Ultrasound of the Diaphragm Excursion Ratio as Physiological Biomarker in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Conditions: COPD
Sponsor: Isala

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Template nWMO studie protocol 2025. V12 
 
 
 
 
 
 
 
Ultrasound of the Diaphragm Excursion Ratio as 
physiological biomarker in acute exacerbations of 
Chronic Obstructive Pulmonary Disease 
UNDATED 2; 22392 
 
 
(non-WMO study protocol) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date of document: 
 
09-06-2025 
Protocol version number: 
v1.03 
 
 

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Template nWMO studie protocol 2025. V12 
CONTENT 
 
1. Study organization 
3 
2. Protocol Signature Sheet 
7 
3. Study summary 
8 
4. Study design 
9 
5. Population 
9 
6. Study data, and analysis 
10 
7. Recruitment and informed consent/objection 
12 
8. Only complete in case of collaboration with parties outside of the UMCG (also called: third parties)
 
15 
9. Data Management Plan (DMP) 
17 
10. FAIR Data and Data Sharing 
18 
11. Management of Biomaterials (either newly collected or from an existing biobank) 
19 
12. Burden, Risks & Benefits 
19 
13. Incidental findings 
20 
14. References 
20 
15. Appendices 
21 
 
 

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Template nWMO studie protocol 2025. V12 
1. Study organization 
Study title: 
Ultrasound of the Diaphragm Excursion Ratio as physiological 
biomarker in acute exacerbations of Chronic Obstructive Pulmonary 
Disease 
 
Planned start date and estimated completion date 
Please note that the study may only start after approval and that the start date 
should allow for time needed for the approval process. 
Immediately after approval, 
july/august/september 2025.  
Estimated completion date: 
july 2026 
 
Members of the UMCG 
study team. 
Please extend section if 
there are more than 9 
members in the study 
team.  
Please note that this is not 
a delegation log. 
 
Information 
Name/ function/ department / 
center 
Role in study 
E.g: Principal investigator, 
coordinating investigator, 
researcher, research nurse. 
1 
<text> 
CI 
2 
M.L. Duiverman, 
Pulmonologist, Pulmonology, 
UMCG 
PI UMCG 
3 
E.A.M.D. ter Haar, physician-
researcher, Pulmonology, 
UMCG 
Researcher 
4 
J.E. Hartman 
Researcher 
5 
<text> 
<text> 
6 
<text> 
<text> 
7 
<text> 
<text> 
8 
<text> 
<text> 
9 
<text> 
<text> 
If applicable:  
Senior members of the 
non-UMCG study team(s). 
Information 
Name/ function/ department / 
centre 
Role in study 
Limit to: Principal investigator, 
coordinating investigator. 

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Template nWMO studie protocol 2025. V12 
Please limit to the principal 
and coordinating 
investigators for each 
centre. Extend section if 
there are more than 7 non-
UMCG members in the 
study team(s).  
Please note that this is not 
a delegation log. 
1 
W.S. de Boer, PhD candidate 
and AIOS, Pulmonology, UMCG 
and Isala. 
PI Isala 
2 
Q.S.D. Muller 
Researcher 
3 
M.A. Edens 
Epidemiologist 
4 
<text> 
<text> 
5 
<text> 
<text> 
6 
<text> 
<text> 
7 
<text> 
<text> 
Principal investigator , 
contact information 
(The Principal Investigator 
heads the research team. Is 
responsible for planning and 
conducting the scientific 
study. The role is akin to that 
of project leader. In Dutch 
also ‘hoofdonderzoeker’.) 
Name 
W.S. de Boer 
E-mail 
W.s.de.boer@isala.nl / 
W.s.de.boer@umcg.nl  
Corresponding researcher 
UMCG, contact 
information 
Name 
Wytze de Boer 
E-mail 
W.s.de.boer@isala.nl / 
W.s.de.boer@umcg.nl 
Telephone 
0646312031 
Sponsor (Dutch: 
verrichter/opdrachtgever) 
UMCG:      ☒ 
Investigator initiated. 
Other:     ☐ 
If other please note name of sponsor: 
<text> 
Financial support / subsidy 
provider 
NA  
☒ 
Organisation name 
<text> 
Collaboration with non-
profit Laboratory /   
research sites  
(in- and outside UMCG) 
NA  
☒ 
Organisation name 
Isala 
Contact person 
W.S. de Boer 
Email 
w.s.de.boer@isala.nl 

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Telephone 
06-46312031 
Collaboration with  for-
profit / commercial parties 
/ companies  
(in- and outside UMCG) 
NA 
☐ 
Organisation name 
<text> 
Contact person 
<text> 
Email  
<text> 
Telephone 
<text> 
Is this study connected to 
a previous nWMO or 
WMO application 
Yes 
☐ 
No 
☒ 
If yes, please provide the 
following information 
and/or documentation 
regarding the previous 
application 
Please add the name of 
the previous study 
<text> 
Please add the panama 
number of the 
previous study 
<text> 
Has the ethical 
approval of the 
previous application 
been added to the 
current application 
NA 
☐ 
 
