Physical Inactivity, Functional Status and Exercise Capacity in COPD Patients Receiving Home-Based Oxygen Therapy

ABSTRACT

Chronic obstructive pulmonary disease (COPD) has systemic consequences that lead to reduced physical activity in daily life (PADL). Little is known about PADL and its associations in individuals with COPD on home-based long-term oxygen therapy (LTOT). The objective of the study was to determine whether there is an association between severe physical inactivity and pulmonary function, fatigue, dyspnea, functional status and exercise capacity in individuals with COPD on home-based LTOT using electric oxygen concentrators and to investigate which of these variables could influence inactivity in these individuals. The population sample included 39 individuals with COPD who were on LTOT (69 ± 8 years, FEV₁: 32 ± 14% predicted). They were assessed in terms of PADL (number of steps/day), fatigue (Fatigue Severity Scale – FSS), dyspnea (Medical Research Council – MRC scale), functional status (London Chest ADL scale [LCADL] and Timed Up and Go [TUG] test) and functional exercise capacity (Six-Minute Step test [6MST] and Sit-to-Stand test [STST]). PADL was markedly low (1444 ± 1203 steps/day) and associated with daily duration of LTOT (r = –0.50), fatigue (r = –0.36), LCADL (r = –0.41), 6MST (r = 0.48), and STST (r = 0.53) (p < .05 for all). Multiple linear regression revealed that daily duration of LTOT and STST explained 39% of the variability of PADL. Longer daily duration of LTOT, fatigue, worse functional status and exercise capacity were all associated with physical inactivity in individuals with COPD on LTOT, whereas daily duration of LTOT and the STST were determinants of reduced physical activity.

KEYWORDS:

• Oxygen Inhalation therapy
• physical activity
• activities of daily living
• chronic obstructive pulmonary disease

Introduction

Chronic obstructive pulmonary disease (COPD) is predicted to be the third leading cause of death by 2020. The disease leads to high morbidity and is a major challenge for public health (1). Although it mainly affects the lungs, COPD can be considered a systemic disease in which the inflammatory component is strongly associated with levels of physical activity in daily life (PADL) (2). In addition to systemic inflammation, other extrapulmonary factors, such as muscle dysfunction and abnormal body composition, play an important role in worsening of the disease (1). These factors, together with others such as sociodemographic characteristics, psychosocial factors, lifestyle, environment and a range of clinical and functional factors are determinants of PADL (3).

As the disease progresses, pulmonary function deteriorates and the risk of hypoxemia increases. This is primarily due to the progressive decrease in airflow and destruction of the pulmonary capillary bed, which leads to a ventilation-perfusion (V/Q) mismatch. Oxygen supplementation is recommended for patients with severe resting hypoxemia or those with moderate hypoxemia and signs of heart failure, polycythemia or pulmonary hypertension (4).

Long-term oxygen therapy (LTOT) in COPD patients with chronic hypoxemia has been shown to have several benefits, such as improved hemodynamic parameters, better quality of life and increased survival (5). However, little is known about levels of PADL in patients receiving home-based LTOT or the factors that influence them. Once identified, the factors strongly associated with (or perhaps even determinants of) low levels of PADL in these individuals could be assessed in clinical practice, stimulating interventions to improve them.

Physical inactivity is a modifiable risk factor for various comorbidities in COPD patients, including diabetes, cardiovascular disease and obesity, and is also associated with dyspnea, an increase in the number of exacerbations, worse quality of life and reduced exercise capacity (6). According to Caspersen (7), physical activity can be defined as any body movement produced by skeletal muscle that requires energy expenditure. It is not necessarily associated with physical exercise, which involves a planned activity that is intended to improve the individual's physical condition. The level of PADL can be quantified with monitors or questionnaires (8).

Differences in levels of PADL in patients receiving LTOT and those not receiving LTOT have already been described in the literature (9). Sandland et al. (9) found that activity counts for patients on LTOT were around 50% lower than those for patients not on LTOT even when they had similar pulmonary function. Although they did not state which LTOT device their patients used, Sandland et al. reported that physical activity levels in the patients on LTOT remained low throughout the day, suggesting that these patients do not normally leave their homes.

In a recent study, Furlanetto and Pitta investigated the effects of oxygen therapy devices in COPD patients (8). They found that physical inactivity related to specific LTOT equipment was underinvestigated and that there was no solid evidence indicating that the type of equipment influenced PADL levels.

