Gender Differences in Inhaled Pharmacotherapy Utilization in Patients with Obstructive Airway Diseases (OADs): A Population-Based Study

Figures & data

Figure 1 Flowchart of study cohort formation.

Abbreviations: CPRD, Clinical Practice Research Datalink; OADs, obstructive airway diseases; COPD, chronic obstructive pulmonary disease; ACO, asthma-COPD overlap; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting beta agonist; SAMA, short-acting muscarinic antagonist; Rx, prescription.

Table 1 Baseline Characteristics Among Patients Diagnosed with Asthma, COPD and Asthma-COPD Overlap

Characteristics	Asthma, N = 205,596	COPD, N = 24,672	Asthma-COPD Overlap, N = 11,811	Overall, N = 242,079
Age (mean, STD)	46.86 (±19.6)	79.38 (±12.6)	76.08 (±15.9)	51.60 (±22.0)
Gender
Male	92,849 (45.2%)	14,350 (58.2%)	6,513 (55.1%)	128,367 (53%)
Female	112,747 (54.8%)	10,322 (41.8%)	5,298 (44.9%)	113,712 (47%)
Year of cohort entry
January 1998–December 2007	143,333 (69.7%)	11,210 (45.4%)	6,417 (54.3%)	160,960 (66.5%)
January 2008–July 2018	62,263 (30.3%)	13,462 (54.6%)	5,394 (45.7%)	81,119 (33.5%)
Body mass index (BMI)
Underweight	16,841 (11.2%)	1,251 (5.6%)	479 (4.4%)	18,571 (10.2%)
Normal	59,896 (40.0%)	8,751 (39.5%)	3,885 (36.1%)	72,532 (39.7%)
Overweight	42,006 (28.0%)	7,101 (32.0%)	3,755 (34.9%)	52,862 (28.9%)
Obese	31,086 (20.8%)	5070 (22.9%)	2654 (24.6%)	38,810 (21.2%)
Rx received as initial treatment
ICS	71,024 (34.6%)	3245 (13.2%)	2869 (24.3%)	77,138 (31.9%)
ICS/LABA	3737 (1.8%)	2084 (8.5%)	1017 (8.6%)	6838 (2.8%)
LABA	1253 (0.6%)	875 (0.4%)	410 (3.4%)	2538 (1.1%)
LAMA	97 (0.1%)	2436 (9.9%)	538 (4.7%)	3071 (1.3%)
SABA	128,379 (62.4%)	13,609 (55.2%)	6069 (51.4%)	148,057 (61.1%)
SAMA	1106 (0.5%)	2423 (9.8%)	908 (7.6%)	4437 (1.8%)
Index of deprivation
Least deprived	46,363 (22.6%)	3760 (15.3%)	1873 (15.9%)	51,996 (21.5%)
Less deprived	43,752 (21.3%)	4673 (19.0%)	2292 (19.4%)	50,717 (21.0%)
Deprived	42,186 (20.5%)	4915 (16.0%)	2320 (19.7%)	49,421 (20.4%)
More deprived	38,377 (18.7%)	5257 (21.3%)	2606 (22.1%)	46,240 (19.1%)
Most deprived	34,681 (16.9%)	6026 (24.4%)	2714 (22.9%)	43,421 (18.0%)
Smoking status
No	89,199 (56.4%)	2493 (10.4%)	2199 (19.1%)	93,891 (48.5%)
Yes	38,991 (24.6%)	11,214 (46.8%)	4220 (36.6%)	54,425 (28.1%)
Ex-smoker	29,998 (19.0%)	10,246 (42.8%)	5112 (44.3%)	45,356 (23.4%)
Respiratory drugs before cohort entry
Oral corticosteroid
Yes	21,803 (10.6%)	4562 (18.5%)	2446 (20.7%)	28,811 (11.9%)
No	183,793 (89.4%)	20,110 (81.5%)	9365 (79.3%)	213,268 (88.1%)
Methylxanthine
Yes	574 (0.3%)	331 (1.3%)	241 (2.0%)	1146 (0.5%)
No	205,022 (99.7%)	24,341 (98.7%)	11,570 (98.0%)	240,933 (99.5%)
Other drugs before cohort entry
NSAIDs
Yes	24,211 (11.8%)	3771 (15.3%)	1798 (15.2%)	29,780 (12.3%)
No	181,385 (88.2%)	20,901 (84.7%)	10,013 (84.8%)	212,299 (87.7%)
Opioids
Yes	6219 (3.0%)	2429 (9.9%)	1025 (8.7%)	9673 (4.0%)
No	199,377 (97.0%)	22,243 (90.1%)	10,786 (91.3%)	232,406 (96.0%)
Acetaminophen
Yes	12,782 (6.2%)	4245 (17.2%)	1637 (13.9%)	18,664 (7.7%)
No	192,814 (93.8%)	20,427 (82.8%)	10,0174 (85.1%)	223,415 (92.3%)
Comorbidity in year before cohort entry
0	164,782 (80.2%)	7771 (31.5%)	4569 (38.7%)	177,122 (73.2%)
1	26,980 (13.1%)	7332 (29.7%)	3403 (28.8%)	37,715 (15.6%)
>1	13,834 (6.7%)	9569 (38.8%)	3839 (32.5%)	27,242 (11.2%)
Physician visits in year before cohort entry
1–17	184,396 (89.7%)	16,077 (65.2%)	8270 (70.0%)	208,743 (86.2%)
18–35	18,440 (9.0%)	6,885 (27.9%)	2896 (24.5%)	28,221 (11.7%)
>36	2760 (1.3%)	1710 (6.9%)	645 (5.5%)	5115 (2.1%)
No. of hospitalization in year before cohort entry
0	176,156 (85.7%)	16,226 (65.8%)	8643 (73.2%)	201,025 (83.0%)
1	20,662 (10.1%)	5027 (20.4%)	1939 (16.4%)	27,628 (11.4%)
>1	8778 (4.2%)	3419 (13.8%)	1229 (10.4%)	13,426 (5.6%)

