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Exercise testing in patients with diaphragm paresis
Accepted Manuscript Title: Exercise testing in patients with diaphragm paresis Authors: Tristan Bonnevie, Francis-Edouard Gravier, Agathe Ducrocq, David Debeaumont, Catherine Viacroze, Antoine Cuvelier, Jean-Franc¸ois Muir, Catherine Tardif PII: DOI: Reference:
S1569-9048(17)30348-8 https://doi.org/10.1016/j.resp.2017.11.006 RESPNB 2891
To appear in:
Respiratory Physiology & Neurobiology
Received date: Revised date: Accepted date:
4-10-2017 13-11-2017 14-11-2017
Please cite this article as: Bonnevie, Tristan, Gravier, Francis-Edouard, Ducrocq, Agathe, Debeaumont, David, Viacroze, Catherine, Cuvelier, Antoine, Muir, Jean-Franc¸ois, Tardif, Catherine, Exercise testing in patients with diaphragm paresis.Respiratory Physiology and Neurobiology https://doi.org/10.1016/j.resp.2017.11.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Type: Original research Exercise testing in patients with diaphragm paresis. Short title: Diaphragm paresis and exercise capacity Tristan Bonnevie, PT, Msc (1, 2); Francis-Edouard Gravier, PT (1); Agathe Ducrocq, MD (3,4); David Debeaumont, MD (1,3); Catherine Viacroze, MD (4); Antoine Cuvelier, MD, PhD (2,4); Jean-François Muir, MD (1,2); Catherine Tardif, MD (1,2,3).
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1. ADIR Association, Bois-Guillaume, France 2. Normandie University, UNIROUEN, EA UPRES 3830, Rouen university hospital, Haute Normandie Research and Biomedical Innovation, Rouen, France 3. Rouen university hospital, Physiology Department, Rouen, France 4. Rouen university hospital, Pulmonary, Thoracic oncology and Respiratory intensive Department, Rouen, France Correspondence for contact purposes only: Tristan Bonnevie
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Department ADIR Association
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France
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+336.50.49.97.69
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+332.35.59.29.71
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[email protected]
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Exercise capacity is slightly reduced in patients with DP ; Dyspnea is the main factor limiting exertion ; Diaphragm function is correlated with exercise ventilation ; Overall inspiratory muscle function is correlated with both exercise capacity and ventilation suggesting the importance of the accessory inspiratory muscles during exercise in patients with DP.
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abstract: 180. Number of figure: 0 Number of table: 3 1
Funding support: None. Statement of submission: Authors have read and approved submission of the manuscript and the manuscript has not been published and is not being considered for publication elsewhere in whole or part in any language except as an abstract.
Condensed abstract The impact of diaphragmatic paresis on exercise capacity is not well known. This retrospective
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study included fourteen patients who underwent both respiratory force assessment and
cardiopulmonary exercise testing. The exercise capacity was slightly reduced due to ventilatory
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limitation. Diaphragm function was correlated with exercise ventilation whereas overall
inspiratory muscle function was correlated with both exercise capacity and ventilation
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suggesting the importance of the accessory inspiratory muscles during exercise.
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Structured abstract Purpose: Diaphragm paresis (DP) is characterized by abnormalities of respiratory muscle function. However, the impact of DP on exercise capacity is not well known. This study was performed to assess exercise tolerance in patients with DP and to determine whether inspiratory muscle function was related to exercise capacity, ventilatory pattern and
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cardiovascular function during exercise.
Methods: This retrospective study included patients with DP who underwent both
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diaphragmatic force measurements, and cardiopulmonary exercise testing (CPET).
Results: Fourteen patients were included. Dyspnea was the main symptom limiting exertion
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(86%). Exercise capacity was slightly reduced (median VO2peak: 80% [74.5%-90.5%]), mostly
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due to ventilatory limitation. Diaphragm and overall inspiratory muscle function were
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correlated with exercise ventilation. Moreover, overall inspiratory muscle function was related
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with oxygen consumption (r=0.61) and maximal workload (r=0.68). Conclusions: DP decreases aerobic capacity due to ventilatory limitation. Diaphragm function
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is correlated with exercise ventilation whereas overall inspiratory muscle function is correlated with both exercise capacity and ventilation suggesting the importance of the accessory
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inspiratory muscles during exercise for patients with DP. Further larger prospective studies are
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needed to confirm these results.
Key-word: Cardiopulmonary exercise testing; Diaphragmatic paresis; Diaphragm weakness;
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Dyspnea; Exercise
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1. Introduction Diaphragmatic paresis (DP) is characterized by abnormalities of pulmonary and respiratory muscle function. It may occur unilaterally or bilaterally although unilateral paresis is more frequent. Idiopathic DP is the most frequent etiology (50%) (Gibson, 1989; Higgs et al., 2002; Piehler et al., 1982; Riley, 1962). The condition is generally under-diagnosed and there are few
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epidemiologic data available, except for post-surgical traumatic injury (Deslauriers, 1998).
Studies of pulmonary function in patients with DP have shown little impairment in
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ventilation but a decrease in vital capacity (VC) (Eisele et al., 1972). The main symptom of DP
is dyspnea (Chuang et al., 2005; Graham et al., 1990; Laroche et al., 1988a) and it intensity
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depends on the etiology, extent of the impairment of diaphragm function, comorbidities and the
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patient’s level of fitness (Le Pimpec-Barthes et al., 2014).
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However, the impact of DP on exercise capacity is not well known. Hart et al found
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exercise tolerance to be reduced, with no differences between patients with uni- or bilateral DP (Hart et al., 2002). Conversely, Chuang et al found no effect on exercise capacity, despite a
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decrease in total lung capacity (TLC) (Chuang et al., 2005). The aim of this study was to assess exercise tolerance in patients with unilateral and
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bilateral DP and to determine whether inspiratory muscle function was related to exercise
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capacity, ventilatory pattern and cardiovascular function during exercise.
2. Method
2.1. Study design and patient selection
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This retrospective study included all consecutive patients assessed for diaphragmatic dysfunction between 2004 and 2015 in Rouen University Hospital. For this type of study, ethical approval and formal consent was not required. 2.2. Inclusion criteria
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Patients were included if they had uni- or bilateral DP relating to the phrenic nerve confirmed by diaphragmatic evoked motor potentials (EMP) and fluoroscopy. Patients had to be at least 18 years old and have undergone both pulmonary function testing and cardiopulmonary exercise testing. They were excluded if they had history of neurological or neuro-muscular disease.
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2.3. Data extraction
Age, gender, height, weight, body mass index (BMI), dyspnea score, pulmonary function,
capacity were extracted through a retrospective chart review. 2.4. Assessment
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2.4.1. Pulmonary function
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diaphragm assessment, exercise capacity and comorbid factors that could influence exercise
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2.4.2. Inspiratory muscle assessment
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Pulmonary function tests were carried out according to the ATS and the ERS guidelines.