Yes 
☐ 
No 
☐ 
Has the study protocol 
of the previous 
application been added 
to the current 
application 
NA 
☐ 
 
Yes 
☐ 
No 
☐ 
Has the patient 
information (DIF) of 
the previous 
application been added 
to the current 
application 
NA 
☐ 
 
Yes 
☐ 
No 
☐ 
Has the Informed 
Consent form (IC) of 
the previous 
NA 
☐ 
 
Yes 
☐ 
No 
☐ 

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Template nWMO studie protocol 2025. V12 
application been added 
to the current 
application 

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2. Protocol Signature Sheet 
The undersigned principal investigator (NL: hoofdonderzoeker) UMCG and head of department 
UMCG confirm that the study protocol is compliant with the UMCG researchcode, the nWMO 
Kaderreglement UMCG and other legislation (such as the (U)AVG and WGBO).  
 
Name 
Signature 
Date 
Principal Investigator UMCG: 
 
M.L. Duiverman, pulmonologist 
 
 
 
 
<dd-mm-yyyy> 
Head of the department UMCG: 
Prof. Slebos, Head of Department 
for Pulmonary Medicine. 
 
 
 
<dd-mm-yyyy> 
Departmental Scientific review board (if 
applicable) 
<name and function> 
<dd-mm-yyyy> 
 
 
If tissues are requested from a biobank or 
data from a databank, please add a 
signature from the biobank administrator 
(NL: beheerder)  here. 
<name and function> 
 
<dd-mm-yyyy> 
 
If tissues are requested from the UMCG 
biobank pathology, please add a signature 
from the tissue review board pathology 
here. 
<name and function> 
<dd-mm-yyyy> 
 
 
 
 
 

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3. Study summary 
Max 1000 words 
3.1 Introduction and rationale 
In 2020 an estimate of 562.700 people had Chronic Obstructive Pulmonary Disease (COPD) in the 
Netherlands, resulting in 21.335 hospital admissions.[1] An acute exacerbation COPD (AECOPD) in 
combination with hospital admission is associated with high mortality and morbidity. [2] 
 
Noninvasive ventilation (NIV) has been very effective in the context of AECOPD, since it efficiently 
offloads respiratory muscles and counteracts dynamic hyperinflation. This method often prevents 
intubation as a bridge to administering effective therapies (e.g., glucocorticoids, bronchodilators, 
and antibiotic agents)[3], and may reduce mortality.[4]  
Current guidelines recommend NIV for the treatment of acute respiratory failure in patients with 
respiratory distress, pH < 7.35, and PaCO2 > 6 kPA (with exclusion of patients requiring invasive 
ventilation, see guideline).[5,6] National guidelines do not recommend NIV in AECOPD with 
increased work of breathing without respiratory acidosis due to lack of evidence. [5] 
 
Ultrasound of the diaphragm can identify atrophy and impaired motion or contractility of the 
diaphragm[10], and has been shown to predict mortality and NIV failure during NIV treatment for 
respiratory acidosis due to AECOPD.[11-15] Whether ultrasound of the diaphragm may predict 
mortality or need for (non-)invasive ventilation in AECOPD without respiratory acidosis on initial 
presentation is unknown.  
 
During exploratory analysis of a previous study (unpublished; NCT05671198) we might have found 
a marker that has the potential to predict progression to NIV or death during hospitalization for 
AECOPD without respiratory acidosis: 
 
The difference between diaphragm motion during tidal breathing and maximal breathing, used as 
a surrogate for inspiratory reserve volume (IRV), was significantly lower in patients requiring NIV or 
who died in-hospital compared to those who did not (1.59 cm, SD 1.91 vs. 3.14 cm, SD 2.45; p = 
0.033). We performed a ROC curve analysis to assess the predictive value of these variables, which 
yielded an area under the ROC curve (AUROC) of 0.752 (95% CI: 0.535 - 0.968, p = 0.033), indicating 
a statistically significant discriminatory ability. The best cut-off value, as determined with the 
Youden's J statistic, was 1.74 cm, with a sensitivity of 86% and specificity of 70% for predicting NIV 
requirement or inhospital death. 
  
However, the number of events was low and the study was primarily powered for another 
outcome. Therefore, prospective validation is needed before we impose treatment based on this 
marker. In case the suggested ultrasound measurement (see introduction) proofs to be a 
discriminatory marker for deterioration during hospitalization or predictive of progression to Non-
Invasive Ventilation, we hope to be able to perform a follow-up study in which patient will be 
randomized to either standard of care or ‘elective’ NIV (to avoid emergency NIV need) based on 
yet to determine cut-off values. 
 
3.2 Design (including population, method, confounders and outcomes) 
A multi-center, prospective observational cohort study conducted at Isala Hospital and UMCG 
aimed at determining the value of the sonographic motion ratio (tidal/maximum) of the 
diaphragm in AECOPD after hospital admission. After enrollment, the sonographic diaphragm 
motion will be assessed as additional measurement during standard-of-care lung ultrasound 
(POCUS), after which hospital outcomes will be registered. Primary outcome will be the sensitivity 

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Template nWMO studie protocol 2025. V12 
of this ultrasound marker for in-hospital deterioration (progression to NIV of death). Secondary 
analysis will include predictive models.  
 