Abbreviations: ICS, inhaled corticosteroid; SABA, short-acting beta₂-agonist; LABA, long-acting beta₂-agonist; SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; COPD, chronic obstructive pulmonary disease; CI, confidence interval; ACO, asthma-COPD overlap; Rx, prescription; STD, standard deviation; NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 2 Univariate (Unadjusted) Analyses of Factors Associated with Different Inhaled Pharmacotherapies

Factors	Pharmacotherapies
	ICS	ICS/LABA	LABA	LAMA	SABA	SAMA
Age	0.95 (0.95–0.96)**	1.70 (1.67–1.74)**	2.19 (2.11–2.27)**	2.84 (2.74–2.94)**	0.82 (0.81–0.83)**	3.34 (3.24–3.45)**
Gender
Female	1	1	1	1	1	1
Male	0.97 (0.95–0.99)*	1.19 (1.13–1.25)**	1.28 (1.19–1.39)**	1.83 (1.70–1.97)**	0.94 (0.92–0.95)**	1.49 (1.41–1.59)**
Year of cohort entry
January 1998–December 2007	1	1	1	1	1	1
January 2008–July 2018	3.86 (3.77–3.94)**	0.45 (0.43–0.47)**	2.68 (2.41–2.98)**	0.04 (0.04–0.05)**	0.39 (0.38–0.39)**	1.43 (1.34–1.53)**
OAD diagnoses
Asthma	1	1	1	1	1	1
COPD	0.29 (0.28–0.30)**	4.98 (4.72–5.27)**	6.0 (5.49–6.54)**	5.45 (5.24–5.65)**^#	0.74 (0.72–0.76)**	20.14 (18.73–21.65)**
Asthma-COPD Overlap	0.61 (0.58–0.63)**	5.09 (4.74–5.47)**	5.86 (5.24–6.57)**	4.62 (4.40–4.83)**^#	0.64 (0.61–0.66)**	15.40 (14.07–16.85)**
p-value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Body mass index (BMI)
Underweight	1	1	1	1	1	1
Normal	0.78 (0.75–0.81)**	1.95 (1.73–2.20)**	1.63 (1.35–1.96)**	1.59 (1.36–1.86)**	1.10 (1.07–1.14)**	1.49 (1.30–1.71)**
Overweight	0.75 (0.72–0.78)**	2.28 (2.02–2.58)**	1.81 (1.50–2.19)**	1.80 (1.53–2.11)**	1.09 (1.05–1.13)**	1.71 (1.49–1.97)**
Obese	0.69 (0.67–0.72)**	2.34 (2.11–2.70)**	1.72 (1.42–2.09)**	1.95 (1.66–2.30)**	1.16 (1.12–1.21)**	1.52 (1.31–1.75)**
p-value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Index of deprivation
Least deprived	1	1	1	1	1	1
Less deprived	1.02 (0.99–1.04)	0.98 (0.91–1.05)	1.06 (0.93–1.20)	1.31 (1.17–1.47)**	0.96 (0.94–0.98)*	1.26 (1.14–1.39)**
Deprived	0.97 (0.95–0.99)*	1.02 (0.94–1.09)	1.10 (0.97–1.24)	1.27 (1.13–1.43)**	1.00 (0.97–1.02)	1.25 (1.13–1.39)**
More deprived	0.93 (0.90–0.95)**	10.97 (0.90–1.04)	1.32 (1.17–1.49)**	1.36 (1.21–1.53)**	1.02 (1.00–1.05)	1.44 (1.30–1.59)**
Most deprived	0.92 (0.89–0.94)**	0.98 (0.91–1.06)	1.29 (1.13–1.46)**	1.51 (1.35–1.70)**	1.00 (0.97–1.02)	1.95 (1.78–2.15)**
p value (type 3)	<0.0001	0.7061	<0.0001	<0.0001	<0.0001	<0.0001
Smoking status
No	1	1	1	1	1	1
