- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07599839
BASE: Bronchiectasis Severity and Exacerbation Risk Study (BASE)
BASE: Bronchiectasis Assessment of Severity and Exacerbations for Baseline Severity Classification and One-Year Exacerbation Risk Prediction in Non-Cystic Fibrosis Bronchiectasis
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic airway disease characterized by permanent bronchial dilatation, impaired mucus clearance, recurrent infection, airway inflammation, and repeated exacerbations. Existing bronchiectasis severity tools are clinically useful, but many depend on prior exacerbation history, hospitalization history, subjective symptom assessment, or culture-based microbiological classification.
This prospective observational cohort study aims to develop and validate the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework. BASE is designed to classify current bronchiectasis severity and predict 12-month exacerbation risk using objective baseline functional, radiological, oxygenation, and inflammatory variables. Detailed methodological specifications, including variable definitions, scoring architecture, endpoint hierarchy, development-validation governance, and analytical integrity rules, are archived in a restricted-access Zenodo record: https://doi.org/10.5281/zenodo.20143505
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Participants will receive routine clinical care, and no treatment or intervention will be assigned by the study protocol. Patients will be followed for 12 months to record bronchiectasis exacerbations, hospitalization, lung-function change, inflammatory marker change, and clinical outcomes. The Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework includes two linked baseline models: the BASE Severity model (BASE-S) for current bronchiectasis severity classification and the BASE Prognostic model (BASE-P) for prediction of 12-month exacerbation risk. Both models will be derived in the development cohort and applied unchanged to the validation cohort.
Přehled studie
Postavení
Detailní popis
Non-cystic fibrosis bronchiectasis (NCFB) is a chronic airway disease characterized by permanent bronchial dilatation, impaired mucociliary clearance, recurrent infection, persistent airway inflammation, and repeated exacerbations. Disease severity and future exacerbation risk are heterogeneous among patients, and accurate baseline risk stratification remains clinically important for follow-up planning, preventive strategies, and early identification of patients at higher risk of clinical deterioration.
Existing bronchiectasis severity tools provide useful clinical stratification, but several established approaches include variables such as previous exacerbation history, previous hospitalization, subjective dyspnea assessment, or culture-based microbiological classification. These variables may be influenced by health-care access, documentation quality, patient perception, physician decision thresholds, sputum sampling quality, timing of culture, and prior antibiotic exposure. Therefore, there is a need to evaluate whether a focused objective disease-signature framework can classify current disease severity and predict future exacerbation risk using baseline functional, radiological, oxygenation, and inflammatory variables.
The Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework is designed as a baseline clinical assessment model for adults with non-cystic fibrosis bronchiectasis (NCFB). The framework includes two linked baseline models: the BASE Severity model (BASE-S) for current bronchiectasis severity classification and the BASE Prognostic model (BASE-P) for prediction of 12-month bronchiectasis exacerbation risk. Detailed variable definitions, scoring rules, point-conversion methods, endpoint hierarchy, development-validation governance, and analytic specifications are archived in a restricted-access Zenodo record before final model derivation and validation: https://doi.org/10.5281/zenodo.20143505
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This is a prospective observational cohort study. Participants will not be assigned to any treatment or intervention by the study protocol. All clinical management decisions, including airway clearance, antibiotic treatment, inhaled therapy, microbiological testing, follow-up frequency, and hospitalization decisions, will follow routine clinical care and institutional practice.
Eligible participants will undergo baseline clinical assessment, pulmonary function assessment, chest imaging review, resting room-air oxygenation assessment, and inflammatory marker assessment. Follow-up will continue for 12 months. During follow-up, bronchiectasis exacerbations, severe exacerbations requiring hospitalization, lung-function change, inflammatory marker change, treatment escalation, and clinical outcomes will be recorded using structured data collection forms.
The study will use a development-validation design. The BASE-S and BASE-P equations, point structures, severity categories, and risk bands will be derived in the development cohort. The final locked models will then be applied unchanged to the validation cohort. No refitting, recalibration, variable substitution, point-score modification, or threshold retuning will be performed in the validation cohort. Model performance will be assessed using discrimination, calibration, risk-band separation, clinical utility where applicable, and comparison with established bronchiectasis severity tools where complete data are available.
The intended output is a practical baseline disease-signature framework that can support severity classification and one-year exacerbation-risk prediction in adults with non-cystic fibrosis bronchiectasis (NCFB), while preserving separation from any future interventional treatment studies.
