The 1-minute sit-to-stand test to detect desaturation during 6-minute walk test in interstitial lung disease.

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT.

Introduction

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that encompass a large and varied range of conditions[1,2]. In some patients with chronic fibrotic ILDs, a progressive phenotype is comparable to that observed in idiopathic pulmonary fibrosis (IPF), including worsening respiratory symptoms, a decline in lung function, decreased quality of life, and early mortality despite conventional treatment[2,3]. These fibrotic ILDs have recently been termed “progressive fibrosing ILDs” (PF-ILDs)[4]. Predicting the prognosis of patients with ILDs is not only becoming increasingly crucial, but it is also challenging for clinicians.

Although hypoxemia is often absent at rest in patients with ILD, exertional desaturation is more likely seen even in ILD patients with normal oxygen levels at rest[5,6]. For patients with idiopathic interstitial pneumonia (IIP), oxygen desaturation during the 6 min walk test (6MWT) was a strong predictor for mortality[7]. Even in IPF patients with the preserved resting arterial partial pressure of oxygen (PaO2), the presence of exertional desaturation during the 6MWT was a significant prognostic factor for poor survival[8]. The international guidelines recommend that exercise-induced desaturation should be assessed in most patients with ILD as an important prognostic indicator[9]. In Japan, desaturation on 6MWT is included in the disease severity staging system for IIPs[10]. Moreover, the serial 6MWT measurements at certain intervals were proposed as a criterion that may be used in clinical practice to assess disease progression in PF-ILDs[11].

The 6MWT is a well-established assessment of exercise tolerance and exercise-induced desaturation in various chronic lung diseases[12]. However, the 6MWT is time-consuming and requires a 30 m corridor[12], which is not common in primary care settings or clinical settings. In fact, even the Swedish IPF Registry, which was implemented in 22 respiratory medicine units across Sweden, reported that only 56% of patients underwent 6MWT[13]. Therefore, a simple exercise tolerance test is needed not only for general practitioners (GPs) but also for pulmonologists. To overcome these spatial and technical limitations, several alternative exercise tests, such as the 1 min sit-to-stand test (1STST), have recently been evaluated[14]. The 1STST requires only a chair and is easily applicable in a small amount of time, making it feasible for use in the primary healthcare setting. In patients with ILD, nadir desaturation during the 1STST was correlated with nadir desaturation during 6MWT[15,16]. However, little is known about 1STST reliability as an alternative tool to the 6MWT in ILD patients with normal resting blood oxygen levels. Therefore, this study aimed to evaluate the usefulness of the 1STST for assessing exertional desaturation in ILD patients with normal resting blood oxygen levels.

Methods

Study patients

We retrospectively collected the data of ILD patients with normal resting blood oxygen levels who underwent both 6MWT and 1STST within 1 month at Yamaguchi University Hospital and National Hospital Organization Yamaguchi-Ube Medical Center from October 2020 to May 2021. Normal resting blood oxygen levels were defined as PaO2 ≥ 80 Torr, and if PaO2 was not performed, SpO2 ≥ 96% was substituted. ILD diagnoses were based on a multidisciplinary discussion. IPF was diagnosed according to the 2018 Clinical Practice Guidelines[17]. IIPs other than IPF were diagnosed based on the 2013 Official Statement of the American Thoracic Society (ATS)/European Respiratory Society (ERS)[1]. CTD-ILD patients fulfilled standard criteria[18-22]. Patients with HP sarcoidosis, and PAP were diagnosed according to the respective criteria[23-25]. The study protocol and its amendments were approved by the ethics committee of the Yamaguchi Medical University (Institutional Review Board number. 2021-057). The requirement for informed consent was waived by the ethics committee because no invasive procedures, interventions, or human samples were used in this retrospective study, and anonymity was secured. This study was compliant with the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects[26], which do not require informed consent from patients enrolled in studies that did not utilize human biological specimens. However, we provided opportunities to the participants to opt out of the study by announcing the study information on the bulletin boards in the hospital and the hospital website.

Study assessments

Medical records were used to collect data on baseline demographic information. Pulmonary function tests within 3 months of the date of 1STST were also performed. According to the ATS/ERS recommendations, pulmonary function was assessed using the CHESTAC-8800 DN type (Chest Ltd., Tokyo, Japan)[27]. Disease severity was assessed using the sex, age, and physiology (GAP) staging system[28] and the Japanese Respiratory Society (JRS) severity grading[29] based on the PaO2 at rest and minimum SpO2 during the 6MWT. In addition, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and mMRC dyspnea grades were assessed by the physicians at the time of the 1STST. The ECOG PS is a scale used to assess how a patient’s disease is progressing and how the disease affects the daily living abilities of the patient[30]. It is comprised of five conditions (0 = “normal activity,” 1 = “some symptoms, but no bed rest during daytime,” 2 = “bed rest for less than 50% of daytime,” 3 = “bed rest for more than 50% of daytime,” 4 = “unable to get out of bed”), and good PS was defined as ECOG PS 0 or 1. The mMRC scale comprises five categories that describe the extent of respiratory disability from no disability to almost complete incapacity[31], and good mMRC was defined as mMRC 0 or 1.

The 6MWT was performed following the international recommendation[12]. In brief, the test was performed on a marked 30 m indoor corridor, and the patients were asked to walk as far as possible within 6 min. The walking distance was recorded at the end of the test. Participants were allowed to take breaks during the test, if necessary. Before and after the test, SpO2 and pulse rate were measured using a pulse oximeter. Desaturation was defined as an SpO2 < 90%[8].