Yes	0.72 (0.70–0.75)**	1.73 (1.58–1.90)**	2.30 (1.99–2.66)**	12.00 (9.77–14.73)**	0.91 (0.88–0.94)**	5.46 (4.78–6.23)**
Ex-smoker	0.64 (0.61–0.66)**	2.57 (2.36–2.80)**	2.51 (2.17–2.91)**	16.61 (13.56–20.34)**	0.86 (0.83–0.89)**	6.03 (5.28–6.89)**
p value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Other drugs
NSAIDs
No	1	1	1	1	1	1
Yes	1.09 (1.07–1.12)**	0.89 (0.83–0.96)*	0.78 (0.70–0.86)**	0.97 (0.87–1.08)	0.97 (0.95–0.99)*	0.73 (0.68–0.79)**
Opioids
No	1	1	1	1	1	1
Yes	1.60 (1.52–1.67)**	0.49 (0.45–0.54**	0.55 (0.47–0.64)**	0.28 (0.25–0.31)**	0.95 (0.92–0.99)*	0.48 (0.43–0.54)**
Acetaminophen
No	1	1	1	1	1	1
Yes	1.16 (1.12–1.20)**	0.68 (0.63–0.73)**	0.65 (0.58–0.74)**	0.36 (0.33–0.39)**	1.12 (1.08–1.15)**	0.44 (0.41–0.48)**
Comorbidity
0	1	1	1	1	1	1
1	0.80 (0.78–0.82)**	2.23 (2.10–2.37)**	2.22 (2.02–2.44)**	4.99 (4.53–5.51)**	0.90 (0.88–0.92)**	3.48 (3.23–3.74)**
>1	0.52 (0.51–0.54)**	3.26 (3.07–3.46)**	2.75 (2.49–3.04)**	12.50 (11.45–13.64)**	0.93 (0.91–0.96)**	5.29 (4.92–5.68)**
p value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Indicators for disease severity measured in the year before cohort entry
Rx of methylxanthine
No	1	1	1	1	1	1
Yes	0.60 (0.53–0.68)**	0.44 (0.34–0.56)**	0.16 (0.12–0.20)**	0.91 (0.55–1.49)	3.12 (2.76–3.52)**	0.19 (0.15–0.23)**
Rx of oral corticosteroid
No	1	1	1	1	1	1
Yes	0.75 (0.73–0.77)**	0.56 (0.53 0.60)**	0.51 (0.46–0.56)**	0.72 (0.65–0.79)**	1.55 (1.51–1.59)**	0.62 (0.57–0.67)**
No. of hospitalization
0	1	1	1	1	1	1
1	0.87 (0.85–0.90)**	1.83 (1.72–1.96)**	1.58 (1.42–1.77)**	2.88(2.64–3.14)**	0.89(0.87–0.92)**	2.00(1.85–2.16)**
>1	0.74 (0.71–0.77)**	2.45 (1.73–1.96)**	2.23 (1.96–2.53)**	4.73(4.30–5.21)**	0.86 (0.83–0.89)**	2.59 (2.35–2.84)**
p value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Physician visits
1–17	1	1	1	1	1	1
18 –35	0.60 (0.58–0.61)**	2.33 (2.19–2.47)**	1.76 (1.59–1.95)**	5.29 (4.89–5.71)**	1.08 (1.05–1.11)**	2.09 (1.94–2.25)**
>36	0.36 (0.33–0.38)**	3.07 (2.75–3.43)**	1.63 (1.30–2.05)**	9.26 (8.22–10.44)**	1.25 (1.18–1.32)**	2.33 (2.01–2.71)**
p value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Comorbidities
0	1	1	1	1	1	1
1	0.80 (0.78–0.82)**	2.23 (2.10–2.37)**	2.22 (2.02–2.44)**	4.99 (4.53–5.51)**	0.90 (0.88–0.92)**	3.48 (3.23–3.74)**
>1	0.52 (0.51–0.54)**	3.26 (3.07–3.46)**	2.75 (2.49–3.04)**	12.50 (11.45–13.64)**	0.93 (0.91–0.96)**	5.29 (4.92–5.68)**
p value (type 3)	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001

