Diaphragm assessment by multimodal ultrasound imaging in patients with interstitial lung disease: a prospective observational study
Highlight box
Key findings
• Multimodal ultrasound effectively evaluates diaphragmatic function in patients with interstitial lung disease (ILD). ILD patients exhibit diaphragmatic structural and functional abnormalities (thickening, reduced contractility/excursion, increased activation) that correlate with disease severity.
What is known and what is new?
• The dyspnea experienced by patients with ILD is partly attributable to diaphragmatic dysfunction. However, similar studies using ultrasound to assess diaphragmatic function in patients with ILD remain scarce. Tissue Doppler imaging (TDI) has not yet been applied to the quantitative assessment of diaphragmatic motion in this patient population.
• This study is the first to use TDI for diaphragmatic motion assessment in ILD, detecting ILD-related diaphragmatic changes compared with healthy controls. Diaphragmatic ultrasound parameters in ILD patients correlate with several clinical indicators, including pulmonary function test results, St George’s Respiratory Questionnaire scores, and modified Medical Research Council Dyspnoea Scale grades.
What is the implication, and what should change now?
• As a non-invasive, simple tool, diaphragmatic ultrasound parameters correlate with clinical indicators of ILD severity, which may indirectly reflect patients’ respiratory function. Its clinical utility for guiding drug interventions or pulmonary rehabilitation requires prospective validation with larger cohorts.
Introduction
Interstitial lung disease (ILD) is a restrictive pulmonary disease characterized by impaired lung expansion and reduced total lung capacity (TLC) (1). Most patients with ILD present with predominant clinical manifestations, including cough, progressively worsening dyspnoea, impaired lung function, and reduced exercise tolerance (2). Recent research has demonstrated that dyspnoea and impaired exercise capacity in these patients are at least partially associated with respiratory muscle dysfunction—particularly dysfunction of the diaphragm (3,4).
The diaphragm, the primary inspiratory muscle, accounts for 60–80% of respiratory work at rest. Diaphragm elevation causes traction in restrictive lung disease. This elevation induces diaphragmatic overload, ultimately leading to diaphragmatic fatigue and dyspnoea (3,5). Concurrently, multiple factors in patients with ILD—including hypoxaemia, systemic inflammation, glucocorticoid use, reduced physical activity, and malnutrition—further impair diaphragmatic structure and function (6). Evaluating diaphragm function is crucial for ILD patients. Current methods for assessing diaphragmatic function primarily include transdiaphragmatic pressure (Pdi) measurement, electrophysiological testing, chest X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound. Transdiaphragmatic pressure is considered the gold standard for evaluating diaphragmatic function; however, its invasiveness and operational complexity limit its clinical applicability. Electrophysiological testing is also invasive and requires high technical expertise. Chest X-ray and CT involve ionizing radiation, precluding short-term repeated use. In contrast, diaphragmatic ultrasound is a radiation-free, easy-to-perform, and readily repeatable assessment tool that enables real-time dynamic visualization of diaphragmatic motion. Currently, B-mode and M-mode ultrasound are commonly used to evaluate diaphragmatic thickness and mobility, and these modalities have been widely applied in patients with chronic obstructive pulmonary disease (COPD) and critically ill individuals in recent years (7).
Previous research has shown that diaphragmatic mobility is altered in patients with idiopathic pulmonary fibrosis (a subtype of ILD) compared with healthy individuals, and this alteration strongly correlates with pulmonary function parameters and clinical indicators (e.g., the 6-minute walk test) (7). However, diaphragmatic motion characteristics in the broader population of patients with ILD have not been fully characterized. Tissue Doppler imaging (TDI) is an ultrasonic technique designed to assess tissue motion, which is widely used in echocardiographic evaluation of cardiac function. The TDI curve is a velocity-time waveform that allows quantification of diaphragmatic velocity and acceleration during contraction and relaxation. Previously, Soilemezi et al. used TDI to demonstrate that peak diaphragmatic contraction velocity in critically ill patients correlates with Pdi and the pressure-time product across the diaphragm (PTPdi; a marker of diaphragmatic respiratory drive) (8).
However, similar studies using ultrasound to assess diaphragmatic function in patients with ILD remain scarce. TDI has not yet been applied to the quantitative assessment of diaphragmatic motion in this patient population. The present study aims to quantitatively evaluate diaphragmatic function in patients with ILD using multimodal ultrasound (including B-mode, M-mode, and TDI). This approach provides a more comprehensive understanding of diaphragmatic characteristics in patients with ILD, while further analyzing the correlations between diaphragmatic ultrasound parameters and clinical features of ILD. Ultimately, this study seeks to provide theoretical support for the application of diaphragmatic ultrasound in rehabilitation management and disease monitoring for patients with ILD. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2393/rc).
