Persistent Uncontrolled Asthma: Long-Term Impact on Physical Activity and Body Composition

Figures & data

Table 1 Baseline Clinical Characteristics of Patients with Asthma and Healthy Controls

Characteristics	Healthy Controls	Controlled Asthma	Uncontrolled Asthma	P-value
n	84	106	127	–
Age, years	46.2 ±18.6	51.2 ±13.5	52.6 ±14.5	0.015*
Sex (% male)	53	45	41	0.20
BMI (kg/m2)	24.9 ±4.0	26.7 ± 4.4	28.5 ±5.5	<0.0001
Smoking history, %	19	21	25	0.54
ICS (%)	–	12	8	0.08
ICS/LABA (%)	–	76	92	0.09
ICS dose (µg)	–	408 ±309	748 ±535	<0.0001
LAMA (%)	–	13	42	<0.0001
OCS (%)	–	14	32	<0.0001
Biological therapy (%)	–	8	16	<0.001
FEV1%	103 ±11	88 ±18	72 ±20	<0.0001
FEV1/FVC (%)	76 ±7	68 ± 11	60 ±13	<0.0001
PEF (l/s)	9.0 ±2.0	7.6 ±2.2	6.1 ± 2.0	<0.0001
ACT score	–	23.0 ±1.7	13.5 ±4.0	<0.0001
ACQ5 score	–	0.56 ±0.49	2.33 ±1.1	<0.0001
Severe exacerbations in the previous 12 months	–	0 (0.0–1.0)	2 (0.0–5.0)	<0.0001
Average daily steps	7839 (6577–9430)	7806 (6337–10,004)	6641 (4886–9280)	<0.001
Average daily time of at least moderate activity, min	132 (72–175)	133 (93–192)	108 (54–183)	0.012
SM (%)	36±7.0	34 ±6.0	32 ±6.0	<0.0001
FM (%)	30 ±7.0	32 ±7.0	35 ±7.0	<0.0001

Notes: Values are presented in mean and standard deviation or median and interquartile range. *Post hoc analysis: controlled asthma vs uncontrolled p=0.75, controlled asthma vs healthy controls p=0.088, uncontrolled asthma vs healthy controls p=0.012. Physical activity was similar between controlled asthma and healthy controls.

Abbreviations: BMI, body mass index (kg/m²); smoking history, current or former smoker >10 pack years; ICS dose, inhaled corticosteroids fluticasone equivalent (µg); LABA, long-acting β2-adrenoceptor agonists; LAMA, long-acting muscarinic receptor antagonists; OCS, regular daily oral corticosteroid therapy; biological therapy, omalizumab or mepolizumab; FEV1, predicted forced expiratory volume in the 1 second; FVC, forced vital capacity; PEF, peak expiratory flow (l); ACT, asthma control test; ACQ, asthma control questionnaire; SM, skeletal muscle mass; FM, fat mass.

Table 2 Clinical Characteristics of Asthma Patients Based on Skeletal Muscle Mass and Gender