3.3 Research question 
What is the sensitivity of the diaphragm motion ratio (tidal/maximum) during ultrasound for in-
hospital deterioration (progression to NIV or death) in AECOPD. 
 
 
4. Study design 
4.1 Mono- or multicenter study. 
Monocenter study 
☐ 
Multicenter study 
☒ 
4.2 Retrospective study (available data/ 
biomaterials only) or prospective study (data/ 
biomaterials from [some] participants will be 
collected), (click both if mixed-method). 
Retrospective study 
☐ 
 
Prospective study 
☒ 
4.3 Cross-sectional or follow-up study (click both if 
mixed-method). 
Cross-sectional study 
☐ 
Follow-up study 
☒ 
4.4 Quantitative or qualitative study (click both if 
mixed-method). 
Quantitative study 
☒ 
Qualitative study 
☐ 
4.5 Pilot or explorative study? 
Not applicable 
☐ 
Pilot study 
☒ 
Explorative study 
☒ 
Explain why it is a pilot or explorative study. 
See next question/answer  
In case of a pilot study, what are the concrete follow-up plans. 
In case the suggested ultrasound measurement (see introduction) proofs to be a discriminatory 
marker for deterioration during hospitalization or predictive of progression to Non-Invasive 
Ventilation, we hope to perform a follow-up study in which patient will be randomized to either 
standard of care or ‘elective’ NIV (to avoid emergency NIV need) based on this marker.  
5. Population  
5.1  Research participants (tick all that apply) 
Healthy volunteers 
Patients 
☐ 
☒ 
5.2  Participant classification (tick all that apply) 
 
Participants ≥ 16 years 
☒ 
Children between 12 and 16 years (if applicable, written informed consent will be 
obtained from child and both parents - if both have authority, or guardian [or 
parents/guardian only if incapacitated child]) 
☐ 
 
 
Children < 12 years (if applicable, written informed consent will be obtained from 
both parents - if both have authority, or guardian) 
☐ 
Explain purpose limitation (‘doelbinding’ in Dutch) if you plan to include minors below 16 of age. This 
means that this data may only be gathered if participation of that age group is utterly essential  
(Dutch: persoonsgegevens alleen verzamelen met een gerechtvaardigd doel waarvoor die 
leeftijdsgroep noodzakelijk is). 
<text> 

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5.3 Incapacitated adults 
 
Participants can be incapacitated/decisionally impaired adults (if applicable, written 
informed consent must be obtained from legal representative) 
Yes 
☐ 
No 
☒ 
If yes, explain purpose limitation (‘doelbinding’ in Dutch). This means that this data may only be 
gathered if participation of this group is utterly essential (persoonsgegevens alleen verzamelen met 
een gerechtvaardigd doel waarvoor deze groep noodzakelijk is). 
<text> 
5.4 Inclusion and exclusion criteria  
• Inclusion criteria:  
In order to be eligible to participate in this study, a subject must meet all of the following criteria: 
- Hospitalization primarily because of severe acute exacerbation of COPD 
- Spirometry record within last 5 years, with: post-bronchodilator FEV1/FVC < 0,70 and FEV1% < 
80%predicted 
- Minimum of 10 packyears 
 
• Exclusion criteria:  
A potential subject who meets any of the following criteria will be excluded from participation in this 
study: 
- Established diagnosis of diaphragm diaphragm paralysis.  
- Inability for diaphragm imaging (e.g. mechanical ventilation, or unable to follow vocal instructions). 
- Those not able or unwilling to give written informed consent.  
- Pregnant women 
6. Study data, and analysis  
This section needs to be completed for both quantitative as well as qualitative designs.   
Outcomes should be realistic, sample size adequate, minimal but sufficient data should be collected, 
patient burden should be balanced with the usefulness of the outcomes and the analysis should be 
appropriate. To clarify that this has been given careful consideration, completion of section 6 is 
required. 
6.1 Data collected 
For primary outcomes: 
 
- 
Tidal excursion of the diaphragm as measured with ultrasound (time expenditure: 
aprox. 1 minute)  
- 
Maximal excursion of the diaphragm as measured with ultrasound (time expenditure: 
aprox. 1 minute)  
- 
Progression to NIV or in-hospital death, data collected from the EPD. 
 
For secondary outcomes and other outcomes: 
 
- 
Baseline dyspnea score as determined with a numeric rating scale (NRS) 
- 
From EPD: Age, sex, BMI, FEV1 (% predicted), pH, PaCO₂ 
 
If not applicable to your study please explain the reason and the alternative outcomes: 
<text> 
Have all the data for the primary and secondary 
outcomes been described or the alternatives? 
Yes 
x 
No 
☐ 

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6.2 Number of participants: 
Target total number of participants: 186 
Target number of UMCG participants: 62 
6.3 Justification of sample size 
Sample size justification is required according to the AVG/GDPR law. The number of subjects should 
always be large enough to reliably answer the research questions; but not more than necessary.  
 
