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Corresponding author. Interstitial Lung Disease Program, National Jewish Health, Southside Building, Office #G011, 1400 Jackson Street, Denver, CO 80206, USA.
Patients with interstitial lung disease often require supplemental oxygen.
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When patients with ILD carry their portable oxygen, they perceive greater dyspnea and walk shorter distances.
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Costs associated with carrying oxygen include greater dyspnea and less distance covered.
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More functionally impaired patients with ILD appear to be affected most.
Abstract
Background
May patients with interstitial lung disease (ILD) require supplementary oxygen (O2) therapy to maintain normoxia. However, ambulatory O2 delivery devices are constraining and cumbersome. The physiologic and symptomatic impact of these devices on ILD patients is unknown.
Methods
We conducted a prospective study of 30 clinically stable ILD patients (with varying disease severity), half of whom used O2 at baseline. Each subject completed two six-minute walk tests (6MWTs); for O2 users, one walk was completed while wearing a backpack (weight 7.2 pounds) containing a tank with compressed O2, and for non-users, one walk was completed with a similarly-weighted backpack. For each subject, during the second walk, no backpack was worn; for the second walk, O2 users received oxygen via a stationary delivery system. For both walks, O2 non-users wore a portable metabolic system, which measured variables related to respiratory physiology and gas exchange. Borg dyspnea and exertion ratings were recorded after each walk.
Results
Wearing the O2-containing backpack resulted in decreased distance covered during the 6MWT, and increased dyspnea and perceived exertion among O2 users. While wearing the weighted backpack, O2 non-users had a significantly lower peripheral O2 saturation and distance-saturation product. Compared with carrying O2 in the backpack, receiving O2 via the stationary concentrator resulted in the largest improvement in walk distance for the three subjects with greatest impairment at baseline (6MWT ≤ 300 m).
Conclusion
Among ILD patients, carrying portable O2 versus receiving O2 via a stationary concentrator results in significantly greater dyspnea and shorter distances covered in timed testing. Patients with the greatest impairment may be affected most. When prescribing O2, practitioners should alert patients to this effect and help patients decide on the best O2 delivery mode to meet their needs.
The interstitial lung diseases (ILD) are a heterogenous group of disorders with known causes, including autoimmune disease and repeated exposure to aerosolized, organic antigens. In many patients, an exhaustive search for cause is unrevealing, and thus, their ILD is idiopathic. Regardless of etiology, ILD may cause hypoxemia, and many patients require the use of supplemental oxygen (O2) to maintain normoxia.
In patients with chronic cardiac or pulmonary conditions, long-term, ambulatory O2 therapy is prescribed with the intent of halting progression or preventing the development of hypoxia-induced pulmonary hypertension, cardiovascular morbidity, or cognitive dysfunction – and in hopes of improving symptoms and quality of life.
], data suggest many patients with ILD benefit from using O2: in lab-based tests, O2 is associated with decreased dyspnea or increased distance covered during a timed walk test [
]: patients are physically constrained by oxygen delivery equipment; portable oxygen concentrators (POCs) do not generate high enough flows for many patients; air travel is impossible for patients who are unable to use POCs; and patients feel stigmatized when seen wearing their oxygen cannula in public [
In addition, when away from home, patients must carry, pull, or push their oxygen delivery devices that typically weigh between 8 and 10 pounds. Intuition and very limited data from patients with chronic obstructive pulmonary disease (COPD) would suggest carrying an O2 delivery device affects physical functioning and symptoms [
]. Compared to patients with COPD, patients with similarly severe ILD desaturate more frequently and profoundly, so O2 may be more critically important for them [
We were curious how the added weight of carrying O2 might affect dyspnea and physiological variables during physical activity in patients with ILD. We hypothesized that during a timed walk test, patients who used O2 while exerting would perceive greater dyspnea and cover less distance when carrying their O2 versus receiving it from a stationary concentrator, and that patients who do not use O2 while exerting would perceive greater dyspnea, expend more energy and cover less distance when wearing, versus not wearing, a weighted backpack meant to simulate an O2 delivery device.
2. Methods
2.1 Recruitment
Regardless of disease severity, consecutive, clinically stable patients with ILD who received routine care in the ILD Program at National Jewish Health (NJH), did not use a walk assist device (e.g., cane, walker), and had no musculoskeletal (e.g., ankle sprain, sciatica, active synovitis) or other health problems (e.g., angina) that would preclude them performing two 6-min walk tests (6MWT) in the same day were recruited to participate. We enrolled 30 subjects into this prospective study: 15 subjects who were currently using long-term, ambulatory O2 (continuous or with exertion only, heretofore referred to as O2 users) and 15 subjects who did not need ambulatory O2 (O2 non-users). This sample size was chosen to allow for a small confidence interval around the correlation between distance covered during the 6MWT and Borg dyspnea rating.
The diagnosis of ILD and the decision to prescribe O2 had been made by each subject's treating physician in the NJH ILD Program, in the context of clinical care and in accordance with accepted standards and criteria. The study was approved by the NJH Institutional Review Board (HS-2955). Informed consent was obtained in-person, in a private room on the NJH campus. After consent was obtained, subjects were scheduled to perform study testing within two weeks. All subjects were reminded to wear comfortable shoes and clothing for their day of testing. The most recent physiological variables (forced vital capacity and diffusing capacity of the lung for carbon monoxide or FVC and DLCO) were extracted from subjects' records. Except for DLCO in two subjects (whose data are not included in certain analyses), all FVCs and DLCOs had been performed within eight weeks – and most within four – of the day the walks were performed.
2.2 6MWT procedure
Each subject completed two 6MWTs on the same back-and-forth track in a hallway, and all walks were performed while strictly following American Thoracic Society guidelines for monitoring and encouragement. After each walk, each subject was asked to rate their shortness of breath and perceived exertion on a Borg scale. Two 6MWTs were completed by each subject, 1 h apart, on the same day, and in random order established by the flip of a coin (Fig. 1). Subjects were seated for 10 min of rest prior to the start of each 6MWT.
Fig. 1Methods of two separate walks performed by O2 users and O2 non-users.
For O2 users, O2 was delivered at their physician-prescribed flow for each walk. One walk was performed while they carried a tank of compressed O2 gas (D tank) in a backpack, and one walk was performed while they received O2 from a stationary concentrator situated at mid-track. Prior to the study, O2 output and flow was confirmed to be equivalent between the tank and the concentrator when placed on the same settings. The D tank was weighed before each subject walked, and weight was added to the backpack as needed to ensure the weight was 7.2 pounds for each walk.
For O2 non-users, both walks were performed while they wore a wearable metabolic system (K4b2; Cosmed; Rome, Italy). Prior to each walk, the system was calibrated according to the manufacturer's directions. After each walk, the data were downloaded onto the research computer. One walk was performed while they carried a 7.2-pound weight in the same backpack worn by O2 users, and one walk was performed without wearing the weighted backpack.
2.3 Statistical analysis
Summary statistics were generated for baseline characteristics. Paired t tests were used to compare continuous outcomes between walks for the cohort as a whole (when the backpack was worn vs. not worn) and within and between subgroups, O2 users and O2 non-users. Pearson correlation was used to examine pairwise associations between variables. All analyses were performed using SAS version 9.3 (SAS, Inc.; Cary, NC).
To account for distance walked and either oxygen saturation or dyspnea, we calculated two statistics used for between-walks comparisons: the Distance-Saturation Product (6MWD x nadir peripheral oxygen saturation [SpO2] [
]) and what we call the Dyspnea Distance index (calculated as 6MWD x ((10 – Borg dyspnea rating)/10). Each “adjusts” distance walked by either SpO2 or dyspnea rating by “penalizing” distance for lower saturation or greater dyspnea. These variables allow more valid comparisons between two walks when there are differences between walks in distance, SpO2 and/or dyspnea.
3. Results
3.1 Baseline characteristics
Baseline characteristics of the cohort are displayed in Table 1. Most had either connective tissue disease-related pulmonary fibrosis (CTD-PF, N = 11) or idiopathic pulmonary fibrosis (IPF, N = 11). Although not statitistically significant, O2 users were older and heavier.
Table 1Characteristics of cohort.
Entire cohort N = 30
No O2 N = 15
O2 N = 15
P for difference
Male, n (%)
14 (47)
8 (53)
6 (40)
0.46
Age, years
68.7 ± 7.1
66.5 ± 7.7
70.7 ± 6.0
0.11
Weight, kg
84.3 ± 13.7
82.7 ± 14.5
85.9 ± 13.1
0.53
Diagnosis
CHP
1
1
0
0.70 for IPF
CPFE
2
0
2
CTD-PF
11
7
4
FPF
4
1
3
IfNSIP
1
0
1
IPF
11
6
5
Medications
None
7
5
2
Mycophenolate mofetil
9
4
5
Nintedanib
6
3
3
Pirfenidone
3
0
3
Prednisone
2
1
1
Rituximab
3
2
1
Supplemental O2
With exertion (range with exertion)
15 (2-8L/min)
N/A
15 (2-8L/min)
Continuous (range at rest)
11 (1-4L/min)
11 (1-4L/min)
FVC%
78.7 ± 10.7
81.0 ± 9.2
76.3 ± 11.8
0.24
DLCO%*
62.5 ± 14.8
67.9 ± 16.8
57.1 ± 10.4
0.04
CHP, chronic hypersensitivity pneumonitis; CPFE, combined pulmonary fibrosis and emphysema; CTD-PF, connective tissue disease pulmonary fibrosis; FPF, familial pulmonary fibrosis; lfNSIP, non-specific interstitial pneumonia; IPF, idiopathic pulmonary fibrosis; FVC, forced vital capacity; and DLCO, diffusion capacity of the lungs for carbon monoxide; *N = 13.