Parameter	Males					Females
	First Quartile	Second Quartile	Third Quartile	Fourth Quartile	P-value	First Quartile	Second Quartile	Third Quartile	Fourth Quartile	P-value
SM quartile	<33.5	33.5–36.9	37.0 40.9	≥41	–	<26.3	26.4–28.8	28.9–32.6	>32.6	–
n	22	30	27	21	–	28	40	27	38	–
Age, years	59.9 ±11.4	54.4 ±14.6	54.0 ±11.1	49.0 ±13	0.06	54.3 ±11	54.4 ±14	48.7 ±12.9	43.7 ±16	<0.01
SM (%)	31 ±2	35 ±1	39 ±1	44 ±2	<0.01	24 ±2	28 ±1	30 ±1	36 ±4	<0.01
BMI (kg/m^2)	32.8 ±3.8	28.2 ±2.6	27.4 ±3.7	25.2 ± 2.9	<0.01	34.7 ±5.0	27.5 ±4.1	25.6 ±2.8	22.3 ±2.8	<0.01
FM (%)	37 ±3	31 ±1	27 ±2	21 ±2	<0.01	46 ±3	39 ±3	36 ±2	29 ±6	<0.01
ACQ5 score	1.9 ±1.2	1.44 ±1.2	1.20 1.0	0.96 ± 0.9	0.03	2.3 ±1.5	1.8 ±1.5	1.3 ±1.1	1.2 ±1.1	<0.01
ACT score	15.9 ±4.8	18.0 ±6.1	19.2 ±4.8	20.0 ±5.2	0.06	14.7 ±5.4	17.2 ±5.9	18.4 ±5.8	18.9 ±5.4	0.02
FEV1 (%)	72 ±14	81 ±24	77 ±18	99 ±20	0.52	73 ±20	81 ±28	83 ±18	85 ±21	0.14
FEV1/FVC (%)	59 ±13	64 ±11	60 ±11	62 ±12	0.41	62 ±12	65 ±14	66 ±12	68 ±13	0.39
PEF (l/s)	7.4 ±2.6	8.00 ±2.5	8.1 ±2.3	8.2 ±2.5	0.74	5.9 ±1.7	5.9 ±1.7	5.8 ±1.1	6.0 ±1.6	0.9
ICS dose (µg)	775 (400–1000)	500 (250–900)	500 (250–1000)	400 (250–500)	0.04	695 (460 −1000)	500 (500–1000)	500 (250–500)	450 (118–500)	0.01
OCS, (%)	22	14	30	27	0.55	48	25	22	10	0.02

Notes: Values are in mean ±sd except for ICS due to skewness are represented in median and IQR. A post hoc analysis showed statistically significant differences in age only between the first and fourth/first and third quartiles in females. In females, the differences in the ACQ5 score were significant between the first and fourth, first and third quartiles, while the difference of ACT score was significant only between the first and fourth quartiles. In males, the ACQ5 was significantly different only between the first and fourth quartiles.

Abbreviations: SM, skeletal muscle mass; BMI, body mass index (kg/m²); FM, fat mass; ACQ, asthma control questionnaire; ACT, asthma control test; FEV1, predicted forced expiratory volume in the 1 second; FVC, forced vital capacity; PEF, peak expiratory flow (l); ICS dose, inhaled corticosteroids fluticasone equivalent (µg); OCS, oral corticosteroid; OCS, regular daily oral corticosteroid therapy.

Figure 1 Physical activity in asthma patients in relation to skeletal muscle mass quartiles and gender: (A) the distribution of average daily steps in muscle mass quartiles. (B) the distribution of at least daily time in moderate activity according to muscle mass quartiles. In females, the post hoc analysis showed statistically significant differences in means of average daily steps between the first and fourth quartiles (p<0.0001), first and third quartiles (p=0.005), and second and fourth quartiles (p=0.01), (A, upper panel). The average daily time of at least moderate activity was significantly different between all quartile (p<0.001) except between the second and third quartiles (p=0.08) (B, upper panel). In males, average daily steps were only significantly different between the first and fourth quartiles (p=0.031), and between the second and fourth quartiles (p=0.002) (A, lower panel). Likewise, the average daily time of at least moderate activity was also significantly different between the first and fourth (p=0.031), and between the second and fourth quartiles (p=0.026) (B, lower panel).

