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This study aims to analyze if patients with chronic obstructive lung disease who experience a decline of blood oxygen saturation during physical exercise have a disease course different from that of COPD patients who do not experience a decline in blood oxygen saturation during exercise. Patients will be followed for a total of 3 years.
The major aim of the study is to test whether intermittent hypoxaemia is a major driver of the progression of chronic obstructive lung disease (COPD). The second aim is to analyse whether dysregulation of the L-arginine / dimethylarginine pathway is a mechanistic link between intermittent hypoxemia and lung function decline, and whether plasma biomarkers are suitable to identify COPD patients at high risk of rapid lung function decline and mortality.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| COPD patients with exertional desaturation | Patients with chronic obstructive pulmonary disease stages 2-3, groups B or E according to the GOLD Guideline (2023), who experience a drop in arterial oxygen saturation (by pulse oximetry) to <90% or a drop by 4% or greater of the basal value during a six-minute walk test. |
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| COPD patients without exertional desaturation | Patients with chronic obstructive pulmonary disease stages 2-3, groups B or E according to the GOLD Guideline (2023), who do not experience a drop in arterial oxygen saturation (by pulse oximetry) to <90% or a drop by 4% or greater of the basal value during a six-minute walk test. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No active intervention, but observational follow-up | Other | Patients remain in usual care by their pulmonary medicine specialists and are being observed during annual follow-up investigations during up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in FEV1(% of LLN) between baseline and end-of-follow-up | The difference in measured FEV1 assessed by spirometry and expressed as percent of the lower limit of the normal distribution based upon the Global Lung Function 2022 Equations, by comparing results of the baseline measurement with those of the last investigation during up to three years of follow-up | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in all-cause mortality during follow-up between groups | Number of patients who died from any cause during follow-up in either of the two groups. | 3 years |
| Difference in COPD-related mortality during follow-up between groups |
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Inclusion Criteria:
Exclusion Criteria:
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This study will be conducted a patients with chronic obstructive pulmonary disease of all sexes aged 18 - 80 years. They must be graded as stage 2 - 3 according to GOLD criteria (FEV1 between 30 and 79% of the age-adjusted predicted value) and belong to groups B or E according to symptom scores (mMRC or CAT questionnaires) and exacerbation history.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rainer Böger, Prof. Dr. | Contact | +49-40-7410 | 59759 | boeger@uke.de |
| Juliane Hannemann, PD Dr. | Contact | +49-40-7410 | 59701 | ju.hannemann@uke.de |
| Name | Affiliation | Role |
|---|---|---|
| Rainer Böger, Prof. Dr. | Universitätsklinikum Hamburg-Eppendorf | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Hamburg-Eppendorf, Institute of Clinical Pharmacology and Toxicology | Hamburg | 20246 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38816826 | Derived | Boger R, Hannemann J. Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease - the PROSA study: rationale and study design. BMC Pulm Med. 2024 May 30;24(1):262. doi: 10.1186/s12890-024-03074-x. |
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Upon reasonable individual request, IPD can be made available for further analyses by other researchers.
Data can be made available after conclusion of the trial and final analysis.
Written, reasoned request to either of the two principal contact persons of the study.
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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Blood samples will be collected for plasma biomarker analysis and DNA extraction for genotyping of single nucleotide polymorphisms in target genes of the L-arginine-dimethylarginine-NO pathway.
Number of patients who died from COPD and its complications during follow-up in either of the two groups.
| 3 years |
| Difference in frequency of hospital admissions for exacerbation of COPD during follow-up between groups | Number of patients who were admitted to hospital because of exacerbated COPD during follow-up in either of the two groups. | 3 years |
| Difference in frequency of hospital admissions for causes other than exacerbation of COPD during follow-up between groups | Number of patients who were admitted to hospital for any other reason than exacerbated COPD during follow-up in either of the two groups. | 3 years |
| Sensitivity of plasma biomarkers (spec. ADMA and SDMA) to predict the prevalence of exertional desaturation in COPD patients | Sensitivity analysis (ROC analysis) of biomarkers and presence of exertional desaturation (as defined in the protocol) or not in study participants. | 3 years |
| Sensitivity and specificity of plasma biomarkers (spec. ADMA and SDMA) measured at baseline to prospectively predict the slope of lung function decline in COPD patients | Prospective survival analysis (Kaplan-Meier) of plasma biomarkers measured at the time of study inclusion and the difference in FEV1(% of lower limit of normal) between baseline and last measurement during follow-up. | 3 years |
| Sensitivity and specificity of plasma biomarkers at baseline to prospectively predict the mortality rate in COPD patients | Prospective survival analysis (Kaplan-Meier) of plasma biomarkers measured at the time of study inclusion and total mortality during follow-up. | 3 years |
| Difference in incidence and extent of exercise hypoxemia between carriers and non-carriers of single nucleotide polymorphisms (SNPs) in genes of the L-arginine - dimethylarginine pathway | Comparison of the rates of prevalence of exertional desaturation between homozygous carriers of the major versus minor allele of SNPs in the NOS III, DDAH1, DDAH2, PRMT1-9, AGXT2, and ARG1-2 genes. | 3 years |
| Difference in positive and negative predictive value of bicycle ergometry, 6-minute walk test, and 15-sec breath-hold test to discriminate between COPD patients with exertional desaturation versus those without exertional desaturation | Comparison of sensitivity and specificity analyses (ROC analyses) of the outcome of named exercise tests to detect exertional desaturation in study participants. | 3 years |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |