Short- and Long-term Effects of Robot-assisted Plication in Diaphragmatic Paralysis - the Prospective RAPIDLY-study
Conditions: Diaphragmatic Plication, Diaphragmatic Paralysis, Diaphragmatic Eventration
Sponsor: Uppsala County Council, Sweden

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Short- and long-term e/ects of robot-assisted plication in 
diaphragmatic paralysis – the prospective RAPIDLY-study 
 
NCT Number: Yet not available 
 
Date last updated: 1 April 2025 
 
 
 
 
 
Andreas Palm, MD, PhD 
Department of Medical Sciences 
Lung-, allergy-, and sleep research 
Uppsala University 
SE-781 85, Uppsala 
Sweden 
 
andreas.palm@medsci.uu.se 
 
 

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Participating centers/ co-workers 
 
Uppsala 
Össur Emilsson, ossur.emilsson@medsci.uu.se 
Karin Ersson, karin.ersson@medsci.uu.se 
Tomas Hansen, tomas.hansen@uu.se 
Per Landelius, per.johan.landelius@akademiska.se 
Andrei Malinovschi, andrei.malinovschi@medsci.uu.se 
Emma Thorén, emma.thoren@akademiska.se 
Andreas Palm, andreas.palm@medsci.uu.se 
 
Linköping 
Miklos Boros, miklos.boros@regionostergotland.se 
Kricka Ozren, kricka.ozren@regionostergotland.se 
 
Lund 
Jesper Andreasson, jesper.andreasson@skane.se 
Jonas Einarsson, jonas.einarsson@med.lu.se 
Magnus Ekström, pmekstrom@gmail.com 
 
Umeå 
Anders Blomberg, anders.blomberg@umu.se 
Mattias Karlsson, mattias.karlsson@regionvasterbotten.se 
Ala Muala, ala.muala@umu.se 
 
Göteborg 
Anders Andersson, anders.andersson@lungall.gu.se 
Maya Landenhed-Smith, maya.landenhed.smith@vgregion.se 
Martin Silverborn, martin.silverborn@vgregion.se 
 
 
 
Introduction 
Diaphragmatic paralysis is a rare condition caused by damage to the phrenic nerve and 
can be either idiopathic or originate from, for example, an infection or previous surgery. 
This condition often causes signiﬁcant suQering through breathlessness, accentuated 
when lying down and during exertion. Over the years, selected patients have found relief 
from their symptoms through diaphragmatic plication. This operative procedure tightens 
and lowers the elevated diaphragmatic dome. Furthermore it recruits lung volume and 
reduces paradoxical diaphragmatic movement (1). Traditionally, these operations have 
been performed with open thoracotomy, but in recent years, minimally invasive 
techniques, video-assisted thoracoscopic surgery (VATS) (2, 3) have been developed. 
Compared to traditional open surgical techniques, VATS can provide faster recovery, 
reduced need for postoperative pain medication, and shorter hospital stays, with 
equally good surgical outcomes (1, 4). In several single-center cohorts, post-operative 
improvement in forced expiratory volume in 1 second (FEV1) and vital capacity (VC) with 

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12-21% and 12-25%, respectively, have been reported. Dyspnea quantiﬁed by the 
Medical Research Council (MRC) scale improved by up to 2 steps (5) and 6-minutes 
walking distance improved by 51 meters (6). However, a new technique, robot-assisted 
diaphragmatic plication, is spreading and increasingly replacing VATS. (7). One small 
retrospective study of 43 patients found comparable results between these techniques 
with a 7% increase in FEV1 in both groups. In this study, symptom improvement was not 
analysed. Other published studies on robot-assisted thoracic surgery are also single-
center studies on small cohorts consisting of 11-46 patients (8-12), often focusing on 
surgical safety and complications.  Lung function and radiological changes have also 
sometimes been measured along with retrospective evaluation of symptoms before and 
after the operation, a design with major methodological weakness. However, no 
signiﬁcant complications have been reported, and patients seem to improve their lung 
function and their symptom burden (8-12). Prospective studies evaluating RATS 
diaphragmatic plication are lacking. 
This prospective cohort study, the Robot-assisted plication in diaphragmatic paralysis 
study (The RAPIDLY-study) aims to evaluate the short- and long-term eQect of robot-
assisted diaphragmatic plication on physical performance, subjective breathlessness, 
lung function, blood gases, and radiology at ﬁve Swedish university hospitals, 
Gothenburg, Linköping, Lund, Umeå, and Uppsala. 
 
