Favorable Response to Long-Term Azithromycin Therapy in Bronchiectasis Patients with Chronic Airflow Obstruction Compared to Chronic Obstructive Pulmonary Disease Patients without Bronchiectasis

Figures & data

Table 1 Baseline Characteristics at the Time of Azithromycin Treatment Initiation

	Total (N = 59)	Bronchiectasis with CAO (n = 43)	COPD without Bronchiectasis (n = 16)	P-value
Age, years	64.0 (58.0–72.0)	62.0 (57.0–70.0)	70.0 (62.5–76.3)	0.023
Sex, male	33 (55.9)	20 (46.5)	13 (81.3)	0.017
BMI, kg/m^2	21.0 (18.2–23.1)	21.4 (18.5–23.1)	20.8 (16.8–22.8)	0.549
Smoking history
Never	31 (52.5)	29 (67.4)	2 (12.5)	<0.001
Former	26 (44.1)	13 (30.2)	13 (81.3)
Current	2 (3.4)	1 (2.3)	1 (6.3)
History of PTB	20 (33.9)	16 (37.2)	4 (25.0)	0.378
Bronchial asthma	7 (11.9)	6 (14.0)	1 (6.3)	0.661
mMRC	2.0 (2.0–3.0)	2.0 (2.0–3.0)	2.0 (2.0–3.0)	0.348
≥2	49 (83.1)	34 (79.1)	15 (93.8)	0.259
CAT score (n = 50)	27.5 (22.8–31.0)	26.5 (20.8–31.5)	28.0 (23.5–30.5)	0.471
≥10	49 (98.0)	33 (97.1)	16 (100.0)	1.000
Exacerbations in the previous year
Any exacerbations	54 (91.5)	39 (90.7)	15 (93.8)	1.000
≥2 moderate or ≥1 severe	51 (86.4)	36 (83.7)	15 (93.8)	0.427
Post-bronchodilator spirometry
FVC, L	2.47 (1.90–3.15)	2.26 (1.82–2.86)	2.83 (2.65–3.48)	0.010
FVC, % pred	69.0 (56.0–82.0)	66.0 (54.0–79.0)	72.5 (64.5–86.5)	0.039
FEV1, L	1.11 (0.88–1.40)	1.11 (0.91–1.40)	1.13 (0.77–1.47)	0.580
FEV1, % pred	41.0 (54.0–33.0)	41.0 (33.0–57.0)	40.0 (34.0–48.8)	0.406
≥50% pred	19 (32.2)	16 (37.2)	3 (18.8)	0.177
<50% pred	40 (67.8)	27 (62.8)	13 (81.3)
FEV1/FVC, % pred	46.0 (38.0–63.0)	55.0 (40.0–63.0)	39.0 (33.0–44.5)	0.002
Bronchodilator response	9 (15.3)	7 (16.3)	2 (12.5)	1.000
Laboratory finding
WBC, × 10^3 /uL	8.2 (6.2–10.6)	8.3 (6.2–11.1)	7.9 (5.6–9.9)	0.422
CRP, mg/dL (n = 58)	0.4 (0.1–2.1)	0.4 (0.2–2.7)	0.1 (0.0–1.7)	0.059
Eosinophils, /uL	130.0 (39.4–245.7)	145.6 (86.6–250.0)	44.0 (10.0–144.8)	0.019
Sputum culture (n = 50)
Pseudomonas	6/50 (12.0)	6/40 (15.0)	0/10 (0.0)	0.327
Other organisms^a	4/50 (8.0)	4/40 (10.0)	0/10 (0.0)	0.571

Notes: Data are presented as number (%) or median (interquartile range). ^aTwo patients had Haemophilus influenzae, and the others had M. catarrhalis and Enterobacteriaceae coli, respectively.

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CAO, chronic airflow obstruction; CAT, COPD Assessment Test; CRP, C-reactive protein; FEV_1, forced expiratory volume in one second; FVC, forced vital capacity; mMRC, modified Medical Research Council dyspnea questionnaire; PTB, pulmonary tuberculosis; WBC, white blood cell.