The sample size can be justified in several ways. Often the easiest is a power analysis, alternatively a 
comparison with the sample size of closely related studies may be applicable (specification is required), 
or a saturation design. Other options may apply.  
 
Pilot studies and/or exploratory studies comply with different sample size rules, but for these please 
also indicate on what basis the sample sized has been decided.  
 
The primary outcome of this study is the sensitivity of the diaphragm ultrasound marker for predicting 
in-hospital deterioration (defined as progression to non-invasive ventilation or in-hospital death). Based 
on preliminary findings (NCT05671198), we expect a sensitivity of approximately 86%. To estimate this 
sensitivity with a 95% confidence interval and a total width of 10% (±5%), a minimum of 186 patients is 
required. 
 
Has the sample size justification been described? 
NA 
☐ 
Yes 
☒ 
No 
☐ 
If no please 
indicate why:  
<text> 
 
6.4 Data minimisation 
  
Only the essential baseline characteristics and data, that are required to answer 
the research question, will be collected:  
Yes 
☒ 
No 
☐ 
6.5 Statistical and/or qualitative analysis 
Please specify Statistical Analysis Plan (SAP): 
a. Description of study population: 
 
prospective observational cohort study evaluating the predictive value of the diaphragm motion 
ratio in AECOPD patients.              
b. Description of preparation of the data for analyses: 
Primary Predictor: 
Diaphragm motion ratio = Tidal excursion / Maximal excursion. 
 
Primary Outcome: 
Composite of progression to NIV or in-hospital death; dichotomized. 
 
Other Variables (for adjustment or secondary analysis): 
Age, sex, BMI, FEV1 (% predicted), pH, PaCO₂, baseline dyspnea score. 
 

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c. Specify all applicable statistical and/ or qualitative methods. This usually requires an extensive 
description of the planned analyses and covariates: 
The primary endpoint is the sensitivity of the diaphragm motion ratio (ultrasound marker) for predicting 
in-hospital deterioration (defined as progression to non-invasive ventilation or in-hospital death). 
Sensitivity will be calculated as: True Positives/(True Positives+False Negatives) 
Additionally, univariate logistic regression to assess association between diaphragm motion ratio and in-
hospital deterioration is performed. Results reported as odds ratios (ORs) with 95% CIs. Additionally we 
will supply, a Receiver Operating Characteristic (ROC) analysis, including Area Under the Curve (AUROC), 
the optimal cut-off point determined by Youden’s J statistic, and  sensitivity, specificity, 
positive/negative predictive values, and likelihood ratios at the optimal cut-off. 
 
Continuous variables will be presented as mean ± standard deviation for normally distributed data or 
median and range for non-normally distributed data. Categorical variables will be summarized using 
frequencies and percentages. Statistical significance will be set at p < 0.05, and all analyses will be 
conducted using SPSS Statistics version 28.0. 
d. Clarify how this analysis plan, study setup, sample size and design will answer the study 
questions: 
This prospective, multi-center observational study is specifically designed to evaluate whether the 
diaphragm motion ratio is a sensitive and predictive tool in-hospital deterioration (progression to non-
invasive ventilation or death) in patients with AECOPD. The analysis plan includes ROC analysis and 
logistic regression to assess the predictive performance and independent association of this ultrasound 
marker. The sample size is based on the expected event rate and the need for sufficient events per 
variable to ensure statistical validity. Together, the focused design, appropriate sample size, and 
targeted analysis approach will address the study question and provide clinically relevant insights into 
early risk stratification using bedside ultrasound for future intervention studies. 
 
Has the statistical analysis section (6.5) been completed? 
Yes 
☒ 
No 
☐ 
7. Recruitment and informed consent/objection  
7.1 Data collection  
Please check the data source that is applicable to your study, more may apply: 
Data will be prospectively collected (data/ biomaterials from [some] 
participants will be collected) 
☒ 
Data will be collected from (electronic) patient records (e.g. ‘EPD 
UMCG’) 
☒ 
Data will be collected from an already existing bio- or databank  
Please add documents that demonstrate (ethical) approval at the 
instalment of the bio- or databank 
☐ 
 
Data will be collected from a previous study (e.g. 'FAIR data' - 
internal/external). 
Please note that the templates of the patient information and the 
(original) Informed Consent form need to be added to the application.  
☐ 
 

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7.2 Informed consent procedure 
7.2.1 Participants will be asked informed consent 
Yes 
☒ 
If yes: please 
complete 7.2.2 
and 7.3. 
No 
☐ 
If no: 
please 
complete 
7.2.3 and 
7.3. 
7.2.2 If consent is asked complete this section 
7.2.2.1 if the potential participant is a patient:  
 
 
First contact with potential participant is made by the treatment 
provider, either by accompanying letter or in person. 
Yes 
x 
No 
 
