Ultrasound assessment of diaphragmatic excursion in chronic obstructive pulmonary disease patients with different severities

Background Chronic obstructive pulmonary disease (COPD) is associated with dysfunctional diaphragmatic breath‑ ing we assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound. Objective The present study aimed to assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound. Patients and methods In this observational case–control study, 80 COPD patients were included according to GOLD guidelines 2020 attending the Chest Clinic in Badr Hospital, Helwan University. All patients were divided equally into 5 groups according to FEV1 measured by spirometer: group (1) normal person; group (2) mild stage FEV1_80% predicted; group (3) moderate stage 50%_FEV1 < 80% predicted; group (4) severe stage 30%_FEV1 < 50% predicted; and group (5) very severe stage FEV1 < 30% predicted. We measured diaphragmatic movement in all these patients using ultrasound. Results The outcomes result of normal, mild, moderate, severe, and very severe groups in terms of post‑bronchodila‑ tor FEV1/FVC are 0.66 ± 0.05, 0.65 ± 0.05, 0.63 ± 0.04, 0.51 ± 0.068 respectively showed was a significant difference. There was a significant difference of FEV1 are 86.70 ± 5.62, 63.00 ± 13.81, 43.00 ± 6.78, 24.00 ± 4.17, respectively ( P < 0.001). There was a significant difference in diaphragmatic thickness at the end of normal expiration are 0.49 ± 0.12, 0.51 ± 0.09, 0.47 ± 0.16, 0.37 ± 0.07, respectively ( P < 0.001). There was a significant difference in the diaphragmatic thickness during maximum inspiration are 0.70 ± 0.16, 0.8 ± 0.17, 0.64 ± 0.19, and 0.47 ± 0.08, respectively ( P < 0.001). There was a significant difference in the diaphragmatic excursion during normal breathing are 2.45 ± 0.39, 1.78 ± 0.67, 1.86 ± 0.67, 1.09 ± 0.16, respectively ( P < 0.001). There was a significant difference in diaphragmatic Excursion dur‑ ing maximum inspiration are 4.41 ± 0.91, 3.83 ± 0.78, 3.36 ± 0.74, 2.36 ± 0.66 respectively ( P < 0.001). Conclusion The use of ultrasonography for assessing the diaphragmatic excursion. Sonographically determined diaphragmatic excursion strongly correlates with FEV1/FVC.


Introduction
Restricted airflow is a characteristic of the various and progressive diseases known as chronic obstructive pulmonary disease (COPD) [1].Patients with COPD have dysfunctional diaphragmatic breathing.There are several reasons why diaphragmatic dysfunction occurs in people with COPD, but the earliest explanation is a mechanical disadvantage brought on by lung overinflation.More recently, the causes of diaphragmatic weakness have been linked to remodeling, oxidative stress, and a decrease in myosin filaments because of decreased protein synthesis and an increase in muscle cell death [2].
A correlation has been shown between reduced diaphragm mobility and measures of air trapping (residual volume and residual volume to total lung capacity ratio) in individuals with COPD [3].One of the main risk factors for higher mortality is the decrease in diaphragmatic motion, which reflects compromised respiratory muscle function.higher resistive and elastic loads brought on by higher airway resistance and decreased dynamic pulmonary compliance result in a mechanical strain on the inspiratory muscles.The diaphragm muscle fibers' orientation in a zone of apposition (ZOA) is altered by thoracic hyperinflation brought on by air trapping, which reduces the contraction's effectiveness during lower rib cage expansion.In order to regain its ability to generate pressure, fewer sarcomeres are also present.Muscle flattening as a result of remodeling leads to a reduction in diaphragmatic excursion [4].
The forced expiratory volume in the first second (FEV1) is not a reliable indicator of the severity of COPD, according to earlier research.Because of this, an evaluation based on symptoms and inflammation was suggested in the 2011 update of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in order to assess the severity of the disease, oversee therapy, and calculate the prognosis of COPD.On the other hand, the 2017 update recommended that FEV1 be excluded from the assessment and that spirometry be the only method used to diagnose COPD, as this value could lead to misunderstanding when classifying patients into different disease groups [5].
The respiratory muscle that is most important to maintaining ventilation is the diaphragm.Even though the diaphragm only moves 1-2 cm when breathing at rest, it moves 7-11 cm when forced to breathe [6].Diaphragmatic dysfunction is not commonly recognized since there are no appropriate tests to ascertain the diaphragm's function; yet, both inpatients and outpatients should have an evaluation, particularly in an emergency.The diaphragmatic function can be assessed in a variety of ways, but transdiaphragmatic pressure measurement is the gold standard for diagnosis [7].
Conventionally, diaphragmatic weakness or paralysis is diagnosed using intrusive, radiation-exposed, or roomextended procedures (electromyography and fluoroscopy).Additionally, they could be costly and complicated (dynamic ecoplanar magnetic resonance imaging) or time-consuming, indirect, and painful (transdiaphragmatic pressure measurement and plethysmography) [8].Thus, ultrasonography is being used more often to assess the diaphragm's structure and function.Measurements of the diaphragmatic thickness fraction have been shown to be useful in identifying lung hyperinflation in COPD patients.Because of this, diaphragm assessment by point-of-care US may be beneficial for assessing the state of the disease and its consequences in patients with COPD [9].A useful procedure that can be performed at the patient's bedside for critical care patients, particularly those using mechanical ventilators, is chest ultrasound.
Therefore, this study aimed to assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound.