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2.4.2.1. Pressure measurements: Oesophageal and gastric pressures (respectively Poes and
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Pga) were recorded using two latex balloon probes (80mm) (Marquat, Boissy Saint Léger, France) connected to a pressure transducer (Benton Dickinson monitoring system, Santa
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Barbara, CA USA). Transdiaphragmatic pressure (Pdi) was calculated as: Pdi=Pga-Poes. The best of three maximal inspiratory maneuvers was recorded as maximal Poes (Poes max).
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Poes sniff was recorded as the best value obtained from 3 sets of 10 sniff (Heritier et al., 1994). 2.4.2.2. Evoked motor potentials (EMP): Unilateral and bilateral twitch oesophageal (Poes
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tw bilat), gastric (Pga tw bilat) and transdiaphragmatic pressures (Pdi tw bilat) were recorded following cervical magnetic stimulation at the end of expiration using a circular coil (2,5 Telsa) (Magstim 200 Ltd., Whitland, UK) positioned at the C7 level (Similowski et al., 1989). Diaphragmatic paresis was defined as Pdi tw bilat below 20cmH2O (Laroche et al., 1988b; Prigent et al., 2008) or Poes tw bilat below 10cmH2O (Verin et al., 2006). Poes sniff was
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considered as pathological if the pressure was less than 70cmH2O for males or less than 60cmH2O for females (Heritier et al., 1994). Finally, fluoroscopic examination was performed during both quiet and deep breathing to assess for paradoxical movement of the affected hemidiaphragm. 2.4.3. Exercise testing:
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Incremental CPET was performed according to the ATS guidelines (ATS, 2003). Gases (VO2 and VCO2) and minute ventilation (VE) were measured breath by breath. Patients were asked
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whether they were limited by respiratory or muscular symptoms. Reference values from the ATS guidelines and from Wasserman et al. were used (ATS, 2003). 2.5. Statistical analysis
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Continuous data were expressed as means (SD) or medians [25th-75th percentile] as appropriate.
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Normality of the distributions was assessed using a Shapiro-Wilk test. Relationships between
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Poes sniff, Poes max, Poes tw bilat and data from CPET were assessed using Pearson or
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Spearman correlation tests according to the normality of the data distribution. Moreover, we
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also assessed the relationship between baseline dyspnea (mMRC score) and data from CPET. Differences between uni- and bilateral DP were assessed using a Wilcoxon Rank Test. A p-
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value < 0.05 was considered statistically significant. Prism 5 software was used for all analyses.
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3. Results 3.1. Patients
Fourteen patients were included, ten of whom had unilateral DP (seven left and three right) and
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four had bilateral DP. No patients had complete diaphragmatic paralysis. Main etiologies were idiopathic (n=4) and post traumatic (n=4). Other etiologies included iatrogenic causes and post cervical oesoarthrosis DP. Patient characteristics are presented in Table 1. Briefly, median age was 66.5 [50-75] years and mean BMI was 29.3 (4.7) kg/m², including five patients with obesity (BMI > 30kg/m²) and one with morbid obesity (BMI > 40kg/m²). Mean dyspnea for the whole
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group (mMRC score) was 2.4 (0.9). It was significantly higher in patients with bilateral than unilateral DP (p<0.01). 3.2. Pulmonary function (Table 2) FEV1% and liter (L) were significantly lower in patients with bilateral DP (50.5% [38.7%58.6%] and 1.1 [0.7-1.5] L respectively) than in patients with unilateral DP (75.8% (18.9%)
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and 1.9 (0.7) L respectively) (both p<0.04). Among the patients with unilateral DP (n=10), two had a restrictive pattern (RP) and one experienced a moderate obstructive pattern. None of the
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patients with bilateral DP had a RP (TLC was > 80% for all patients). Three out of four patients with bilateral DP also had mild obstruction. Median inspiratory capacity was preserved in all but two patients with unilateral DP (those who had a RP) and was decreased in three out four
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3.3. Inspiratory muscle assessment
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patients with bilateral DP (77.5% [62.2-85.3]).
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EMP were performed in all patients except one who had contraindications to the test (allergy
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to latex and history of epilepsy). A gastric balloon could not be used for six patients. Therefore
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only Poes tw bilat was considered. Diaphragmatic paresis was confirmed for all patients except one (Pdi tw bilat 20cmH2O and Poes tw bilat 10cmH2O). However, for this patient and the one
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who was allergic to latex, fluoroscopy revealed that the hemidiaphragm was elevated, motionless during quiet breathing and exhibited paradoxical movement during maximal
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inspiration, thus a diagnosis of unilateral DP was attributed. 3.4. Exercise testing (Table 3)
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The median time between inspiratory muscle assessment and exercise testing was 73.5 [38.5128.5] days. CPET were maximal for all patients. Dyspnea was the main symptom limiting exertion (n=12 (86%)). There were no significant differences between patients either with unior bilateral DP for any parameters measured from the CPET. The exercise capacity of the whole cohort was slightly reduced (median VO2peak: 80% [74.5%-90.5%]). Almost all patients had
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ventilatory limitation with a breathing reserve (BR) below 30% (mean BR: 16.7% (9.2%). Nine patients had a pathological ventilatory pattern with a tidal volume at exhaustion below 60% of the VC, four of whom had a respiratory rate (RR) above 45cpm. The Vd/Vt trend during exercise was normal, progressively decreasing in thirteen patients. Four patients had a Vd/Vt above 0.28 at the end of the exercise.
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3.5. Correlations between inspiratory muscle function and exercise capacity:
Poes sniff: There was a non-significant relationship between Poes sniff and Wpeak (r=0.55,
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p<0.06).
Poes max: Poes max was significantly correlated with Wpeak (r=0.68, p=0.01), VO2peak (r=0.61, p=0.03), VEpeak (r=0.69, p<0.01), Vtpeak (r=0.72, p<0.01) and VO2/heart rate (HR)
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(r=0.64, p=0.02).
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Poes tw bilat: There were significant correlations between Poes tw bilat and VEpeak (r=0.67,
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p=0.01), Vtpeak (r=0.58, p=0.04) and oxygen pulse (VO2/HR) (r=0.56, p=0.05).
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Dyspnée (mMRC): There was no significant relationships between baseline dyspnea and
4. Discussion
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exercise capacity.
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In this cohort of patients with uni and bilateral DP, exercise capacity was slightly decreased,
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limited by impaired ventilation. BR was abolished and ventilatory pattern was pathological (low tidal volume and excessive respiratory rate). Diaphragm and overall inspiratory muscle function were correlated with exercise capacity and ventilation.