 
Informed consent procedure, including signing the IC, will be 
carried out by the researcher/ research nurse (not the treatment 
provider). 
Yes 
☒ 
No 
☐ 
7.2.2.2 For participants that are either patients or non-patients: 
⦁  Recruitment:  
Please describe how eligible participants will be approached and recruited 
 
The physician in the emergency ward will present the patient the trial information. On arrival on the 
pulmonology ward, the researcher will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk and benefit of the study. The patient 
will be given the opportunity to ask questions and enough time for consideration. The patient will 
receive the Patient Information / Informed Consent Form in duplicate. If signed, one of the two 
original Patient Information / Informed Consent Forms must be stored by the principal investigator. 
The second signed Patient Information / Informed Consent Form will be given to the patient.  
⦁  Information provision: 
The participant will only be contacted via telephone if they 
have given prior permission for this: 
 
NA 
☒ 
 
Yes 
☐ 
 
No 
☐ 
Contact via telephone only serves to provide additional 
information, it cannot be used to ask informed consent: 
 
NA 
☒ 
 
Yes 
☐ 
 
No 
☐ 
If either of the above 2 items are answered with ‘no’ please elaborate on the reason for this:   
<text> 
⦁ Time to consider:  
The participant will have at least 14 days to consider 
participation: 
Yes  
☐ 
 
No 
x 
If this is not the case please describe the reason for this and what time is allotted for the participant 
to consider participation. 
The intended measurements are time-sensitive and must take please immediately after 
hospitalization to be of any potential predictive value. Since we don’t know when patient might need 
hospitalization in advance, we cannot comply with the suggested 14 days to consider.  
The additional measurements during standard of care POCUS are non-invasive, cause no harm, are 
quick (aprox. 2 minutes total), and are  very well tolerated; we therefore suggest a minimal amout of 
time for consideration of 1 hour.  

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Template nWMO studie protocol 2025. V12 
⦁ Informed consent recording:  
Informed consent will be recorded either on paper via 
signature or electronically:  
Yes 
☒ 
 
No 
☐ 
If no, please elaborate on how will the informed consent be recorded?  
See above, on paper via signature. 
⦁  Use of templates 
Have the UMCG templates been used for both DIF and IC-form: 
 
Attach participant information letter and informed consent form to the 
present study protocol. Please note that all sections of the templates need 
to be present in the file DIF and IC. 
Yes 
☒ 
No 
☐ 
7.2.3 If consent cannot be asked please complete this section: 
Total number of participants who will not be asked informed consent: <number> 
Total number of UMCG participants who will not be asked informed consent: <number> 
Which WGBO argumentation applies to your study (see SOP Obtaining Informed Consent nWMO): 
⦁  Asking permission is reasonably impossible, because it would burden the patient to 
such an extent that it might cause psychological distress.  
 
☐ 
⦁  Asking permission is reasonably impossible, because a large part of the participant 
group is likely deceased or cannot be located.  
 
☐ 
⦁  Consent cannot be required because obtaining it would entail a disproportionate 
amount of time and effort, such as in the case of large numbers of patients or patients 
who were treated a long time ago 
 
☐ 
⦁  Consent cannot be required because requesting consent would lead to selective 
response, thereby potentially biasing the research results 
 
☐ 
⦁  Consent cannot be required, because:  
<text> 
 
☐ 
Required: In addition to the broad categories above, please clarify why these arguments apply to 
your specific study: 
<text> 
The objection registry will be checked in case one or more UMCG 
patients will not be asked informed consent, the data from those who 
objected will be excluded from the analyses. 
NA 
x 
Yes 
☐ 
7.3 Linking with (other) bio-/databank 
 
In case the data will be linked with a /another bio-/databank, 
informed consent will be/has been obtained for this linkage(s) 
Yes, 
consent  
☐ 
No 
consent 
☐ 
Data will 
not be 
linked 
 ☒ 
8. Only complete in case of collaboration with parties outside of the 
UMCG (also called: third parties) 
8.1 Which party is in the lead? 
UMCG 
☒ 
 
Not the UMCG 
☐ 
 
8.2 Is the leading party a commercial party? 
Yes 
☐ 
No 
☒ 

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8.3 Only complete if UMCG is not in the lead: Is the role of the UMCG 
limited to supplying data? 
Yes 
☐ 
No 
x 
8.4 Description of the cooperation 
Please describe the role and tasks that will be performed by the UMCG and by the partner(s). Please 
note that only the role and tasks described here can be mentioned in the contract.  
  
The study will be conducted collaboratively between the University Medical Center Groningen (UMCG) 
and Isala Hospital. Both centers will serve as recruitment sites and will contribute to data collection. 
● UMCG 
 
○ 
Acts as the coordinating center for the study. 
 
○ 
Responsible for study design, protocol development, and obtaining ethical approval. 
 
○ 
Will oversee central data management, statistical analysis, and reporting of study 
results. 
 
○ 
Provides training and supervision for diaphragm ultrasound measurements to ensure 
protocol standardization. 
 
○ 
Responsible for monitoring study progress, ensuring data quality, and safeguarding 
compliance with GDPR 
 
● Isala Hospital 
 
○ 
Acts as a recruitment and data collection site. 
 
