Correlation of diaphragm thickness with pulmonary function test in Parkinson’s disease

Abstract

BACKGROUND

Dopaminergic neurons are lost in Parkinson’s disease (PD), a degenerative neurological condition. While the effects of PD on motor functions are well understood, its impact on respiratory function is less clear. In PD patients with suspicious pulmonary symptoms, the presence and degree of impairment in lung function often cannot be optimally assessed through pulmonary function tests (PFTs) due to the patients' neurological symptoms.

AIM

To examine the relationship between diaphragmatic thickness as determined by ultrasonography (US) and conventional PFTs in PD patients. Additionally, we evaluated the potential use of diaphragmatic thickness as an alternative measure for assessing respiratory function in PD patients who are unable to perform PFTs.

METHODS

A total of 43 PD patients who presented to the clinics between June 15, 2021, and June 30, 2022, were included. Patients with coronavirus disease 2019 infection history, conditions affecting diaphragmatic motility, recent thoracic or abdominal surgery, or imaging showing restrictive masses were excluded. Demographic data, disease duration, Hoehn-Yahr stage, and medication use were recorded. PFTs were used to evaluate forced vital capacity, forced expiratory volume in the first second, and other parameters, while US was used to measure diaphragmatic thickness. Breathlessness was assessed using the modified medical research council dyspnea scale.

RESULTS

Significant correlations were found between peak expiratory flow (PEF) and diaphragm fraction (P = 0.019), as well as between PEF percentage and diaphragmatic thickness during expiration (P = 0.023). In early-stage PD, diaphragmatic thickness during inspiration correlated with oxygen saturation (P = 0.048). In advanced-stage PD, PEF and PEF% were significantly correlated with diaphragm thickness during expiration [r = 0.405, P = 0.049 (for PEF); r = 0.463, P = 0.023 (for PEF%)] and diaphragm fraction [r = -0.476, P = 0.019 (for PEF); r = -0.617, P = 0.001 (for PEF%)].

CONCLUSION

Present study assessed the relationship between PFTs and diaphragmatic thickness in PD patients. Diaphragmatic thickness measured by US was found to correlate with certain PFT parameters, suggesting it could be used as an alternative measure for assessing respiratory function in Parkinson’s patients who have difficulty performing PFTs.

Key Words: Parkinson’s disease; Ultrasonography; Diaphragmatic thickness; Pulmonary function test; Respiratory function

Core Tip: In addition to motor impairments, Parkinson’s disease is also associated with respiratory dysfunction. This study investigated the relationship between diaphragm thickness measured by ultrasound and pulmonary function test (PFT) parameters. The results demonstrated significant correlations, particularly in advanced-stage patients, between diaphragm thickness and PFT values. Ultrasound-based diaphragm assessment may serve as a promising non-invasive alternative for monitoring respiratory function in Parkinson’s patients who are unable to perform PFTs.

INTRODUCTION

Parkinson’s disease (PD) is a progressive neurological disorder characterized by the loss of dopaminergic neurons in the central nervous system. This disease affects motor functions, leading to extrapyramidal system dysfunctions such as tremor, bradykinesia, akinesia, cogwheel rigidity, and impaired postural reflexes[1,2]. Due to these motor impairments, patients experience significant difficulties in performing daily living activities. While muscle strength is generally preserved, patients often struggle with performing rapid and successive movements, which allow them to complete simple motor tasks but present challenges in more complex and repetitive actions[3]. In addition to the motor symptoms, the impact of PD on respiratory function is gaining increasing attention.

Respiratory dysfunction is a lesser-known yet significant complication of PD. In the early stages of the disease, the respiratory system is generally not noticeably affected; however, as the disease progresses, respiratory issues become more apparent. The effects of PD on the respiratory system can result from a combination of both motor and non-motor symptoms. Motor symptoms lead to the weakening of respiratory muscles and reduced diaphragm mobility, while non-motor symptoms, particularly autonomic nervous system dysfunction, may interfere with the regulation of breathing[4,5]. In advanced stages, the strength and mobility of respiratory muscles decrease, leading to slower breathing, loss of depth in respiration, and sometimes respiratory failure[6,7].

