Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive disease characterized by restricted airflow. It is associated with high morbidity and mortality and increasing social and economic burdens worldwide [
As no suitable tests are available to determine the function of the diaphragm, diaphragmatic dysfunction is not generally recognized; however, the need for an evaluation is significant for both inpatients and outpatients, especially during emergencies [
The techniques traditionally used to diagnose diaphragmatic weakness or paralysis are invasive, expose patients to radiation, or require them to leave the room (electromyography and fluoroscopy). In addition, they may be time-consuming, indirect, and uncomfortable (transdiaphragmatic pressure measurement and plethysmography) or complex and expensive (dynamic ecoplanar magnetic resonance imaging) [
M- and B-mode ultrasonography (US) was first used by Haber et al. in 1975 to evaluate diaphragm movement [
The use of US for structural and functional evaluations of the diaphragm is increasing. It has been reported that diaphragmatic thickness fraction measurements are suitable for determining lung hyperinflation in patients with COPD [
The purpose of the present study was to evaluate the relationship between COPD severity and the diaphragmatic function measured by point-of-care US in patients with stable COPD.
This observational case-control study was performed at a large tertiary referral academic institution after receiving the institutional review board approval. All patients provided their verbal consent and signed a written consent form. The diagnosis of COPD was based on medical history, clinical examinations, and pulmonary function tests (PFTs), and all diagnoses were made in accordance with the GOLD criteria [
The study involved patients aged >40 years who had a post-bronchodilator FEV1/forced vital capacity ratio <70% on PFTs (Vmax® Encore PFT System; CareFusion, Yorba Linda, CA, USA) performed by the same trained operator in accordance with the American Thoracic Society standards. A total of 61 patients with COPD and 40 healthy subjects who had been admitted to Ufuk University Hospital between December 2018 and May 2019 were enrolled. Patients with malignancies, neuromuscular conditions, cerebrovascular diseases, unilateral or bilateral pleural effusion, pneumothorax, atelectasis, pneumonia, interstitial lung diseases, recent surgical operations, COPD exacerbations within the previous 3 months, and refusal to participate in the study were excluded. Comorbidities, including cardiac insufficiency, hypertension, renal insufficiency, and diabetes mellitus, were queried and recorded.
US was performed with a Terason Usmart 3200T ultrasound system (77 Terrace Hall Avenue Burlington, MA 01803 United States) and a 3.5 MHz curved probe.
The upward and downward movements of the lung silhouette in the scapular line were measured. All participants were evaluated in a sitting position. The transducer was placed at the lowest part of the lung silhouette in the scapular line. The probe orientation should be longitudinal scan. The patient was instructed to exhale as deeply as possible to the residual volume and then to inhale deeply to the total lung capacity. This manoeuver was filmed, and the distance between the highest and lowest points of the lung silhouette was measured 3 times and the mean value was calculated. This manoeuver was performed on the right and left sides [
(a) Sonographic measurement of the upward and downward movements of the lung silhouette, here on the right side (lung silhouette method). The patient is sitting; the transducer is placed at the lowest point of the lung silhouette in the scapular line. While the patient breathes as deeply as possible, a video sequence is performed. Afterward, the distance between maximal inspiration and maximal expiration can be measured. (b) Sonographic measurement of the upward and downward movements of the lung silhouette, here on the right side. E marks the lowest point of the lung silhouette at maximal end expiration. (c) Sonographic measurement of the upward and downward movements of the lung silhouette—here on the right side. E marks the lowest point of the lung silhouette at maximal end expiration, and I marks the lowest point at maximal inspiration. In this example, the distance between E and I is 35.3 mm.