Methods
Study design and subjects
This study was a prospective observational study. Forty-four patients with ILD and 31 healthy volunteers were consecutively enrolled between December 2024 and July 2025 at the Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University. Patient inclusion criteria: age >18 years, fulfilling current American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guideline criteria (2), and clinically diagnosed with ILD based on clinical presentation, pulmonary function tests (PFTs), chest CT, and histological examination. Patient exclusion criteria included: existing complications such as obstructive ventilatory dysfunction (e.g., COPD), active infection, history of upper abdominal or thoracic surgery (except for ILD biopsy diagnosis), neuromuscular disease, or inability to cooperate with examinations. Healthy volunteer inclusion criteria: age >18 years, absence of any cardiopulmonary or neuromuscular disease, no history of thoracic/upper abdominal surgery, and normal PFT results.
This study was approved by the Institutional Review Board of The First Affiliated Hospital of Guangzhou Medical University (No. ES-2025-151-01). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and the relevant guidelines and regulations of the aforementioned Ethics Committee. Written informed consent was obtained from all participants prior to enrollment (consistent with the committee’s requirements for prospective observational studies).
Clinical data collection
Baseline data of all participants were extracted from the electronic medical records system of The First Affiliated Hospital of Guangzhou Medical University. The extracted data included three categories: (I) demographic and anthropometric data: age, sex, and body mass index (BMI); (II) clinical characteristics: clinical manifestations, disease duration, smoking history, oxygen therapy status, detailed treatment regimens (e.g., antifibrotic agents, glucocorticoids), and comorbidities; (III) functional, symptomatic, and laboratory assessments: results of PFTs, scores of the St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council Dyspnoea Scale (mMRC), and serum levels of Krebs von der Lungen 6 (KL-6).
Diaphragmatic ultrasound measurements
All diaphragmatic ultrasound measurements were performed using an ultrasound system (Resona 9, Mindray Medical International, Shenzhen, China) equipped with three probes: a convex array probe (SC6-1, 1–6 MHz), a linear array probe (L14-3WU, 3–14 MHz), and a phased array probe (SP5-1U, 1–5 MHz). All diaphragmatic ultrasound measurements were performed by a single experienced sonographer who was blinded to the grouping status (ILD patients vs. healthy controls) of all subjects, so as to minimize subjective operational bias induced by prior knowledge of group allocation. To ensure data accuracy, ultrasound images were acquired over at least three consecutive respiratory cycles, and the mean value of three repeated measurements was recorded for each parameter. For the assessment of intra-operator repeatability, the same sonographer conducted repeated measurements of all diaphragmatic ultrasound parameters for all 77 subjects at the same examination session with a 10-minute interval between the two measurement sets, with all measurement procedures strictly consistent with the first round to avoid additional variability. All participants (both ILD patients and healthy volunteers) maintained a supine position during the examination and breathed spontaneously without artificial ventilation. Notably, left diaphragmatic imaging is frequently obscured by gastric and intestinal gas, which compromises image quality and measurement reliability. Therefore, diaphragmatic measurements in this study were confined to the right hemidiaphragm. Deep breathing (DB) was defined as a full respiratory cycle of maximal voluntary inspiration followed by slow, complete expiration for healthy controls. For ILD patients, DB was modified to comfortable maximal DB to avoid respiratory distress induced by forced breathing. All DB measurements were performed in a supine position. Prior to formal measurement, the same sonographer provided 2–3 standardized DB demonstrations and training for all subjects until consistent performance was achieved. For data acquisition, 3 consecutive valid DB cycles with uniform excursion amplitude and cycle duration were recorded for each subject; cycles with abnormal amplitude or incomplete expiration were discarded and repeated. The mean value of the 3 valid cycles was used for statistical analysis. Breathing effort was monitored via combined subjective and objective approaches: the sonographer provided real-time verbal guidance to confirm consistent effort and simultaneously monitored the diaphragmatic motion curve by M-mode ultrasound to ensure uniform effort for all included cycles. No subjects were excluded due to irregular DB performance or poor cooperation, and all DB-related measurement data were complete.
Diaphragm thickness (DT) and thickening fraction (TF)
The 3–14 MHz linear array probe (L14-3WU) was placed at the costophrenic angle between the 8th and 10th ribs along the right mid-axillary line. On two-dimensional ultrasound images, the diaphragm appeared as a hypoechoic muscular layer sandwiched between the hyperechoic pleural and peritoneal membranes, with a linear hyperechoic band at its center. DT was defined as the vertical distance between the pleural and peritoneal layers. Measurements were performed at two time points: quiet breathing (QB) at end-expiration and DB at end-inspiration. To ensure reliability, three consecutive measurements were obtained at each time point, and the mean value was recorded as the final DT. TF was calculated using the formula (9): TF = [DT-DB − DT-QB]/DT-QB × 100% (Figure 1).