○ 
Responsible for identifying eligible patients, obtaining informed consent, performing 
ultrasound measurements, and recording clinical data as per protocol. 
 
○ 
Ensures timely and secure transfer of pseudonymized data to UMCG for analysis. 
 
○ 
Participates in regular coordination meetings and contributes to interpretation of 
findings and dissemination of results. 
8.5 Data and/or biomaterial management in combination with the partners 
Please elaborate on the following aspects: 
● Which data (and/or biomaterials) will be shared with the partners  
In this study, only pseudonymized clinical data will be shared between the participating centers (UMCG 
and Isala Hospital). No biomaterials (e.g., blood, tissue, or other biological specimens) will be collected 
or exchanged. 
The following types of data will be shared: 
● Demographic data: age, sex, height, weight, BMI 
 
● Clinical data: COPD history (e.g., GOLD stage, FEV1), current medications, comorbidities, blood 
gas values (pH, PaCO₂), vital signs, and relevant admission parameters 
 

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● Ultrasound data: diaphragm excursion measurements during tidal and maximal breathing, 
diaphragm motion ratio (tidal/max) 
 
● Outcome data: requirement of non-invasive ventilation (NIV), in-hospital mortality, length of 
hospital stay, ICU admission if applicable 
 
All shared data will be pseudonymized at the site of collection before being transferred to the 
coordinating center (UMCG) for analysis. No direct identifiers (e.g., name, date of birth, patient ID) will 
be shared. Data transfer will follow institutional data protection protocols and applicable GDPR 
guidelines. 
● How is the data (and/or biomaterials) saved and/or destroyed after study end. 
No biomaterials will be collected or stored in this study. All pseudonymized data collected during the 
study will be stored securely on encrypted, access-controlled servers at the coordinating center (UMCG) 
and at the partner site (Isala Hospital), in accordance with institutional and GDPR data protection 
standards. 
After the end of the study: 
● Study data will be retained for a period of 15 years in accordance with Dutch regulations. 
● During this retention period, access will be limited to authorized study personnel for purposes 
such as audits, publication, or regulatory review. 
● After the retention period, all digital data will be permanently deleted and any physical records 
will be shredded or incinerated in accordance with institutional procedures. 
8.6 With Informed consent 
Please complete only if patients are asked for Informed Consent: 
 
In case of collaboration with commercial/for-profit organizations. Has 
the research participant been informed in the DIF, or will they be 
informed, about the collaboration with commercial third parties. 
 
 
 
Yes  
x 
 
 
 
 
No 
☐ 
Has or will informed consent be(en) obtained for data sharing with the 
third party? 
Yes 
x 
 
No 
☐ 
8.7 Contracts 
For both with informed consent and without informed consent: will 
you contact the loket Contract Research to arrange the proper 
contracts? 
 
Yes 
x 
 
No 
☐ 
8.8 Data Protection Impact Assessment (DPIA) 
Will a DPIA be drawn up? 
 
Yes 
☐ 
No 
x 
If a DPIA will not be drawn up please elaborate on the reason for this: 
A Data Protection Impact Assessment (DPIA) will not be drawn up for this study because the processing 
of personal data poses a low risk to the rights and freedoms of the participants. The study involves 
minimal data collection limited to routinely available clinical information and ultrasound 
measurements, without processing of special categories of data beyond standard health information. 
No large-scale or systematic monitoring will take place, and data will be pseudonymized prior to 
analysis. Additionally, the study is conducted in accordance with the General Data Protection Regulation 
(GDPR) and the participating hospitals’ existing data protection policies. Given the limited scope and 
low privacy risk, a formal DPIA is not required. 

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9. Data Management Plan (DMP) 
In this study the data will be collected, processed, and archived in accordance with the General Data 
Protection Regulation (GDPR) and the FAIR (Findable, Accessible, Interoperable, Reusable) principles 
under the responsibility of the Principal Investigator, as is required by the GDPR law. 
Please note that completion of this section is required. A separate DMP will not be reviewed. 
9.1 Handling and storage of data 
The following are requirements with regards to handling and storage of data, please mark all that 
apply: 
● Digital data will be archived following a strict security and back-up policy (akin 
to UMCG security level). 
x 
● Paper source data and study files will be archived according the UMCG policy 
x 
● Source data, study files and digital data will be archived 15 years after the study 
is completed. 
x 
● Tooling (eg. software and procedures) used for collecting, processing, 
analysing, and storing data will be compliant with the UMCG policy and 
Standard Operating Procedures in the UMCG Research Toolbox. 
x 
9.1.1 If applicable: Not all items in the above section 10.1 apply to my study. Please elaborate on the 
reason for this and the solutions. 
<text> 
9.2 Anonymization and pseudonymization 
Data will be anonymized during data collection. 
 