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4.1. Diagnosis of diaphragmatic paresis
Pdi tw bilat and Poes tw bilat were used to diagnose diaphragm paresis in the present study. Although reliable and widely used (Hart et al., 2002; Hughes et al., 1999; Laroche et al., 1988b; Prigent et al., 2008; Verin et al., 2006), the most appropriate cut-off threshold has not been determined. Based on their clinical experience, Hart et al. chose a Pdi tw of less than 3.5cmH2O
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to diagnose paralysis (Hart et al., 2002). Based on our clinical experience, a previous report from our laboratory (Verin et al., 2006) and values in the literature, we chose a Poes tw bilat of less than 10cmH2O (Verin et al., 2006) and a Pdi twi bilat of less than 20cmH2O (Laroche et al., 1988b; Prigent et al., 2008). We acknowledge that these thresholds encompass a range of severity of diaphragm weakness, however individual data confirmed that no patients had
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diaphragm paralysis. 4.2. Diaphragm function at rest
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The results showed that vital capacity was decreased in patients with bilateral DP. It was also
decreased in patients with unilateral DP, although to a lesser extent (non-significant difference between groups). This is in accordance with the literature, with reports of decreases in total
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lung capacity and vital capacity that was not different between patients with uni- or bilateral
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DP (Hart et al., 2002). Conversly, some studies found a decrease in vital capacity, inspiratory
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capacity and total lung capacity (Chuang et al., 2005; Hart et al., 2002; Higgs et al., 2002; Verin
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et al., 2006; Welvaart et al., 2013) that are greater in patients with bilateral DP (Laroche et al.,
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1988a; Loh et al., 1977). However, the sample sizes of these studies were very small and further studies are needed to conclude about the difference in respiratory function between uni- or
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bilateral DP.
4.3. Exercise capacity
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Exercise capacity was slightly decreased in the present cohort. As the clinical impact of unilateral DP is considered to be minimal, it was expected to find significantly larger decrease
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in exercise capacity in patients with bilateral DP. However, in accordance with Hart et al, the extent of the decrease was similar between patients with unilateral and bilateral DP (Hart et al., 2002). The loss exercise capacity could therefore be attributed to the pathological pattern of ventilation found in the present study (i.e. low tidal volume and a high respiratory rate). Since respiratory rate is known to influence the rate of perceived dyspnea, this might explain why
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dyspnea limited exertion in almost all patients (Kearon et al., 1991; Lansing et al., 2009; Manning and Schwartzstein, 1995). More specifically, Hart et al. showed that paradoxical abdominal motion can occur in patients with DP. They suggested that in patients with unilateral DP, paradoxical abdominal motion relates a physiologically non-efficient ventilation because the ascension of the diaphragm on the affected side restricts inspiratory airflow (Hart et al.,
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2002). Although not assessed in the present study, this might explain why loss of exercise
capacity was greater than predicted in patients with unilateral DP. This is supported by the fact
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that Welvaart et al. found improvements in peak tidal volume and respiratory rate during
cardiopulmonary exercise testing following surgical plication in patients with unilateral DP (Welvaart et al., 2013).
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Nonetheless, exercise capacity was relatively preserved in the present cohort, suggesting that
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adaptive mechanisms were in place. For example, changes in the fibers of the contralateral hemi
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diaphragm (increasing contraction power) (Wilcox et al., 1990; Pellegrino et al. 2005) and
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fibrosis of the paralyzed hemi diaphragm (limiting paradoxical movement) (Hughes et al. 1999;
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Katz et al. 1998) might occur to improve function. Recruitment of accessory respiratory muscles could occur through the inhibition of an inhibitor signal to diaphragm contraction
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(Luedemann et al. 2002; Xu et al. 2014). Moreover, recruitment of the abdominal muscles would facilitate inspiration due to the passive recoil of the diaphragm (Hart et al. 2002; Valls-
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Sole et al. 2002; Pellegrino et al. 2005). Some patients may also have an accessory phrenic nerve (Hugues et al. 1999).
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4.4. Correlations between inspiratory muscle assessment and exercise capacity
The results suggest that overall inspiratory muscle (Poes max) and diaphragm function (Poes tw bilat) were both positively corelated with peak tidal volume and peak exercise ventilation. This is not surprising since the diaphragm is the main inspiratory muscle. It could be hypothesized that better inspiratory muscle function resulted in better ventilation during
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exercise, which in turn helped patients to sustain higher level of exercise, as suggested by the relationship between inspiratory muscle function and maximal workload. Oxygen pulse was also positively corelated with Poes max and Poes tw bilat presumably due to a better oxygen consumption. This was confirmed by the positive relationship between between Poes max and oxygen consumption. Finally, there was a significant positive relationship between Poes max
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(i. e. global inspiratory muscle function) and maximal workload and peak oxygen consumption, but not between Poes tw bilat and Wpeak and peak oxygen consumption, highlighting the
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important role of the accessory inspiratory muscles during exercise for patients with DP.
Since ventilation during exercise is correlated with inspiratory and diaphragm function, exercise capacity may also change over time due to spontaneous recovery. Interestingly, the reversibility
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of diaphragmatic paresis is debated. Studies describe paralysis, paresis or even diaphragmatic
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“weakness” with different etiologies and with a wide range of follow-up and assessment tools
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(Bai et al., 2006; Dernaika et al., 2008; Hughes et al., 1999; Lisboa et al., 1986; Mulvey et al.,
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1993; Riley, 1962; Sacher et al., 2006; Valls-Sole and Solans, 2002; Verin et al., 2006; Wilcox
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et al., 1990). Wilcox et al and Murray et al stated that the recovery time of the phrenic nerve depends on the type and the extent of the injury (Wilcox et al., 1990). Gayan-Ramirez et al
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retrospectively assessed DP recovery over a median follow-up of 15 months. Recovery of respiratory function (defined as an increase in FVC of 400mL) occurred in 43% and 52% of
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cases at 1 and 2 years respectively. No factors (including the type or the etiology of the paresis) were found to influence the reversibility of respiratory function (Pellegrino et al., 2005).
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Finally, Verin et al found a positive relationship between diaphragm function (Poes sniff) and the time between the onset of symptoms and assessment in patients with unilateral DP, suggesting an improvement over time. Conversely, several studies in both humans (Chuang et al., 2005; Katz et al., 1998; Luedemann et al., 2002; Verin et al., 2006) and animals (Gauthier et al., 2006; Xu et al., 2014) do not support the reversibility of diaphragm paresis.
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4.5. Patient considerations: Data from only 14 patients were available during the 11 years study period. This could be explained by (1) the low incidence of this condition (Gayan-Ramirez et al., 2008) and (2) the lack of symptoms at rest that do not incite patients to consult a doctor. Moreover, diaphragm paresis may resolve spontaneously, masking the real prevalence of this condition (Dernaika et
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al., 2008; Verin et al., 2006). Thereby, the true incidence of the disease is not known. Nevertheless, the results are in accordance with the literature and unilateral DP was more
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frequent (2-4, 37). The main symptoms are exercise dyspnea and orthopnea, which are more
frequent in the case of bilateral DP (Chuang et al., 2005; Clague and Hall, 1979; Elefteriades et al., 2008; Gibson, 1989; Graham et al., 1990; Laroche et al., 1988a; Loh et al., 1977; McCredie
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et al., 1962). In the present study, dyspnea appeared to be more intense in patients with bilateral
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DP (MRC score: 2 for unilateral, 3-4 for bilateral, p<0.01).