Patients and methods
In this observational case-control study, COPD patients were included attending the Chest clinic at Badr Hospital, Helwan University.Eighty subjects were divided into 5 subgroups according to GOLD 2020 as follows: • Group 1 (40 patients) normal person.

Inclusion criteria
Individuals with COPD who are 40 years of age or older and have a history of the disease meet clinical criteria with supportive physical findings, exhibit hyperinflation on a chest radiograph, and meet GOLD guidelines 2023 (FEV1/FVC ratio < 0.70 indicates poor bronchodilator reversibility and airflow limitation) were included in this study and divided into four severity-based subgroups (based on post-bronchodilator FEV1% of predicted).

Exclusion criteria
Disorders that either directly or indirectly impact the diaphragm, such as elevated intra-abdominal pressure.Any illnesses of the nervous system or metabolism that impact the diaphragm.Other conditions affecting the chest wall or lung parenchyma include lung cancer, bronchiectasis, and others.Morbid obesity and recent abdominal or thoracic surgery were also excluded.

Ethical consideration
Ethical permission for the study was obtained from the patient who was fully informed about all study procedures and their consent was obtained.This study was approved by the ethical committee of the Faculty of Medicine, at Helwan University.Serial number:49-2021.

Clinical assessment
A thorough history was taken of everyone, with particular attention paid to personal information, past smoking history, respiratory symptoms, and previous medical histories.Complete clinical evaluation, including chest X-ray and examination, was carried out.Using a portable stadiometer, height was measured to the closest 0.1 cm.Using a calibrated scale, weight was recorded in an upright position to the nearest 0.1 kg.Body mass index was calculated by dividing weight (kg) by height (m 2 ).

Spirometry pre and post-bronchodilator
The MIR Spiro bank II Spirometer (MIR Medical International Research, MIR ITALY Headquarters: Via del Maggiolo 125 00155 Roma) was used to do dynamic spirometry.The test was conducted both before and after 5 mg of salbutamol sulfate were nebulized with 2 ml of 0.9% saline for 3 min.

Performing spirometry
The equipment was calibrated beforehand or at the start of the session to ensure accuracy before performing spirometry.It is important to verify the patient's identity, measure their height and weight without shoes or boots, and note their age, sex, and race.Arm span can be used as a rough estimate of height if the patient is unable to stand during the measurement process.It is recommended that all patients apply bacterial-viral filters, which they should discard after testing.The following is the proper stance for measurement: If the patient is sitting up straight and there are no obstructions, there should not be any difference in the volume of air they can exhale from a sitting posture compared to a standing position.Legs uncrossed and feet flat on the floor: this position does not need the utilization of the abdominal muscles.When exhaling as much as possible, patients may experience lightheadedness, swaying, or fainting.Therefore, loosen close-fitting clothing, utilize an armchair, and leave dentures in place.
Before measuring, calibration was carried out, nose clips were applied, tidal (regular) breaths were taken with the mouthpiece first, followed by a complete, deep breath in, the forced full expiration (emptying the lungs in 6 s), and a final, rapid, full inspiration.Encouragement is quite important, so when the patient is almost done with the maneuver, speak up to them.

