hepatic disease, and diabetes mellitus. Multivariate logistic regression analyses were performed on the whole sample and subgroups.

After adjustment for demographic characteristics, the factors of asthma (OR = 3.36, 95% CI = 1.88‐6.01), non‐asthma COPD (OR = 3.15, 95% CI = 2.51‐3.96), cardiac disease (OR = 1.72, 95% CI = 1.32‐2.23), cancer/immunosuppression (OR = 1.65, 95% CI = 1.21‐2.26), chronic renal/hepatic disease (OR = 1.71, 95% CI = 1.33‐2.21), and diabetes mellitus (OR = 1.52, 95% CI = 1.16‐2.01) were found to be associated with an increased risk of IPD. For males, the factors of asthma, non‐asthma COPD, cardiac disease, cancer/immunosuppression, and chronic renal/hepatic disease were related to increased risk of IPD. The factors including asthma, non‐asthma COPD, and diabetes mellitus were found to spur increased risk of IPD in females. In terms of age, among children aged 0 to 4 years, only asthma was associated with the risk of IPD. In the age group 5 to 17 years, all risk factors were the least strongly related to IPD. Among those aged 18 to 64 years, most factors were related to increased risk of IPD except for cardiac disease. In the age group 65 years and over, the highest risk was among those with non‐asthma COPD and cardiac disease (Table ).