Please note that this means that the data can never be linked back to the 
participant and that in practice this usually means that very large 
numbers of participants in the dataset are required. 
Yes 
☐ 
No 
x 
If data is anonymized:  
● Please explain what procedure is used: 
               <text> 
● Please reflect on the applicability of K1-anonimity on your dataset: 
<text> 
If anonymized data please skip the rest of section 9. 
Data will be pseudonymized during data collection (i.e. data cannot 
directly be linked back to the participant). 
Yes 
x 
No 
☐ 
If data is pseudonymized, please explain what procedure is used. 
All participant data collected in this study will be pseudonymized at the point of collection at each 
study site (UMCG and Isala Hospital) before being stored or shared. The pseudonymization procedure 
includes the following steps: 

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Template nWMO studie protocol 2025. V12 
1. Assignment of a unique study code to each participant at inclusion. This code will replace all 
directly identifying personal data in the study database. 
2. A secure, site-specific key file (linking study codes to patient identities) will be stored 
separately in a restricted-access, encrypted location within each participating hospital. This 
file will only be accessible to designated local study personnel and will not be shared with the 
coordinating center or other partners. 
3. The pseudonymized dataset, containing only study codes and research-relevant variables, will 
be securely transferred to the coordinating center (UMCG) for analysis. 
4. All data transfers will occur through encrypted and authorized channels (e.g., secure hospital 
servers, institutional file transfer systems) to prevent unauthorized access.  
9.3 Pseudonymization requirements 
9.3.1 The following are requirements when pseudonymized data is used, please mark all that apply:  
● Indirect and direct identifiable information collected will be minimized and only 
collected for the purpose of this study 
x 
● Direct identifiable information (e.g. contact details, code list, encryption key, 
participant identification log) will be stored separately from pseudonymized 
data 
x 
● Direct identifiable information can only be accessed by the Principal 
Investigator and study delegates after authorization by the Principal 
Investigator. 
x 
● Pseudonymized data can only be accessed by the Principal Investigator and 
study delegates after authorization by the Principal Investigator. 
x 
● Data roles, responsibilities, access and authorization, during the study and after 
study completion, will be managed and documented (e.g. in the DMP or study 
delegation log). 
x 
9.3.2 If applicable: not all items in the above list of pseudonymization requirements apply to my 
study. Please elaborate on the reason for this and the alternative solutions. 
 
NA 
10. 
FAIR Data and Data Sharing 
10.1 FAIR data 
The following statements concern FAIR data, which is the UMCG policy. Please note that FAIR is not 
the same as Open Access.  
Data will be made findable by including the description of the study 
(and type of data (i.e. metadata) in the UMCG FAIR data catalogue and 
other discipline specific catalogue(s). 
Yes 
x 
No 
☐ 
If ‘no’ is answered on the above question, please elaborate on the reason for this. 
<text> 
10.2 Data Sharing 

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Template nWMO studie protocol 2025. V12 
In case data (and biomaterials) will leave or enter the UMCG, will you 
contact the loket Contract Research to arrange the proper contracts? 
(Loket_Contract_Research@umcg.nl) 
Yes 
x 
No 
☐ 
No data 
will leave 
or enter 
UMCG 
☐ 
11. 
Management of Biomaterials (either newly collected or from an 
existing biobank) 
11.1 Will biomaterials be collected, processed, analyzed and/or 
stored for the purpose of this study? 
Yes 
☐ 
No 
x 
skip and delete rest of 
section 11 
12. 
Burden, Risks & Benefits  
13. 
Incidental findings  
 
Is there a risk of incidental findings?  
yes, 
minimal 
risk 
x 
yes, ≥ substantial 
risk 
 
☐ 
No 
 
 
☐ 
If yes, please explain the nature of the incidental findings.  
12.1 Burden 
Is there a (potential) burden for the participant as a 
result of participating in this study? 
For example: feeling tired after performing tests, 
reliving bad memories. 
Yes, minimal 
burden 
 
☐ 
Yes, more 
than minimal 
burden 
☐ 
No 
 
 
x 
 
If yes, please explain what the burden is/might be 
NA 
Clarify what is done to alleviate the burden 
NA 
12.2 Risk 
Does the participant run a risk of injuries and/or other 
discomfort as a result of participating in this study? 
For example: risk of falling while doing exercises 
Yes, minimal 
risk 
 
☐ 
Yes, more 
than minimal 
risk 
☐ 
No 
 
x 
If yes, please explain what the risk entails.   
NA 
Clarify what is done to alleviate the risk. 
NA 
12.3 Benefits  
Does the participant receive benefits/reward/incentives for participating 
in this study: 
Yes 
☐ 
No 
x 
If yes, please explain what the benefits/reward/incentives entail. 
NA 