Diaphragm excursion (DE)
The 1–6 MHz convex array probe (SC6-1) was positioned at the lower margin of the costal arch along the right midclavicular line, angled medially and cephalad. The liver was used as an acoustic window to visualize the diaphragm, which appeared as a hyperechoic linear structure covering the liver surface. M-mode ultrasound was activated to record the real-time movement curve of the diaphragm. Participants were instructed to perform QB and DB sequentially. DE was defined as the maximum vertical distance from the peak of the movement curve (end-inspiration) to the baseline (end-expiration). Three independent DE measurements were taken for each breathing pattern, and the mean value was used for analysis (Figure 2).
Diaphragmatic peak velocity and acceleration (TDI mode)
The 1–5 MHz phased array probe (SP5-1U) was placed at the same location as DE measurement (right midclavicular line at the lower margin of the costal arch) to identify the hyperechoic structure at the diaphragmatic dome. TDI mode was enabled, with the sampling volume adjusted to 30 mm to cover the full range of diaphragmatic motion and the scan speed set to 25 mm/s. For TDI measurements, real-time TDI mode guidance was applied to calibrate the probe insonation angle at 0° relative to the diaphragmatic movement direction. The subcostal margin at the right midclavicular line was used as the unified acoustic window for all subjects, with the probe position fixed to avoid operational bias. Prior to formal measurement, ultrasonic assessment of diaphragmatic morphology and position was performed for each subject; adaptive fine-tuning of probe position and angle was conducted for ILD patients with abnormal diaphragmatic morphology or position to optimize visualization. TDI image quality screening criteria were strictly followed: only images with clear diaphragmatic motion curves were included for subsequent statistical analysis, and ambiguous or unqualified images were discarded and the measurement repeated. TDI curves were acquired during QB. From the velocity-time curve, two parameters were measured: peak contraction velocity (PCV): maximum velocity during diaphragmatic contraction (upward movement); peak relaxation velocity (PRV): maximum velocity during diaphragmatic relaxation (downward movement). Diaphragmatic acceleration was calculated as the slope of the steepest segment of the TDI curve during both contraction and relaxation (8). For each parameter, three repeated measurements were averaged (Figure 3).
Statistical analysis
Statistical analyses were performed using SPSS 25.0 software. Normally distributed continuous data were presented as mean ± standard deviation (SD). Non-normally distributed continuous data were presented as median [interquartile range (IQR)]. Categorical variables were presented as frequency (percentage). For categorical variables: comparisons were conducted using the Chi-squared test; Fisher’s exact test was used if the expected frequency of any cell was <5. For continuous variables: independent samples t-test was employed for normally distributed data, while Mann-Whitney U test was used for non-normally distributed data. The intraclass correlation coefficient (ICC) (two-way mixed-effects model, absolute agreement) was used to quantitatively evaluate the intra-operator repeatability of all diaphragmatic ultrasound parameters, with ICC values interpreted as follows: <0.50 (poor consistency), 0.50–0.74 (moderate consistency), 0.75–0.89 (good consistency), and ≥0.90 (excellent consistency). Bland-Altman analysis was further performed to assess the measurement agreement and systematic bias between the two rounds of repeated measurements: the mean bias (difference between the first and second measurements) and 95% limits of agreement (95% LoA; mean bias ± 1.96 × SD of the differences) were calculated, and the number and proportion of outlying points outside the 95% LoA were counted for each parameter. To address potential confounding factors (age, sex, steroid use and disease duration) and explore whether steroid use mediates the effect of ILD on diaphragmatic mechanics, multivariate linear regression analyses were performed. Key diaphragmatic parameters were used as dependent variables separately. The independent variables included: (I) core exposure: ILD status (1= ILD patient, 0= healthy control); (II) potential confounders: age, sex, steroid use, and disease duration. The core exposure was forced into the model, while confounders were included via stepwise selection (entry criterion: P<0.05, removal criterion: P>0.10). Model assumptions (linearity, normality, homoscedasticity) were verified through residual analysis, and multicollinearity was evaluated by variance inflation factor (VIF; <5 considered acceptable). Spearman’s rank correlation analysis was performed to evaluate the associations between diaphragmatic ultrasound parameters and clinical variables (e.g., PFT, SGRQ scores). All statistical tests were two-tailed, and a P<0.05 was considered statistically significant.
Results
Baseline characteristics
A total of 75 participants were enrolled in this study, including 44 ILD patients and 31 healthy controls. No significant differences were observed in age, sex, or BMI between the ILD group and the control group (all P>0.05). Among the ILD patients, connective tissue disease-related interstitial lung disease (CTD-ILD) was the most prevalent subtype. High-resolution CT imaging mainly showed interstitial infiltration in the bilateral lower lobes. Detailed demographic and baseline characteristics of the two groups are summarized in Table 1.