Ultrasonography
We used a portable ultrasound instrument called Sono site M-Turbo.To detect the diaphragmatic motion, the patient was evaluated while breathing on their own.Due to its higher repeatability and reduced variability, the examination was conducted in a supine posture.In comparison to sitting or standing, diaphragmatic excursion is larger when lying down.Deep breathing, quiet breathing, or sniffing was used.
The liver examination was used to examine the right diaphragmatic cupola.The spleen's existence makes it more challenging to visualize the left diaphragmatic cupola.By shifting the ultrasonic probe location near 90° to the diaphragm, more coronal views might be obtained.Anterior subcostal view in the anterior axillary line was the strategy and plane employed to visualize the diaphragm.
A transducer with a shallow probe was used to assess excursion data, but a transducer with sufficient spatial resolution was required to measure the thickness of the diaphragm at the zone of apposition.It was necessary to use an anterior subcostal approach to view the diaphragmatic excursion.
The diaphragm encompassed the liver in a hyperechogenic line in B-mode; the probe was angled to reveal the maximal convexity.In the M-mode, the diaphragm was visualized as a hyperechogenic line, with the peak of the sinusoidal wave indicating maximal inspiration and the bottom representing expiration.By M-mode, the following was measured: 1-The diaphragmatic excursion was represented by the curve's maximum point.2-The diaphragmatic thickness and the thickness of the hyperechogenic line in M-mode matched.

3-We measured the thickness at different lung volumes:
During a breath-holding maneuver following maximal inspiration (total lung capacity, TLC) at the conclusion of a normal expiration (equivalent to functional residual capacity, FRC).
A sample size calculation was performed regarding the ultrasound evaluation of diaphragmatic excursion in individuals with varying degrees of chronic obstructive pulmonary disease.The FEV1/FVC mean (SD) was 5.04 ± 3.31 which did according to Qaiser et al. [10].Using one-way analysis of variance and test ratio, we determined that the minimum appropriate sample size was 38 participants in each group to be able to reject the null hypothesis with 80% power at α = 0.05 level and with an acceptable 15% dropout rate.The MS Windows version of the epi-info software (7.2.4.0) was used to calculate the sample size.

Statistical analysis
Statistical package for social sciences (SPSS) software, specifically statistical computer package version 11, was used to statistically analyze the data.For quantitative data, the student (t) test was used to statistically analyze the difference between two means after the mean and standard deviation were computed.The distribution of numbers and percentages was computed using qualitative data.Chi-square was employed as a significance test, and when the Fisher exact test was determined to be unsuitable, the significance level was changed to P > 0.05 to understand the test results.One-way ANOVA was used to analyze between more than two groups.We also use specificity and ROC curves to predict the correlation between groups.

