Burden of Pertussis in Individuals with a Diagnosis of Asthma: A Retrospective Database Study in England

Figures & data

Figure 1 Study periods.^a

Notes: ^aRound arrow ends indicate that the time period starts or ends exactly on the indicated time point; pointed arrow ends indicate that the time period ends the day before (for right-facing arrows) or starts the day after (for left-facing arrows) the indicated time point.

Abbreviations: asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis.

Figure 2 Incidence rate of reported pertussis among individuals with a diagnosis of asthma: overall, by calendar year, and by age group.

Notes: ^aCell counts of 1–4, blinded as per Clinical Practice Research Datalink policy.

Abbreviations: CI, confidence interval; ND, not displayed (due to low counts); PYFU, person-years of follow-up.

Table 1 Baseline Demographic and Clinical Characteristics for the Matched Cohorts

	Asthma+/Pertussis+ Cohort (n=314)	Asthma+/Pertussis– Cohort (n=1256)	SMD	p-value
Data source, n (%)			0.01	0.863
Aurum	285 (90.8)	1136 (90.4)
GOLD	29 (9.2)	120 (9.6)
Age at index date, years, mean (SD)	61 (9)	61 (9)	0.02	0.575
≥65 years, n (%)	98 (31.2)	403 (32.1)	0.02	0.787
Female, n (%)	194 (61.8)	763 (60.7)	0.02	0.747
Ethnicity, n (%)	n=269	n=1023	–	0.686
White	258 (95.9)	965 (94.3)
Asian	6 (2.2)	31 (3.0)
Black	Low^a	12 (1.2)
Mixed	Low^a	5 (0.5)
Other	Low^a	10 (1.0)
Year of index date, n (%)			–	0.898
2009	Low^a	14 (1.1)
2010	Low^a	13 (1.0)
2011	7 (2.2)	18 (1.4)
2012	72 (22.9)	292 (23.2)
2013	36 (11.5)	111 (8.8)
2014	28 (8.9)	114 (9.1)
2015	34 (10.8)	143 (11.4)
2016	55 (17.5)	245 (19.5)
2017	49 (15.6)	206 (16.4)
2018	24 (7.6)	100 (8.0)
Season, n (%)			–	0.466
Spring (March–May)	64 (20.4)	233 (18.6)
Summer (June–August)	78 (24.8)	330 (26.3)
Autumn (September–November)	111 (35.4)	485 (38.6)
Winter (December–February)	61 (19.4)	208 (16.6)
IMD, n (%)			–	0.853
Quintile 1	105 (33.4)	463 (36.9)
Quintile 2	77 (24.5)	275 (21.9)
Quintile 3	67 (21.3)	220 (17.5)
Quintile 4	44 (14.0)	176 (14.0)
Quintile 5	21 (6.7)	122 (9.7)
Smoking status,^b n (%)	n=204	n=803	–	0.953
Current	48 (23.5)	192 (23.9)
Past	102 (50.0)	407 (50.7)
Never	54 (26.5)	204 (25.4)
BMI,^c kg/m^2, mean (SD)	30 (6) (n=194)	30 (6) (n=757)	<0.01	0.849
Obese,^d n (%)	88 (28.0)	341 (27.1)	0.02	0.777
Most common health conditions,^e n (%)
Hypertension	113 (36.0)	474 (37.7)	0.04	0.602
Depression	78 (24.8)	313 (24.9)	<0.01	>0.999
Hyperlipidemia	58 (18.5)	249 (19.8)	0.03	0.633
Diabetes mellitus	46 (14.6)	215 (17.1)	0.07	0.310
COPD	38 (12.1)	169 (13.5)	0.04	0.576
Malignant cancer	35 (11.1)	156 (12.4)	0.04	0.629
GERD	33 (10.5)	85 (6.8)	0.13	0.031
Chronic/persistent cough	36 (11.5)	72 (5.7)	0.21	<0.001
Asthma-related hospitalizations,^f n (%)			0.03	0.564
0	Low^a	Low^a
1	Low^a	Low^a
≥2	0 (0.0)	0 (0.0)
FEV1,^c n (%)	n=28	n=105	–	0.071
≥80% predicted	15 (53.6)	35 (33.3)
50% to <80% predicted	10 (35.7)	53 (50.5)
30% to <50% predicted	Low^a	Low^a
<30% predicted	Low^a	Low^a
Treatment corresponding to asthma GINA step 4/5,^g n (%)	49 (15.6)	198 (15.8)	<0.01	>0.999
Pertussis vaccine in past 10 years, n (%)	0 (0.0)	0 (0.0)	–	–
DMC,^h £, mean (SD)	1497 (2731)	1409 (2389)	0.03	0.200