Table 1
| Variables | ILD (n=44) | Control (n=31) | P |
|---|---|---|---|
| Age (years) | 56 [50.00–61.50] | 53 [51.00–59.00] | 0.17 |
| Sex | 24 (54.55) | 16 (51.61) | 0.80 |
| BMI (kg/m2) | 23.76±3.53 | 23.41±2.52 | 0.64 |
| Smoking | 18 (40.91) | NA | – |
| Disease duration (months) | 12.50 [6.50–60.00] | NA | – |
| ILD diagnoses | – | ||
| CTD-ILD | 12 | NA | |
| IPF | 7 | NA | |
| HP | 1 | NA | |
| IPAF | 8 | NA | |
| Other | 16 | NA | |
| Comorbidities | – | ||
| High blood pressure | 10 (22.73) | NA | |
| Diabetes | 4 (9.09) | NA | |
| Coronary heart disease | 2 (4.55) | NA | |
| Corticosteroid use | 26 (59.09) | NA | |
| Specific fibrosis therapy | 33 (75.00) | NA | |
| mMRC | – | ||
| 0 | 7 (15.91) | NA | |
| 1 | 12 (27.27) | NA | |
| 2 | 9 (20.45) | NA | |
| 3 | 6 (13.64) | NA | |
| 4 | 10 (22.73) | NA | |
| KL-6 level (U/mL) | 1,202.00 [707.00–2,054.00] | NA | – |
| SGRQ score | 32 [18.00–47.00] | NA | – |
| Lung function test | – | ||
| FVC (L) | 2.54±0.72 | NA | |
| DLCO (L) | 4.34±1.49 | NA | |
| TLC (L) | 3.80±0.94 | NA |
Data are presented as median [interquartile range], n (%), mean ± standard deviation or n. CTD-ILD, connective tissue disease-associated interstitial lung disease; DLCO, diffusing capacity of the lung for carbon monoxide; FVC, forced vital capacity; HP, hypersensitivity pneumonitis; ILD, interstitial lung disease; IPAF, interstitial pneumonia with autoimmune features; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von der Lungen 6; mMRC, modified Medical Research Council Dyspnoea Scale; SGRQ, St George’s Respiratory Questionnaire; TLC, total lung capacity.
Diaphragm measurements
All diaphragmatic ultrasound data related to DB were complete for all subjects, with no cases excluded due to non-standard DB maneuver or poor cooperation. Diaphragmatic ultrasound parameters of the two groups are summarized in Table 2. During QB, DT was significantly greater in the ILD group than in the healthy control group (P=0.004). In contrast, during DB, DT was significantly lower in the ILD group (P=0.003). The TF of ILD patients was significantly reduced compared with healthy controls (P<0.001). Diaphragm mobility during DB was significantly decreased in the ILD group relative to the control group (P<0.001). No significant difference in DE during QB was observed between the two groups (P=0.87). In the ILD group, TDI revealed significantly higher PRV (P=0.02), contraction acceleration (P=0.02), and relaxation acceleration (P<0.001) compared with healthy controls. There was no significant intergroup difference in PCV during QB (P=0.08).
Table 2
| Parameters | ILD (n=44) | Control (n=31) | P |
|---|---|---|---|
| Diaphragm thickness | |||
| At end-expiration (QB) (cm) | 0.21±0.05 | 0.17±0.04 | 0.004 |
| At end-inspiration (DB) (cm) | 0.33 (0.25–0.37) | 0.38 (0.31–0.45) | 0.003 |
| Thickening fraction (%) | 46.89 (22.23–76.10) | 114.29 (92.71–157.19) | <0.001 |
| Diaphragm excursion | |||
| QB (cm) | 1.36 (1.15–1.62) | 1.46 (1.08–1.72) | 0.87 |
| DB (cm) | 3.19 (2.07–4.23) | 6.24 (5.18–7.21) | <0.001 |
| Diaphragm peak velocity | |||
| Contraction (cm/s) | 2.03±0.63 | 1.85±0.28 | 0.08 |
| Relaxation (cm/s) | 1.87 (1.44–2.53) | 1.60 (1.44–1.90) | 0.02 |
| Diaphragm acceleration | |||
| Contraction (cm/s2) | 3.80 (2.31–5.43) | 2.68 (2.09–3.49) | 0.02 |
| Relaxation (cm/s2) | 5.27 (3.82–6.04) | 3.04 (2.21–3.49) | <0.001 |
Data are presented as mean ± standard deviation or median (interquartile range). DB, deep breathing; ILD, interstitial lung disease; QB, quite breathing.