Electric oxygen concentrators are less expensive devices for supplying oxygen and may be the only option available to some people. This study therefore sought to determine whether there is an association between severe physical inactivity in daily living and pulmonary function, fatigue, dyspnea, functional status and exercise capacity in individuals with COPD on home-based LTOT using electric oxygen concentrators and to investigate which of these variables could influence inactivity in these individuals. We hypothesize that the use of home oxygen therapy with nonportable oxygen concentrators is directly related to reduced PADL levels, as are other factors such as symptoms of the disease, functional status and exercise capacity.

Methods

The study was a cross-sectional, observational study and was carried out between May and December 2016. The population sample consisted of patients registered on a long-term home oxygen therapy program in a city in the south of Brazil. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations (10).

After the study had been approved by the Ethics Committee (Ethics Committee of the local Municipal Health Department, no. 1.552.888), eligible patients were contacted by telephone to schedule the first home visits. On the first of these visits, the study aims were explained, patients signed a voluntary informed-consent form (VICF) and pulmonary function was assessed. On the second visit, all the functional and exercise-capacity tests were conducted, and the questionnaires were applied. All assessments were performed by a previously trained, qualified physical therapist.

Inclusion criteria were: having a clinical and functional diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (1); currently being on LTOT; being clinically stable in any stage of the disease (i.e., the disease had been stable for at least one month); not having been on a physical rehabilitation or training program in the previous year; having signed the VICF; and having used the pedometer correctly. Exclusion criteria were: presenting with neuromuscular and/or neurodegenerative diseases, lower-limb arthrodeses and/or prostheses, severe cardiac arrhythmia or any dysfunction that made it difficult to perform the tests; having impaired cognition according to the Mini-Mental State Examination (MMSE) (<13 for illiterate individuals; <18 for individuals with 1 to 7 years of education and <26 for individuals with 8 years or more of education) (11); and using noninvasive ventilation (CPAP or BiPAP).

The flow rate (liters/minute) and daily usage of oxygen therapy (hours) were determined from the medical prescription. All the equipment and interfaces used were supplied under the municipal long-term home oxygen therapy program. The oxygen supply came from an EverFlo 5 LPM electric oxygen concentrator (Philips HealthCare), and the interface used by all the study participants was a nasal cannula.

Pulmonary function was assessed with a spirometer (Spirobank G, MIR, Italy) using the American Thoracic Society/European Respiratory Society guidelines (12) and reference values for the Brazilian population (13). The severity of airway obstruction was classified according to the GOLD criteria (1).

Fatigue was measured using the Brazilian Portuguese version of the Fatigue Severity Scale (FSS) (14). The FSS is a self-report scale that describes the impact of fatigue on activities of daily living in the previous two weeks. A cutoff point of 4 was used to identify fatigue (15). Dyspnea was assessed using the Brazilian Portuguese version (16) of the Medical Research Council (MRC) scale (17). This questionnaire requires that the patient chooses from five statements, each with an associated grade, the one that best describes their perceived breathlessness. Grades 3 to 5 were considered to indicate the presence of dyspnea (16).

Functional status was assessed subjectively using the London Chest Activity of Daily Living (LCADL) scale (18) and objectively with the Timed Up and Go (TUG) test (19). The LCADL scale is a questionnaire covering 15 activities divided into 4 domains that assesses the extent to which dyspnea limits COPD patients' daily routines. A subscore is calculated for each domain, and these are then added to give a total score, with higher values indicating greater limitation (20). In the TUG test, the individual is timed while he gets up from a chair, walks for 3 meters at a comfortable pace, turns around, returns to the chair and sits down.

Exercise capacity was assessed using the 6-Minute Step test (6MST) and 1-Minute Sit-to-Stand test (STST). The 6MST was performed on a single 20 cm-high step, and the patient was asked to go up and down the step as fast as possible for 6 minutes. The patient was allowed to slow down or stop if necessary. At the end of the test, the number of steps was counted (21, 22). The STST was conducted using a 46 cm-high armless chair. Participants were instructed to keep their arms crossed on their chest and their hands resting on their shoulders and to sit down and stand up as many times as possible in one minute after being told to start. At the end of the test, the number of times they had stood up and sat down was recorded (23, 24).