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Template nWMO studie protocol 2025. V12 
Incidental findings in this study are expected to be minimal, as the ultrasound examination is focused 
solely on assessing diaphragm motion (tidal and maximal excursion) for research purposes. However, 
there is a small risk that during the ultrasound procedure, other unexpected abnormalities—such as 
diaphragmatic paralysis, severely impaired motion, or atypical thoracic or upper abdominal 
structures—may be visualized.  
Procedure to assess if a finding should be returned to the participant, or not 
These findings are outside the scope of the study but may have clinical relevance. In such cases, the 
findings will be communicated to the treating physician for further evaluation if deemed clinically 
significant. 
Procedure to inform the participant 
 The treating physician will assess the significance of the finding in the context of the patient’s overall 
clinical condition. If the finding is considered relevant, the participant will be informed in a timely and 
appropriate manner by their treating physician, who can provide medical context, follow-up steps, and 
answer any related questions.  
14. 
References 
1. Gommer A.M., Hendriks C. (2022, sep 01). COPD Zorg. VZinfo. 
https://www.vzinfo.nl/copd/zorg 
2. Roche N, Zureik M, Soussan D, Neukirch F, Perrotin D; Urgence BPCO (COPD 
Emergency) Scientific Committee. Predictors of outcomes in COPD exacerbation cases 
presenting to the emergency department. Eur Respir J. 2008 Oct;32(4):953-61. doi: 
10.1183/09031936.00129507. Epub 2008 May 28. PMID: 18508819. 
3. Munshi L, Mancebo J, Brochard LJ. Noninvasive Respiratory Support for Adults with Acute 
Respiratory Failure. N Engl J Med. 2022 Nov 3;387(18):1688-1698. doi: 
10.1056/NEJMra2204556. PMID: 36322846. 
4. Ram FS, Picot J, Lightowler J, Wedzicha JA, Ram FSF, Picot J, et al. Non-invasive 
positive pressure ventilation for treatment of respiratory failure due to exacerbations of 
chronic obstruc¬tive pulmonary disease. Update of Cochrane Database Syst Rev. 2004;(1). 
CD004104. 
5. Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose. Non-invasieve 
beademing bij COPD. 2013. 
6. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for 
Prevention, Diagnosis and Management of COPD: 2022 report. 
7. Gibson GJ. Diaphragmatic paresis: pathophysiology, clinical features, and investigation. 
Thorax. 1989 Nov;44(11):960-70. doi: 10.1136/thx.44.11.960. PMID: 2688182; PMCID: 
PMC462156. 
8. Ricoy J, Rodríguez-Núñez N, Álvarez-Dobaño JM, Toubes ME, Riveiro V, Valdés L. 
Diaphragmatic dysfunction. Pulmonology. 2019 Jul-Aug;25(4):223-235. doi: 
10.1016/j.pulmoe.2018.10.008. Epub 2018 Dec 1. PMID: 30509855. 
9. Laghi F, Tobin MJ. Disorders of the respiratory muscles. Am J Respir Crit Care Med. 2003 
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10. Boon AJ, Sekiguchi H, Harper CJ, Strommen JA, Ghahfarokhi LS, Watson JC, Sorenson 
EJ. Sensitivity and specificity of diagnostic ultrasound in the diagnosis of phrenic neuropathy. 

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Neurology. 2014 Sep 30;83(14):1264-70. doi: 10.1212/WNL.0000000000000841. Epub 2014 
Aug 27. PMID: 25165390; PMCID: PMC4180486. 
11. Shaikh H, Laghi F. Role of Diaphragm Ultrasound When NIV Fails in COPD 
Exacerbations. Respir Care. 2019 Dec;64(12):1600-1602. doi: 10.4187/respcare.07523. 
PMID: 31767688. 
Cammarota G, Sguazzotti I, Zanoni M, Messina A, Colombo D, Vignazia GL, Vetrugno L, 
Garofalo E,  
12. Bruni A, Navalesi P, Avanzi GC, Della Corte F, Volpicelli G, Vaschetto R. Diaphragmatic 
Ultrasound Assessment in Subjects With Acute Hypercapnic Respiratory Failure Admitted to 
the Emergency Department. Respir Care. 2019 Dec;64(12):1469-1477. doi: 
10.4187/respcare.06803. Epub 2019 Aug 27. PMID: 31455684. 
13. Kocyigit H, Gunalp M, Genc S, Oguz AB, Koca A, Polat O. Diaphragm dysfunction 
detected with ultrasound to predict noninvasive mechanical ventilation failure: A prospective 
cohort study. Am J Emerg Med. 2021 Jul;45:202-207. doi: 10.1016/j.ajem.2020.08.014. Epub 
2020 Aug 17. PMID: 33046306. 
14. archioni A, Castaniere I, Tonelli R, Fantini R, Fontana M, Tabbì L, Viani A, Giaroni F, 
Ruggieri V, Cerri S, Clini E. Ultrasound-assessed diaphragmatic impairment is a predictor of 
outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease 
undergoing noninvasive ventilation. Crit Care. 2018 Apr 27;22(1):109. doi: 10.1186/s13054-
018-2033-x. PMID: 29703214; PMCID: PMC5921560. 
15. Antenora F, Fantini R, Iattoni A, Castaniere I, Sdanganelli A, Livrieri F, Tonelli R, Zona S, 
Monelli M, Clini EM, Marchioni A. Prevalence and outcomes of diaphragmatic dysfunction 
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Respirology. 2017 Feb;22(2):338-344. doi: 10.1111/resp.12916. Epub 2016 Oct 14. PMID: 
27743430. 
15. 
Appendices 
<If applicable: text>