COPD patients were retrospectively recruited between March 2020 and November 2020 at Yeouido St. Mary’s Hospital. They were diagnosed with COPD by pulmonologists. The patients were ≥ 40 years of age and satisfied the spirometry definition of persistent airflow limitation, such as a post-bronchodilator forced expiratory volume in 1 sec/forced vital capacity ratio (FEV1/FVC) < 0.70.
Among them, patients who underwent DUS were enrolled. DUS was performed in the stable COPD group when they visited the outpatient clinic for a regular follow-up. DUS was performed within 48 hours of admission in patients with acute exacerbation. Exacerbation was defined by an acute change in respiratory symptoms requiring a medication change, such as a systemic steroid or antibiotics. Patients who required hospitalization had the following indications: 1) acute respiratory failure, 2) cyanosis or edema, 3) very severe symptoms, such as dyspnea at rest or mental change, 3) severe comorbidities, such as cardiovascular disease, and 4) need for refractory to acute management. Patients who did not undergo DUS or underwent DUS after 48 hours of admission were excluded. Patients with confounding factors of diaphragm function, such as hemiplegia, quadriplegia, sequelae from an abdominal or thoracic operation, or diaphragm paralysis due to phrenic nerve palsy, were also excluded. All patients enrolled in this study completed the modified Medical Research Council (mMRC) scale, COPD assessment test (CAT), and history taking for comorbidities.
Histories of medication and comorbidities were collected during the DUS exam. Electrical medical records were reviewed to confirm the comorbidities of the patients. The modified Charlson Comorbidity Index (mCCI), in which the chronic pulmonary disease categories are removed, was calculated to predict prognosis and mortality based on the ICD-10 diagnosis for the COPD patients14.
Diaphragm ultrasound protocol
All DUS exams were performed with a single high-resolution ultrasound machine (Affiniti 70, Phillips, Inc., Best, the Netherlands). The exams were conducted by a respiratory physician who specializes in DUS. DUS findings are well established in many studies7,8,13. Patients were placed in a supine position, and the tests were performed at the right hemidiaphragm. A linear ultrasound probe (5–12 MHz) was used to measure the thickness of the diaphragm. Diaphragm excursion was measured with a convex ultrasound probe (1–5 MHz). B-mode was used to measure the thickness of the diaphragm (DT), and diaphragm excursion (DE) was measured in M-mode. These measurements were repeated three times in the same position and the mean value was used as the representative value.
Diaphragm thickness and diaphragm excursion
DT was measured in the zone of opposition in the right hemithorax over the mid-axillary line between the eighth and eleventh intercostal spaces in longitudinal intercostal view. DT was defined by the distance between the diaphragmatic pleura and the peritoneal membrane. First, it was measured at the end of expiration, which is correlated with functional residual capacity. Then, it was measured at the end of the inspiration during both quiet tidal breathing and maximal deep breathing.
DE was measured at the anterior subcostal margin of the right hemidiaphragm. A convex probe was positioned below the costal margin at the mid-clavicular line. The incidence angle of the ultrasound beam was perpendicular to the posterior third of the diaphragm, or the so-called DE line. The DE was the diaphragm inspiratory amplitude during respiration measured at the DE line in M-mode. DE was measured during quiet tidal breathing and maximal deep breathing (DEmax) (see Supplemental Figure 1).
Diaphragm thickening fraction
The thickening fraction of the diaphragm (TF) has been evaluated in many studies7,8,12. It is related to the generation of diaphragm muscle pressure. The TF was calculated with the DT value. TF was defined as the ratio of DT changes between the end of expiration and the end of inspiration. The TF equation was [(DT at end-inspiration) - (DT at end-expiration)]/(DT at end-expiration) × 100. TF was also calculated during tidal breathing and maximal deep breathing (TFmax).
We used Student’s t test and the Mann-Whitney U test for analyzing continuous variables according to the normality test results. Pearson’s chi-square test or Fisher’s exact test were used to compare categorical variables between groups. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the DUS findings for classifying the exacerbation group. The Youden index was used to identify the optimal cut-off value and compare the ROC curves. Binary univariate and multivariate logistic regression analyses were conducted to calculate the odds of being classified in the exacerbation group. A p-value < 0.05 was considered to indicate significance. Student’s t test, the Mann-Whitney U test, Pearson’s chi-square test, Fisher’s exact test, and the logistic regression analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). The ROC curve analyses, the Youden’s index, and the comparison of the ROC curves were performed using MedCalc® Statistical Software version 19.5.6 (MedCalc Software Ltd., Ostend, Belgium; https://www.medcalc.org; 2020).
This study was approved by the Institutional Review Board of The Catholic University of Korea Yeouido St. Mary’s Hospital (approval no. SC20RIS0181). The need for informed consent was waived due to the retrospective nature of the study.