Risk factors for IPD among all subjects and other subgroups

	IPD	Non‐IPD	Adjusted OR (95%CI)
Comorbidities	n (%)	n (%)	P‐value
Total (n = 4500)	900	3600
Asthma	33 (3.67)	26 (0.72)	3.36 (1.88, 6.01)	<0.0001
Non‐asthma COPD	274 (30.44)	509 (14.14)	3.15 (2.51, 3.96)	<0.0001
Cardiac disease	270 (30.00)	700 (19.44)	1.72 (1.32, 2.23)	<0.0001
Cancer/immunosuppression	122 (12.44)	173 (4.81)	1.65 (1.21, 2.26)	0.0016
Chronic renal/hepatic disease	201 (22.33)	436 (12.11)	1.71 (1.33, 2.21)	<0.0001
Diabetes mellitus	153 (17.00)	342 (9.50)	1.52 (1.16, 2.01)	0.0028
Male (n = 2845)
Asthma	20 (3.51)	16 (0.70)	3.41 (1.63, 7.14)	0.0011
Non‐asthma COPD	190 (33.39)	373 (16.39)	3.05 (2.32, 4.01)	<0.0001
Cardiac disease	190 (33.39)	489 (21.49)	1.86 (1.37, 2.53)	<0.0001
Cancer/immunosuppression	81 (14.24)	133 (5.84)	1.66 (1.16, 2.39)	0.0056
Chronic renal/hepatic disease	147 (25.83)	324 (14.24)	1.86 (1.38, 2.50)	<0.0001
Diabetes mellitus	103 (18.10)	244 (10.72)	1.33 (0.96, 1.85)	0.0836
Female (n = 1655)
Asthma	13 (3.93)	10 (0.76)	3.35 (1.29, 8.69)	0.0130
Non‐asthma COPD	84 (25.38)	136 (10.27)	3.62 (2.39, 5.49)	<0.0001
Cardiac disease	80 (24.17)	211 (15.94)	1.37 (0.82, 2.28)	0.2258
Cancer/immunosuppression	31 (9.37)	40 (3.02)	1.62 (0.86, 3.05)	0.1318
Chronic renal/hepatic disease	54 (16.31)	112 (8.46)	1.29 (0.77, 2.16)	0.3293
Diabetes mellitus	50 (15.11)	98 (7.40)	2.35 (1.38, 3.99)	0.0016
Aged 0‐4 years (n = 1665)
Asthma	14 (4.20)	11 (0.83)	4.46 (1.83, 10.87)	0.0010
Non‐asthma COPD	23 (6.91)	46 (3.45)	1.68 (0.93, 3.06)	0.0884
Cardiac disease	11 (3.30)	29 (2.18)	0.87 (0.38, 2.00)	0.7393
Cancer/immunosuppression	5 (1.50)	3 (0.23)	2.98 (0.56, 15.85)	0.2002
Chronic renal/hepatic disease	1 (0.30)	2 (0.15)	3.79 (0.34, 42.25)	0.2788
Aged 5‐17 years (n = 570)
Asthma	1 (0.88)	3 (0.66)	0.89 (0.06, 13.91)	0.9321
Non‐asthma COPD	11 (9.65)	31 (6.80)	1.70 (0.74, 3.90)	0.2109
Cardiac disease	6 (5.26)	11 (2.41)	2.82 (0.87, 9.11)	0.0831
Chronic renal/hepatic disease	3 (2.63)	2 (0.44)	0.92 (0.03, 26.93)	0.9619
Aged 18‐64 years (n = 1235)
Asthma	12 (4.86)	5 (0.51)	7.16 (2.17, 23.69)	0.0013
Non‐asthma COPD	93 (37.65)	105 (10.63)	3.99 (2.72, 5.85)	<0.0001
Cardiac disease	88 (35.63)	176 (17.81)	0.97 (0.65, 1.44)	0.8602
Cancer/immunosuppression	51 (20.65)	51 (5.16)	2.05 (1.25, 3.35)	0.0042
Chronic renal/hepatic disease	100 (40.49)	175 (17.71)	1.87 (1.28, 2.72)	0.0011
Diabetes mellitus	74 (29.96)	108 (10.93)	1.85 (1.22, 2.82)	0.0040
Aged 65‐74 years (n = 280)
Asthma	2 (3.57)	1 (0.45)	2.43 (0.19, 31.49)	0.4973
Non‐asthma COPD	34 (60.71)	78 (34.82)	2.20 (1.13, 4.27)	0.0205
Cardiac disease	46 (82.14)	107 (47.77)	3.48 (1.59, 7.63)	0.0018
Cancer/immunosuppression	7 (12.50)	22 (9.82)	0.91 (0.33, 2.49)	0.8493
Chronic renal/hepatic disease	28 (50.00)	69 (30.80)	1.46 (0.74, 2.88)	0.2728
Diabetes mellitus	23 (41.07)	61 (27.23)	1.42 (0.72, 2.81)	0.3079
Aged 75 years and above (n = 750)
Asthma	4 (2.67)	6 (1.00)	1.10 (0.30, 4.09)	0.8892
Non‐asthma COPD	113 (75.33)	249 (41.50)	3.70 (2.41, 5.68)	<0.0001
Cardiac disease	119 (79.33)	377 (62.83)	1.54 (0.97, 2.45)	0.0700
Cancer/immunosuppression	42 (28.00)	97 (16.17)	1.42 (0.90, 2.23)	0.1324
Chronic renal/hepatic disease	69 (46.00)	188 (31.33)	1.47 (0.99, 2.19)	0.0575
Diabetes mellitus	56 (37.33)	173 (28.83)	1.13 (0.75, 1.71)	0.5617

Abbreviations: COPD: chronic obstructive pulmonary disease; IPD, invasive pneumococcal disease.

In conclusion, our study has demonstrated that asthma, non‐asthma COPD, cardiac disease, cancer/immunosuppression, chronic renal/hepatic disease, and diabetes mellitus were significantly associated with risk of IPD. Notably, asthma was an independent risk factor for IPD in children 0 to 4 years, while non‐asthma COPD was a major risk factor for IPD in elders. Interestingly, no risk factors included in our study showed significant impacts on patients aged 5 to 17, which might be partly due to their mature innate and adaptive immune responses. Patients who have almost all the above‐mentioned comorbidities are currently recommended for pneumococcal vaccination except those with asthma in Taiwan. Therefore, the importance of self‐paid pneumococcal vaccination among asthmatic patients aged 18 to 65 without routine immunization should be emphasized.

ACKNOWLEDGMENT

The authors are also grateful to Research Center of Medical Informatics, Kaohsiung Veterans General Hospital, for data management and statistical analysis.

CONFLICTS OF INTEREST

All authors declare no conflicts of interests.