Many PD patients are unaware of their respiratory difficulties as the disease progresses[8]. This lack of awareness is often due to the focus on motor symptoms and the adoption of a sedentary lifestyle, which may mask respiratory problems and prevent patients from recognizing respiratory dysfunction[3,9]. Additionally, the motor symptoms of PD often make it difficult to perform standard pulmonary function tests (PFTs) accurately. Patients with PD struggle to perform the rapid, repetitive movements required for these tests, creating a need for alternative methods to assess respiratory function.

In this context, diaphragmatic thickness that measured by ultrasonography (US) may serve as a promising alternative for assessing respiratory function in PD patients. The diaphragm, being the primary muscle involved in breathing, plays a critical role in respiratory function. Changes in diaphragmatic thickness can provide valuable information regarding the strength and function of respiratory muscles. Measuring diaphragmatic thickness via ultrasound in a non-invasive manner may offer a practical and effective way to assess respiratory function in PD patients. Furthermore, for those who find it difficult to perform PFTs, this method could become an essential tool in monitoring changes in respiratory function and guiding treatment decisions.

The aim of this study was to evaluate the use of diaphragmatic thickness that measured by US as an alternative measure for assessing respiratory function in patients with PD who face difficulties in performing PFTs.

MATERIALS AND METHODS

Study population

This prospective cohort study was approved by the Ethics Committee of our institution (approval No. 2021/146, approval date: June 8, 2021). The study was conducted in the radiology, pulmonology, physiotherapy, and neurology departments. A total of 43 patients diagnosed with PD who presented to our clinics between June 15, 2021, and June 30, 2022, were included.

Inclusion and exclusion criteria

Patients with a confirmed diagnosis of PD who were willing to participate in the study were included. Exclusion criteria were: Individuals with recent coronavirus disease 2019 infection history, conditions increasing intra-abdominal pressure, disorders affecting diaphragmatic motility, recent thoracic or abdominal surgery or the presence of restrictive masses (parenchymal, pleural, or chest wall). The diagnosis of PD was established based on the clinical diagnostic criteria from the United Kingdom PD Society Brain Bank[10].

Demographic and clinical data collection

Demographic data, including gender, age, disease duration, body mass index, and current anti-Parkinson medications, were collected. The Hoehn-Yahr scale was used to categorize disease stages: Scores < 2 were considered early-stage PD, and scores ≥ 2 were considered advanced-stage PD.

PFT

Standard spirometric measurements were performed using a MasterScreen PFT device (CareFusion, Hoechberg, Germany). Each maneuver was repeated at least three times, and the best results were recorded. The parameters assessed included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the FEV1/FVC ratio. Oxygen saturation and pulse were measured with a pulse oximeter. The degree of breathlessness was assessed by a physiotherapist using the modified medical research council (mMRC) dyspnea scale. Breathlessness is categorized into six stages using the mMRC dyspnea scale. No dyspnea is indicated by a category of 0. People in category 1 have mild dyspnea, which is characterized by shortness of breath when they rush on flat ground or climb a small incline. Category 2, indicates patients who has mild dyspnea, move more slowly than people at their age on flat ground because due to the out of breath. A moderately severe case of dyspnea is indicated by category 3, for the patients that must stop walking at their own pace on level ground due to dyspnea. People in category 4 have severe dyspnea, which causes them to stop for air after walking on flat ground for a few minutes or for approximately 100 yards. Last but not least, category 5 denotes a very severe form of dyspnea, in which patients are either too out of breath to leave the house or become out of breath while putting on or taking off their clothes.

Measurement of diaphragm thickness

Diaphragm thickness was measured using an Esaote MyLab Five ultrasound device with a low-frequency convex probe (3 MHz). The transducer was positioned on the chest wall at the level of the right ninth intercostal space while the patient was in a supine position. Diaphragm thickness was measured at the end of expiration and inspiration, and diaphragmatic motion was noted during inspiration (Figure 1). The diaphragm thickness fraction (%) was calculated using the formula: [(thickness_max insp - thickness_max exp)/thickness_max exp] × 100.

