Development and validation of a model to predict the risk of exacerbations in chronic obstructive pulmonary disease

Figures & data

Table 1 Baseline demographic and clinical characteristics of the derivation and validation cohort, with and without exacerbations within 24 months from study entry

Characteristics	Derivation cohort		Validation cohort
	Exacerbation (n=70)	No exacerbation (n=170)	Exacerbation (n=222)	No exacerbation (n=571)
Mean age, years (±SD)	73.6 (±5.2)	73.3 (±5.0)	67.9 (±10.0)	67.2 (±9.7)
Male, n (%)	51 (72.9)	113 (66.5)	119 (53.6)	301 (52.7)
Current smokers, n (%)	24 (34.3)	34 (20.0)	92 (41.4)	202 (35.4)
Never smokers, n (%)	5 (7.1)	31 (18.2)	15 (6.8)	59 (10.3)
Pack years, median (IQR)a	32.8 (18.4–54.0)	23.3 (4.1–51.8)	37.0 (23.0–47.0)	30.0 (20.0–45.0)
Mean FEV1 %predicted (±SD)b	64.2 (±20.5)	74.0 (±20.0)	65.6 (±18.1)	72.5 (±16.7)
Inhaled corticosteroids, n (%)	56 (80.0)	102 (60.0)	56 (25.2)	123 (21.5)
Inhaled β2-mimetics, n (%)	56 (80.0)	111 (65.3)	126 (56.8)	233 (40.8)
Inhaled anti-cholinergics, n (%)	45 (64.3)	88 (51.8)	122 (55.0)	271 (47.5)
Previous exacerbations, n (%)c	33 (47.1)	23 (13.5)	55 (24.8)	39 (6.8)
Ischemic heart disease, n (%)d	14 (20.0)	38 (22.4)	36 (16.2)	101 (17.7)
Vascular disease, n (%)e	10 (14.3)	12 (7.1)	41 (18.5)	76 (13.3)

Notes:

a n=395: n=116 for exacerbation and n=279 for no exacerbation

b n=782: n=218 for exacerbation and n=564 for no exacerbation

c previous exacerbations = occurrence of an exacerbation in the year before study entry

d ischemic heart disease = history of myocardial infarction, angina pectoris, percutaneous coronary intervention, or coronary artery bypass grafting

e vascular disease = history of stroke, minor stroke, or peripheral arterial disease.

Abbreviations: FEV₁, forced expiratory volume in 1 second; IQR, interquartile range; SD, standard deviation.

Table 2 Disease classification according to the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria¹³ for both cohorts, with and without exacerbations within 24 months from baseline assessment

GOLD classification	Derivation cohort		Validation cohorta
	Exacerbation (n=70)	No exacerbation (n=170)	Exacerbation (n=220)	No exacerbation (n=564)
GOLD I, n (%)	14 (20.0)	66 (38.8)	54 (24.5)	181 (32.1)
GOLD II, n (%)	35 (50.0)	81 (47.6)	121 (55.0)	327 (58.0)
GOLD III, n (%)	21 (30.0)	23 (13.5)	40 (18.2)	53 (9.4)
GOLD IV, n (%)	0 (0.0)	0 (0.0)	5 (2.3)	3 (0.5)

Notes: GOLD I: %predicted forced expiratory volume in 1 second (FEV₁) >80%; GOLD II: 50%< %predicted FEV₁ ≤80%; GOLD III: 30%< %predicted FEV₁ ≤50%; GOLD IV: %predicted FEV₁ ≤30%.

a Classification according to the GOLD criteria missing in nine patients.

Table 3 Final prediction model to predict exacerbations in COPD patients

	ORa	95% CIa
Previous exacerbations	5.07	2.55–10.07
FEV1, %predicted (Or per 5%)b	0.95	0.88–1.03
Pack years of smoking (2log transformed)c	1.16	1.01–1.35
History of vascular disease	1.92	0.89–4.12

Notes:

a After adjustment for overfitting by shrinkage (shrinkage factor =0.90).

b OR for each interval change of 5%;

c doubling of the number of log-transformed pack years results in 1.16 times higher OR. Risk of COPD exacerbation within the next 24 months = 1/(1 + exp − (−1.33 + 1.62 × previous exacerbation − 0.05 × FEV₁ (% predicted, per 5% interval change) + 0.15 × 2log(pack years) + 0.65 × history vascular disease)). Examples: a male person aged 73 years with a history of exacerbations in the previous year, FEV₁ of 32.9 as %predicted, a history of 38 pack years of smoking, and prior stroke. His chance of an exacerbation in the next 2 years is: 1/(1 + exp − (−1.33 + 1.62 − 0.05 × (32.9/5) + 0.15 × 2log(38) + 0.65)) = 0.79 = 79%. A female person aged 77 years, without any exacerbations in the previous year, FEV₁ of 77.7 as %predicted, who never smoked, and who does not have a history of stroke or peripheral artery disease. Her chance of an exacerbation in the next 2 years is: 1/(1 + exp − (−1.33 + 0 − 0.05 × (77.7/5) + 0.15 × 2log(0) + 0)) = 0.09 = 9%.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; OR, odds ratio.

Figure 1 Calibration plots of the final prediction model for exacerbations of COPD within the proceeding 24 months in both the derivation and validation cohort.

Notes: Left: calibration plot in the derivation cohort. Right: calibration plot in the validation cohort. The dotted line shows the actual relation between observed outcomes and predicted risks; the solid line shows the smoothed relation. Ideally, these lines equal the dashed diagonal line that represents perfect calibration.
Abbreviation: COPD, chronic obstructive pulmonary disease.

RabeKFHurdSAnzuetoAGlobal Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summaryAm J Respir Crit Care Med2007176653255517507545

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