PADL was assessed by calculating the mean number of steps measured during five consecutive days with a Digiwalker SW 200 pedometer (Yamax, Tokyo, Japan), which is considered a suitable device for counting steps and gives a reproducible result (25, 26). Participants were instructed to wear the pedometer on their left hip and remove it only to have a shower or when they went to bed at night. The cutoff point used to determine severe physical inactivity was 4580 steps/day, as proposed by Depew et al. (27).

Statistical analysis

The sample size required^{Figure 1} to allow a significant correlation between PADL and STST to be identified based on the results of a previous study (28) was 36 individuals. This would allow a significant correlation to be found using a power of 80% and an α of 0.02.

The data were analyzed with Statistical Package for Social Sciences (SPSS) version 22. The Shapiro-Wilk test was used to test for normality, and the results were presented as mean and standard deviation or median and 25–75% interquartile range. For the multiple linear regression, only the two independent variables with the strongest correlation (LTOT and STST) with PADL (the dependent variable) were chosen. The choice of two independent variables was based on the proportion of 1 independent variable for approximately 20 measurements of dependent variable. The stepwise insertion method and a significance level of 0.05 were used.

Results

Thirty-nine individuals with COPD who were on LTOT were included in the study (Figure 1). Just under three-quarters (74.3%) were female, and the majority were classified as having severe or very severe airway obstruction. Anthropometric, demographic and clinical data and information about oxygen therapy are shown in Table 1.

Figure 1. Data-collection flowchart based on the STROBE Statement.

Table 1. Anthropometric, demographic and clinical data for the population sample.

Variable	n = 39
Sex (F/M)	29/10
Age (years)	69 ± 8
BMI (kg/m^2)	26 ± 7
MMSE (points)	23 [20–26]
FEV1 (L)	0.65 [0.5–0.85]
FEV1 (% predicted)	29 [22–40]
FEV1/FVC ratio	46 ± 8
GOLD I/II/III/IV (n)	0/4/15/20
Cigarette pack.years	44 [24–76]
O2 flow rate (L/min)	2.5 [2.0–3.0]

Notes: Data are given as mean and standard deviation or median and 25–75% interquartile range. M, male; F, female; BMI, body mass index; FVC, forced vital capacity; FEV₁, forced expiratory volume in the 1st second; LTOT, long-term oxygen therapy; MMSE, Mini-Mental State Examination; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

The pedometer was used for 13 h/day on average over five consecutive days. Based on the number of steps/day, all the participants in the study were classified as severely inactive. In addition to being severely inactive, the patients reported fatigue and dyspnea as well as reduced functional status and exercise capacity (Table 2).

Table 2. Variables analyzed

Variable	Values
Number of steps/day	973 [482–2.473]
Duration of LTOT (hours/day)	18 [15–24]
FSS (points)	5.8 [4.9–6.4]
MRC (points)	4 [3–5]
LCADL (points)	41 [30–50]
TUG (s)	14 [12–15]
6MST (no. of steps)	15 [10–19]
STST (no. of repetitions)	12 ± 4

Notes: Data are given as mean and standard deviation or median and 25–75% interquartile range. LTOT, long-term oxygen therapy; FSS, Fatigue Severity scale; MRC, Medical Research Council scale; LCADL, London Chest Activity of Daily Living; TUG, timed up and go; 6MST, 6-Minute step test; STST, sit to stand test.

No correlation was observed between number of steps/day and severity of airway obstruction as assessed by FEV₁ (r = 0.05, p = 0.74). However, there was a significant correlation between number of steps/day and daily duration of LTOT (h/day), fatigue (FSS) functional status (LCADL) and capacity to exercise (6MST and STST) (Table 3).

Table 3. Correlation between PADL and clinical and functional variables.

Variable	Correlation coefficient r	p Value
LTOT (h/day)	−0.50	0.01
FSS (points)	−0.36	0.03
MRC (points)	−0.24	0.14
LCADL (points)	−0.41	0.01
TUG (s)	−0.33	0.07
6MST (no. of steps)	0.48	<0.01
STST (no. of repetitions)	0.53	<0.01

LTOT, long-term oxygen therapy; FSS, fatigue severity scale; MRC, Medical Research Council; LCADL, London Chest Activity of Daily Living; TUG, timed up and go; 6MST, 6-Minute step test; STST, sit to stand test.