Figure 1 Measurement of diaphragm thickness by ultrasonography. A: Diaphragm thickness during inspirium; B: Diaphragm thickness during expirium.

Ethical considerations

The study was approved by the Abant Izzet Baysal University Ethics Committee (approval No. 2021/146, approval date: June 8, 2021), and written informed consent was obtained from all participants before enrollment. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki.

Statistical analysis

The statistical package for the social sciences (SPSS 16.0 for Windows, IBM Co, Chicago, IL, United States) software was used to analyze the data. The normality distribution was confirmed using histograms and the Shapiro-Wilk test. The descriptive data were presented as percentages (%) or as numbers (n) or mean ± SD. For comparisons between groups, the χ² test (for categorical variables) and the Student’s t-test (for numerical variables) were used. For correlation analysis, Pearson’s correlation coefficients were employed. Statistical significance was set on a P value lower than 0.05.

RESULTS

A total of 43 patients with PD were included in the study, with a mean age of 67.5 ± 10 years. Among the participants, 22 were female and 21 were male.

Early-stage PD

In the early-stage PD group (Hoehn-Yahr score < 2), the relationship between clinical findings, PFT parameters, and sonographic measurements was evaluated. A significant inverse correlation was found between maximal mid-expiratory flow (MMEF) and diaphragm fraction (r = -0.564, P = 0.036). This suggests that changes in diaphragm thickness, especially during expiration, may reflect early-stage respiratory compromise in patients with PD. Furthermore, diaphragm thickness during inspiration was significantly and negatively correlated with peripheral oxygen saturation (pSO2) (r = -0.535, P = 0.048). This finding implies that inspiratory diaphragm function could be an indicator of oxygenation status in early-stage PD.

Advanced-stage PD

For the advanced-stage PD group (Hoehn-Yahr score ≥ 2), more pronounced correlations were observed between peak expiratory flow (PEF) values and diaphragm thickness. Specifically, in advanced-stage PD, PEF and PEF% were significantly correlated with diaphragm thickness during expiration [r = 0.405, P = 0.049 (for PEF); r = 0.463, P = 0.023 (for PEF%)] and diaphragm fraction [r = -0.476, P = 0.019 (for PEF); r = -0.617, P = 0.001 (for PEF%)]. These findings indicate that in advanced-stage PD, impaired diaphragmatic motion during expiration and thinner diaphragm thickness are associated with worse pulmonary function, highlighting the progressive nature of respiratory dysfunction as the disease advances.

Clinical disability

The clinical disability was assessed using the Hoehn-Yahr scale. Patients with scores < 2 were classified as having early-stage disease, while those with scores ≥ 2 were classified as having advanced-stage disease. When comparing the demographic, clinical, PFT, and sonographic measurements of the 16 patients with early-stage PD and 27 patients with advanced-stage PD, there were no significant differences in PFT parameters and sonographic measurements between the two groups (Table 1).

Table 1 Comparison of demographic, clinical, spirometry, and ultrasound findings in early and advanced stage Parkinson’s disease patients.

	Early stage (n = 16)	Advanced stage (n = 27)	Total (n = 43)	P value
Age	66.1 ± 8.3	68.3 ± 10.9	67.5 ± 1	0.490
Gender (M/F)	8/8	13/14	21/22	0.907
mMRC	1 (0-4)	2 (0-3)	1 (0-4)	0.012
pSO2	96 (93-99)	96 (57-98)	96 (57-99)	0.487
Disease duration (months)	12 (1-120)	72 (1-300)	48 (1-300)	0.001
Heart rate	79.8 ± 12.6	80 ± 16.4	79.9 ± 15	0.974
FEV1%	81.1 ± 17.2	87.5 ± 12.4	85.1 ± 14.5	0.168
FVC%	83 ± 15.4	85.4 ± 19	84.5 ± 17.6	0.666
FEV1/FVC%	78.8 ± 6.3	81 ± 8.8	80.2 ± 8	0.392
PEF%	56.4 ± 15.8	63.9 ± 17.2	61.1 ± 16.9	0.162
MMEF%	68.6 ± 28.7	83.2 ± 24.1	77.6 ± 26.6	0.084
Diaphragm thickness during inspiration	3.7 ± 1.1	3.5 ± 1	3.6 ± 1	0.619
Diaphragm thickness during expiration	2.7 ± 0.7	2.5 ± 0.8	2.6 ± 0.8	0.482
Diaphragm fractional index	36.4 ± 21.4	40.3 ± 25.7	38.9 ± 24	0.639