Intra-operator repeatability of diaphragmatic ultrasound parameters
Intra-operator repeatability analysis (ICC and Bland-Altman) for all diaphragmatic ultrasound parameters (77 subjects) is detailed in Table 3. All parameters exhibited excellent intra-operator consistency (ICC >0.90, all P<0.001). Bland-Altman analysis further confirmed no significant systematic bias across all measurements; a small number of scattered outlying points were observed outside the 95% LoA: DB excursion 6 points (7.8%, 6/77), TF 4 points (5.2%, 4/77), QB excursion 3 points (3.9%, 3/77), contraction acceleration 4 points (5.2%, 4/77), and PRV/relaxation acceleration 2 points each (2.6%, 2/77). The low and clinically acceptable proportion of outlying points, combined with excellent ICC values, validated the high intra-operator repeatability and accuracy of the standardized diaphragmatic ultrasound measurements in this study.
Table 3
| Parameters | ICC | 95% CI | P | Mean bias | 95% LOA |
|---|---|---|---|---|---|
| Diaphragm thickness | |||||
| At end-expiration (QB) | 0.973 | 0.958–0.983 | <0.001 | 0.0001 | −0.023 to 0.023 |
| At end-inspiration (DB) | 0.996 | 0.994–0.998 | <0.001 | 0.001 | −0.020 to 0.021 |
| Thickening faction | 0.987 | 0.979–0.991 | <0.001 | 0.011 | −0.184 to 0.206 |
| Diaphragm excursion | |||||
| QB | 0.998 | 0.997–0.999 | <0.001 | 0.002 | −0.052 to 0.055 |
| DB | 0.995 | 0.991–0.997 | <0.001 | 0.046 | −0.360 to 0.453 |
| Diaphragm peak velocity | |||||
| Contraction | 0.987 | 0.980–0.992 | <0.001 | −0.002 | −0.164 to 0.161 |
| Relaxation | 0.994 | 0.991–0.996 | <0.001 | −0.001 | −0.147 to 0.145 |
| Diaphragm acceleration | |||||
| Contraction | 0.994 | 0.991–0.996 | <0.001 | 0.010 | −0.556 to 0.575 |
| Relaxation | 0.998 | 0.997–0.999 | <0.001 | 0.048 | −0.466 to 0.562 |
ICC was calculated using a two-way mixed-effects model with absolute agreement. ICC ≥0.90 indicates excellent consistency, 0.75–0.89 indicates good consistency, 0.50–0.74 indicates moderate consistency, and <0.50 indicates poor consistency. Bland-Altman analysis was performed for all parameters to assess systematic bias and measurement agreement; quantitative results are presented in the text (no separate plots provided for conciseness). CI, confidence interval; DB, deep breathing; ICC, intraclass correlation coefficient; LOA, limits of agreement; QB, quite breathing.
Multivariate linear regression analysis
To control for potential confounding factors and verify the independent effect of ILD status on diaphragmatic parameters, multivariate linear regression analyses were performed (Table 4). After adjusting for age, sex, steroid use, and disease duration, ILD status remained an independent factor associated with key diaphragmatic parameters: DT-QB [standardized β =0.33; 95% confidence interval (CI): 0.01 to 0.06; P=0.004], DT-DB (standardized β =−0.32; 95% CI: −0.13 to −0.02; P=0.006), TF (standardized β =−0.60; 95% CI: −0.99 to −0.52; P<0.001), DE-DB (standardized β =−0.71; 95% CI: −3.62 to −2.26; P<0.001), PRV (standardized β =0.33; 95% CI: 0.15 to 0.77; P=0.004), contraction acceleration (standardized β =0.32; 95% CI: 0.52 to 2.95; P=0.006), relaxation acceleration (standardized β =0.35; 95% CI: 1.14 to 4.99; P=0.002).
Table 4
| Parameters | Independent variable | Standardized β coefficient | 95% CI | P | VIF |
|---|---|---|---|---|---|
| Diaphragm thickness | |||||
| At end-expiration (QB) | ILD status (1= presence, 0= absence) | 0.33 | 0.011 to 0.056 | 0.004 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.28 | – | |
| Age | – | – | 0.68 | – | |
| BMI | – | – | 0.69 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.65 | – | |
| Disease duration | – | – | 0.52 | – | |
| At end-inspiration (DB) | ILD status (1= presence, 0= absence) | −0.32 | −0.129 to −0.023 | 0.006 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.14 | – | |
| Age | – | – | 0.97 | – | |
| BMI | – | – | 0.38 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.08 | – | |
| Disease duration | – | – | 0.13 | – | |
| Thickening fraction | ILD status (1= presence, 0= absence) | −0.60 | −0.987 to −0.520 | <0.001 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.31 | – | |
| Age | – | – | 0.48 | – | |
| BMI | – | – | 0.47 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.16 | – | |
| Disease duration | – | – | 0.21 | – | |
| Diaphragm excursion-DB |
ILD status (1= presence, 0= absence) | −0.71 | −3.618 to −2.257 | <0.001 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.08 | – | |
| Age | – | – | 0.92 | – | |
| BMI | – | – | 0.58 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.12 | – | |
| Disease duration | – | – | 0.28 | – | |
| Diaphragm peak velocity-relaxation |
ILD status (1= presence, 0= absence) | 0.33 | 0.148 to 0.771 | 0.004 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.89 | – | |
| Age | – | – | 0.45 | – | |
| BMI | – | – | 0.32 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.37 | – | |
| Disease duration | – | – | 0.98 | – | |
| Diaphragm acceleration | |||||
| Contraction | ILD status (1= presence, 0= absence) | 0.32 | 0.518 to 2.948 | 0.006 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.98 | – | |
| Age | – | – | 0.58 | – | |
| BMI | – | – | 0.20 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.87 | – | |
| Disease duration | – | – | 0.41 | – | |
| Relaxation | ILD status (1= presence, 0= absence) | 0.35 | 1.136 to 4.991 | 0.002 | 1.00 |
| Sex (1= male, 0= female) | – | – | 0.91 | – | |
| Age | – | – | 0.051 | – | |
| BMI | – | – | 0.55 | – | |
| Steroid use (1= yes, 0= no) | – | – | 0.74 | – | |
| Disease duration | – | – | 0.40 | – |
BMI, body mass index; CI, confidence interval; DB, deep breathing; ILD, interstitial lung disease; QB, quite breathing; VIF, variance inflation factor.