Multiple linear regression was performed to determine which variables could explain the variability of PADL (Table 4). Daily duration of LTOT (h/day) and the result of the STST together explained approximately 39% of this variability in the study population.

Table 4. Results of multiple linear regression.

	B ± SE	t	p
Model 1
STST	142.18 ± 64.28	2.212	0.03^*
Model 2
STST	103.75 ± 56.28	1.843	0.08
LTOT	−164.37 ± 56.09	−2.930	<0.00^**

Notes: STST, sit to stand test; LTOT, long-term oxygen therapy.

^* p < 0.05

^** p < 0.01.

Discussion

Physical^{Table 2, Table 3} inactivity has disastrous consequences for the lives of individuals with COPD and directly influences important outcomes such as quality of life, number of exacerbations and mortality (3). Some factors, such as a lack of infrastructure, intrinsic factors and social influences, are important barriers to increase PADL in individuals with COPD (29).

In this study we have shown an association between physical inactivity and daily duration of LTOT, fatigue and measures of functional and exercise capacity in individuals with COPD. Our results indicate that patients with longer daily duration of LTOT had reduced PADL. This may be explained by the fact that all our patients used an electric oxygen concentrator rather than a portable oxygen concentrator or refillable cylinders, which are expensive to refill and therefore not readily affordable by the study population. As median daily use of LTOT was 18 hours (Table 2), our patients were limited during most of the day by the length of the nasal cannula tubing to the concentrator, preventing them from going outside or even moving around the house.

There was a moderate, inverse correlation between fatigue and physical activity, and 90% of the study population (n = 35) reported fatigue during their daily activities (reflected in a total score ≥4 on the FSS). Although this correlation was also previously reported by Andersson et al. (30), further studies are required to determine whether there is a clear causal relationship between these variables. As with dyspnea, fatigue or tiredness is a limiting factor for physical activity and at the same time a result of deconditioning in these patients, forming a vicious circle (31).

Corroborating the findings of Hernandes et al. (32) and Miravitlles et al. (33), we found a relationship between PADL and functionality in individuals with COPD. Nevertheless, in this study functional status was not a predictor of PADL, probably because of the presence of other factors more closely related to daily physical activity, such as daily duration of LTOT.

The 6MST^{Table 4} and STST can objectively assess exercise capacity and correlate well with other tests in the literature (21, 24, 34). Both are easy to apply in a patient's home, where there is unlikely to be a corridor in which to carry out the 6-minute walk test. In addition, the 6MST and STST had a moderate, positive correlation with number of steps/day in our analysis. In the study by Depew et al. (27), only 42.2% of the patients were severely inactive. They showed that the number of repetitions in the STST was independently associated with PADL but could not predict severe inactivity in patients with COPD. In our study, both the result of the STST and daily time on LTOT were able to significantly explain severe physical inactivity in these individuals.

Hartman et al. (35) investigated possible physical and psychosocial factors associated with physical activity levels in COPD patients and found that physical activity was significantly lower in LTOT users. Although they did not specify the type of oxygen-supply equipment used, they observed that LTOT was also an independent predictor of more time spent in a sitting position by individuals with worse disease severity (severe and very severe).

No significant correlation between FEV₁ and number of steps/day was found in this study or in a study by Pitta et al. (36). This relationship is controversial, as some authors report a significant correlation, while others failed to find a correlation. This may be due to the different methods used to assess PADL and to the characteristics of the populations studied. Other spirometric variables, such as inspiratory capacity and maximum voluntary ventilation, appear to correlate better with PADL (36).

This study has several limitations. Although it is recommended that functional-capacity and exercise-capacity tests be repeated (37), these were only conducted once as patients reported feeling tired after the tests, which were performed during the same visit. Furthermore, as the study population consisted of individuals with COPD who were on LTOT with an oxygen concentrator, caution should be exercised when generalizing the results to other populations. Finally, PADL was not measured by accelerometry, the currently recommended method for objective assessment of this parameter, but with a pedometer; however, in terms of clinical practice, the latter is easier to use and more accessible (28).

In summary, longer daily duration of LTOT, fatigue, worse functional status and exercise capacity were all associated with physical inactivity in individuals with COPD on LTOT, whereas daily duration of LTOT and the results of the STST were determinants of reduced physical activity.

Declaration of interest statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.