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní kontakt
- Jméno: Ahmad M Shaddad, MD
- Telefonní číslo: +201111171930
- E-mail: shaddad_ahmad@aun.edu.eg
Studijní místa
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Asyut Egypt
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Asyut, Asyut Egypt, Egypt, 71515
- Nábor
- Assiut university-Faculty of Medicine
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Kontakt:
- Ahmad M Shaddad, MD
- E-mail: shaddad_ahmad@aun.edu.eg
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Metoda odběru vzorků
Studijní populace
Popis
Inclusion Criteria:
- Adult patients aged 18 years or older.
- Diagnosis of non-cystic fibrosis bronchiectasis (NCFB) based on clinical assessment and high-resolution computed tomography (HRCT).
- Clinically stable or routinely assessed patients with non-cystic fibrosis bronchiectasis (NCFB) eligible for baseline severity and risk assessment.
- Patients attending outpatient clinic, inpatient ward, or respiratory follow-up services at Assiut University Hospitals during the study enrollment period.
- Patients suitable for prospective baseline assessment using the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework.
- Ability to undergo routine clinical, functional, radiological, oxygenation, and inflammatory assessment according to the study protocol.
- Ability to complete planned 12-month follow-up for bronchiectasis exacerbation and outcome assessment.
- Written informed consent obtained from the patient or legal representative.
Exclusion Criteria:
- Cystic fibrosis-related bronchiectasis.
- Traction bronchiectasis due to advanced fibrotic interstitial lung disease as the dominant respiratory diagnosis.
- Active pulmonary tuberculosis at enrollment.
- Active nontuberculous mycobacterial pulmonary disease requiring specific treatment at enrollment.
- Active malignancy or terminal non-respiratory illness expected to prevent 12-month follow-up.
- Acute life-threatening illness preventing safe enrollment or baseline assessment.
- Recent major thoracic surgery or acute thoracic trauma interfering with baseline respiratory assessment.
- Inability to complete the required baseline or Bronchiectasis Assessment of Severity and Exacerbations (BASE) assessment according to the study protocol.
- Inability or unwillingness to complete planned 12-month follow-up.
- Refusal to participate.
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
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Development Cohort
Adults with non-cystic fibrosis bronchiectasis (NCFB) enrolled in the prospective observational cohort and assigned to the development subset.
This cohort will be used to derive the Bronchiectasis Assessment of Severity and Exacerbations (BASE) equation, point structure, severity classification, and 12-month exacerbation-risk bands.
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Validation Cohort
Adults with non-cystic fibrosis bronchiectasis (NCFB) enrolled in the prospective observational cohort and assigned to the validation subset.
This cohort will be used to evaluate the fixed Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework without refitting, recalibration, variable substitution, or threshold modification.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Twelve-Month Bronchiectasis Exacerbation Risk Predicted by the BASE Prognostic Model (BASE-P)
Časové okno: Baseline to 12 months follow-up.
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Occurrence of at least one bronchiectasis exacerbation during 12-month follow-up, used as the primary clinical endpoint for development and validation of the BASE Prognostic model (BASE-P).
BASE-P is the 12-month risk-prediction component of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework for adults with non-cystic fibrosis bronchiectasis (NCFB).
Specific point ranges and risk categories have not yet been established and will be derived in the development cohort before locked validation.
Higher BASE-P predicted risk values indicate higher expected exacerbation risk.
Unit of Measure: Percentage of participants.
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Baseline to 12 months follow-up.
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Current Bronchiectasis Severity Classification by the BASE Severity Model (BASE-S)
Časové okno: Baseline Day 1
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Baseline bronchiectasis severity classification using the BASE Severity model (BASE-S).
BASE-S is the current severity-classification component of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework for adults with non-cystic fibrosis bronchiectasis (NCFB).
Specific severity point ranges and categories have not yet been established and will be derived in the development cohort before locked validation.
Higher BASE-S severity categories indicate greater baseline bronchiectasis disease burden.
Unit of Measure: Percentage of participants.
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Baseline Day 1
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Time to First Bronchiectasis Exacerbation
Časové okno: Baseline to 12 months follow-up.
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Time from baseline assessment to the first recorded bronchiectasis exacerbation during follow-up.
Participants without exacerbation will be censored at the last available follow-up date or at 12 months.