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4.6. Limitations
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This study has several limitations. First, there may be bias due to the retrospective design. For
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example, the time between symptom-onset and assessment was not known. Secondly, not all data for the diaphragmatic assessment were available: Pdi could not always be calculated if Pga
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was not measured, and one patient did not undergo magnetic stimulation. Thirdly, the sample was small due to the low incidence of PD and might have lacked power to detect differences
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between groups. Moreover, the sample might not be representative of the whole population since no patients had diaphragmatic paralysis, few had idiopathic DP and some had obesity or
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obstructive disease, both of which are known to reduce exercise capacity and induce dyspnea (Sava et al., 2010).
5. Conclusion Uni- or bilateral DP may lead to a decrease in aerobic capacity due to ventilatory limitation. Diaphragm function is correlated with exercise ventilation whereas overall inspiratory muscle
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function is correlated with both exercise capacity (oxygen consumption and maximal workload) and ventilation suggesting the importance of the accessory inspiratory muscles during exercise for patients with DP. Further prospective studies, with a larger sample of patients, are needed to confirm these results and identify prognostic factors that could help clinicians to manage
Ethical approval: For this type of study, formal consent is not required.
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patients and refer them, if necessary, for surgical treatment.
Conflict of interest: The authors state that they have no conflicts of interest.
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Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R.O., Burgos, F., Casaburi, R., Coates, A., van der Grinten, C.P., Gustafsson, P., Hankinson, J., Jensen, R., Johnson, D.C., MacIntyre, N., McKay, R., Miller, M.R., Navajas, D., Pedersen, O.F., Wanger, J., 2005. Interpretative strategies for lung function tests. The European respiratory journal 26, 948-968. Piehler, J.M., Pairolero, P.C., Gracey, D.R., Bernatz, P.E., 1982. Unexplained diaphragmatic paralysis: a
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harbinger of malignant disease? The Journal of thoracic and cardiovascular surgery 84, 861-864. Prigent, H., Orlikowski, D., Fermanian, C., Lejaille, M., Falaize, L., Louis, A., Fauroux, B., Lofaso, F., 2008.
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Sniff and Muller manoeuvres to measure diaphragmatic muscle strength. Respiratory medicine 102, 1737-1743.
Riley, E.A., 1962. Idiopathic diaphragmatic paralysis; a report of eight cases. The American journal of
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medicine 32, 404-416.
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Sacher, F., Monahan, K.H., Thomas, S.P., Davidson, N., Adragao, P., Sanders, P., Hocini, M., Takahashi,
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Y., Rotter, M., Rostock, T., Hsu, L.F., Clementy, J., Haissaguerre, M., Ross, D.L., Packer, D.L., Jais, P.,
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2006. Phrenic nerve injury after atrial fibrillation catheter ablation: characterization and outcome in a multicenter study. Journal of the American College of Cardiology 47, 2498-2503.
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Sava, F., Laviolette, L., Bernard, S., Breton, M.J., Bourbeau, J., Maltais, F., 2010. The impact of obesity
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on walking and cycling performance and response to pulmonary rehabilitation in COPD. BMC pulmonary medicine 10, 55.
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Similowski, T., Fleury, B., Launois, S., Cathala, H.P., Bouche, P., Derenne, J.P., 1989. Cervical magnetic stimulation: a new painless method for bilateral phrenic nerve stimulation in conscious humans. Journal of applied physiology (Bethesda, Md. : 1985) 67, 1311-1318.
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Valls-Sole, J., Solans, M., 2002. Idiopathic bilateral diaphragmatic paralysis. Muscle & nerve 25, 619623.
Verin, E., Marie, J.P., Tardif, C., Denis, P., 2006. Spontaneous recovery of diaphragmatic strength in unilateral diaphragmatic paralysis. Respiratory medicine 100, 1944-1951.
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Welvaart, W.N., Jak, P.M., van de Veerdonk, M.C., Marcus, J.T., Ottenheijm, C.A., Paul, M.A., Vonk Noordegraaf, A., 2013. Effects of diaphragm plication on pulmonary function and cardiopulmonary exercise parameters. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 44, 643-647. Wilcox, P.G., Pare, P.D., Pardy, R.L., 1990. Recovery after unilateral phrenic injury associated with
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coronary artery revascularization. Chest 98, 661-666. Xu, Y., Rui, J., Zhao, X., Xiao, C., Bao, Q., Li, J., Lao, J., 2014. Effect of isolated unilateral diaphragmatic
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paralysis on ventilation and exercise performance in rats. Respiratory physiology & neurobiology 196, 25-32.
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Total cohort 14 (100)a 66.50 (50-75)c 29.3 (4.7)b 2.4 (0.9)b
Values expressed as numbers (%); bValues expressed as means (SD); cValues expressed as medians (25th-75th percentile).
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a
Bilateral paresis 4 (29)a 75 (63-76.5)c 30.3 (26.1-33.9)c 3.5 (3-4)c
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Table 1: Patient characteristics (n=14) Unitaleral paresis Variable, (units) n (%) 10 (71)a Age (years) 60.60 (12.1)b BMI (kg/m²) 29.87 (5.1)b Dyspnea (MRC) 2 (1.8-2.3)c*
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mMRC: modified Medical Research Council score.
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*: score significantly lower than for bilateral paresis, p<0.01.
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Table 2: Pulmonary function (n=14) Unilateral paresis 2.1 (1.8-3.8)a 83.2 (20.4)a 98.4 (30.2)a 91.8 (17.8)a 90.9 (19.9)a 1.9 (0.7)a 75.8 (18.9)a 74.2 (9.2)a
Bilateral paresis 1.9 [1.3-2.2]b 63.6 [55.4-72.1]b 77.5 [62.2-85.3]b 84.3[82.4-98.6]b 101.9 [91.2-121.5]b 1.1 [0.7-1.5]b* 50.5 [38.7-58.6]b* 67 [62.6-71.3]b*
Total cohort 2 [1.7-3.1]b 77.9 (19.8)a 91.7 (28)a 90.9 (15.6)a 94.9 (19.4)a 1.6 (0.7)a 68.2 (20.7)a 72.1 (8.6)a
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Variable, (units) VC (L) VC (%) IC (%) TLC (%) FRC (%) FEV1 (L) FEV1 (%) FEV1/VC (% ratio)
a
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TLC: total lung capacity; VC: vital capacity; FEV1: forced expiratory volume in one second; IC: inspiratory capacity; FRC: functional residual capacity. Values expressed as means (SD); bValues expressed as medians [25th-75th percentile].
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*: score significantly lower than for unilateral paresis, p<0.03.
