Clinical profile of predefined asthma phenotypes in a large cohort of UK primary care patients (Clinical Practice Research Datalink)

Figures & data

Figure 1 Asthma phenotypes, based on cluster analysis.

Notes: Reprinted with permission of the American Thoracic Society. Copyright© 2018 American Thoracic Society. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–24.⁷ The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.

Figure 2 Cohort timeline.

Abbreviations: BMI, body mass index; UTS, up-to-standard.

Figure 3 Flowchart of study eligibility and participation.

Abbreviations: BMI, body mass index; CPRD, Clinical Practice Research Datalink; HES, Hospital Episode Statistics; A&E, accidents and emergencies; ONS, Office for National Statistics; NOS, not otherwise specified.

Table 1 Baseline characteristics of the study population by phenotype

	Benign asthma	Atopic asthma	Obese non-eosinophilic	NOS no medication	NOS with only SABA	NOS with maintenance	Total
Total	7,495	55,455	9,372	20,204	11,926	89,547	193,999 (100.0%)
Percentage of total	3.9%	28.6%	4.8%	10.4%	6.1%	46.2%	100.0%
Follow-up median and IQR	4.28 (2.05–6.36)	4.34 (2.10–6.46)	4.54 (2.21–6.84)	3.46 (1.41–5.26)	4.11 (1.93–6.11)	4.35 (2.10–6.46)	4.24 (1.99–6.34)
Gender
Female	4,727 (63.1%)	38,060 (68.6%)	9,372 (100.0%)	13,627 (67.4%)	7,142 (59.9%)	53,828 (60.1%)	126,756 (65.3%)
Age category (years)
18–30	0	10,693 (19.3%)	813 (8.7%)	6,536 (32.4%)	1,966 (16.5%)	9,600 (10.7%)	29,608 (15.3%)
31–50	4,201 (56.1%)	19,762 (35.6%)	3,127 (33.4%)	6,810 (33.7%)	4,736 (39.7%)	26,585 (29.7%)	65,221 (33.6%)
51–70	3,294 (43.9%)	17,005 (30.7%)	3,888 (41.5%)	4,365 (21.6%)	3,451 (28.9%)	32,381 (36.2%)	64,384 (33.2%)
≥71	0	7,995 (14.4%)	1,544 (16.5%)	2,493 (12.3%)	1,773 (14.9%)	20,981 (23.4%)	34,786 (17.9%)
Socioeconomic status
1: least deprived	2,092 (27.9%)	13,647 (24.6%)	1,260 (13.4%)	4,696 (23.2%)	2,465 (20.7%)	17,971 (20.1%)	42,131 (21.7%)
2	1,724 (23.0%)	12,153 (21.9%)	1,644 (17.5%)	4,306 (21.3%)	2,405 (20.2%)	18,813 (21.0%)	41,045 (21.2%)
3	1,513 (20.2%)	11,090 (20.0%)	1,801 (19.2%)	4,154 (20.6%)	2,450 (20.5%)	18,352 (20.5%)	39,360 (20.3%)
4	1,219 (16.3%)	10,189 (18.4%)	2,149 (22.9%)	3,844 (19.0%)	2,423 (20.3%)	17,655 (19.7%)	37,479 (19.3%)
5: most deprived	943 (12.6%)	8,350 (15.1%)	2,513 (26.8%)	3,192 (15.8%)	2,180 (18.3%)	16,702 (18.7%)	33,880 (17.5%)
Smoking status
Current smoker	1,473 (19.7%)	10,523 (19.0%)	2,485 (26.5%)	4,637 (23.0%)	3,541 (29.7%)	22,165 (24.8%)	44,824 (23.1%)
Ex-smoker	2,884 (38.5%)	22,930 (41.3%)	3,813 (40.7%)	6,679 (33.1%)	4,090 (34.3%)	38,000 (42.4%)	78,396 (40.4%)
Never smoker	3,138 (41.9%)	22,002 (39.7%)	3,074 (32.8%)	8,888 (44.0%)	4,295 (36.0%)	29,382 (32.8%)	70,779 (36.5%)
BMI
<20	278 (3.7%)	3,257 (5.9%)	0	1,477 (7.3%)	756 (6.3%)	6,018 (6.7%)	11,786 (6.1%)
20–25	2,041 (27.2%)	16,819 (30.3%)	0	6,596 (32.6%)	3,488 (29.2%)	25,468 (28.4%)	54,412 (28.0%)
25–30	2,703 (36.1%)	18,814 (33.9%)	0	6,267 (31.0%)	4,080 (34.2%)	31,068 (34.7%)	62,935 (32.4%)
>30	2,473 (33.0%)	16,565 (29.9%)	9,369 (100.0%)	5,864 (29.0%)	3,602 (30.2%)	26,993 (30.1%)	64,866 (33.4%)
BTS step
BTS1	4,401 (58.7%)	11,612 (20.9%)	754 (8.0%)	20,204 (100.0%)	11,926 (100.0%)	0	48,897 (25.2%)
BTS2	1,186 (15.8%)	18,898 (34.1%)	2,526 (27.0%)	0	0	29,809 (33.3%)	52,419 (27.0%)
BTS3	520 (6.9%)	6,220 (11.2%)	1,164 (12.4%)	0	0	12,309 (13.7%)	20,213 (10.4%)
BTS4	978 (13.0%)	11,710 (21.1%)	2,625 (28.0%)	0	0	26,173 (29.2%)	41,486 (21.4%)
BTS5	263 (3.5%)	5,346 (9.6%)	1,831 (19.5%)	0	0	15,825 (17.7%)	23,265 (12.0%)
BTS6	3 (>0%)	243 (>4%)	129 (1.4%)	0	0	1,457 (1.6%)	1,832 (>9%)
Non BTS	144 (1.9%)	1,426 (2.6%)	343 (3.7%)	0	0	3,974 (4.4%)	5,887 (3.0%)
Comorbid conditions
Atopy	3,069 (40.9%)	45,632 (82.3%)	3,965 (42.3%)	9,283 (45.9%)	1,388 (11.6%)	26,577 (29.7%)	89,914 (46.3%)
GORD	1,291 (17.2%)	11,331 (20.4%)	2,374 (25.3%)	2,965 (14.7%)	1,859 (15.6%)	18,242 (20.4%)	38,062 (19.6%)
Anxiety	2,161 (28.8%)	17,841 (32.2%)	3,584 (38.2%)	5,835 (28.9%)	3,397 (28.5%)	26,182 (29.2%)	59,000 (30.4%)
Depression	2,874 (38.3%)	21,826 (39.4%)	5,125 (54.7%)	7,240 (35.8%)	4,394 (36.8%)	34,056 (38.0%)	75,515 (38.9%)
COPD	351 (4.7%)	5,676 (10.2%)	1,836 (19.6%)	1,005 (5.0%)	1,313 (11.0%)	20,512 (22.9%)	30,693 (15.8%)
Eosinophils
Eosinophils <300/µL and <4%	7,495 (100.0%)	24,967 (45.0%)	9,372 (100.0%)	9,800 (48.5%)	6,439 (54.0%)	38,539 (43.0%)	96,612 (49.8%)
Eosinophils >300/µL or >4%	0	30,488 (55.0%)	0	10,404 (51.5%)	5,487 (46.0%)	51,008 (57.0%)	97,387 (50.2%)
SABA
0 prescriptions	7,495 (100.0%)	0	0	20,204 (100.0%)	0	16,306 (18.2%)	44,005 (22.7%)
1–2 prescriptions	0	0	0	0	7,430 (62.3%)	21,671 (24.2%)	68,381 (35.2%)
3–9 prescriptions	0	16,175 (29.2%)	7,519 (80.2%)	0	3,585 (30.1%)	36,703 (41.0%)	63,982 (33.0%)
10+ prescriptions	0	0	1,853 (19.8%)	0	911 (7.6%)	14,867 (16.6%)	17,631 (9.1%)