Compared with walks performed when subjects did not wear the O2- or weight-containing backpack, the mean distance covered during the 6MWT when the backpack was worn was significantly shorter; also, dyspnea and perceived exertion were significantly greater (Table 2); and the Dyspnea Distance index and Distance-saturation product were significantly lower (Fig. 2, panels A and B).
Table 2Results of six-minute walk test.
Outcome
Stationary Concentrator O2/No Backpack
Carry O2/Backpack
Difference, p
Walk Distance, m
434.2 ± 67.7
426.4 ± 72.0
7.8 ± 15.9, p = 0.01
Borg Dyspnea
2.2 ± 1.8
2.7 ± 1.8
−0.5 ± 1.1, p = 0.02
Borg Exertion
2.5 ± 1.6
2.9 ± 1.6
−0.4 ± 1.1, p = 0.04
Nadir SpO2
85.4 ± 3.7
84.9 ± 5.1
0.6 ± 3.3, p = 0.36
SpO2 drop
5.9 ± 4.0
7.0 ± 5.4
−1.1 ± 3.8, p = 0.13
Distance-saturation
371.3 ± 62.9
362.4 ± 69.1
8.9 ± 20.4, p = 0.02
Distance Dyspnea
336.2 ± 92.7
311.9 ± 93.6
24.3 ± 53.2, p = 0.01
m, meters.
SpO2, oxygen saturation as measured by finger pulse oximetry.
Fig. 2Plots of distance covered and dyspnea-adjusted distance (i.e., Dyspnea Distance) during the walks performed under the two different testing circumstances.
O2users. Compared to when O2 was carried in the backpack, when O2 was delivered via the stationary concentrator, O2 users walked significantly farther and had less dyspnea (Table 3). There were three subjects whose baseline walk distance was ≤300 m; for them, when O2 was delivered via the stationary concentrator, their walk distances improved by 39.2, 39.9 and 44.3 m (Fig. 2), and their dyspnea decreased by 1, 1 and 3 points, respectively. In only one other subject, also an O2 user, did walk distance improve by 30 m or more, but their baseline walk distance was >300 m. There was no difference in outcomes between users who needed O2 at rest vs. those who needed O2 only with exertion (data not shown).
Table 3For subjects who had been prescribed and used O2 during both walks, results when carrying O2 in backpack or receiving O2 via stationary concentrator.
Outcome
O2 via Concentrator
O2 via Backpack
Difference, p
Walk Distance
418.2 ± 84.1
407.1 ± 90.8
11.0 ± 18.8, p = 0.03
Borg Dyspnea
2.2 ± 1.9
3.0 ± 2.0
−0.8 ± 1.3, p = 0.02
Borg Exertion
3.0 ± 1.4
3.5 ± 1.3
−0.5 ± 1.2, p = 0.15
Nadir SpO2
86.7 ± 3.8
87.7 ± 4.8
−1.0 ± 3.6, p = 0.30
SpO2 drop
5.3 ± 4.7
4.9 ± 5.2
0.4 ± 3.9, p = 0.70
Distance-saturation
363.3.3 ± 79.4
359.0 ± 91.7
4.3 ± 26.0, p = 0.53
Distance Dyspnea
325.3 ± 104.1
285.3 ± 103.7
40.5 ± 57.6, p = 0.01
SpO2, oxygen saturation as measured by finger pulse oximetry.
O2non-users. Compared to when the backpack was worn, when no backpack was worn, non-users’ nadir SpO2 and distance-saturation product were significantly greater (Table 4).
Table 4For subjects who had not been prescribed and did not use O2 during either walk, results when wearing or not wearing weighted backpack.
