This was a prospective, cross-sectional observational study that enrolled ILD patients ≥ 60 years of age from January 2020 to May 2021. Subjects gave their written, informed consent, and the study was approved by the Human Ethics Review Committee of Nagasaki University Hospital (approval number: 19121610).
Patients with ILD, including idiopathic interstitial pneumonias (IIPs), connective tissue disease-associated interstitial pneumonia, and hypersensitivity pneumonitis were recruited at the Department of Respiratory Medicine, Nagasaki University Hospital. Diagnostic criteria for IIPs and hypersensitivity pneumonitis were consistent with the International Consensus Statement. Subjects were included if they were under the care of a respiratory physician, were ambulant, and were clinically stable with no changes in medication for at least four weeks before enrollment. Exclusion criteria were comorbid conditions affecting exercise performance (e.g., musculoskeletal or neurological disorders, cardiac disease), severe cognitive impairment, pregnancy, recent thoracic surgery, and active cancer treatment.
The interstitial lung disease-gender, age and lung physiology (ILD-GAP) model was created by adding the ILD subtype variable to the original GAP model. The two lung physiology variables in this model include forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco). Points were assigned for each variable to obtain a total point score (range: 0–6). Demographic and clinical information including physical function, biochemistry of blood and pulmonary function test results were obtained from medical records.
The SARC-F Questionnaire, the SARC-CalF Questionnaire, and CalF
The SARC-F Questionnaire was used to measure probable sarcopenia. This questionnaire is composed of five items: strength, assistance in walking, rising from a chair, climbing stairs, and falls. The SARC-F scores range from 0 to 10, with 0 to 2 points for each component [scoring range: 0 (best) to 10 (worst)]. Patients with a total score ≥ 4 were classified as having a risk of sarcopenia. The SARC-CalF questionnaire is a combination of calf circumference and SARC-F, and a score of ≥ 11 points indicates probable sarcopenia. The maximum CalF was measured in a sitting position with hip and knee joint flexed at approximately 90°. CalF was measured at the point of the largest circumference. Calf < 34 cm for males and < 33 cm for females indicated sarcopenia. The CalF item is scored as 0 points if the CalF is > 34 cm for males and >33 cm for females and 10 points if the calf circumference is ≤ 34 cm for males and ≤33 cm for females.
Diagnostic Criteria for Sarcopenia
Since the participants were older Japanese patients, they were evaluated according to the AWGS 2019 criteria of sarcopenia. The diagnostic criteria for sarcopenia as used in AWGS 2019 is shown in figure 1. Estimation of sarcopenia at the first stage requires measurement by three screening methods: CalF, SARC-F and SARC-CalF. The second stage involves measurement of gait speed, grip strength, and muscle mass. Based on the AWGS 2019, low muscle strength is defined as handgrip strength < 28 kgf for males and < 18 kgf for females, while low physical performance is characterized as gait speed <1.0 m/s. In addition, body composition and skeletal muscle mass were evaluated in ILD patients using the bioelectrical impedance analysis (BIA) method (InBody 270, InBody Japan, Tokyo, Japan). Low muscle mass diagnosis was defined as skeletal muscle index (SMI) < 7.0 kg/m2 for males and < 5.7 kg/m2 for females.
Assessment of peripheral muscle force
Peripheral muscle force was evaluated via measurements of quadriceps and handgrip forces. Peak force developed during a maximal isometric knee extension was used as a measure of quadriceps force (QF). A hand-held dynamometer with a fixing belt (μ-Tas F-1; Anima Corporation, Tokyo, Japan) was used following a standard protocol. The QF for the dominant side was tested in the sitting position with the hip and knee joints flexed at approximately 90°. The handgrip force (HF) was assessed in the dominant hand using a dynamometer (T.K.K.5401; Takei-Kiki-Kogyou Corporation, Niigata, Japan). HF was tested in sitting position with the elbow flexed at 90° and the arms fixed to the body. The average value of three attempts was recorded.
The Short Physical Performance Battery (SPPB)
Physical performance was measured using the SPPB, which consists of three measures: walking speed, chair stands, and standing balance. A score from 0 (unable to complete the task) to 4 (best performance possible) was assigned to each measurement. The total score (0–12) was used to estimate overall physical performance level. Similar to previous studies[17-19], patients were separated into low physical performance-related risk (SPPB ≤ 9) or high physical performance-related risk (SPPB > 9).
Functional exercise capacity
The 6-minute walk test was performed based on published guidelines[20, 21]. The greater distance of two attempts was recorded. Oxygen saturation (SpO2) was monitored continuously throughout both tests (Konica Minolta Pulsox Me Oximeter, Osaka, Japan). If SpO2 decreased below 80%, the tests were terminated. Pre-exercise SpO2 and the lowest SpO2 during the tests were recorded.
Activities of daily living
Activities of daily living (ADL) were evaluated using the Kats basic ADL scale. The scale evaluates activities including feeding, ability to transfer, dressing, bathing, shopping and transportation. For each of the 6 activities, a score of 0 (dependent) or 1 (independent) was assigned. The sum of scores was used to obtain a measure of ADL performance.
Health-related quality of life
Health-related quality of life (HRQL) was evaluated using the King's Brief Interstitial Lung Disease (K-BILD) health status Japanese version questionnaire. The K-BILD is an ILD-specific HRQL questionnaire that measures health impairment. It is comprised of 15 items in three domains: breathlessness and activities, chest symptoms, and a psychological health. The K-BILD score ranged from 0 to 100, where higher values indicated better health.
Baseline characteristics were summarized with frequencies and percentages for categorical data, while means and standard deviations for continuous data. The Shapiro-Wilk test was used to examine data distribution. Comparisons between male and female groups were made with unpaired t-tests, Mann-Whitney U tests, or Fisher's exact test. To evaluate the accuracy of screening by SARC-F, the SARC-CalF, and CalF, sensitivity, specificity, positive predictive value (PV+) and negative predictive value (PV-) were calculated for each screening method. The gold standard for calculating sensitivity and specificity was set at AWGS 2019 criteria. ILD-GAP model was used to evaluate the applicability of the three screening methods to ILD patients. To compare the accuracy among the screening tools, receiver operating characteristic curves (ROC) were constructed and area under ROC curves (AUC) were calculated. ROC and AUC were analyzed as categorical data of the 3 screening methods. The level of significance was 0.05 for all statistical tests. All statistical analyses were performed using JMP 15.0 software (SAS Institute Japan, Tokyo, Japan).