Abbreviations: BMI, body mass index; BTS, British Thoracic Society; GORD, gastro-oesophageal reflux disease; NOS, not otherwise specified; SABA, short-acting beta agonist.

Figure 4 BTS step by phenotype.

Abbreviations: BTS, British Thoracic Society; eos, eosinophilic; NOS, not otherwise specified; SABA, short-acting beta agonist; Tx, treatment.

Table 2 Exacerbation rates by phenotype

Phenotype	No. of events	Time at risk (1,000 person-years)	Crude rate/1,000 person-years (95% CI)	Minimally adjusted	Adjusted rates
Benign asthma	3,431	30.867	106.8 (101.2–112.3)	116.2 (110.1–122.3)	143.2 (135.6–150.8)
Atopic asthma	68,143	239.664	283.2 (278.6–287.7)	286.9 (282.3–291.5)	322.1 (316.6–327.5)
Obese non-eosinophilic	19,263	42.471	469.0 (451.7–486.2)	454.9 (438.0–471.7)	439.3 (422.5–456.2)
NOS no medication	10,495	70.978	143.8 (139.3–148.3)	148.1 (143.4–152.7)	174.6 (169.0–180.2)
NOS with reliever Tx	9,529	48.238	200.7 (193.2–208.1)	208.6 (200.9–216.3)	240.0 (231.1–249.0)
NOS with maintenance Tx	1,47,527	387.403	388.2 (383.5–392.9)	389.4 (384.6–394.1)	414.0 (408.6–419.3)

Notes: Minimally adjusted: adjusted for age and sex. Adjusted rates: adjusted for age, sex, smoking, BMI, IMD, anxiety, depression, COPD, GORD, vaccination status and asthma treatment step. Unless otherwise indicated, values are given as rates (95% CI).

Abbreviations: BMI, body mass index; GORD, gastro-oesophageal reflux disease; IMD, index of multiple deprivation; NOS, not otherwise specified; Tx, treatment.

Figure 5 IRRs, stratified by treatment step.

Notes: Adjustment for step 6 resulted in very wide CIs due to low sample size. This made the forest plot unreadable, so this adjustment is not displayed.
Abbreviations: BTS, British Thoracic Society; IRR, incidence rate ratio; med; medication; NOS, not otherwise specified.

Figure 6 Time to first exacerbation analysis in years, by phenotype and 95% confidence intervals.

Abbreviation: NOS, not otherwise specified.

HaldarPPavordIDShawDECluster analysis and clinical asthma phenotypesAm J Respir Crit Care Med2008178321822418480428

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