Notes: **p < 0.0001; *p < 0.05; ^#model value.

Abbreviations: ICS, inhaled corticosteroid; SABA, short-acting beta₂-agonist; LABA, long-acting beta₂-agonist; SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; COPD, chronic obstructive pulmonary disease; CI, confidence interval; ACO, asthma-COPD overlap; STD, standard deviation; NSAIDs, nonsteroidal anti-inflammatory drugs; Rx, prescription.

Table 3 Multivariable Analyses of Gender Differences in Inhaled Pharmacotherapies by Three Obstructive Airway Diseases

Pharmacotherapies^#	Asthma		COPD		Asthma-COPD Overlap
	OR: 95% CI	(aOR: 95% CI)	OR: 95% CI	aOR: 95% CI	OR: 95% CI	aOR: 95% CI
ICS
Female	1	1	1	1	1	1
Male	1.03 (1.01–1.05)*	0.97 (0.95–0.99)*	0.99 (0.92–1.07)	0.98 (0.90–1.07)	0.89 (0.82–0.97)*	0.91 (0.83–1.00)
ICS/LABA
Female	1	1	1	1	1	1
Male	0.98 (0.92–1.05)	1.15 (1.08–1.23)**	1.07 (0.98–1.17)	1.06 (0.97–1.18)	1.11 (0.97–1.26)	1.09 (0.96–1.25)
LABA
Female	1	1	1	1	1	1
Male	0.94 (0.83–1.05)	1.04 (0.92–1.18)	1.27 (1.10–1.46)*	1.29 (1.12–1.49)*	1.23 (1.01–1.50)*	1.26 (1.03–1.55)*
LAMA
Female	1	1	1	1	1	1
Male	1.14 (0.77–1.70)	1.40 (0.93–2.10)	1.20 (1.11–1.31)**	1.21 (1.10–1.33)**	1.33 (1.11–1.59)*	1.27 (1.05–1.53)*
SABA
Female	1	1	1	1	1	1
Male	0.97 (0.95–0.99)*	1.00 (0.98–1.02)	0.87 (0.83–0.91)**	0.84 (0.80–0.89)**	0.93 (0.86–0.99)*	0.89 (0.82–0.96)*
SAMA
Female	1	1	1	1	1	1
Male	1.12 (0.99–1.26)	1.13 (0.98–1.30)	1.08 (0.99–1.17)	1.11 (1.01–1.21)*	1.22 (1.06–1.40)*	1.28 (1.11–1.48)*

Notes: **p < 0.0001; *p < 0.05; ^#Adjusted for all factors listed in Table 2.

Abbreviations: OR, unadjusted odds ratio; aOR, adjusted odds ratio; ICS, inhaled corticosteroid; SABA, short-acting beta₂-agonist; LABA, long-acting beta₂-agonist; SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; COPD, chronic obstructive pulmonary disease; CI, confidence interval; ACO, asthma-COPD overlap.