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Table 3: Cardiopulmonary exercise testing (n=14) Unilateral paresis 98.5 (34.2)a 81.2 (22.1)a 18.4 (6.4)a
Variable, (units)
Bilateral paresis
Total cohort
91.1 (34.9)a Metabolic load 78 (20.6)a 15.5 (12.219.6)b 80 (77.3-93.3)b 78.5 (62.4-94.5)b 80 (74.590.5)b VEpeak (L/min) 62.4 (22.2)a 36 (24.3-53.8)b 55.4 (22.9)a a Ventilatory VEpeak (%) 118.9 (18.1) 122.4 (112.2- 119.8 (15.9)a pattern 131.3)b a RRpeak (cpm) 41.5 (5.9) 36 (32.3-39.8)b 39.9 (5.9)a Vd/Vtpeak 26.1 (6.9)a 39.5 (35-44)b 28.8 (8.5)a Vtpeak (L) 1.5 (0.6)a 1 (0.7-1.4)b 1.4 (0.5)a a b Vt/VC (%) 58.9 (7.6) 50 (53.5-63.8) 58.9 (6.9)b BR (%) 17.6 (10.2)a 13.9 (8.2-21.2)b 16.7 (9.2)a a b HRpeak/HRtheo (%) 81.5 (7.8) 78 (64.8-80.8) 79.5 (84.9)a Cardiovascular VO2/HRpeak 10.4 (4)a 8.6 (6.5-12)b 10 (3.7)a a Values expressed as means (SD); bValues expressed as medians (25th-75th percentile).
70 (42.5-105)b 70.6 (54.5-85)b 12.4 (11.6-15.6)b
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Wpeak (W) Wpeak (%) VO2peak (ml/kg/min) VO2peak (%)
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W: workload; VO2: oxygen consumption; VE: minute ventilation; RR: respiratory rate; Vd: dead space; Vt: tidal volume; VC: vital capacity; HR: heart rate; theo: theoretical value; BR: breathing reserve.
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S1569-9048(17)30348-8 https://doi.org/10.1016/j.resp.2017.11.006 RESPNB 2891
To appear in:
Respiratory Physiology & Neurobiology
Received date: Revised date: Accepted date:
4-10-2017 13-11-2017 14-11-2017
Please cite this article as: Bonnevie, Tristan, Gravier, Francis-Edouard, Ducrocq, Agathe, Debeaumont, David, Viacroze, Catherine, Cuvelier, Antoine, Muir, Jean-Franc¸ois, Tardif, Catherine, Exercise testing in patients with diaphragm paresis.Respiratory Physiology and Neurobiology https://doi.org/10.1016/j.resp.2017.11.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Type: Original research Exercise testing in patients with diaphragm paresis. Short title: Diaphragm paresis and exercise capacity Tristan Bonnevie, PT, Msc (1, 2); Francis-Edouard Gravier, PT (1); Agathe Ducrocq, MD (3,4); David Debeaumont, MD (1,3); Catherine Viacroze, MD (4); Antoine Cuvelier, MD, PhD (2,4); Jean-François Muir, MD (1,2); Catherine Tardif, MD (1,2,3).
Name
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1. ADIR Association, Bois-Guillaume, France 2. Normandie University, UNIROUEN, EA UPRES 3830, Rouen university hospital, Haute Normandie Research and Biomedical Innovation, Rouen, France 3. Rouen university hospital, Physiology Department, Rouen, France 4. Rouen university hospital, Pulmonary, Thoracic oncology and Respiratory intensive Department, Rouen, France Correspondence for contact purposes only: Tristan Bonnevie
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Department ADIR Association
Country
France
Tel
+332.35.59.29.70
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+336.50.49.97.69
Fax
+332.35.59.29.71
[email protected]
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Word Count (text only): 2531.
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Highlight
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Exercise capacity is slightly reduced in patients with DP ; Dyspnea is the main factor limiting exertion ; Diaphragm function is correlated with exercise ventilation ; Overall inspiratory muscle function is correlated with both exercise capacity and ventilation suggesting the importance of the accessory inspiratory muscles during exercise in patients with DP.
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abstract: 180. Number of figure: 0 Number of table: 3 1
Funding support: None. Statement of submission: Authors have read and approved submission of the manuscript and the manuscript has not been published and is not being considered for publication elsewhere in whole or part in any language except as an abstract.
Condensed abstract The impact of diaphragmatic paresis on exercise capacity is not well known. This retrospective
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study included fourteen patients who underwent both respiratory force assessment and
cardiopulmonary exercise testing. The exercise capacity was slightly reduced due to ventilatory
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limitation. Diaphragm function was correlated with exercise ventilation whereas overall
inspiratory muscle function was correlated with both exercise capacity and ventilation
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suggesting the importance of the accessory inspiratory muscles during exercise.
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Structured abstract Purpose: Diaphragm paresis (DP) is characterized by abnormalities of respiratory muscle function. However, the impact of DP on exercise capacity is not well known. This study was performed to assess exercise tolerance in patients with DP and to determine whether inspiratory muscle function was related to exercise capacity, ventilatory pattern and
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cardiovascular function during exercise.
Methods: This retrospective study included patients with DP who underwent both
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diaphragmatic force measurements, and cardiopulmonary exercise testing (CPET).
Results: Fourteen patients were included. Dyspnea was the main symptom limiting exertion
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(86%). Exercise capacity was slightly reduced (median VO2peak: 80% [74.5%-90.5%]), mostly
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due to ventilatory limitation. Diaphragm and overall inspiratory muscle function were
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correlated with exercise ventilation. Moreover, overall inspiratory muscle function was related
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with oxygen consumption (r=0.61) and maximal workload (r=0.68). Conclusions: DP decreases aerobic capacity due to ventilatory limitation. Diaphragm function
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is correlated with exercise ventilation whereas overall inspiratory muscle function is correlated with both exercise capacity and ventilation suggesting the importance of the accessory
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inspiratory muscles during exercise for patients with DP. Further larger prospective studies are
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needed to confirm these results.
Key-word: Cardiopulmonary exercise testing; Diaphragmatic paresis; Diaphragm weakness;
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Dyspnea; Exercise
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1. Introduction Diaphragmatic paresis (DP) is characterized by abnormalities of pulmonary and respiratory muscle function. It may occur unilaterally or bilaterally although unilateral paresis is more frequent. Idiopathic DP is the most frequent etiology (50%) (Gibson, 1989; Higgs et al., 2002; Piehler et al., 1982; Riley, 1962). The condition is generally under-diagnosed and there are few
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epidemiologic data available, except for post-surgical traumatic injury (Deslauriers, 1998).
Studies of pulmonary function in patients with DP have shown little impairment in
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ventilation but a decrease in vital capacity (VC) (Eisele et al., 1972). The main symptom of DP
is dyspnea (Chuang et al., 2005; Graham et al., 1990; Laroche et al., 1988a) and it intensity
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depends on the etiology, extent of the impairment of diaphragm function, comorbidities and the
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patient’s level of fitness (Le Pimpec-Barthes et al., 2014).