Notes: ^a“Low” indicates cell counts of 1–4, blinded as per Clinical Practice Research Datalink policy. If only one event count in a stratification block was 1–4 and a total is given, the next lowest non-zero event count is marked “low” to prevent identification of any exact cell count of 1–4. ^bMost recent record from –18 months to before –6 months. ^cMost recent record during the 18 months before the index date. ^dMost recent BMI ≥30 kg/m² during the 18 months before the index date, or obesity in the clinical record during the 18 months before the index date (and no subsequent BMI <30 kg/m² before the index date). ^eAt any time before the index date. ^fNumber of hospitalizations for ≥1 night with a primary diagnosis code of asthma, excluding admissions <14 days after a previous admission, during the 18 months before the index date. ^gA prescription for a medium- or high-dose inhaled corticosteroid/long-acting beta 2 agonist combination during the 18 months before the index date. ^hBaseline DMC included costs for general practitioner/nurse, outpatient specialist, and accident and emergency visits, and inpatient stays from –18 months to before –6 months.

Abbreviations: asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; BMI, body mass index; COPD, chronic obstructive pulmonary disease; DMC, direct medical costs; FEV₁, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma; GERD, gastroesophageal reflux disease; IMD, Index of Multiple Deprivation; n, number of people; SD, standard deviation; SMD, standardized mean difference.

Table 2 Rates of HCRU per 100 PY (95% CI) in the Asthma+/Pertussis+ and Asthma+/Pertussis– Cohorts During Predefined Periods from –6 Months to +11 Months Around the Index Date

	–6 to –1 Month	–1 Month to Index	Index to 2 Months	2 to 5 Months	5 to 11 Months
GP/nurse
Asthma+/pertussis+	1593^a (1442–1760)	4176^a (3838–4544)	2446^a (2262–2644)	1451^a (1297–1624)	1264^b (1142–1398)
Asthma+/pertussis–	1226 (1153–1304)	1335 (1226–1453)	1207 (1121–1300)	1206 (1130–1288)	1200 (1131–1274)
GP prescriptions
Asthma+/pertussis+	4748 (4208–5357)	6405^a (5699–7200)	5109 (4492–5810)	4727 (4147–5388)	4636 (4057–5298)
Asthma+/pertussis–	4611 (4301–4944)	4897 (4500–5330)	4797 (4468–5151)	4620 (4310–4953)	4817 (4495–5161)
Clinical assessments
Asthma+/pertussis+	3991^b (3378–4715)	11,140^a (9258–13,403)	4629^a (3724–5755)	3969 (3148–5003)	4057 (3359–4901)
Asthma+/pertussis–	3874 (3481–4311)	4074 (3388–4900)	3746 (3226–4351)	3595 (3161–4088)	3774 (3424–4160)
Outpatient specialist
Asthma+/pertussis+	271 (223–329)	357 (280–455)	290 (229–366)	315^b (256–387)	279 (223–349)
Asthma+/pertussis–	282 (252–315)	292 (253–336)	274 (241–312)	259 (229–292)	266 (237–299)
A&E
Asthma+/pertussis+	59^a (45–77)	128^a (87–187)	55 (36–82)	34 (23–51)	31 (22–43)
Asthma+/pertussis–	34 (28–41)	30 (21–44)	39 (31–50)	28 (21–36)	33 (28–40)
Hospitalizations
Asthma+/pertussis+	51 (38–69)	74 (43–128)	61^b (41–90)	50 (35–73)	33 (22–47)
Asthma+/pertussis–	52 (43–62)	44 (32–60)	42 (33–55)	40 (32–50)	48 (40–57)

