Population-based study of the association between asthma and pneumococcal disease in children

Figures & data

Table 1 Selected characteristics of live births, Denmark, 1994–2007

	Overall		Child asthma		No child asthma
	n	%	n	%	n	%
Characteristics	888,655	100	53,024	100	835,631	100
Child’s sex
Male	456,001	51.3	33,790	63.7	422,211	50.5
Female	432,654	48.7	19,234	36.3	413,420	49.5
Home birth
No	880,712	99.1	52,646	99.3	828,066	99.1
Yes	7,943	0.9	378	0.7	7,565	0.9
Gestation
Term (≥37 weeks)	840,509	94.6	48,311	91.1	792,198	94.8
Preterm (<37 weeks)	48,146	5.4	4,713	8.9	43,433	5.2
Fetal presentation
Cephalic	847,165	96.1	50,168	95.3	796,997	96.1
Breech, other	34,794	3.9	2,498	4.7	32,296	3.9
Mode of delivery
Vaginal	692,673	77.9	40,442	76.3	652,231	78.1
Cesarean	128,240	14.4	8,743	16.5	119,497	14.3
Forceps, vacuum	67,742	7.6	3,839	7.2	63,903	7.6
Birth weight
Normal (≥2,500 g)	852,004	95.9	49,379	93.1	802,625	96.1
Low (<2,500 g)	36,651	4.1	3,645	6.9	33,006	3.9
5-minute Apgar score
Normal (≥7)	872,416	99.2	51,934	98.9	820,482	99.2
Below normal (<7)	6,959	0.8	561	1.1	6,398	0.8
Maternal place of birth
Denmark	770,497	86.7	46,677	88.0	723,820	86.6
Other country	118,158	13.3	6,347	12.0	111,811	13.4
Maternal age at delivery
<20 years	27,201	3.1	2,291	4.3	24,910	3.0
21–35 years	765,090	86.1	45,957	86.7	719,133	86.1
>35 years	96,364	10.8	4,776	9.0	91,588	11.0
Maternal parity
Primiparous	398,450	44.8	22,279	42.0	376,171	45.0
Multiparous	490,205	55.2	30,745	58.0	459,460	55.0
Maternal ohabitation status
No	144,202	17.4	11,017	21.5	133,185	17.2
Yes	682,901	82.6	40,292	78.5	642,609	82.8
Maternal smoking status at pregnancy
No	667,141	78.2	34,674	68.6	632,467	78.8
Yes	186,071	21.8	15,849	31.4	170,222	21.2
Congenital malformation
No	848,600	95.5	49,479	93.3	799,121	95.6
Yes	40,055	4.5	3,545	6.7	36,510	4.4
Underlying comorbidity
No	882,014	99.3	51,770	97.6	830,244	99.4
Yes	6,641	0.7	1,254	2.4	5,387	0.6

Abbreviation: n, number.

Table 2 Pneumococcal disease incidence rates per 100,000 child-years and IRRs of the association between childhood asthma and incident pneumococcal disease, Denmark, 1994–2007

	Cases	Person-years	Rate per 100,000 child-years	IRR	95% CI	Adjusted IRRa	95% CI
Age group
Asthma	319	465,381	69	2.4	2.1–2.6	2.2	2.0–2.5
No asthma	1,934	6,619,575	29	Ref	–	Ref	–
0 to <6 months old
Asthma	9	26,565	34	0.4	0.2–0.8	0.4	0.2–0.8
No asthma	341	417,414	82	Ref	–	Ref	–
6 to <24 months old
Asthma	153	78,717	194	2.3	1.9–2.7	2.1	1.8–2.5
No asthma	1,027	121,520	85	Ref	–	Ref	–
24 to <60 months old
Asthma	116	139,975	83	4.8	3.9–6.0	4.1	3.3–5.1
No asthma	351	203,120	17	Ref	–	Ref	–
≥60 months old
Asthma	41	220,124	19	2.6	1.8–3.6	2.3	1.6–3.2
No asthma	214	295,575	7	Ref	–	Ref	–

Note:

a IRR adjusted for sex, year of birth weight, congenital malformations, and comorbidity.

Abbreviations: IRRs, incidence rate ratios; CI, confidence interval; Ref, reference.