The upward and downward movements of the right diaphragmatic dome were measured from the anterior position. All participants were evaluated by US in a completely supine position. The transducer was placed in the area between the anterior axillary line and the midclavicular line, with the liver as a US window directed toward the diaphragmatic dome. The probe orientation should be longitudinal scan. The participant was instructed to exhale as deeply as possible to the residual volume and then to inhale deeply to the total lung capacity. This manoeuver was filmed, and the distance between the highest and lowest points of the right hemidiaphragmatic dome was measured. This method was performed only on the right hemidiaphragmatic side because of the known difficulties that accompany left side measurements with the spleen and stomach as the US window (Figures
(a) The convex probe is positioned on the abdomen to examine the right diaphragmatic dome. The upward and downward movements of the right diaphragmatic dome were measured from the anterior position. The probe orientation should be longitudinal scan (right hemidiaphragm US method in B-mode and M-mode). (b and c) B-mode ultrasound evaluation of the craniocaudal displacement of the left branch of the portal vein in a patient with COPD. The position of the vessel was marked by the calliper during forced expiration and inspiration manoeuvres. The line shows displacement of the left branch of the portal vein during maximal inspiratory and expiratory breathing in the sagittal plane. The craniocaudal displacement of this branch was registered in millimetres. E marks at maximal end expiration, and I marks the lowest point at maximal inspiration. The distance between E and I is 41 mm (Ant B-Mode R). (d). M-mode scan of the right hemidiaphragmatic dome at maximal inspiration The first calliper was placed at the foot of the inspiration slope on the diaphragm echoic line and the second one at the apex of this slope for the deep breathing measurements (Ant M-Mode R: 42.7 mm).
The probe was placed between the midclavicular and anterior axillary lines into the subcostal area and was directed medially, cranially, and dorsally, so that the US beam was perpendicular to the posterior third of the right and left hemidiaphragms. The probe orientation should be longitudinal scan. Diaphragmatic movements were recorded in M-mode. This manoeuver was started at the end of normal expiration, and the volunteers and COPD patients were asked to inhale as deeply as possible. The subcostal or low intercostal probe position was chosen between the anterior and mid axillary lines to obtain the best image of the left hemidiaphragmatic dome. Motion was recorded during the same respiratory manoeuvers as for the right hemidiaphragm. The inspiratory amplitudes (excursions) of the diaphragm were measured by M-mode US. The first calliper was placed at the foot of the inspiration slope on the diaphragm echoic line and the second one at the apex of this slope for the deep breathing measurements (Figure
All ultrasonographic measurements (lung silhouette method, right hemidiaphragm US method in B-mode, and right and left hemidiaphragms US method in M-mode) were made by the same emergency medicine specialist certified in lung and diaphragmatic US (POCUS), who was blinded to the clinical characteristics and pulmonary function status of each patient. Several respiratory cycles were recorded, and the measurements from at least three different cycles were averaged for each US method.
The data were statistically analysed with the SPSS 25.0 software (IBM Corp., Armonk, NY, USA). The categorical measurements were reported as numbers and percentages, and the Shapiro–Wilk test was performed to determine the normality of the continuous variable distributions, the results of which are presented as medians (quartiles). The Kruskal–Wallis test served to compare nonnormally distributed variables. Differences in the continuous variables among the four groups were considered significant at
A total of 85 patients with COPD met the inclusion criteria of this study. Of these, 21 were excluded because they had suffered from COPD exacerbations within the past 3 months, and 3 were excluded because they could not undergo bedside US owing to patient or technical limitations. Therefore, 61 patients with COPD who did not meet the exclusion criteria were included in the study; 80.3% (
Demographic characteristics and significance levels in control group and COPD patients according to their stages.