 
 
Method 
Study design and population 
This multicenter observational cohort study will include patients with symptomatic 
unilateral diaphragmatic paralysis persisting for ≥1 year (6), scheduled for RATS at 
thoracic surgery clinics in ﬁve Swedish university hospitals (Gothenburg, Linköping, 
Lund, Umeå, and Uppsala). The expected number of patients per center is estimated to 
3-5 annually. 
Exclusion criteria are inability to complete forms in Swedish, neuromuscular disease as 
the cause of diaphragmatic paralysis, and other signiﬁcant causes of dyspnea and 
impaired physical capacity than diaphragmatic paralysis. 
Patients will be assessed preoperatively and postoperatively after one to three months 
and after one and three years. 
 
 
Assessments 
 
Patient characteristics 
Age, sex, height, and weight will be recorded. Body mass index (BMI) is calculated by 
dividing a person’s weight by their height in meters squared. 
Aetiology of diaphragmatic paralysis, relevant co-morbidities and use of long-term 
oxygen therapy and/or mechanical ventilation will be recorded. 
The date for symptom debut, if known, is recorded.  
Smoking history is deﬁned as current smoker, ex-smoker (smoking history of ≥100 
cigarettes and having quit smoking ≥6 months ago), and never smoker (smoking history 
of <100 cigarettes) (13). Smoking is quantiﬁed by pack-years (the number of packs of 

4 
 
cigarettes a person has smoked daily, multiplied by the number of years they have 
smoked) (14). 
 
Primary outcome 
The patients’ exercise capacity will be evaluated using the 6-minute walking distance 
(6MWD). The patients are asked to walk as far as possible on a ﬂat, straight surface for 
six minutes, and the total distance walked is measured (15-17). 
 
Secondary outcomes 
Questionnaires 
The modiﬁed Borg Scale is a tool with a range from 0 to 10 used to measure an 
individual's perceived level of breathlessness or muscle fatigue during physical activity, 
where 0 represents no breathlessness, and 10 represents maximal breathlessness (15). 
The modiﬁed Medical Research Council (mMRC) dyspnea scale is used to assess the 
severity of breathlessness. The scale ranges from 0 to 4, with higher scores indicating 
more signiﬁcant breathlessness (18). 
The Dyspnea-12 is a questionnaire used to measure the severity and quality of 
breathlessness in individuals with respiratory or cardiovascular conditions. It assesses 
dyspnea's physical and emotional aspects, providing a comprehensive picture of how 
breathlessness aQects a person’s life. It consists of 12 items, each with a scale range 
between 0 (no dyspnea) and 3 (severe dyspnea) (19-21). 
The EQ-5D is one of the most widely used tools for assessing health-related quality of 
life. It includes ﬁve dimensions: mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression. These dimensions create a descriptive proﬁle that can be 
converted into a single summary index, where a score of 1.0 indicates perfect health. 
Additionally, the tool includes a Visual Analog Scale (VAS), ranging from 0 (worst 
imaginable health) to 100 (best imaginable health), for self-assessment of overall health 
status (22).  
 
Spirometry 
Spirometry will be conducted 15 minutes after bronchodilation (inhalation of 200 µg 
salbutamol) in both supine and upright positions. Body plethysmography and single-
breath DLCO measurement will be performed. Predicted values will be determined 
using reference equations from the Global Lung Function Initiative (GLI) (23).  
 