Table 3 Predictors of Body Composition in Asthma

Predictors of Skeletal Muscle Mass
Factor	Estimator	Standard Error	P-value
Male sex	2.748 e^−02	4.774e^−03	<0.001
ACT score	1.186 e^−03	5.139 e^−04	0.021
Age	−6.497 e^−04	1.646 e^−04	<0.001
Physical activity	2.913 e^−04	2.738 e^−05	<0.001
OCS use	−9.242 e^−03	6.142 e^−03	0.16
ICS dose	−5.031 e^−06	5.073e^−06	0.40
Intercept	2.748 e^−01	1.031e^−02	<0.001
Predictors of Fat Mass
Male sex	−7.77 e^−02	5.994 e^−03	<0.001
ACT score	−1.452 e^−03	6.237 e^−04	0.021
Age	3.355 e^−04	2.089 e^−04	0.15
Physical activity	−3.993 e^−04	3.419 e^−05	<0.001
OCS use	1.369 e^−02	9.083 e^−03	0.080
ICS dose	6.385 e^−05	8.533 e^−06	0.38
Intercept	4.292 e^−01	1.451 e^−02	<0.001

Notes: Multivariate regressions including predictors of SM: multiple R2=0.61, p< 0.0001, and predictors of fat mass: multiple R2=0.61, p< 0.0001. Age in years, sex: being male. In alternative regressions that did not include the ACT score as predictors, OCS use and ICS dose were significant predictors of muscle mass and fat mass (Online Supplementary 3).

Abbreviations: ACT, asthma control test; OCS, regular oral corticosteroid use (categorical variable); physical activity, average daily time in moderate activity in minutes; ICS dose, fluticasone equivalent in µg.

Table 4 Measures of Body Composition, Physical Activity and Symptom Control at Baseline and Follow-Up

Parameter	Persistent Uncontrolled				Controlled or Transitionally Uncontrolled
	Baseline	Follow-Up	Mean Difference	P-value	Baseline	Follow-Up	Mean Difference	P-value
BMI (kg/m^2)	28.5 ±4.9	28.7 ±5.0	+0.20	0.39	26.6 ±4.6	26.7 ±4.5	+0.10	0.66
FM (%)	34.6 ±7	35.8 ±7	+1%	0.015	32.3 ±6	32.7% ±6	0.0	0.29
FM (kg)	30.1 ±10.0	31.2 ±10.0	+1.06	0.012	25.8 ±8.51	26.2 ±8.2	+0.4	0.45
SM (%)	32.2 ±6	31.0 ±6	−1.2%	<0.01	33.8 ±5	33.5% ±5	−0.3%	0.30
SM (kg)	27.39 ±6.7	26.51 ±6.4	−0.88	<0.01	26.8 ±6.7	26.7 ±6.9	−0.1	0.53
Daily steps	6614 ±2854	6195 ±2642	−445	0.14	8670±3723	9058 ±3610	+195	0.56
Moderate activity	118 ±75	115 ±79	−3.0	0.11	156 ± 85	153 ±81	−3.0	0.43
FEV1 (%)	73 ±20.0	71 ±20.0	−1.9%	0.33	86 ±20	84 ± 20	−2%	0.11
ACQ5 score	2.27 ±1.13	2.47 ±1.13	+0.17	0.29	0.85 ±0.8	0.81 ±0.7	−0.06	0.54
ACT score	13.12 ±4.24	14.14 ±3.5	+1.02	0.08	21.1 ±3.8	21.8 ±2.9	+0.69	0.10

Notes: Values are presented in mean and standard deviation. P-values are from either paired t-test or paired Wilcoxon test and represent the statistical significance of the longitudinal change of the tested measures.

Abbreviations: SM, skeletal muscle mass (skeletal muscle mass/total body mass x %); BMI, body mass index kg/m²; FM, fat mass to total body mass %; ACQ, asthma control questionnaire; ACT, asthma control test; FEV1, predicted forced expiratory volume in the 1 second.

Figure 2 Longitudinal differences in muscle mass (A) average daily steps (B) and time of at least moderate activity (C) between persistent uncontrolled and controlled asthma patients at baseline and follow-up. Patients with persistent uncontrolled asthma had lower muscle mass (A), lower average daily steps (B) and time in at least moderate activity (C) at baseline and at follow-up p<0.01 compared to the rest of patients.

Note: Controlled*: patients with controlled asthma at both study visits or uncontrolled symptoms at only one of the study visits.