Notes: Data are events per 100 PY (95% CI) estimated by fitting a negative binomial model. ^aUncorrected p<0.001 vs the asthma+/pertussis– cohort (statistically significant after cut-off adjustment for multiplicity) are displayed in bold. ^bUncorrected p<0.05 vs the asthma+/pertussis– cohort (suggestive of a trend).

Abbreviations: A&E, accident and emergency; asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; CI, confidence interval; GP, general practitioner; HCRU, health care resource utilization; PY, person-years.

Figure 3 HCRU per 100 PY in the asthma+/pertussis+ and asthma+/pertussis– cohorts during (A) –1 month to index and (B) index to 2 months.

Notes: ^aEvent rates and 95% CIs were estimated by fitting a negative binomial model. Uncorrected p<0.001 is displayed in bold and indicates statistical significance after cut-off adjustment for multiplicity. Uncorrected p<0.05 is suggestive of a trend.

Abbreviations: A&E, accident and emergency; asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; CI, confidence interval; GP, general practitioner; HCRU, health care resource utilization; PY, person-years.

Table 3 Use of the Five Most Common Prescriptions (in the Asthma+/Pertussis+ Cohort During Each Time Period) in the Asthma+/Pertussis+ and Asthma+/Pertussis– Cohorts During Each Time Period Around the Index Date

	–6 to –1 Month		–1 Month to Index		Index to 2 Months		2 to 5 Months		5 to 11 Months
	%	Rate per 100 PY (95% CI)	%	Rate per 100 PY (95% CI)	%	Rate per 100 PY (95% CI)	%	Rate per 100 PY (95% CI)	%	Rate per 100 PY (95% CI)
Salbutamol 100 µg/dose inhaler CFC free
Asthma+/pertussis+	22.6	119 (89–158)	14.6	194^a,b (144–256)	16.6	134^c (100–178)	14.5	108 (76–152)	16.5	98 (67–143)
Asthma+/pertussis–	17.7	97 (82–115)	7.6	109 (88–134)	11.4	101 (84–121)	12.9	98 (81–119)	18.2	97 (82–116)
Ventolin (GSK) 100 µg/dose Evohaler (GSK)
Asthma+/pertussis+	21.7	116 (87–156)	14.0	194^b,c (144–256)	13.7	124 (89–174)	16.4	112 (82–154)	21.8	109 (80–148)
Asthma+/pertussis–	20.6	122 (104–142)	8.9	121 (101–146)	13.3	113 (95–133)	16.4	118 (100–138)	21.6	115 (98–134)
Prednisolone 5 mg tablets
Asthma+/pertussis+	25.8	98^a (78–124)	20.7	314^a (247–400)	NA	NA	NA	NA	NA	NA
Asthma+/pertussis–	9.1	42 (33–53)	2.8	41 (29–58)	NA	NA	NA	NA	NA	NA
Amoxicillin 500 mg capsules
Asthma+/pertussis+	24.5	78^a (63–98)	NA	NA	NA	NA	NA	NA	NA	NA
Asthma+/pertussis–	9.4	30^b (26–35)	NA	NA	NA	NA	NA	NA	NA	NA
Clarithromycin 500 mg tablets
Asthma+/pertussis+	NA	NA	16.9	225^a (174–291)	14.0	83^a (62–111)	NA	NA	NA	NA
Asthma+/pertussis–	NA	NA	0.8	10^b (5–18)	1.8	12 (8–18)	NA	NA	NA	NA
Omeprazole 20 mg gastro-resistant capsules
Asthma+/pertussis+	23.6	171^c (126–232)	17.5	260^a (198–341)	16.9	195 (140–271)	18.0	164 (118–228)	20.8	176 (122–253)
Asthma+/pertussis–	17.8	142 (118–171)	10.4	150 (126–180)	13.9	151 (126–180)	15.2	147 (122–176)	17.9	156 (128–190)
Bendroflumethiazide 2.5 mg tablets
Asthma+/pertussis+	NA	NA	NA	NA	6.7	98 (54–176)	7.4	94 (52–169)	6.9	85 (41–176)
Asthma+/pertussis–	NA	NA	NA	NA	6.4	56 (43–72)	6.7	61 (46–81)	6.7	61 (43–85)
Paracetamol 500 mg tablets
Asthma+/pertussis+	NA	NA	NA	NA	NA	NA	9.3	89 (55–145)	11.6	93 (56–155)
Asthma+/pertussis–	NA	NA	NA	NA	NA	NA	8.3	67 (52–85)	10.5	72 (56–93)