Correlations between diaphragm measurements and clinical parameters
Correlations between diaphragmatic ultrasound parameters and clinical indices (including SGRQ scores, mMRC grades, serum KL-6 levels, and PFT results) in ILD patients are summarized in Table 5. Key findings are as follows: TF was negatively correlated with SGRQ score (r=−0.37, P=0.01), mMRC grade (r=−0.48, P=0.001), and serum KL-6 level (r=−0.40, P=0.007). Conversely, it was positively correlated with forced vital capacity (FVC) (r=0.42, P=0.007) and TLC (r=0.34, P=0.03). DE during QB was negatively correlated with serum KL-6 level (r=−0.34, P=0.03). DE during DB was strongly negatively correlated with SGRQ score (r=−0.56, P<0.001), mMRC grade (r=−0.67, P<0.001), and serum KL-6 level (r=−0.40, P=0.007). It was also positively correlated with FVC (r=0.61, P<0.001), diffusing capacity of the lung for carbon monoxide (DLCO) (r=0.44, P=0.008), and TLC (r=0.49, P=0.002). Contraction acceleration was positively correlated with SGRQ score (r=0.31, P=0.03) and mMRC grade (r=0.44, P=0.002), but negatively correlated with FVC (r=−0.39, P =0.01) and DLCO (r=−0.43, P=0.009). Relaxation acceleration was positively correlated with mMRC grade (r=0.39, P=0.008) and negatively correlated with DLCO (r=−0.40, P=0.01).
Table 5
| Parameters | SGRQ | mMRC | KL-6 | FVC | DLCO | TLC | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| r | P | r | P | r | P | r | P | r | P | r | P | ||||||
| Diaphragm thickness | |||||||||||||||||
| At end-expiration (QB) | 0.27 | 0.07 | 0.21 | 0.16 | 0.28 | 0.06 | −0.06 | 0.70 | −0.19 | 0.27 | −0.05 | 0.74 | |||||
| At end-inspiration (DB) | 0.02 | 0.85 | −0.09 | 0.54 | −0.06 | 0.69 | 0.21 | 0.19 | 0.07 | 0.65 | 0.17 | 0.31 | |||||
| Thickening fraction | −0.37 | 0.01 | −0.48 | 0.001 | −0.40 | 0.007 | 0.42 | 0.007 | 0.33 | 0.051 | 0.34 | 0.03 | |||||
| Diaphragm excursion | |||||||||||||||||
| QB | −0.13 | 0.38 | −0.29 | 0.053 | −0.34 | 0.03 | 0.10 | 0.53 | 0.01 | 0.91 | 0.02 | 0.86 | |||||
| DB | −0.56 | <0.001 | −0.67 | <0.001 | −0.40 | 0.007 | 0.61 | <0.001 | 0.44 | 0.008 | 0.49 | 0.002 | |||||
| Diaphragm peak velocity | |||||||||||||||||
| Contraction | 0.07 | 0.64 | 0.27 | 0.06 | 0.28 | 0.06 | −0.26 | 0.10 | −0.09 | 0.57 | −0.21 | 0.21 | |||||
| Relaxation | 0.09 | 0.52 | 0.24 | 0.10 | 0.15 | 0.32 | −0.17 | 0.28 | −0.07 | 0.66 | −0.16 | 0.34 | |||||
| Diaphragm acceleration | |||||||||||||||||
| Contraction | 0.31 | 0.03 | 0.44 | 0.002 | 0.19 | 0.22 | −0.39 | 0.01 | −0.43 | 0.009 | −0.25 | 0.13 | |||||
| Relaxation | 0.27 | 0.06 | 0.39 | 0.008 | 0.26 | 0.09 | −0.23 | 0.14 | −0.40 | 0.01 | −0.25 | 0.13 | |||||
DB, deep breathing; DLCO, diffusing capacity of the lung for carbon monoxide; FVC, forced vital capacity; KL-6, Krebs von der Lungen 6; mMRC, modified Medical Research Council Dyspnoea Scale; SGRQ, St George’s Respiratory Questionnaire; TLC, total lung capacity; QB, quite breathing.