Control group ( |
GOLD A ( |
GOLD B ( |
GOLD C ( |
GOLD D ( |
| |
---|---|---|---|---|---|---|
Male, |
34 (85.0) | 1 (16.7) | 3 (50.0) | 13 (86.7) | 32 (94.1) | <0.001 |
Age, median (IQR) | 67.5 (10.0) | 58.0 (7.0) | 78.5 (15.0) | 65.0 (16.0) | 71.0 (13.0) | <0.001 |
Number of exacerbations in the previous year, median (IQR) | — | 0.50 (1.0) | 1.0 (1.0) | 1.0 (0.0) | 2.0 (1.0) | <0.001 |
Smoking, |
23 (57.5) | 6 (100.0) | 6 (100.0) | 15 (100.0) | 31 (91.2) | 0.836 |
BMI, median (IQR) | 27.1 (3.8) | 28.2 (5.1) | 25.9 (6.5) | 26.5 (7.5) | 24.5 (4.0) | 0.095 |
CHD, |
1 (2.5) | 0 (0.0) | 3 (50.0) | 2 (13.3) | 11 (32.4) | 0.115 |
CHF, |
1 (2.5) | 3 (50.0) | 1 (16.7) | 2 (13.3) | 4 (11.8) | 0.115 |
DM, |
5 (12.5) | 0 (0.0) | 1 (16.7) | 6 (40.0) | 9 (26.5) | 0.279 |
HT, |
10 (25.0) | 6 (100.0) | 1 (16.7) | 10 (66.7) | 20 (58.8) | 0.033 |
Data are expressed as mean ± standard deviation for normally distributed data and percentage for categorical variables. COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; IQR: interquartile range; BMI: body mass index; CHD: coronary heart disease; CHF: congestive heart failure; DM: diabetes mellitus; HT: hypertension.
Pulmonary function test values and significance levels with ultrasonographic findings according to the COPD stage and control group.
Control group ( |
GOLD A ( |
GOLD B ( |
GOLD C ( |
GOLD D ( |
| |
---|---|---|---|---|---|---|
Lung Sil R (mm), median (IQR) | 66.0 (4.5) | 48.8 (3.1) | 44.1 (9.5) | 41.0 (9.6) | 27.6 (15.1) | <0.001 |
Lung Sil L (mm), median (IQR) | 66.1 (4.0) | 48.8 (4.4) | 44.3 (8.9) | 40.7 (9.1) | 27.7 (12.1) | <0.001 |
Ant B-Mode R (mm), median (IQR) | 71 (5.0) | 53.2 (3.8) | 45.5 (8.2) | 42.2 (8.5) | 34.0 (13.0) | <0.001 |
Ant M-mode R (mm), median (IQR) | 69.0 (3.8) | 45 (4.0) | 44 (5.0) | 43 (9.0) | 34 (7.0) | <0.001 |
Ant M-mode L (mm), median (IQR) | 70 (6.0) | 46 (3.0) | 45 (5.0) | 42 (7.0) | 34 (6.0) | <0.001 |
FVC (%), median (IQR) | 98.5 (20) | 92.5 (7) | 72.0 (18.0) | 67.0 (17.0) | 55.0 (29.0) | <0.001 |
FEV1 (%), median (IQR) | 94.0 (19) | 72.0 (8.0) | 59.5 (14.0) | 54.0 (18.0) | 34.5 (19.0) | <0.001 |
FEV1/FVC (%), median (IQR) | 91.0 (9) | 66.5 (2.0) | 63. (6.0) | 63.0 (13.0) | 47.5 (18.0) | <0.001 |
COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; IQR: interquartile range; FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s.
Box and whisker plot. Lung Sil R (mm), Lung Sil L (mm), Ant M-mode R (mm), Ant M-Mode L (mm), and Ant B-Mode R (mm) values in patients with COPD in accordance with GOLD classification in 95% confidence interval.
The correlations between the US findings and FEV1 and their significance levels are shown in Table
Correlation between FEV1 and ultrasonographic findings.
Variables | Control ( |
COPD ( | ||
---|---|---|---|---|
Correlation coefficient |
|
Correlation coefficient |
| |
Lung Sil R | 0.522 |
|
0.963 |
|
Lung Sil L | 0.535 |
|
0.956 |
|
Ant B-Mode R | 0.599 |
|
0.953 |
|
Ant M-Mode R | 0.682 |
|
0.917 |
|
Ant M-Mode L | 0.747 |
|
0.947 |
|
FEV1: forced expiratory volume in 1 s.
Correlation between (a) Lung Sil R (mm) and FEV1 (%) in COPD patients and (b) Ant M-Mode R (mm) and FEV1 (%) in COPD Patients.
