Frequency and costs of pulmonary exacerbations in patients with cystic fibrosis in the United States

Figures & data

Figure 1. Patient identification. CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; FEV₁: forced expiratory volume in 1 second; IP: inpatient stay. ^a300 charts were not abstracted because the physician declined to participate/provide the chart, the chart lacked ≥2 FEV₁ measurements in the 18-month observation period, and/or there was evidence in the chart of patient participation in a phase 2/3 CFTR modulator trial.

Table 1. Baseline demographic and clinical characteristics.

Characteristic	Lung disease stage^a
	All patients (n = 241)	Mild (n = 173)	Moderate (n = 56)	Severe (n = 12)	p
% of all patients	100	71.8	23.2	5.0
Mean age, y (SD)	23.9 (12.5)	20.7 (10.1)	30.7 (14.1)	38.1 (14.5)	<.001
Age (at index date of observation), n (%)
6–11	33 (13.7)	30 (17.3)	3 (5.4)	0	.028
12–17	56 (23.2)	50 (28.9)	5 (8.9)	1 (8.3)	.004
18–24	57 (23.7)	44 (25.4)	12 (21.4)	1 (8.3)	.365
25–29	34 (14.1)	18 (10.4)	14 (25.0)	2 (16.7)	.023
30–34	18 (7.5)	14 (8.1)	3 (5.4)	1 (8.3)	.790
35–39	14 (5.8)	5 (2.9)	7 (12.5)	2 (16.7)	.007
≥40	29 (12.0)	12 (6.9)	12 (21.4)	5 (41.7)	<.001
Male, n (%)	125 (51.9)	84 (48.6)	34 (60.7)	7 (58.3)	.257
Mean BMI, kg/m^2 (SD)	21.0 (4.1)	20.8 (4.2)	21.6 (3.5)	21.4 (4.8)	.454
ppFEV1
Best result in the baseline year, mean (SD)	82.2 (23.6)	94.0 (14.7)	56.7 (8.9)	30.8 (5.9)	<.001
Worst result in the baseline year, mean (SD)	75.3 (23.7)	86.2 (17.1)	51.5 (11.3)	29.4 (4.8)	<.001
≥1 PEx, any type, n (%)^b	174 (72.2)	120 (69.4)	43 (76.8)	11 (91.7)	.170
≥1 PEx-IV, n (%)	74 (30.7)	41 (23.7)	25 (44.6)	8 (66.7)	<.001
≥1 PEx-O, n (%)	152 (63.1)	108 (62.4)	34 (60.7)	10 (83.3)	.320
Genotype in chart, n (%) (total n = 125)	125 (51.9)	97 (56.1)	25 (44.6)	3 (25.0)	.053
Homozygous F508del, n (%)	56 (44.8)	43 (44.3)	11 (44.0)	2 (66.7)	.743
Heterozygous F508del, n (%)	37 (29.6)	29 (29.9)	8 (32.0)	0	.513
Indeterminate F508del, n (%)^c	13 (10.4)	9 (9.3)	3 (12.0)	1 (33.3)	.388
Not recorded, n (%)^d	7 (5.6)	7 (7.2)	0	0	.343

BMI: body mass index; IP: inpatient; IV: intravenous; PEx: pulmonary exacerbation; PEx-IV: PEx episode requiring IV antibiotics and/or IP stay; PEx-O: PEx episode requiring oral antibiotics only; ppFEV₁: percent predicted forced expiratory volume in 1 second.

^a Disease stage defined by baseline ppFEV₁: mild, ≥70%; moderate, 40% to <70%; severe, <40%.

^b Includes PEx requiring IP stay and/or IV antibiotics or PEx requiring oral antibiotics.

^c “Indeterminate F508del” defines patients with 1 F508del mutant CFTR allele and 1 unknown CFTR allele.

^d Medical chart notes that patient was genotyped, but genetic mutation not specified.

Table 2. PEx frequency and mean annual PEx-related costs by disease stage during 12-month follow-up.

Measure	All patients (n = 241)	Mild (n = 173)	Lung disease stage^a		p
			Moderate (n = 56)	Severe (n = 12)
≥1 PEx, any type^b
n (%)	212 (88.0)	146 (84.4)	55 (98.2)	11 (91.7)	.020
Count, mean (SD)	2.90 (2.06)	2.75 (2.05)	3.30 (2.15)	3.17 (1.75)	.192
Count, median	3.00	3.00	3.00	3.00
≥1 PEx-IV
n (%)	116 (48.1)	76 (43.9)	30 (53.6)	10 (83.3)	.020
Count, mean (SD)	0.83 (1.18)	0.69 (1.06)	1.07 (1.33)	1.75 (1.48)	.002
Count, median	0.00	0.00	1.00	1.50
Annual PEx-related costs, any PEx, mean (SD)^c
Mean (SD)	$37,025 (71,301)	$30,066 (49,345)	$40,771 (54,611)	$119,862 (222,751)	<.001
Median	$10,833	$9456	$14,262	$48,263

IP: inpatient; IV: intravenous; PEx: pulmonary exacerbation; PEx-IV: PEx episode requiring IV antibiotics and/or IP stay; ppFEV₁: percent predicted forced expiratory volume in 1 second.

^a Disease stage defined by baseline ppFEV₁: mild, ≥70%; moderate, ≥40% to <70%; severe, <40%.

^b Includes PEx requiring IV antibiotics and/or IP stay or PEx requiring oral antibiotics.

^c 2013 US dollars.

Figure 2. (A) Mean PEx episode duration (days ± SD) during follow-up. (B) Mean costs per PEx episode during follow-up. IP: inpatient; IV: intravenous; PEx: pulmonary exacerbation.

Table 3. Logistic regression models for risk of PEx requiring IV antibiotics and/or IP stay during 12-month follow-up.

Independent variable	Model 1^a			Model 2^b			Model 3^c
	Odds ratio	95% CI	p	Odds ratio	95% CI	p	Odds ratio	95% CI	p
Age category, years (ref: ≥25)
6–11	0.428	0.197, 0.926	.031	0.653	0.195, 2.182	.488	0.925	0.245, 3.501	.909
12–17	1.375	0.702, 2.694	.354	2.227	0.919, 5.394	.076	2.286	0.873, 5.985	.092
18–24	1.125	0.548, 2.310	.748	1.420	0.628, 3.212	.399	1.277	0.518, 3.149	.595
Male (ref: female)	0.558	0.328, 0.949	.031	0.522	0.295, 0.925	.026	0.703	0.375, 1.317	.271
Baseline ppFEV1^d	—	—	—	0.972	0.957, 0.986	<.001	0.978	0.962, 0.994	.006
Baseline BMI	—	—	—	0.945	0.860, 1.039	.245	0.971	0.876, 1.076	.573
Baseline IV PEx (ref: none)	—						7.992	3.843, 16.621	<.001

BMI: body mass index; IV: intravenous; PEx: pulmonary exacerbation; ppFEV₁: percent predicted forced expiratory volume in 1 second.

^a 241 observations used. Likelihood ratio chi-square =12.82, p = .0122.

^b 235 observations used. Likelihood ratio chi-square =34.54, p < .001.

^c 235 observations used. Likelihood ratio chi-square =71.41, p < .001.

^d Best result in the baseline year.