Persistent disabling breathlessness in chronic obstructive pulmonary disease

Figures & data

Table 1 Patient characteristics at baseline

Patient characteristics at baseline	All (mMRC 0–4) N=1,689 (100%)	No disabling breathlessness (mMRC <2) at baseline N=785 (47%)	Disabling breathlessness (mMRC ≥2) at baseline N=894 (53%)
Sex
Male, n (%)	795 (47)	364 (46)	431 (48)
Female, n (%)	894 (53)	421 (54)	473 (52)
Age (years), mean (SD)	69.8 (8.57)	68.7 (8.59)	70.7 (8.44)
Current smokers (N=1,666), n (%)
No	1,186 (71)	507 (65)	679 (76)
Yes	480 (29)	268 (35)	212 (24)
Body mass index (N=1,680), n (%)
<22.0	357 (21)	145 (19)	212 (24)
22.0–29.9	941 (56)	480 (61)	461 (51)
≥30	382 (23)	158 (20)	224 (25)
Body mass index, mean (SD)	26.4 (5.50)	26.1 (4.67)	26.6 (6.13)
Frequent exacerbations, n (%)	307 (18)	62 (8)	245 (27)
FEV1%pred, mean (SD) (N=1,635)	51.3 (17.0)	58.4 (14.7)	44.8 (16.4)
COPD stage (N=1,635), n (%)
I	75 (5)	56 (7)	19 (2)
II	781 (48)	495 (64)	286 (33)
III	599 (36)	206 (27)	393 (46)
IV	180 (11)	17 (2)	163 (19)
Heart failure, n (%)	82 (5)	18 (2)	64 (7)
Ischemic heart disease, n (%)	182 (11)	77 (10)	105 (12)
Depression, n (%)	185 (11)	60 (8)	125 (14)
Hypoxic respiratory failure, n (%)	32 (2)	1 (0)	31 (3)

Notes: Results from cross-tabulations of the baseline population (N=1,689, median time between visits: 12 months [IQR 4 months]).

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁%pred, forced expiratory volume in one second in percentage of predicted; IQR, interquartile range; mMRC, modified Medical Research Council; SD, standard deviation.

Table 2 Risk factors for disabling breathlessness in longitudinal analyses

Variables at baseline	Disabling breathlessness at follow-up
	Univariate analysis OR (95% CI)	Multivariate analysis OR (95% CI)
Female sex	1.02 (0.84–1.24)	0.98 (0.78–1.23)
Age (effect of 10 years difference)	1.43 (1.27–1.61)	1.38 (1.20–1.58)
FEV1%pred (effect of 10% change)	0.58 (0.54–0.62)	0.60 (0.55–0.64)
Current smokers	0.57 (0.46–0.71)	0.86 (0.66–1.11)
Frequent exacerbations	3.21 (2.39–4.29)	1.81 (1.30–2.52)
Body mass index
<22.0	1.23 (0.95–1.57)	0.86 (0.64–1.16)
22.0–29.9
≥30	1.32 (1.03–1.68)	1.36 (1.03–1.79)
Heart failure	4.09 (2.27–7.35)	2.42 (1.23–4.74)
Ischemic heart disease	1.81 (1.20–2.52)	1.44 (0.98–2.11)
Depression	1.99 (1.42–2.79)	2.05 (1.40–3.02)
Hypoxic respiratory failure	23.0 (3.11–169.6)	7.83 (1.02–60.0)

Notes: Univariate and multivariate longitudinal analyses of disabling breathlessness at follow-up with independent variables at baseline (n=1,607). Disabling breathlessness = mMRC ≥2. Median follow-up time =12 (IQR: 4) months.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁%pred, forced expiratory volume in one second in percentage of predicted; IQR, interquartile range; OR, odds ratio; mMRC, modified Medical Research Council.

Figure 1 Distribution of mMRC grades in the baseline COPD population.

Note: Percentages of patients with different mMRC grades in the baseline population (n=1,689).

Abbreviations: COPD, chronic obstructive pulmonary disease; mMRC, modified Medical Research Council.

Figure 2 Change in breathlessness status over time (n=1,689).

Table 3 Persistent disabling breathlessness despite COPD treatment

Maintenance treatment at baseline	Number of patients (N=1,689)	Patients with persistent disabling breathlessness, n (%)
LABA only	35	8 (23)
LAMA only	214	61 (29)
LABA + ICS	170	64 (38)
LAMA + LABA only	74	37 (50)
LABA + LAMA + ICS	771	436 (57)
Physiotherapy	330	226 (69)
Per-oral steroids	41	30 (73)
LTOT	22	21 (96)
Physiotherapy + LABA + LAMA + ICS	211	155 (74)

Note: Data on total number of patients with maintenance treatment, with row percentages showing proportions of patients with persistent disabling breathlessness within each treatment group.

Abbreviations: COPD, chronic obstructive pulmonary disease; LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-2-agonists; ICS, inhalation corticosteroids; LTOT, long-term oxygen therapy.

Figure 3 Persistent disabling breathlessness (PDB) in treatment groups.

Note: Data presented as percentages of PDB in different treatment groups (n=1,689).

Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta- 2-agonists; ICS, inhalation corticosteroids; LTOT, long-term oxygen therapy.

Figure 4 Distribution of treatment groups within patients with persistent disabling breathlessness (PDB).

Note: Data presented as percentages of patients in different treatment groups with PDB (n=732).
Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta-2-agonists; ICS, inhalation corticosteroids; LTOT, long-term oxygen therapy.

Table 4 Risk factors for change in disabling breathlessness over time

Variables at baseline	Worsening to disabling breathlessness	Persistent disabling breathlessness
Female sex	1.01 (0.71–1.44)	1.19 (0.83–1.72)
Age (effect of 10 years difference)	1.44 (1.14–1.81)	1.15 (0.93–1.44)
FEV1%pred (effect of 10% change)	0.71 (0.62–0.80)	0.67 (0.60–0.75)
Current smokers	0.84 (0.56–1.25)	0.93 (0.60–1.43)
Frequent exacerbations	1.19 (0.63–2.23)	1.27 (0.79–2.04)
Body mass index
<22.0	0.89 (0.55–1.43)	0.67 (0.42–1.08)
22.0–29.9
≥30	1.27 (0.82–1.97)	0.98 (0.63–1.52)
Heart failure	2.13 (0.73–6.20)	1.85 (0.67–5.11)
Ischemic heart disease	1.38 (0.79–2.41)	2.28 (1.09–4.75)
Depression	2.27 (1.25–4.09)	1.29 (0.72–2.30)

Notes: Results from multivariate logistic regression in conditional change model with worsening and persistent disabling breathlessness as dependent variables (n=1,607). Median follow-up time =12 (IQR: 4) months. Persistent disabling breathlessness = mMRC ≥2 at baseline and follow-up.

Abbreviations: FEV₁%pred, forced expiratory volume in one second in percentage of predicted; IQR, interquartile range; mMRC, modified Medical Research Council.