Significant negative correlations were detected between the number of exacerbations per year Lung Sil R and Ant M-Mode R (
Correlation between (a) Lung Sil R (mm) and number of exacerbations per year and (b) Ant M-Mode R (mm) and number of exacerbations per year.
The control group consisted of 40 healthy volunteers; 85.0% (
For the assessment of the US operator’s skills across the study period, the correlation between FEV1-US findings (e.g., Lung Sil R) of the first 10 patients and the FEV1-US findings (e.g., Lung Sil R) of the last 10 patients was evaluated (
This is the first study conducted among patients with COPD who were graded in accordance with the updated GOLD classification. Some research concerning lung US followed the former GOLD classification. In many studies, diaphragm replacement was measured with the use of FEV1, and the lung silhouette and anterior US B-mode measurements were correlated with the M-mode measurements [
The lung silhouette method is a technologic-device-supported model of the lung percussion in which diaphragmatic dysfunction is evaluated by the up and down movements of the right and left hemidiaphragms over the scapular line. The method is a version of the former diaphragm model.
Previous studies showed that the results of this method were strongly correlated with those of the anterior axillary method and that the method was easily performed in all patients, including obese ones, feasibly applied together with US, and suitable for evaluating both hemidiaphragms [
One of the most important findings of the present study was the strong correlation detected between the lung silhouette images taken from the interscapular line and images taken with the anterior method and FEV1. A similar correlation was found in a previous study; however, the correlation coefficient was not 100% [
Another important finding of the present study was that as the number of exacerbations per year increased in a patient, the measurements made with the lung silhouette and anterior axillary methods showed negative correlations. The US measurements of the patients were not taken during an exacerbation. However, the role of US diaphragmatic measurements in predicting the number of exacerbations per year should be clarified via more comprehensive studies conducted on the basis of our study results. This may help emergency medicine physicians in deciding on discharge vs. hospitalization.
Patients with stable COPD were included in the present study. For this reason, the use of data from emergency services may be confusing; however, patients who are admitted with respiratory distress to emergency services are relieved by various treatments. The results of this study may help in making the decision on hospitalization vs. discharge after the recovery of the patient’s condition. In addition, this is a pioneer study in terms of its implementation in emergency services. Further research is needed to determine the predictive power of a diaphragmatic functional evaluation by US. If the severity of the exacerbations can be determined with US in the most comfortable position, US may play a role in the decision on early intubation, intensive care follow-up, or hospitalization. A multicentre study in a larger group of patients with exacerbations is needed to support the findings of our study.
The study had some limitations. First, the number of patients with COPD was limited, and the study was conducted at a single centre. Thus, the population might not be representative of all patients with COPD. Second, the diaphragmatic measurements were performed by only one emergency specialist. This may have caused an underestimation of the results based on interobserver variations. The inclusion of patients with stable COPD only was another limitation, because the results are not applicable to COPD patients during an exacerbation period, and this fact limits the therapeutic decisions to be made based on US in exacerbated patients. Since an adequate measurement of diaphragmatic thickness fraction is difficult in daily practice, we did not use its parameters in this study.
In this study, FEV1 and annual number of exacerbations turned out strongly correlated US findings. The use of US in COPD patients could help to support clinical decision, but further clinical studies are necessary to confirm those findings.
The US findings data used to support the findings of this study have been deposited in the Togay Evrin’s repository.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent according to Helsinski declaration was taken from Ufuk University Faculty of Medicine ethics committee before the study (no: 20190430/2).
The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Togay Evrin involved in project development, data collection, data analysis, and manuscript writing. Semih Korkut was responsible for data analysis and manuscript writing. Leyla Ozturk Sonmez involved in project development and manuscript writing. Lukasz Szarpak was responsible for data analysis and data collection. Burak Katipoglu involved in project development and data collection. Jacek Smereka and Ramazan Guven performed data analysis and manuscript writing. Evrim Eylem Akpinar involved in project development and data collection.