Discussion
This study used multimodal ultrasound (B-mode, M-mode, TDI) to systematically evaluate diaphragmatic motion in patients with ILD. Key findings: (I) compared with healthy controls, ILD patients showed resting diaphragmatic thickening, reduced TF and DE-DB, plus elevated PRV and motion acceleration; (II) decreased TF/DE and increased acceleration correlated with poorer health-related quality of life (higher SGRQ scores), more severe dyspnea (higher mMRC grades), elevated KL-6 levels, and impaired pulmonary function (reduced FVC, TLC, DLCO). To our knowledge, this is the first study applying TDI for quantitative assessment of diaphragmatic motion in ILD. Our findings expand understanding of ILD-related diaphragmatic pathophysiology and provide a reliable reference for clinical assessment of these patients.
In our study, ILD patients exhibited significantly thicker DT at rest but reduced DT, DE, and TF during deep inspiration compared with healthy controls—consistent with previous findings (9,10). As a restrictive pulmonary disorder, ILD is characterized by decreased lung compliance and volume, which elevate the diaphragm cephalad, increase diaphragmatic tension, and limit motion range, resulting in impaired diaphragmatic mobility relative to healthy individuals. This aligns with MRI-based observations of diaphragmatic motion in IPF patients by Yang et al. (11). Long-term diaphragmatic overload in ILD may induce both fatigue and a “training effect” (12), leading to compensatory muscle hypertrophy. Combined with systemic factors contributing to diaphragmatic dysfunction, this explains our finding of increased resting DT but reduced contractile function in ILD patients. Notably, our results contradict those of Milesi et al. (7), who reported lower resting DT in idiopathic pulmonary fibrosis patients than in healthy individuals. This discrepancy may stem from more advanced disease in their cohort: end-stage ILD patients may progress to diaphragmatic decompensation and atrophy with disease chronicity and severity.
TDI—a well-established technique for assessing myocardial systolic and diastolic function—accurately captures low-velocity, high-frequency tissue motion. To our knowledge, this is the first study to apply TDI for evaluating diaphragmatic motion in ILD patients, providing TDI curves, peak contraction/relaxation velocities, and acceleration data as a reference for future research. Notably, strict quality control protocols were implemented for TDI measurements, including real-time mode-guided probe angle calibration, a unified acoustic window with fixed probe position, pre-measurement diaphragmatic morphology/position assessment with adaptive probe adjustment for ILD patients, and standardized image quality screening. These measures effectively eliminated TDI measurement errors caused by probe angulation deviation and intergroup differences in diaphragmatic morphology and position between ILD patients and healthy controls, thus ensuring the accuracy and reliability of all TDI-derived measurement results. Key TDI findings included significantly higher PRV, systolic acceleration, and relaxation acceleration in ILD patients versus healthy controls. Dyspnea in restrictive lung diseases like ILD is largely driven by increased neural respiratory drive, a consequence of pathological high lung elastic resistance and neuromechanical inefficiency (13,14). ILD patients face elevated inspiratory muscle loads but fail to achieve adequate tidal volume, potentially compensating by increasing respiratory rate—one plausible mechanism for enhanced diaphragmatic motion velocity. This aligns with Soilemezi et al. (8), who linked diaphragmatic PCV to Pdi and respiratory drive, noting rapid relaxation as a fatigue-mitigating compensatory response. While ILD patients had numerically higher peak systolic velocity, this did not reach statistical significance (P=0.083), likely due to our small sample size. The elevated contraction/relaxation acceleration observed in ILD patients likely reflects increased respiratory drive as a compensatory response to impaired lung function and dyspnea, whereas velocity alone would only capture the magnitude of diaphragmatic motion without accounting for the effort required to generate that motion. This explains why acceleration parameters showed stronger correlations with clinical markers of disease severity (SGRQ scores, mMRC grades) than velocity alone, highlighting the added value of acceleration in assessing diaphragmatic adaptive changes in ILD.
Our multivariate linear regression analyses further confirmed that ILD status is an independent driver of diaphragmatic structural and functional abnormalities, even after adjusting for potential confounding factors (age, sex, steroid use and disease duration). Collectively, these results support the specificity of ILD-related diaphragmatic dysfunction, reinforcing the value of multimodal ultrasound as a non-invasive tool for evaluating diaphragmatic function in this population.