M: Male; F: Female; mMRC: Modified medical research council; FEV1: Forced expiratory volume in the first second; FVC: Forced vital capacity; PEF: Peak expiratory flow; MMEF: Maximal-mid expiratory flow; pSO₂: Peripheral oxygen saturation.

Correlation of clinical findings, PFT parameters, and sonographic data

Early-stage PD: Significant inverse correlations were observed between MMEF and diaphragm fraction (r = -0.564, P = 0.036), and between diaphragm thickness during inspiration and pSO₂ (r = -0.535, P = 0.048). These findings suggest that diaphragm function and its thickness could be early indicators of respiratory changes in PD (Table 2).

Table 2 Correlation between spirometry and clinical measures with ultrasound in early stage.

	Diaphragm thickness during inspiration		Diaphragm thickness during expiration		Diaphragm fractional index
	r	P value	r	P value	r	P value
FVC	-0.107	0.715	0.077	0.793	-0.257	0.376
FVC%	-0.340	0.235	-0.181	0.536	-0.286	0.322
FEV1	-0.184	0.529	0.046	0.877	-0.352	0.217
FEV1%	-0.359	0.208	-0.149	0.612	-0.389	0.169
FEV1/FVC	0.096	0.743	0.248	0.392	-0.165	0.574
PEF	-0.011	0.969	0.186	0.525	-0.454	0.103
PEF%	-0.148	0.613	-0.021	0.943	-0.387	0.172
MMEF	-0.208	0.477	0.157	0.591	-0.564	0.036
MMEF%	-0.396	0.161	-0.232	0.424	-0.360	0.206
pSO2	-0.535	0.048	-0.422	0.133	-0.241	0.406
mMRC	0.248	0.413	0.123	0.688	0.249	0.411
Age	0.119	0.686	-0.112	0.703	0.329	0.251
Heart rate	-0.231	0.426	0.051	0.863	-0.428	0.127
Disease duration (months)	-0.353	0.215	-0.217	0.457	-0.313	0.276

FVC: Forced vital capacity; FEV1: Forced expiratory volume in the first second; PEF: Peak expiratory flow; MMEF: Maximal-mid expiratory flow; mMRC: Modified medical research council; pSO₂: Peripheral oxygen saturation.

Advanced-stage PD: In this group, significant correlations were found between PEF values and PEF% with diaphragm thickness during expiration (r = 0.405, P = 0.049; r = 0.463, P = 0.023) and diaphragm fraction (r = -0.476, P = 0.019; r = -0.617,P = 0.001). This emphasizes that diaphragm function, especially during expiration, is more closely linked to pulmonary dysfunction as the disease progresses (Table 3).

Table 3 Correlation between spirometry and clinical measures with ultrasound in late stage.