Table 3 IRRs for the association between asthma and incident pneumococcal disease, stratified by comorbidity and congenital malformation among the two oldest age groups only, Denmark, 1994–2007

	24 to <60 months old				≥60 months old
	Cases	Person - years	IRR (95% CI)	Adjusted IRRa (95% CI)	Cases	Person - years	IRR (95% CI)	Adjusted IRRa (95% CI)
IRR stratified by comorbidity
Comorbidity + present
Asthma +	19	3,569	3.4 (1.9–6.3)	3.0 (1.6–5.4)	12	6,059	4.2 (1.9–9.3)	4.7 (2.1–10.4)
Asthma −	24	15,450	Ref	Ref	13	27,857	Ref	Ref
No comorbidity − present
Asthma +	97	136,407	4.4 (3.5–5.6)	4.2 (3.4–5.3)	29	214,065	2.0 (1.3–2.9)	1.9 (1.3–2.9)
Asthma −	327	2,015,754	Ref	Ref	201	2,927,900	Ref	Ref
IRR stratified by congenital malformation
Malformation + present
Asthma +	24	8,832	5.3 (3.2–8.7)	4.1 (2.4–6.8)	7	12,810	3.5 (1.5–8.4)	2.9 (1.2–7.1)
Asthma −	43	83,515	Ref	Ref	18	115,835	Ref	Ref
malformation − present
Asthma +	92	131,143	4.5 (3.6–5.7)	4.1 (3.2–5.2)	34	207,315	2.4 (1.7–3.4)	2.2 (1.5–3.1)
Asthma −	308	1,947,689	Ref	Ref	196	2,839,922	Ref	Ref

Notes:

a IRR adjusted for sex, birth weight, and child year of birth; comorbidity strata also adjusted for congenital malformation, and malformation strata also adjusted for comorbidity. The (+) and (−) symbols indicate that the children were either asthma positive or asthma negative.

Abbreviations: IRRs, incidence rate ratios; CI, confidence interval; Ref, reference.

Figure 1 Biologic interaction between asthma and comorbidity on the risk of pneumococcal disease (PD), Denmark, 1994–2007.

Notes: (A) In children 24 to <60 months: the unadjusted incidence rate of PD in children with both asthma and comorbidity was 7.5 times the rate in children with asthma alone (532 cases versus 71 cases per 100,000 child-years, respectively). After adjusting for sex, birth weight, child year of birth, and congenital malformation, 55% (95% CI: 31, 79) of PD cases in children with both asthma and comorbidity was attributable to biologic interaction. (B) In children ≥60 months: the unadjusted incidence rate of PD in children with both asthma and comorbidity was 14 times the rate in children with asthma alone (198 cases versus 14 cases per 100,000 child-years, respectively). After adjusting for sex, birth weight, child year of birth, and congenital malformation, 73% (95% CI: 52, 93) of PD cases in children with both asthma and comorbidity was attributable to biologic interaction.
Abbreviation: CI, confidence interval.

Table S1 ICD-10 codes used to identify asthma, pneumococcal disease, and comorbidities from Danish registries

	ICD-10 code
Clinical diagnoses	J45 and J46
Pneumococcal disease
Pneumococcal meningitis	G00.1
Pneumococcal septicemia	A40.3
Pneumococcal pneumonia	A40.4
Comorbidity
HIV	B20–B24
Sickle cell disease and other sickle cell hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction	D57.0–D57.3; D57.8; Q89.0; D730
Nonasthma COPD	J41–J44; J47; J60–J67; J68.4; J70.1; J70.3; J84.1; J92.0; J96.1; J98.2–J98.3; P23; P25; P27; P29; E84
Cardiac disease, including congenital heart disease	I05–I09; I11–I13; I20–128; I31; I34–I37; I42–I45; I50–I51; Q20–Q28
Cancer or immunosuppression, including transplant recipients and immune function disorders	C00–C26; C30–C34; C37–C39; C41; C43–C85; C88; C90–C97; Z85; D80–D84; D86; D89; T86.0–T86.4; T86.8; Y83.0; Y84.0–Y84.1; Z94.0–Z94.4; Z94.8; Z96.2; Z98.2; Z99.0–Z99.2; Z45.3
Chronic renal or hepatic disease, including cirrhosis	B15.0; B16.0; B16.2; B18; B19.0; I12; I13; K70–K76; N03–N05; N07; N11; N14; N18–N19; P96.0; Q60–Q61; Q63
Diabetes mellitus	E10–E14
Congenital infection	P36 and P37

Abbreviation: ICD, International Classification of Diseases.