Examining Risk Factors Accelerating Time-to-Chronic Obstructive Pulmonary Disease (COPD) Diagnosis among Asthma Patients

Figures & data

Table 2. Bivariate analysis* of the association between patient factors predicting risk of COPD.

Covariates**	Patient-level variance (SE)	uFTR	95% CI	p-value
Male sex	n/a	0.52	(0.47, 0.58)	<0.0001
Age (years)[at baseline]
≥40 years	n/a	0.02	(0.01, 0.03)	<0.0001
31–39 years		0.38	(0.26, 0.55)	<0.0001
<30 years		Ref	Ref	Ref
Length of stay(days)[at baseline]
1		0.11	(0.09, 0.13)	<0.0001
2	n/a	0.04	(0.03, 0.05)	<0.0001
≥3		0.05	(0.04, 0.05)	<0.0001
0		Ref	Ref	Ref
Emergency admission	n/a	0.09	(0.07, 0.11)	<0.0001
Asthma exacerbation	7.28(0.66)	0.78	(0.69, 0.90)	<0.0001
Tobacco use (at baseline)	n/a	0.21	(0.08, 0.52)	0.001
Obesity, BMI ≥ 30kg/m^2 (at baseline)	n/a	1.34	(0.52, 3.49)	0.546
Charlson Comorbidity Index
CCI score 1	n/a	0.52	(0.23, 1.16)	0.112
CCI score ≥ 2		0.12	(0.10, 0.16)	<0.0001
CCI score 0		Ref	Ref	Ref
Sinusitis(baseline)	n/a	0.47	(0.18, 1.22)	0.120
Upper respiratory infection(baseline)	n/a	0.38	(0.19, 0.76)	0.006
Asthma severity (at baseline)
Severe	n/a	0.06	(0.05, 0.07)	<0.0001
Moderate		0.13	(0.12, 0.15)	<0.0001
Mild		Ref	Ref	Ref
SABA overuse ( > 2 SABA canisters) (at baseline)	n/a	0.37	(0.26, 0.54)	<0.0001
MAL: (PDC ≥ 0.80)	1.95(0.53)	1.85	(1.59, 2.15)	<0.0001
MAL: (MPR ≥ 0.80)	2.42(0.47)	1.88	(1.64, 2.15)	<0.0001

Note. *Unadjusted Failure –Time-Ratio (uFTR) in the accelerated analysis of Time-to-COPD diagnosis from baseline.

**Covariates that were significant at 0.20.; ED = Emergency department; CCI = Charlson comorbidity index; SABA = Short Acting Beta Agonist; PDC = Proportion of Days Covered; MPR = Medication Possession Ratio (MPR); MAL = Medication Adherence Level; BMI = Body Mass Index, N/A = non-applicable.

Table 1. Characteristics of physician-diagnosed asthma patients (N = 68,211).