	Diaphragm thickness during inspiration		Diaphragm thickness during expiration		Diaphragm fractional index
	r	P value	r	P value	r	P value
FVC	-0.225	0.229	-0.204	0.340	-0.067	0.754
FVC%	-0.006	0.978	0.091	0.672	-0.162	0.449
FEV1	-0.288	0.172	-0.212	0.320	-0.075	0.728
FEV1%	-0.040	0.853	0.144	0.501	-0.186	0.384
FEV1/FVC	0.129	0.549	-0.117	0.586	0.302	0.151
PEF	0.041	0.849	0.405	0.049	-0.476	0.019
PEF%	0.011	0.960	0.463	0.023	-0.617	0.001
MMEF	-0.259	0.233	-0.170	0.438	-0.113	0.608
MMEF%	-0.157	0.475	-0.113	0.607	-0.020	0.927
pSO2	0.282	0.182	0.189	0.377	0197	0.355
mMRC	0.045	0.864	0.286	0.265	-0.381	0.132
Age	0.065	0.762	-0.045	0.834	0.258	0.224
Heart rate	-0.413	0.045	-0.300	0.154	-0.167	0.436
Disease duration (months)	-0.053	0.805	-0.260	0.221	0.262	0.217

FVC: Forced vital capacity; FEV1: Forced expiratory volume in the first second; PEF: Peak expiratory flow; MMEF: Maximal-mid expiratory flow; mMRC: Modified medical research council; pSO₂: Peripheral oxygen saturation.

These findings suggest that diaphragmatic thickness, measured by ultrasound, may serve as a valuable tool for assessing respiratory function in PD patients, particularly in cases where traditional PFTs are difficult to perform.

DISCUSSION

In present work we found that there were significant correlations between diaphragm thickness and function with respiratory functions in both early and advanced stages of PD. These results suggest that diaphragm thickness measurement could serve as an alternative evaluation tool, particularly for PD patients with motor impairments who are unable to perform standard PFTs.

In present study, a significant negative correlation was found between MMEF and diaphragm fraction index in early-stage PD patients. This suggests that changes in diaphragm thickness, particularly during expiration, could be an early indicator of respiratory muscle weakness. These findings are consistent with previous studies that have reported early-stage respiratory muscle dysfunction in PD[11-15]. Additionally, diaphragm thickness during inspiration was significantly correlated with pSO2, indicating that diaphragm function in early-stage PD may be linked to oxygenation status. These findings suggest that diaphragm thickness could serve as an important biomarker for early detection of respiratory dysfunction in PD.

In advanced-stage PD patients (Hoehn-Yahr ≥ 2), significant correlations were found between diaphragm thickness and PEF and PEF percentage. Specifically, significant relationships were observed between diaphragm thickness during expiration and diaphragm fraction with PEF values. These results suggest that in advanced-stage PD, impaired diaphragm mobility during expiration and thinner diaphragm thickness are associated with worsened respiratory function, highlighting the need for increased respiratory support. The weakening of respiratory muscles and thinning of the diaphragm leads to more pronounced respiratory function deterioration in these patients. This finding emphasizes that in advanced PD, respiratory function is significantly impaired, which may result in increased need for respiratory support.

Respiratory function in PD patients is typically impaired as motor symptoms progress[16]. Our findings suggest that diaphragm thickness could be an alternative to traditional PFTs in assessing respiratory function. In particular, when motor impairments are severe and patients struggle to perform PFTs, diaphragm thickness measurement via ultrasound provides a non-invasive and practical solution. The use of ultrasound for evaluating diaphragm mobility has been increasingly recognized in recent years[17-21]. This method could be integrated into clinical practice to monitor respiratory function and guide treatment decisions for PD patients.

One of the main limitations of our study is the absence of a control group. Without a comparison with healthy individuals, it is not possible to definitively conclude whether the findings are specific to PD. Therefore, future studies should include comparisons between PD patients and healthy controls, using larger sample sizes to improve generalizability. Additionally, the small sample size in our study (43 patients) may have resulted in some findings not reaching statistical significance. Larger studies are needed to validate these results. Furthermore, measurements by US are subject to user-dependent errors and technical limitations, which should also be considered.

CONCLUSION

In conclusion, the findings of present study suggest that diaphragm thickness, measured by ultrasound, could serve as an alternative method for assessing respiratory function in PD patients. Particularly in cases with severe motor impairments, measuring diaphragm thickness can be an important tool for tracking respiratory function. This non-invasive method provides a valuable option for monitoring respiratory health in PD patients and guiding treatment decisions.