The 1STST was performed using a standardized protocol with a standard height chair (46 cm) without armrests positioned against a wall[15,16,32,33]. The test was first demonstrated by the physician and then performed by the patients. The patients were seated upright on a chair with their knees and hips flexed at 90°, feet placed flat on the floor, and their upper limbs folded across the chest without using the hands or arms to assist movement. Patients were asked to perform repetitions of standing upright and then sitting down in the same position at a self-paced motion (safe and comfortable) for as many repetitions as possible in 1 min. Participants were informed of the time when 15 s had remained, but no encouragement was provided during the test. The number of completed repetitions was manually recorded. Measurements of SpO2 and pulse rate were performed before and after the 1STST using the same assessment tools as for the 6MWT. Desaturation was defined as SpO2 < 90%.

Statistical analysis

Although no a priori sample size calculation was conducted, a convenience sample of participants was selected based on a previous study[15]. Data are shown as median (interquartile range). Spearman’s rank-order correlation coefficient was used to determine the correlation between the two variables. A Bland-Altman analysis was performed to graphically examine the limits of agreement between the minimum SpO2 in the 6MWT and 1STST. Agreement between the ability of the two exercise tests to detect desaturation was assessed using Cohen’s kappa (κ) index. The magnitude of the κ coefficient, which ranges from 0 (without concordance) to 1 (maximum concordance), is usually interpreted as follows: poor (<0.20), weak (0.21–0.40), moderate (0.41–0.60 and), good (0.61–0.80), and very good (0.81–1.00)[34]. Using a receiver operating characteristic (ROC) curve, we determined the cutoff points for identifying the predictive factors for desaturation during the 6MWT. The accuracy of each predictive factor was assessed using the area under the ROC curve (AUC). A p-value of less than 0.05 was considered statistically significant. Statistical analyses were performed using JMP Pro ® (version 15.0.0; SAS Institute Inc., Cary, NC, USA).

Table 1

Clinical characteristics of the study participants.

Variable	Value
Age (years)	72 (64–78)
Sex male	64 (55.2)
Body mass index	23.1 (20.8–24.9)
Smoking status (never/ex/current)	51/61/4 (44.0/52.6/3.4)
Pack years	12.8 (0–36.8)
Underlying disease
IPF/IIPs other than IPF/CTD-ILD/HP/Sarcoidosis/PAP	53/18/38/5/1/1 (45.7/15.5/32.8/4.3/0.9/0.9)
Comorbidities
COPD	17 (14.7)
Asthma	13 (11.2)
Heart failure	10 (8.6)
Diabetes mellitus	20 (17.2)
Performance status (0/1/2/3/4)	27/76/13/0/0 (23.3/65.5/11.2/0.0/0.0)
mMRC scale (0/1/2/3/4)	17/64/30/5/0 (14.7/55.2/25.9/4.3/0.0)
Medication
Use of antifibrotic agents	25 (21.6)
Use of corticosteroid	40 (34.5)
Use of immunosuppressive drugs	23 (19.8)
Use of inhaled corticosteroid	14 (12.1)
Use of bronchodilators	23 (19.8)
PaO2 at rest (Torr)	90.0 (83.8−95.1)
FVC (% predicted)	85.7 (74.5−100.1)
FEV1/FVC ratio (%)	82.1 (77.2–86.3)
DLCO (% predicted)	67.4 (56.7−81.4)
GAP index (points)	3 (2–3)
GAP grade (I/II/III)	94/20/2 (81.0/17.2/1.7)
6MWT
Distance (m)	420 (353−479)
Baseline SpO2 (%)	97 (96−98)
Nadir SpO2 (%)	91 (86−94)
Heart rate, pre-test (bpm)	80 (70−87)
Heart rate, post-test (bpm)	113 (99−127)
1STST
Repetitions (no.)	26 (21−30)
Baseline SpO2 (%)	97 (97−98)
Nadir SpO2 (%)	93 (88−95)
Heart rate, pre-test (bpm)	80 (70−87)
Heart rate, post-test (bpm)	108 (91−119)

Data are presented as median (interquartile range) or number (%).

IPF idiopathic pulmonary fibrosis, IIPs idiopathic interstitial pneumonia, CTD-ILD collagen tissue disease-associated interstitial lung disease, HP hypersensitivity pneumonitis, PAP autoimmune pulmonary alveolar proteinosis, mMRC modified Medical Research Council, PaO2 arterial partial pressure of oxygen, 1STST 1 min sit-to-stand test, 6MWT 6 min walk test, bpm beats per minute, FVC forced vital capacity, DLCO diffusion lung capacity for carbon monoxide, SpO arterial blood hemoglobin saturation.

Table 2

Oxygen desaturation during 1STST and 6MWT.

	Nadir SpO2 < 90% in the 6MWT
Nadir SpO2 < 90% in the 1STST	Yes	No
Yes	41 (35.3)	0 (0.0)
No	10 (8.6)	65 (56.0)

Data are presented as numbers (%).

1STST 1 min sit-to-stand test, 6MWT 6 min walk test, SpO pulse oxygen saturation.

Table 3

Diagnostic ability to identify desaturation during 6MWT in all patients.

	AUC (95% CI)	Sensitivity	Specificity	Cutoff value
1STST nadir SpO2	0.94 (0.86–0.98)	92%	91%	92%
FVC % predicted	0.69 (0.59–0.78)	61%	77%	80.1
DLCO % predicted	0.86 (0.77–0.91)	80%	82%	66.0
PaO2 at rest	0.60 (0.47–0.71)	66%	67%	89.2 Torr

SpO pulse oxygen saturation, PaO2 arterial partial pressure of oxygen, 1STST 1 min sit-to-stand test, 6MWT 6 min walk test, FVC forced vital capacity, DLCO diffusion lung capacity for carbon monoxide, AUC area under the curve, CI confidence interval.