One-minute sit-to-stand test (1-MSTST) 
This test assesses a person's functional exercise capacity by recording the number of 
full sit-to-stand repetitions completed in 60 seconds (24). 
 
The Maximal Inspiratory Pressure (MIP) test is a respiratory test that measures the 
strength of the inspiratory muscles, particularly the diaphragm. By inhaling as forcefully 
as possible in a handheld device, the maximum negative pressure generated is recorded 
(25). 
 
Blood gas analysis 

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A capillary or arterial blood gas analysis obtains the partial pressure of Oxýgen and 
Carbon dioxide (PaCO2) and Base excess (BE). Pulse oximetry obtains oxygen 
saturation. 
 
Chest X-ray 
Chest X-rays are acquired in full inspiration and expiration in frontal and lateral views. 
The distance from the most cranial part of the lung to the highest part of the diaphragm 
in both frontal and side views are measured separately. 
 
Computerised tomography (CT) of Thorax 
A CT with a standard protocol to identify and quantify lower lobe atelectasis. 
 
Adverse events 
Operating time, chest-drain duration, length of hospitalisation, per- and postoperative 
complications such as pain, bleeding and infections, 30-day readmission and 30-days 
mortality are recorded.  
 
Statistics 
Descriptive statistics summarise the data, and inferential statistics compare group 
diQerences. 
Associations with the outcomes will be analysed using multivariable regression models, 
including linear regression (for continuous outcome variables) and logistic regression 
(for categorical outcomes). Repeated measurements within individuals will be managed 
through multilevel, random-eQects models. 
 
Power calculation: Based on a standard deviation of 90 meters in the 6-minute walk test 
(6MWT) among the general population (16), and considering that the minimal clinically 
important difference (MCID) is 53 meters (17), a total of 45 patients is required. 
 
Table of study assessments 
 
Baseline 
1-3 months 
post-
operatively 
12 months 
post-
operatively 
3 years 
post-
operatively? 
Demographics 
X 
 
 
 
Height  
X 
 
 
 
Weight 
X 
X 
X 
X 
BMI 
X 
X 
X 
X 
Waist-hip ratio 
X 
X 
X 
X 
Co-morbidities 
X 
 
 
 
Smoking/PY 
X 
 
 
 
Indication for op 
X 
 
 
 
Questionnaires 
(The modiﬁed 
Borg-scale, 
mMRC, Dyspnea-
12, EQ-D5) 
X 
X 
X 
X 
6MWT 
X 
X 
X 
X 

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Body 
plethysmography, 
dynamic 
spirometry in 
seated and 
supine position, 
and DLCO  
X 
X 
X 
X 
MIP 
X 
X 
X 
X 
1 minute Sit-to-
stand test 
X 
X 
X 
X 
Chest X-ray  
X 
X 
X 
X 
CT-scan 
X 
X 
 
 
Saturation 
X 
X 
X 
X 
Arterial/capillary 
blood gas 
X 
X 
X 
X 
Questionnaire 
pain/adverse 
eQects 
 
X 
X 
X 
 
 
Ethical considerations 
Robot-assisted diaphragm plication is performed at several university hospitals in 
Sweden and abroad. The patients in this study have been clinically approved for this 
surgery. They are not exposed to any additional risks in this study beyond being 
examined more thoroughly with surveys and questionnaires, lung function and 
performance tests, and chest X-rays before and after the surgical procedure. An 
application will be submitted to the Ethics Review Authority. 
 
Relevance of research 
Robot-assisted plication in diaphragmatic paralysis is a new operative method 
performed at many thoracic centres worldwide without being scientiﬁcally evaluated in 
prospective studies. This national multicenter study, with a large cohort by international 
standards and with validated, highly relevant outcome variables, is expected to gain 
signiﬁcant attention among thoracic surgeons and pulmonary physicians worldwide. 
The study has been approved by the Swedish Ethical Review Authority, Dnr  2025-01028-
01and, and is registered on ClinicalTrials.gov, Dnr 2025-01028-01. 
 
Preliminary results 
None.  
 
 

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