Tiotropium Add-On and Treatable Traits in Asthma-COPD Overlap: A Real-World Pilot Study

Figures & data

Figure 1 Design of the open-label cross-over study. Solid line, dual therapy with fluticasone propionate/formoterol fumarate (FP/FM); dotted line, tiotropium bromide (TIO) add-on therapy to FP/FM. ACQ, asthma control questionnaire; ASK-12, adherence status with knowledge-12; CAT, chronic obstructive pulmonary disease assessment test; FeNO, fractional exhaled nitric oxide; R, randomization.

Table 1 Patient Characteristics

Age (Years)	75.0 ± 5.1, Range 59–82
Gender (male/female)	18/0
Body mass index (kg/m^2)	22.5 ± 4.0
History of smoking (pack-years)	53.0 ± 42.1
Treatment of theophylline (with/without)	4/14
Treatment of carbocysteine (with/without)	2/16
Treatment of LTRA (with/without)	10/8
Bronchodilator response^# (%)	24.9 ± 5.5

Notes: ^#Bronchodilator response means percent increase in forced expiratory volume in 1 second (FEV1) from the baseline value inhalation of 200 mg of salbutamol sulfate. Data are presented as mean (SD).

Abbreviation: LTRA, leukotriene receptor antagonist.

Table 2 Spirometry Parameters After Each Treatment

	Run-In	Control	TIO Add-On	P-value
Spirometry parameters
VC (L)	2.90 (0.73)	2.82 (0.71)	3.00 (0.69)	< 0.05
FVC (L)	2.61 (0.70)	2.52 (0.75)	2.76 (0.74)	< 0.05
FEV1 (L)	1.20 (0.49)	1.20 (0.51)	1.30 (0.48)	< 0.01
FEV1/FVC (%)	44.6 (13.2)	45.2 (14.3)	46.9 (11.0)	0.20
MEF (L/s)	3.52 (1.68)	3.52 (1.41)	3.84 (1.81)	0.15
MEF50 (L/s)	0.60 (0.51)	0.62 (0.47)	0.65 (0.45)	0.39
MEF25 (L/s)	0.18 (0.12)	0.20 (0.12)	0.21 (0.10)	0.50
FEF25–75% (L/s)	0.45 (0.36)	0.46 (0.34)	0.48 (0.32)	0.27

Notes: Data are presented as mean (SD). P values were determined by one-way analysis of variance (ANOVA).

Abbreviations: FP/FM, fluticasone propionate/formoterol fumarate; TIO, tiotropium bromide; VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; MEF, maximum expiratory flow; MEF50, maximum expiratory flow rate at 50% forced vital capacity; MEF25, maximum expiratory flow rate at 25% forced vital capacity; FEF25–75%, forced expiratory flow at 25–75%.

Figure 2 Individual data for forced vital capacity (FVC) before each treatment with fluticasone propionate/formoterol fumarate (FP/FM) combination therapy and after tiotropium bromide (TIO) add-on therapy to FP/FM in patients with asthma-chronic obstructive pulmonary disease overlap (ACO). Each panel shows the parameter changes for all patients and the mean ± standard deviation (SD). P < 0.05, determined by one-way analysis of variance (ANOVA).

Figure 3 Individual data for forced expiratory volume in 1 s (FEV₁) before each treatment and after fluticasone propionate/formoterol fumarate (FP/FM) combination therapy and tiotropium bromide (TIO) add-on therapy to FP/FM in patients with asthma-chronic obstructive pulmonary disease overlap (ACO). Each panel shows the parameter changes for all patients and the mean ± standard deviation (SD). P< 0.01, determined by one-way ANOVA.

Table 3 FOT Parameters, FeNO, CAT, ACT and Blood Examination Parameters After Each Treatment

	Run-In	Control	TIO Add-on	P-value
FOT parameters
R5 (cmH2O/L/s)	3.8 (1.1)	3.6 (1.2)	3.2 (1.1)	< 0.05
R20 (cmH2O/L/s)	2.9 (0.7)	2.7 (0.9)	2.5 (0.8)	< 0.05
X5 (cmH2O/L/s)	−1.7 (1.0)	−1.7 (1.2)	−1.3 (0.9)	< 0.05
Fres (Hz)	16.9 (5.9)	16.8 (6.4)	15.1 (5.5)	< 0.05
ALX (cmH2O/L/s X Hz)	13.5 (11.0)	13.8 (12.6)	9.9 (9.3)	< 0.05
FeNO (ppb)	18.2 (8.4)	17.3 (7.6)	18.2 (8.3)	0.88
COPD Assessment Test score	15.4 (11.6)	17.6 (10.3)	15.8 (11.4)	0.11
Asthma Control Questionnaire score	6.0 (5.2)	6.4 (5.9)	7.5 (5.6)	0.18
Adherence Starts with Knowledge–12 score	25.1 (6.9)	22.2 (5.5)	22.1 (5.4)	0.08
Serum total Ig E (IU/mL)	899.9 (913.6)	876.9 (1057.8)	804.9 (961.3)	0.39
Peripheral eosinophil count (/mL)	297.5 (208.6)	304.0 (251.3)	281.7 (176.9)	0.78

Notes: Data are presented as mean (SD). P values were determined by one-way ANOVA.

Abbreviations: FOT, forced oscillation technique; R5 and R20, respiratory system resistance at 5 Hz and 20 Hz; X5, respiratory system reactance at 5 Hz; Fres, resonant frequency; ALX, area of low reactance; FeNO, the fraction of exhaled nitric oxide; COPD, chronic obstructive pulmonary disease; Ig, immunoglobulin.

Figure 4 Individual data for resistance at 5 Hz (R5) before each treatment and after fluticasone propionate/formoterol fumarate (FP/FM) combination therapy and tiotropium bromide (TIO) add-on therapy to FP/FM in patients with asthma-chronic obstructive pulmonary disease overlap (ACO). Each panel shows the parameter changes for all patients and the mean ± standard deviation (SD). P < 0.05, determined by one-way ANOVA.