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However, the impact of DP on exercise capacity is not well known. Hart et al found
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exercise tolerance to be reduced, with no differences between patients with uni- or bilateral DP (Hart et al., 2002). Conversely, Chuang et al found no effect on exercise capacity, despite a
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decrease in total lung capacity (TLC) (Chuang et al., 2005). The aim of this study was to assess exercise tolerance in patients with unilateral and
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bilateral DP and to determine whether inspiratory muscle function was related to exercise
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capacity, ventilatory pattern and cardiovascular function during exercise.
2. Method
2.1. Study design and patient selection
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This retrospective study included all consecutive patients assessed for diaphragmatic dysfunction between 2004 and 2015 in Rouen University Hospital. For this type of study, ethical approval and formal consent was not required. 2.2. Inclusion criteria
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Patients were included if they had uni- or bilateral DP relating to the phrenic nerve confirmed by diaphragmatic evoked motor potentials (EMP) and fluoroscopy. Patients had to be at least 18 years old and have undergone both pulmonary function testing and cardiopulmonary exercise testing. They were excluded if they had history of neurological or neuro-muscular disease.
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2.3. Data extraction
Age, gender, height, weight, body mass index (BMI), dyspnea score, pulmonary function,
capacity were extracted through a retrospective chart review. 2.4. Assessment
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2.4.1. Pulmonary function
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diaphragm assessment, exercise capacity and comorbid factors that could influence exercise
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2.4.2. Inspiratory muscle assessment
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Pulmonary function tests were carried out according to the ATS and the ERS guidelines.
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2.4.2.1. Pressure measurements: Oesophageal and gastric pressures (respectively Poes and
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Pga) were recorded using two latex balloon probes (80mm) (Marquat, Boissy Saint Léger, France) connected to a pressure transducer (Benton Dickinson monitoring system, Santa
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Barbara, CA USA). Transdiaphragmatic pressure (Pdi) was calculated as: Pdi=Pga-Poes. The best of three maximal inspiratory maneuvers was recorded as maximal Poes (Poes max).
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Poes sniff was recorded as the best value obtained from 3 sets of 10 sniff (Heritier et al., 1994). 2.4.2.2. Evoked motor potentials (EMP): Unilateral and bilateral twitch oesophageal (Poes
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tw bilat), gastric (Pga tw bilat) and transdiaphragmatic pressures (Pdi tw bilat) were recorded following cervical magnetic stimulation at the end of expiration using a circular coil (2,5 Telsa) (Magstim 200 Ltd., Whitland, UK) positioned at the C7 level (Similowski et al., 1989). Diaphragmatic paresis was defined as Pdi tw bilat below 20cmH2O (Laroche et al., 1988b; Prigent et al., 2008) or Poes tw bilat below 10cmH2O (Verin et al., 2006). Poes sniff was
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considered as pathological if the pressure was less than 70cmH2O for males or less than 60cmH2O for females (Heritier et al., 1994). Finally, fluoroscopic examination was performed during both quiet and deep breathing to assess for paradoxical movement of the affected hemidiaphragm. 2.4.3. Exercise testing:
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Incremental CPET was performed according to the ATS guidelines (ATS, 2003). Gases (VO2 and VCO2) and minute ventilation (VE) were measured breath by breath. Patients were asked
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whether they were limited by respiratory or muscular symptoms. Reference values from the ATS guidelines and from Wasserman et al. were used (ATS, 2003). 2.5. Statistical analysis
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Continuous data were expressed as means (SD) or medians [25th-75th percentile] as appropriate.
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Normality of the distributions was assessed using a Shapiro-Wilk test. Relationships between
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Poes sniff, Poes max, Poes tw bilat and data from CPET were assessed using Pearson or
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Spearman correlation tests according to the normality of the data distribution. Moreover, we
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also assessed the relationship between baseline dyspnea (mMRC score) and data from CPET. Differences between uni- and bilateral DP were assessed using a Wilcoxon Rank Test. A p-
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value < 0.05 was considered statistically significant. Prism 5 software was used for all analyses.
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3. Results 3.1. Patients
Fourteen patients were included, ten of whom had unilateral DP (seven left and three right) and
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four had bilateral DP. No patients had complete diaphragmatic paralysis. Main etiologies were idiopathic (n=4) and post traumatic (n=4). Other etiologies included iatrogenic causes and post cervical oesoarthrosis DP. Patient characteristics are presented in Table 1. Briefly, median age was 66.5 [50-75] years and mean BMI was 29.3 (4.7) kg/m², including five patients with obesity (BMI > 30kg/m²) and one with morbid obesity (BMI > 40kg/m²). Mean dyspnea for the whole
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group (mMRC score) was 2.4 (0.9). It was significantly higher in patients with bilateral than unilateral DP (p<0.01). 3.2. Pulmonary function (Table 2) FEV1% and liter (L) were significantly lower in patients with bilateral DP (50.5% [38.7%58.6%] and 1.1 [0.7-1.5] L respectively) than in patients with unilateral DP (75.8% (18.9%)
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and 1.9 (0.7) L respectively) (both p<0.04). Among the patients with unilateral DP (n=10), two had a restrictive pattern (RP) and one experienced a moderate obstructive pattern. None of the
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patients with bilateral DP had a RP (TLC was > 80% for all patients). Three out of four patients with bilateral DP also had mild obstruction. Median inspiratory capacity was preserved in all but two patients with unilateral DP (those who had a RP) and was decreased in three out four
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3.3. Inspiratory muscle assessment
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patients with bilateral DP (77.5% [62.2-85.3]).
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EMP were performed in all patients except one who had contraindications to the test (allergy
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to latex and history of epilepsy). A gastric balloon could not be used for six patients. Therefore
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only Poes tw bilat was considered. Diaphragmatic paresis was confirmed for all patients except one (Pdi tw bilat 20cmH2O and Poes tw bilat 10cmH2O). However, for this patient and the one
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who was allergic to latex, fluoroscopy revealed that the hemidiaphragm was elevated, motionless during quiet breathing and exhibited paradoxical movement during maximal
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inspiration, thus a diagnosis of unilateral DP was attributed. 3.4. Exercise testing (Table 3)
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The median time between inspiratory muscle assessment and exercise testing was 73.5 [38.5128.5] days. CPET were maximal for all patients. Dyspnea was the main symptom limiting exertion (n=12 (86%)). There were no significant differences between patients either with unior bilateral DP for any parameters measured from the CPET. The exercise capacity of the whole cohort was slightly reduced (median VO2peak: 80% [74.5%-90.5%]). Almost all patients had
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ventilatory limitation with a breathing reserve (BR) below 30% (mean BR: 16.7% (9.2%). Nine patients had a pathological ventilatory pattern with a tidal volume at exhaustion below 60% of the VC, four of whom had a respiratory rate (RR) above 45cpm. The Vd/Vt trend during exercise was normal, progressively decreasing in thirteen patients. Four patients had a Vd/Vt above 0.28 at the end of the exercise.