Outcome
No Backpack
Backpack
Difference, p
Walk Distance
453.8 ± 42.6
445.7 ± 41.5
4.6 ± 12.1, p = 0.17
Borg Dyspnea
2.3 ± 1.8
2.4 ± 1.6
−0.1 ± 0.9, p = 0.59
Borg Exertion
1.9 ± 1.6
2.3 ± 1.7
−0.4 ± 1.1, p = 0.17
Nadir SpO2
84.2 ± 3.4
82.1 ± 5.1
2.1 ± 2.2, p = 0.0019
SpO2 drop
6.6 ± 3.3
9.1 ± 4.9
−2.5 ± 3.2, p = 0.008
Distance-saturation
379.3 ± 42.1
365.8 ± 38.4
13.6 ± 11.7, p = 0.0005
Dyspnea Distance
346.5 ± 82.2
338.5 ± 76.8
8.0 ± 44.6, p = 0.50
VO2, ml/kg/minute
14.5 ± 4.3
14.0 ± 2.9
0.4 ± 2.6, p = 0.52
VO2%
69.7 ± 22.7
69.4 ± 21.1
0.3 ± 12.4, p = 0.93
VE liters/minute
43.2 ± 11.3
44.5 ± 10.3
−1.3 ± 3.7, p = 0.20
RR
31.0 ± 7.7
31.6 ± 7.8
−0.6 ± 2.2, p = 0.34
Vt, liters
1.5 ± 0.4
1.5 ± 0.3
0.0 ± 0.1, p = 0.98
VE/VO2
37.4 ± 7.2
39.6 ± 10.2
−2.3 ± 5.7, p = 0.15
VE/VCO2
42.6 ± 7.0
44.0 ± 9.5
−1.5 ± 4.7, p = 0.25
METS
4.1 ± 1.2
4.0 ± 0.8
0.1 ± 0.8, p = 0.52
EE, kcal
29.0 ± 6.8
29.0 ± 6.4
0.0 ± 3.3, p = 0.97
SpO2, oxygen saturation as measured by finger pulse oximetry.
VO2, maximum rate of oxygen consumption measured.
VO2%, percent of predicted maximum rate of oxygen consumption.
VE, pulmonary ventilation.
RR, respiratory rate.
Vt, tidal volume.
VE/VO2, ventilatory equivalent ratio for oxygen.
VE/VCO2, ventilatory equivalent ratio for carbon dioxide.
METS, metabolic equivalent or oxygen uptake as measured in milliliters per kilogram per minute.
Table 5 shows pairwise correlations among disease severity, 6MWT and exercise physiology variables. Among all variables assessed, dyspnea correlated only with body weight.
Table 5Correlation among variables collected when subjects wore backpack containing O2 or weights.
In this study, we examined the impact of carrying O2 on symptoms and functional capacity in patients with ILD. We observed that when subjects carried O2 (or for subjects who did not need O2, when they carried a weighted backpack), they experienced greater dyspnea and covered less distance during a timed walk test compared to when they did not carry the backpack.
To our knowledge, this is the first study to examine this topic in patients with ILD. Woodcock, Gross and Geddes studied 10 subjects with severe COPD (FEV1 = 0.71 ± 0.29 L, percent predicted not reported); these investigators found that compared to when subjects carried their O2 themselves, when O2 was carried for them, subjects walked a mean 15 m farther, and their dyspnea scores were 1.1 points lower [
]. In two studies of a total of 100 subjects with severe COPD (weighted average percent predicted FEV1 = 43.3), Crisafulli and his colleagues observed similar results: compared with carrying their O2, when subjects pulled a trolley that contained their O2 source, they walked a weighted average 23.6 m farther and experienced less dyspnea (weighted average Borg 1.5 points lower) [
The differences we observed in distance covered and dyspnea were not as large as in any of these three studies, but the lung disease was not nearly as severe in our subjects who, on average had mild or mild-moderate ILD (compared with severe or very severe COPD in those studies). In a subgroup analysis [
], Crisafulli and colleagues observed that the most impaired COPD patients appeared to have the most to gain: among the 37 subjects whose baseline walk distance was ≤300 m, dyspnea (4.0 points vs. 6.0 points, p = 0.001) and distance (213 points vs. 256 points, p = 0.001) both improved. In contrast, among the 23 subjects whose walk distance was >300 m, although dyspnea was less when they pulled (versus carried) the trolley, walk distance was not significantly different (pull O2 trolley: 340 m vs. carry O2 trolley: 349 m, p = 0.15) – nor were other parameters, such as nadir SpO2 or drop in SpO2 from baseline. Only three subjects in our cohort walked ≤300 m at baseline, but they showed the greatest improvement in distance when O2 was delivered via stationary concentrator (versus carrying it in the backpack).