Notes: Data are % of patients and rates of prescriptions per 100 person-years (95% CI), the latter estimated by fitting a negative binomial model unless otherwise specified. ^aUncorrected p<0.001 vs the asthma+/pertussis– cohort (statistically significant after cut-off adjustment for multiplicity) are displayed in bold. ^bThe negative binomial model could not be fitted; Poisson estimates were used instead. ^cUncorrected p<0.05 vs the asthma+/pertussis– cohort (suggestive of a trend).

Abbreviations: asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; CFC, chlorofluorocarbon; CI, confidence interval; NA, not available (as only data for the top five prescriptions in the asthma+/pertussis+ cohort in each time period were compiled).

Figure 4 Mean monthly^a all-cause HCRU in the asthma+/pertussis+ and asthma+/pertussis– cohorts from –18 months to 11 months around the index date (pertussis diagnosis): (A) GP/nurse visits; (B) GP prescriptions; (C) outpatient specialist visits; (D) A&E visits; and (E) hospitalizations.

Notes: ^aMonths are labelled according to the start time of each interval, e.g., utilization reported at 0 month is the average from day 0 to day 30.

Abbreviations: A&E, accident and emergency; asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; GP, general practitioner; HCRU, health care resource utilization .

Figure 5 Annualized per-patient DMC^a in the asthma+/pertussis+ and asthma+/pertussis– cohorts during the various time periods of the study.

Notes: ^aValues above bars show total mean (95% CI) annualized DMC per patient. 95% CI were obtained assuming Student’s t distribution for the annualized DMC means. Absolute mean values and standard deviations can be found in Supplementary Table 10. p-values were calculated using the Wilcoxon rank-sum test. Uncorrected p<0.001 is displayed in bold and indicates statistical significance after cut-off adjustment for multiplicity. Unit costs for GP, nurse, and outpatient specialist visits were derived from the 2019 Unit Costs of Health and Social Care published by the Personal Social Services Research Unit from the University of Kent.²⁵ Unit costs for the five most commonly prescribed medications (in the asthma+/pertussis+ cohort; during each time interval) were derived from the September 2019 NHS Drug Tariff.²⁶ Unit costs for the five most common clinical assessments and A&E costs were derived from the 2018/2019 National Schedule of NHS Reference Costs.²⁷ Hospitalization costs were derived using reference costs from the 2018/2019 National Schedule of NHS Reference Costs.²⁷ bMedians were: £699 vs £464.

Abbreviations: A&E, accident and emergency; asthma+/pertussis+, patients with diagnoses of asthma and pertussis; asthma+/pertussis–, patients with a diagnosis of asthma without pertussis; DMC, direct medical costs; CI, confidence interval; GP, general practitioner.

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