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3.5. Correlations between inspiratory muscle function and exercise capacity:
Poes sniff: There was a non-significant relationship between Poes sniff and Wpeak (r=0.55,
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p<0.06).
Poes max: Poes max was significantly correlated with Wpeak (r=0.68, p=0.01), VO2peak (r=0.61, p=0.03), VEpeak (r=0.69, p<0.01), Vtpeak (r=0.72, p<0.01) and VO2/heart rate (HR)
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(r=0.64, p=0.02).
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Poes tw bilat: There were significant correlations between Poes tw bilat and VEpeak (r=0.67,
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p=0.01), Vtpeak (r=0.58, p=0.04) and oxygen pulse (VO2/HR) (r=0.56, p=0.05).
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Dyspnée (mMRC): There was no significant relationships between baseline dyspnea and
4. Discussion
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exercise capacity.
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In this cohort of patients with uni and bilateral DP, exercise capacity was slightly decreased,
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limited by impaired ventilation. BR was abolished and ventilatory pattern was pathological (low tidal volume and excessive respiratory rate). Diaphragm and overall inspiratory muscle function were correlated with exercise capacity and ventilation.
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4.1. Diagnosis of diaphragmatic paresis
Pdi tw bilat and Poes tw bilat were used to diagnose diaphragm paresis in the present study. Although reliable and widely used (Hart et al., 2002; Hughes et al., 1999; Laroche et al., 1988b; Prigent et al., 2008; Verin et al., 2006), the most appropriate cut-off threshold has not been determined. Based on their clinical experience, Hart et al. chose a Pdi tw of less than 3.5cmH2O
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to diagnose paralysis (Hart et al., 2002). Based on our clinical experience, a previous report from our laboratory (Verin et al., 2006) and values in the literature, we chose a Poes tw bilat of less than 10cmH2O (Verin et al., 2006) and a Pdi twi bilat of less than 20cmH2O (Laroche et al., 1988b; Prigent et al., 2008). We acknowledge that these thresholds encompass a range of severity of diaphragm weakness, however individual data confirmed that no patients had
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diaphragm paralysis. 4.2. Diaphragm function at rest
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The results showed that vital capacity was decreased in patients with bilateral DP. It was also
decreased in patients with unilateral DP, although to a lesser extent (non-significant difference between groups). This is in accordance with the literature, with reports of decreases in total
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lung capacity and vital capacity that was not different between patients with uni- or bilateral
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DP (Hart et al., 2002). Conversly, some studies found a decrease in vital capacity, inspiratory
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capacity and total lung capacity (Chuang et al., 2005; Hart et al., 2002; Higgs et al., 2002; Verin
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et al., 2006; Welvaart et al., 2013) that are greater in patients with bilateral DP (Laroche et al.,
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1988a; Loh et al., 1977). However, the sample sizes of these studies were very small and further studies are needed to conclude about the difference in respiratory function between uni- or
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bilateral DP.
4.3. Exercise capacity
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Exercise capacity was slightly decreased in the present cohort. As the clinical impact of unilateral DP is considered to be minimal, it was expected to find significantly larger decrease
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in exercise capacity in patients with bilateral DP. However, in accordance with Hart et al, the extent of the decrease was similar between patients with unilateral and bilateral DP (Hart et al., 2002). The loss exercise capacity could therefore be attributed to the pathological pattern of ventilation found in the present study (i.e. low tidal volume and a high respiratory rate). Since respiratory rate is known to influence the rate of perceived dyspnea, this might explain why
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dyspnea limited exertion in almost all patients (Kearon et al., 1991; Lansing et al., 2009; Manning and Schwartzstein, 1995). More specifically, Hart et al. showed that paradoxical abdominal motion can occur in patients with DP. They suggested that in patients with unilateral DP, paradoxical abdominal motion relates a physiologically non-efficient ventilation because the ascension of the diaphragm on the affected side restricts inspiratory airflow (Hart et al.,
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2002). Although not assessed in the present study, this might explain why loss of exercise
capacity was greater than predicted in patients with unilateral DP. This is supported by the fact
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that Welvaart et al. found improvements in peak tidal volume and respiratory rate during
cardiopulmonary exercise testing following surgical plication in patients with unilateral DP (Welvaart et al., 2013).
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Nonetheless, exercise capacity was relatively preserved in the present cohort, suggesting that
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adaptive mechanisms were in place. For example, changes in the fibers of the contralateral hemi
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diaphragm (increasing contraction power) (Wilcox et al., 1990; Pellegrino et al. 2005) and
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fibrosis of the paralyzed hemi diaphragm (limiting paradoxical movement) (Hughes et al. 1999;
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Katz et al. 1998) might occur to improve function. Recruitment of accessory respiratory muscles could occur through the inhibition of an inhibitor signal to diaphragm contraction
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(Luedemann et al. 2002; Xu et al. 2014). Moreover, recruitment of the abdominal muscles would facilitate inspiration due to the passive recoil of the diaphragm (Hart et al. 2002; Valls-
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Sole et al. 2002; Pellegrino et al. 2005). Some patients may also have an accessory phrenic nerve (Hugues et al. 1999).
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4.4. Correlations between inspiratory muscle assessment and exercise capacity
The results suggest that overall inspiratory muscle (Poes max) and diaphragm function (Poes tw bilat) were both positively corelated with peak tidal volume and peak exercise ventilation. This is not surprising since the diaphragm is the main inspiratory muscle. It could be hypothesized that better inspiratory muscle function resulted in better ventilation during
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exercise, which in turn helped patients to sustain higher level of exercise, as suggested by the relationship between inspiratory muscle function and maximal workload. Oxygen pulse was also positively corelated with Poes max and Poes tw bilat presumably due to a better oxygen consumption. This was confirmed by the positive relationship between between Poes max and oxygen consumption. Finally, there was a significant positive relationship between Poes max
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(i. e. global inspiratory muscle function) and maximal workload and peak oxygen consumption, but not between Poes tw bilat and Wpeak and peak oxygen consumption, highlighting the
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important role of the accessory inspiratory muscles during exercise for patients with DP.
Since ventilation during exercise is correlated with inspiratory and diaphragm function, exercise capacity may also change over time due to spontaneous recovery. Interestingly, the reversibility
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of diaphragmatic paresis is debated. Studies describe paralysis, paresis or even diaphragmatic
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“weakness” with different etiologies and with a wide range of follow-up and assessment tools
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(Bai et al., 2006; Dernaika et al., 2008; Hughes et al., 1999; Lisboa et al., 1986; Mulvey et al.,
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1993; Riley, 1962; Sacher et al., 2006; Valls-Sole and Solans, 2002; Verin et al., 2006; Wilcox
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et al., 1990). Wilcox et al and Murray et al stated that the recovery time of the phrenic nerve depends on the type and the extent of the injury (Wilcox et al., 1990). Gayan-Ramirez et al
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retrospectively assessed DP recovery over a median follow-up of 15 months. Recovery of respiratory function (defined as an increase in FVC of 400mL) occurred in 43% and 52% of
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cases at 1 and 2 years respectively. No factors (including the type or the etiology of the paresis) were found to influence the reversibility of respiratory function (Pellegrino et al., 2005).