Study variables	n (% of N) or Mean ± SD
Index year (Baseline)
January 1, 1998 to December 31, 1998	49,685 (72.84)
January 1, 1999 to December 31, 1999	18,526 (27.16)
Age, (mean years ± SD)	48.20 ± 18.63
<30 years	12,908 (18.92)
30–39 years	13060 (19.15)
≥40 years	42,243 (61.93)
Sex
Male	27,756(40.69)
Female	40,455(59.31)
Obesity (BMI > 30kg/m^2)	205 (0.30)
Tobacco use/nicotine dependence	96 (0.14)
Charlson Comorbidity Index (CCI)
CCI score 0	66,766 (97.88)
CCI score 1	1,226 (1.80)
CCI score ≥ 2	219 (0.32)
Sinusitis	108 (0.16)
Upper respiratory infection	284 (0.42)
Healthcare utilization
Emergency admission (yes)	1,023 (1.50)
Asthma-related hospitalization (yes)	2,701 (3.96)
Emergency hospitalization (yes)	2,427 (3.56)
Emergency visits (yes)	3,158 (4.63)
Length of hospital stay (Days)
0	65526(96.06)
1	1876(2.75)
2	559(0.82)
≥3	250(0.37)
Asthma medications (dispensed)
Inhaled Corticosteroids (ICS)	24,428 (35.81)
Short-Acting Beta-2 Agonist	26,034 (38.17)
Long-Acting Beta-2 Agonist (LABA)	2,636 (3.86)
ICS/LABA combination	90 (0.13)
Leukotriene receptor antagonists	1,046 (1.53)
Inhaled mast cell stabilizers	201 (0.29)
Theophylline	2,145 (3.14)
Short-acting muscarinic antagonist	633 (0.93)
Inhaled anticholinergics	2,139 (3.14)
Other beta-agonists	58 (0.09)
Other corticosteroids	8,551 (12.54)
Other Xanthine’s	78 (0.11)
Other anti-allergic agents	172 (0.25)
Asthma severity
Severe	3,461 (5.07)
Moderate	15,595 (22.87)
Mild	49155(72.06)
SABA use (>2 canisters)	4811(7.05)
Medication adherence levels (MAL)
MPR scale (mean ± SD)	0.41 ± 0.35
PDC scale (mean ± SD)	0.39 ± 0.32
High adherence level (PDC ≥ 0.80)	11988(17.57)
High adherence level (MPR ≥ 0.80)	13,754 (20.16)

Note. SD = Standard Deviation, IQR = interquartile range, CCI = Charlson Comorbidity Index; PDC = Proportion of days covered, MPR = Medication Possession Ratio.

Table 3. Multivariate analysis of risk factors for time-to-COPD incidence-PDC model*.

Variables	aFTR	95% CI	p-value
Male Sex	0.62	(0.56, 0.68)	<0.0001
Age (years)
≥40 years	0.03	(0.02, 0.04)	<0.0001
30–39 years	0.34	(0.23, 0.50)	<0.0001
<30 years	Ref
Length of stay (days)
≥3	0.08	(0.07, 0.10)	<0.0001
2	0.07	(0.06, 0.09)	<0.0001
1	0.13	(0.12, 0.15)	<0.0001
0	Ref
Emergency admissions	0.21	(0.17, 0.25)	0.000
Asthma exacerbation	0.81	(0.70, 0.94)	0.007
Tobacco use/nicotine dependence	0.29	(0.13, 0.68)	0.004
Obesity (BMI ≥ 30kg/m^2)	1.01	(0.54, 1.89)	0.977
Charlson Comorbidity Index
CCI score ≥ 2	0.28	(0.22, 0.34)	<0.0001
CCI score 1	0.70	(0.39, 1.26)	0.239
CCI score 0	Ref
Sinusitis (yes)	4.66	(1.45, 15.02)	0.010
Upper respiratory infection (yes)	0.49	(0.30, 0.82)	0.006
Asthma severity
Severe	0.10	(0.08, 0.12)	0.000
Moderate	0.23	(0.21, 0.26)	0.000
Mild	Ref.
SABA overuse (> 2 SABA canisters)	0.61	(0.44, 0.84)	0.003
Medication adherence (PDC ≥ 80%)	1.83	(1.54, 2.17)	<0.0001
Random effects
Patient cluster
Variance (constant)				2.31(0.33)
Variance [PDC Medication adherence effect (SE)]	6.87e-5(0.53)
/logs	0.41(0.02)

Note. Where 95% CI = 95% confidence interval; SABA = Short acting beta-2 agonist. Only the PDC variable (proxy for medication adherence) was included in the random effect component. BMI = Body Mass Index.

Figure 1. Plot of association between the effect of patient factors and time to COPD diagnosis.

The model was aadjusted for Sex, age, emergency admissions, tobacco use/nicotine dependence, obesity; Charlson Comorbidity Index, asthma-related comorbidities, sinusitis, and upper respiratory infection

Where ICS = Inhaled corticosteroids; MA = Medication adherence; PDC = Proportion of Days Covered; MPR = Medication Possession Ratio; SABA = Short acting beta-2 agonist