Discussion
Airflow restriction is a characteristic of the diverse and progressive disease known as COPD.The structure and morphology of the diaphragm are modified by COPD pathology [1].
This observational case-control study will be performed including 80 patients diagnosed with COPD according to GOLD guidelines 2020 attending the Chest Clinic in Badr Hospital, Helwan University.The diagnosis of COPD was confirmed based on medical history, clinical examinations, and pulmonary function tests (PFTs), and all diagnoses will be made in accordance with the GOLD criteria.
Subgroup of included studies according to diseased and non-diseased groups.Our study showed the baseline characteristic's age and BMI in diseased and non-diseased groups, which showed no significant difference in terms of age (diseased = 55.58 ± 9.09, nondiseased = 53.00± 7.23, P value = 0.165), on the other hand, there was significant difference in the term of BMI (diseased = 23.29 ± 3.32, non-diseased = 21.69 ± 2.17 P value = 0.013).
Our study showed the gender (male and female) in diseased and non-diseased; diseased group male 31(38.8%),female = 9 (11.3%), in the non-diseased group male 28 (35%), female = 12 (15%).There was no significant difference between the two groups P value = 0.446.We  show the outcomes results of diseased and non-diseased groups in terms of post-bronchodilator FEV1/ FVC 0.61 ± 0.08, 0.84 ± 7.23 showed significant difference P value = < 0.001.According to FEV1, there was a significant difference of 54.18 ± 24.95, 97.60 ± 7.63 with P value = < 0.001.According to diaphragmatic thickness at the end of normal expiration, there was a significant difference of 0.46 ± 0.12, 0.79 ± 0.08 with P value = < 0.001.According to diaphragmatic thickness during maximum inspiration, there was a significant difference of 0.65 ± 0.19, 1.17 ± 0.19 with P value = < 0.001.According to diaphragmatic excursion during normal breathing, there was no significant difference between 1.8 ± 0.7 and 2.05 ± 0.54 with P value = 0.07.According to diaphragmatic thickness during maximum inspiration, there was a significant difference of 3.49 ± 1.07, and 5.86 ± 1.09 with P value = < 0.001.Even in pneumological circumstances, ultrasonography has become an acknowledged modality in recent years.However, little study has been done on the US characteristics of the diaphragm and other respiratory muscles in patients with COPD.The measurement can be repeated and is feasible with standard techniques [11,12].exception is extreme obesity, which was shown to be consistent with previous findings on healthy individuals due to the thickness of subcutaneous tissues and high acoustic impedance.
In comparison to healthy controls, they discovered that COPD patients exhibited reduced diaphragmatic mobility (P = 0.001).Moreover, Rocha et al. [4] showed COPD patients had less diaphragmatic mobility than controls consistent with what we found during our study.
Moreover, Aktürk et al. [13] investigated the diaphragmatic mobility in 30 control subjects and 76 COPD patients using M-mode ultrasonography.They found that during tidal breathing, people with COPD experienced a diaphragmatic excursion of 1.65 ± 0.66 cm, compared to 2.21 ± 0.56 cm in the control group.The mean diaphragmatic excursion during deep breathing was statistically significant by Boussuges et al. [14] who reported that the COPD patients at 4.64 ± 1.34 cm and the control group at 6.23 ± 0.74 cm; this could be the result of differences in posture during the ultrasonographic assessment.
The research by Boussuges et al. [14] showed that individuals were in a semi-recumbent posture, although they were still standing.In a supine position, the diaphragm moves more than in an upright or seated position.Diaphragmatic dysfunction is common in COPD patients.While there are a number of explanations, the two most common ones that result in muscle weakness are hunger and lung hyperinflation.When the lungs are overinflated, the diaphragm is mechanically handicapped.The diaphragmatic weakness has been explained more recently by remodeling, oxidative stress exposure, and a decrease in myosin filaments due to decreased protein synthesis and increased muscle cell death.
Our findings are consistent with those of Dos Santos Yamaguti et al. [3] who discovered a statistically significant difference in the diaphragmatic mobility measured by M-mode ultrasonography between patients with mild blockage (44.2 ± 12.3 mm) and patients with moderate and severe obstruction (34.7 ± 8.0 and 30.7 ± 7.5 mm), respectively.
The positive connection between 6MWT and diaphragmatic excursion may be explained by the detrimental impact of reduced diaphragmatic mobility on exercise capacity.
The evidence found that lung function and diaphragmatic excursion are both impacted by COPD.We discovered that COPD patients had lower diaphragmatic excursion than controls.Reduced diaphragmatic excursion indicates that the diaphragm's capacity to contract is impaired in COPD.
Reduced contractility is caused by the pathophysiology of the illness.Emphysema and bronchitis, which restrict airways and trap air in the lungs, are included in COPD.The diaphragm normally travels cranially during expiration and caudally during inspiration.The diaphragm might migrate caudally because of hyperinflation of the lungs brought on by COPD.The diaphragm muscle suffers because of this mechanical disadvantage.According to earlier research, increasing feeling of dyspnea is linked to decreased diaphragmatic mobility.The diaphragm flattens because of structural alterations, which limits their capacity to move cranially and caudally.The association between spirometry data and the sonographic evaluation of diaphragmatic excursion is another significant conclusion of this investigation.
In the current investigation, we discovered that in the study group, diaphragmatic excursion marginally correlates with FEV1 and highly corresponds with FEV1/ FVC.These results support those of Rocha et al. [4] who established a link between pulmonary variables (FEV1, FEV1/FVC, and FVC) and diaphragmatic motility.As the illness develops, the diaphragm muscle's resting length decreases, and its fibers get shorter.This has an impact on both their lung function and breathing capacity.Because of COPD-related inflammation and airway obstruction, air gets trapped in the alveoli.As the illness worsens, lung function deteriorates.In its advanced stages, COPD can cause hyperkyphosis, which restricts the chest wall's ability to expand.A study found a correlation between diaphragmatic mobility and the kyphotic angle.Thus, it stands to reason that diaphragmatic mobility and lung function are both compromised by COPD.
Most COPD patients visit chest clinics; hence, the study's small sample size of COPD patients is its weakness.Another drawback is that ultrasonography was only used to evaluate the right hemidiaphragm.Standardized guidelines on the assessment of diaphragmatic excursion in patients with COPD would require larger sample sizes and a wider geographic scope for future investigations, especially for patients with severe and very severe COPD.

Conclusion
The use of ultrasonography for assessing the diaphragmatic excursion strongly correlates with FEV1/FVC.Further studies with a larger number of patients, especially with severe and very severe COPD, would be required covering wider geographical areas for standardized guidelines on the assessment of diaphragmatic excursion in COPD patients.

Fig. 3
Fig. 3 ROC curve showing outcome assessment among the studied groups: a mild group, b moderate group, c severe group, and very severe group

Table 1
Outcome assessment of included cases

Table 2
Subgroup outcome assessment of all diseased groups