We further demonstrated correlations between diaphragmatic ultrasound parameters and clinical outcomes: diaphragmatic TF, DE-DB, and acceleration were associated with health-related quality of life (SGRQ scores) and dyspnea severity (mMRC grades). As the primary inspiratory muscle [accounting for 60–80% of respiratory work (5)], diaphragmatic impairment in ILD—exacerbated by chronic overload and systemic factors—aggravates respiratory symptoms and may impact prognosis (15,16). Reduced TF and DE-DB reflect severe respiratory muscle damage, leading to heightened dyspnea, poor exercise tolerance, and diminished quality of life, consistent with Santana et al. (9). Notably, this is the first study to report correlations between TDI-derived acceleration and clinical indicators, suggesting that increased diaphragmatic activation (reflected by higher acceleration) correlates with ILD severity, as patients with advanced disease often rely on elevated respiratory rates and inspiratory muscle activation to maintain ventilation.
Serum KL-6—a glycoprotein promoting pulmonary fibrosis (17) whose levels correlate with fibrosis severity (18)—was negatively associated with diaphragmatic TF and DE (but not velocity parameters) in our ILD cohort. This reflects the link between reduced lung compliance, restricted diaphragmatic motion, and diaphragmatic fatigue, with TF and DE better capturing chronic lung-induced diaphragmatic dysfunction than velocity metrics.
Regarding pulmonary function, FVC correlated with DE-DB, TF, and maximal contraction acceleration; DLCO correlated with DB-DE and acceleration; and TLC correlated with DE-DB and TF—consistent with prior reports of positive associations between diaphragmatic activity and these indices in ILD (10). Additionally, TDI-derived acceleration showed negative correlations with FVC and DLCO, indicating that increased diaphragmatic activation mirrors impaired lung function and disease severity. Given that FVC and DLCO predict poor ILD prognosis (19,20), our findings suggest that diaphragmatic ultrasound may indirectly reflect lung function. As a portable, non-invasive bedside tool, ultrasound offers a practical alternative for evaluating severe or intolerant ILD patients.
A notable consideration is the heterogeneity of our ILD cohort (including CTD-ILD and IPF), which reflects real-world practice but may induce variability in diaphragmatic findings. CTD-ILD may exacerbate diaphragmatic dysfunction via systemic myopathy/chest wall restriction, while IPF primarily elevates respiratory load driving diaphragmatic hyperactivation. Stratified analysis was unfeasible due to small sample size, limiting subtype-specific interpretation of our results.
There are some limitations in this study. First, although excellent intra-operator repeatability of diaphragmatic ultrasound measurements was confirmed via ICC and Bland-Altman analysis, the absence of a second independent sonographer precluded interobserver reliability assessment, which limits the generalizability of the standardized measurement protocol across operators. Second, the single-center design and moderate sample size may restrict the external validity of the study findings. Third, only short-term intra-operator repeatability was evaluated, and the long-term repeatability of these diaphragmatic ultrasound parameters in ILD patients remains undetermined. Fourth, owing to the time constraints of the revision period, we were only able to supplement the disease chronicity (duration from ILD diagnosis to enrollment) for ILD patients in this revision; detailed characterization of ILD (e.g., radiological extent of CT findings, CTD-ILD subtypes) and granular severity assessment were not fully addressed, which may limit a more in-depth correlation between diaphragmatic ultrasound parameters and ILD clinical features.
Subsequent studies will address these limitations by enrolling multiple trained sonographers for interobserver validation using the same ICC and Bland-Altman analytical approaches, and establishing a standardized operational manual to improve protocol reproducibility. Further investigations with multi-center, larger sample cohorts and long-term follow-up are warranted to explore the dynamic changes of diaphragmatic ultrasound parameters. Additionally, we will prospectively collect comprehensive ILD clinical and radiological data to clarify the association between detailed ILD characteristics and diaphragmatic ultrasound findings, which will validate the generalizability and prognostic value of these parameters, and facilitate their translation into routine clinical practice for ILD assessment and monitoring.
Conclusions
This is the first study to use TDI for diaphragmatic motion assessment in ILD, enabling comprehensive diaphragmatic function evaluation. Multimodal ultrasound can detect ILD-related diaphragmatic changes (thickening, reduced mobility, and increased motor activation) compared with healthy controls, and these changes are independent of confounding factors such as age, sex, and steroid use. As a non-invasive, simple tool, diaphragmatic ultrasound parameters correlate with clinical indicators of ILD severity, which may indirectly reflect patients’ respiratory function. Its clinical utility for guiding drug interventions or pulmonary rehabilitation requires prospective validation with larger cohorts.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2393/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2393/dss
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Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2393/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of The First Affiliated Hospital of Guangzhou Medical University (No. ES-2025-151-01) and informed consent was obtained from all individual participants.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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