Table 2 Baseline Characteristics of Given Treatment

	Total (N = 59)	Bronchiectasis with CAO (n = 43)	COPD without Bronchiectasis (n = 16)	P-value
Treatment regimen
Weekly dose, mg	1750 (1736–1750)	1750 (1478–1750)	1750 (1750–1750)	0.171
250 mg once daily	50 (84.7)	35 (81.4)	15 (93.8)	0.421
500 mg once, three days a week	1 (1.7)	0 (0.0)	1 (6.3)	0.271
Others^a	8 (13.6)	8 (18.6)	0 (0.0)	0.093
Duration, months	15.0 (8.0–25.0)	14.8 (7.1–24.6)	16.5 (10.2–29.1)	0.569
Inhaler medication				0.010
None	7 (11.9)	7 (16.3)	0 (0.0)
LAMA	3 (5.1)	2 (4.7)	1 (6.3)
LAMA/LABA	9 (15.3)	9 (20.9)	0 (0.0)
ICS/LABA	9 (15.3)	8 (18.6)	1 (6.3)
ICS/LAMA/LABA	31 (52.5)	17 (39.5)	14 (87.5)
Roflumilast	9 (15.3)	5 (11.6)	4 (25.0)	0.236

Notes: Data are presented as number (%) or median (interquartile range). ^aThree patients received 250 mg three times a week; two patients received 500 mg daily; one patient received 250 mg for five days per month; one patient received 250 mg for ten days per month; and the other received 500 mg for 7 days per month.

Abbreviations: CAO, chronic airflow obstruction; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting beta₂-agonist; LAMA, long-acting muscarinic antagonist.

Table 3 Outcomes of Long-Term Azithromycin Treatment at 12 Months Follow-Up

	Total (N = 59)	Bronchiectasis with CAO (n = 43)	COPD without Bronchiectasis (n = 16)	P-value
Exacerbation
Moderate	27 (45.8)	15 (34.9)	12 (75.0)	0.006
Severe	17 (28.8)	12 (27.9)	5 (31.3)	1.000
≥2 moderate or ≥1 severe	34 (57.6)	20 (46.5)	14 (87.5)	0.005
Adverse event	3 (5.1)	1 (2.3)^a	2 (12.5)^b	0.176

Notes: Data are presented as number (%). ^aA patient reported lip swelling. ^bA patient reported abdominal discomfort, and the other presented general weakness.

Abbreviations: CAO, chronic airflow obstruction; COPD, chronic obstructive pulmonary disease.

Figure 1 The proportion of symptomatic responders* after long-term azithromycin treatment. *Defined as patients with ≥2 points decrement from the initial COPD Assessment Test (CAT) score. CAT was measured in 43, 47, and 35 patients at 3, 6, and 12 months after initiation of azithromycin treatment.

Abbreviations: CAO, chronic airflow obstruction; COPD, chronic obstructive pulmonary disease.

Table 4 Risk Factors for Acute Exacerbations^a During 12 Months of Follow-Up

	Univariable		Multivariable
	Unadjusted OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
Age	1.03 (0.99–1.08)	0.137	1.01 (0.96–1.06)	0.693
Sex, male	3.14 (1.07–9.19)	0.037	2.52 (0.37–17.03)	0.343
Smoking, ever	3.04 (1.03–8.97)	0.044	0.74 (0.11–4.96)	0.760
FEV1 < 50% pred	1.85 (0.61–5.59)	0.274	1.04 (0.26–4.14)	0.959
Bronchiectasis with CAO (vs COPD without bronchiectasis)	0.12 (0.03–0.61)	0.011	0.15 (0.03–0.87)	0.035
ICS use	1.85 (0.61–5.59)	0.274	0.92 (0.25–3.40)	0.904

Notes: ^aDefined as ≥2 moderate (hospital visit) or ≥1 severe (emergency department or hospitalization) acute exacerbations.

Abbreviations: CAO, chronic airflow obstruction; CI, confidence interval; FEV_1, forced expiratory volume in one second; ICS, inhaled corticosteroid; OR, odds ratio.