In a recently published study, Du Plessis and colleagues observed that while adjusting for disease severity, patients with fibrotic ILD desaturated to a greater degree than patients with COPD (decrease in SpO2 from baseline 7.4 ± 5.2 in fibrotic ILD vs 4.5 ± 3.7 in COPD), particularly at lower DLCO values [
]. Taken together, those data and results from our study suggest that patients with more severe ILD have a high likelihood for oxygen desaturation, and those with the greatest baseline impairments in physical functional capacity may stand to benefit most by not having to carry their O2 delivery devices.
We had hypothesized that wearing the backpack would lead to chest constriction and decreased tidal volume, with higher respiratory rate and subsequently greater dyspnea. However, among O2 non-users, although performing the 6MWT while wearing the weighted backpack led to a greater decline from baseline in SpO2, it had no significant effect on distance walked, dyspnea or the Dyspnea Distance index. Additionally, neither oxygen uptake nor any of the ventilatory variables collected from the metabolic system (e.g., tidal volume or respiratory rate) were different between the two walks. Obviously, the Dyspnea Distance index is not a validated metric; however, akin to the distance-desaturation product, it can be used clinically to help decipher change in functional status when walk distance and post-walk dyspnea have both changed in the same direction from a prior visit (e.g., when distance and dyspnea are both greater or both less than the last walk performed). Additional research is required to determine the utility of the Dyspnea Distance index.
Although there is little doubt certain patients with ILD who desaturate at rest or with exertion perceive (and truly derive [
]. Prescribers want O2 to improve their patients' symptoms, and it often does. Khor and her colleagues revealed patients may notice several improvements associated with using O2 – like feeling stronger, noticing less uncomfortable heart pounding, and coughing less – but they may not perceive less shortness of breath per se [
]. Whether that is because with O2 they are more active (and physiologically, may achieve more work but experience the same degree of breathless as before O2) is unclear. The Dyspnea Distance index may help sort that out. What is clear is beside the potential benefits, O2 brings challenges to patients and other members of their homes, and prescribers should make sure patients who need O2 know about them [
Our study shows there is a cost associated with carrying O2: on balance, slightly increased dyspnea, slightly shorter distance covered per unit time and slightly lower SpO2. The increased dyspnea and shorter distance are less than the minimum clinically important difference for the Borg scale (one point [
] (about 30 m) respectively, so for the average patient, for a 7–8 pound O2 delivery system, the cost is insignificant. However, our data suggest that for the more functionally impaired patient (e.g., ones whose 6MWD is ≤ 300 m), the cost is likely to be significant. Nonetheless, as ambulatory patients with ILD consider whether O2 is “right” for them, they will have to weigh the cost and benefits through the lens of their own values and judgments. Those O2 users who want (or need) to leave home will have to pull or carry their O2 delivery devices; those who do not want to deal with pulling a trolley around with them can choose to carry their delivery device in a backpack. Depending on their disease severity, doing so could noticeably slow them down and increase dyspnea.
Limitations of this study include a relatively small cohort. Despite the numbers, we observed significant differences. Most patients in this study had mild to moderate disease, and additional research is needed to determine whether the results we observed hold for patients with more severe disease and/or greater functional impairments. Study methods necessitated that subjects were aware of when they were and were not carrying additional weight in the form of portable O2 or a weighted backpack; this may have introduced bias. The stationary concentrator we used for this study had a maximum flow of 10 L/min; some patients may not have access to concentrators that deliver more than 5 L/min. Although we tested only one delivery set up, we strongly suspect the differences we observed would be magnified (and be even more clinically relevant) with heavier portable deliver devices.
5. Conclusion
Among patients with ILD, carrying O2 leads to increased dyspnea and shorter distance covered during a time walked test, effects that appear to be magnified in patients who are more functionally impaired at baseline. Future research should look to confirm and extend these findings for heavier delivery devices as well as in ILD patients with low and very low physical functional capacity and to identify practical, non-constraining ways in which ILD patients can receive O2.
Author statement
The authors have no competing interests to declare.
Funding
None.
Author contributions
Study conceptualization.and design: MR, TC, AO, JJS.
Data collection: MR, TC, AO.
Statistical analysis: JJS.
Interpretation of results: DR, MR, BG, TC, ALO, JJS.
Manuscript preparation: DR, MR, BG, TC, ALO, JJS.
Approval of final version of the manuscript: DR, MR, BG, TC, ALO, JJS.
Ultimately responsible for content of manuscript as presented: JJS.
References
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