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Finally, Verin et al found a positive relationship between diaphragm function (Poes sniff) and the time between the onset of symptoms and assessment in patients with unilateral DP, suggesting an improvement over time. Conversely, several studies in both humans (Chuang et al., 2005; Katz et al., 1998; Luedemann et al., 2002; Verin et al., 2006) and animals (Gauthier et al., 2006; Xu et al., 2014) do not support the reversibility of diaphragm paresis.
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4.5. Patient considerations: Data from only 14 patients were available during the 11 years study period. This could be explained by (1) the low incidence of this condition (Gayan-Ramirez et al., 2008) and (2) the lack of symptoms at rest that do not incite patients to consult a doctor. Moreover, diaphragm paresis may resolve spontaneously, masking the real prevalence of this condition (Dernaika et
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al., 2008; Verin et al., 2006). Thereby, the true incidence of the disease is not known. Nevertheless, the results are in accordance with the literature and unilateral DP was more
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frequent (2-4, 37). The main symptoms are exercise dyspnea and orthopnea, which are more
frequent in the case of bilateral DP (Chuang et al., 2005; Clague and Hall, 1979; Elefteriades et al., 2008; Gibson, 1989; Graham et al., 1990; Laroche et al., 1988a; Loh et al., 1977; McCredie
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et al., 1962). In the present study, dyspnea appeared to be more intense in patients with bilateral
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DP (MRC score: 2 for unilateral, 3-4 for bilateral, p<0.01).
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4.6. Limitations
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This study has several limitations. First, there may be bias due to the retrospective design. For
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example, the time between symptom-onset and assessment was not known. Secondly, not all data for the diaphragmatic assessment were available: Pdi could not always be calculated if Pga
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was not measured, and one patient did not undergo magnetic stimulation. Thirdly, the sample was small due to the low incidence of PD and might have lacked power to detect differences
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between groups. Moreover, the sample might not be representative of the whole population since no patients had diaphragmatic paralysis, few had idiopathic DP and some had obesity or
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obstructive disease, both of which are known to reduce exercise capacity and induce dyspnea (Sava et al., 2010).
5. Conclusion Uni- or bilateral DP may lead to a decrease in aerobic capacity due to ventilatory limitation. Diaphragm function is correlated with exercise ventilation whereas overall inspiratory muscle
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function is correlated with both exercise capacity (oxygen consumption and maximal workload) and ventilation suggesting the importance of the accessory inspiratory muscles during exercise for patients with DP. Further prospective studies, with a larger sample of patients, are needed to confirm these results and identify prognostic factors that could help clinicians to manage
Ethical approval: For this type of study, formal consent is not required.
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patients and refer them, if necessary, for surgical treatment.
Conflict of interest: The authors state that they have no conflicts of interest.
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Total cohort 14 (100)a 66.50 (50-75)c 29.3 (4.7)b 2.4 (0.9)b
Values expressed as numbers (%); bValues expressed as means (SD); cValues expressed as medians (25th-75th percentile).
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Bilateral paresis 4 (29)a 75 (63-76.5)c 30.3 (26.1-33.9)c 3.5 (3-4)c
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Table 1: Patient characteristics (n=14) Unitaleral paresis Variable, (units) n (%) 10 (71)a Age (years) 60.60 (12.1)b BMI (kg/m²) 29.87 (5.1)b Dyspnea (MRC) 2 (1.8-2.3)c*
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mMRC: modified Medical Research Council score.
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*: score significantly lower than for bilateral paresis, p<0.01.
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Table 2: Pulmonary function (n=14) Unilateral paresis 2.1 (1.8-3.8)a 83.2 (20.4)a 98.4 (30.2)a 91.8 (17.8)a 90.9 (19.9)a 1.9 (0.7)a 75.8 (18.9)a 74.2 (9.2)a
Bilateral paresis 1.9 [1.3-2.2]b 63.6 [55.4-72.1]b 77.5 [62.2-85.3]b 84.3[82.4-98.6]b 101.9 [91.2-121.5]b 1.1 [0.7-1.5]b* 50.5 [38.7-58.6]b* 67 [62.6-71.3]b*
Total cohort 2 [1.7-3.1]b 77.9 (19.8)a 91.7 (28)a 90.9 (15.6)a 94.9 (19.4)a 1.6 (0.7)a 68.2 (20.7)a 72.1 (8.6)a
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Variable, (units) VC (L) VC (%) IC (%) TLC (%) FRC (%) FEV1 (L) FEV1 (%) FEV1/VC (% ratio)
a
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TLC: total lung capacity; VC: vital capacity; FEV1: forced expiratory volume in one second; IC: inspiratory capacity; FRC: functional residual capacity. Values expressed as means (SD); bValues expressed as medians [25th-75th percentile].
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*: score significantly lower than for unilateral paresis, p<0.03.
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Table 3: Cardiopulmonary exercise testing (n=14) Unilateral paresis 98.5 (34.2)a 81.2 (22.1)a 18.4 (6.4)a
Variable, (units)
Bilateral paresis
Total cohort
91.1 (34.9)a Metabolic load 78 (20.6)a 15.5 (12.219.6)b 80 (77.3-93.3)b 78.5 (62.4-94.5)b 80 (74.590.5)b VEpeak (L/min) 62.4 (22.2)a 36 (24.3-53.8)b 55.4 (22.9)a a Ventilatory VEpeak (%) 118.9 (18.1) 122.4 (112.2- 119.8 (15.9)a pattern 131.3)b a RRpeak (cpm) 41.5 (5.9) 36 (32.3-39.8)b 39.9 (5.9)a Vd/Vtpeak 26.1 (6.9)a 39.5 (35-44)b 28.8 (8.5)a Vtpeak (L) 1.5 (0.6)a 1 (0.7-1.4)b 1.4 (0.5)a a b Vt/VC (%) 58.9 (7.6) 50 (53.5-63.8) 58.9 (6.9)b BR (%) 17.6 (10.2)a 13.9 (8.2-21.2)b 16.7 (9.2)a a b HRpeak/HRtheo (%) 81.5 (7.8) 78 (64.8-80.8) 79.5 (84.9)a Cardiovascular VO2/HRpeak 10.4 (4)a 8.6 (6.5-12)b 10 (3.7)a a Values expressed as means (SD); bValues expressed as medians (25th-75th percentile).
70 (42.5-105)b 70.6 (54.5-85)b 12.4 (11.6-15.6)b
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Wpeak (W) Wpeak (%) VO2peak (ml/kg/min) VO2peak (%)
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W: workload; VO2: oxygen consumption; VE: minute ventilation; RR: respiratory rate; Vd: dead space; Vt: tidal volume; VC: vital capacity; HR: heart rate; theo: theoretical value; BR: breathing reserve.
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