Shorter time to first bronchiectasis exacerbation indicates earlier clinical deterioration and worse outcome.
Unit of Measure: Days.
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Baseline to 12 months follow-up.
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Number of Bronchiectasis Exacerbations During Follow-Up
Časové okno: Baseline to 12 months follow-up.
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Total number of bronchiectasis exacerbations recorded for each participant during the 12-month follow-up period.
Higher exacerbation count indicates greater disease instability and worse clinical outcome.
Unit of Measure: Number of events.
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Baseline to 12 months follow-up.
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Severe Bronchiectasis Exacerbation Requiring Hospitalization
Časové okno: Baseline to 12 months follow-up.
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Occurrence of at least one bronchiectasis exacerbation requiring hospital admission during the 12-month follow-up period.
Hospitalization-requiring exacerbation indicates more severe clinical deterioration and worse outcome.
Unit of Measure: Percentage of participants.
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Baseline to 12 months follow-up.
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Change in Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted)
Časové okno: Baseline to 12 months follow-up.
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Change in forced expiratory volume in one second percent predicted (FEV1% predicted) measured by spirometry from baseline to 12 months.
Change will be calculated as the 12-month value minus the baseline value.
Lower or declining FEV1% predicted indicates worsening airflow limitation and worse functional outcome.
Unit of Measure: Percentage points.
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Baseline to 12 months follow-up.
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Change in Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO₂)
Časové okno: Baseline to 12 months follow-up.
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Change in resting room-air oxygen saturation measured by pulse oximetry (SpO₂) from baseline to 12 months, when clinically feasible.
Change will be calculated as the 12-month value minus the baseline value.
Lower or declining SpO₂ indicates worse oxygenation reserve.
Unit of Measure: Percentage points.
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Baseline to 12 months follow-up.
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Change in Neutrophil-to-Lymphocyte Ratio (NLR)
Časové okno: Baseline to 12 months follow-up.
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Change in neutrophil-to-lymphocyte ratio (NLR), calculated from complete blood count as absolute neutrophil count divided by absolute lymphocyte count, from baseline to 12 months.
Higher or increasing NLR indicates greater systemic neutrophilic inflammatory activity.
Unit of Measure: Unitless ratio.
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Baseline to 12 months follow-up.
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Change in C-Reactive Protein (CRP)
Časové okno: Baseline to 12 months follow-up.
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Change in C-reactive protein (CRP) from baseline to 12 months using routine laboratory measurement.
Change will be calculated as the 12-month value minus the baseline value.
Higher or increasing CRP indicates greater systemic inflammatory activity.
Unit of Measure: Milligrams per liter (mg/L).
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Baseline to 12 months follow-up.
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Bronchiectasis-Related Hospital Admission
Časové okno: Baseline to 12 months follow-up.
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Occurrence of hospital admission related to bronchiectasis deterioration, respiratory infection, bronchiectasis exacerbation, worsening respiratory symptoms, or related respiratory failure during follow-up.
Occurrence of bronchiectasis-related hospital admission indicates worse clinical outcome.
Unit of Measure: Percentage of participants.
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Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the Bronchiectasis Severity Index (BSI)
Časové okno: Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework with the Bronchiectasis Severity Index (BSI) for prediction of 12-month bronchiectasis exacerbation outcomes where complete data are available.
Higher discrimination and better calibration indicate better predictive performance.
Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale).
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Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the FACED Score
Časové okno: Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework with the FACED score for prediction of 12-month bronchiectasis exacerbation outcomes where complete data are available.
Higher discrimination and better calibration indicate better predictive performance.
Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale).
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Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the E-FACED Score
Časové okno: Baseline to 12 months follow-up.
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Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework with the E-FACED score for prediction of 12-month bronchiectasis exacerbation outcomes where complete data are available.
Higher discrimination and better calibration indicate better predictive performance.
Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale).
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Baseline to 12 months follow-up.
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Change in Modified Reiff Score
Časové okno: Baseline to 12 months follow-up.
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Change in Modified Reiff score from baseline to 12 months.
The Modified Reiff score assesses radiological bronchiectasis extent and bronchial dilatation severity across six lobes, including the lingula, with a total score ranging from 0 to 18. Change will be calculated as the 12-month value minus the baseline value.
Higher or increasing Modified Reiff score indicates greater structural radiological bronchiectasis burden or progression.
Unit of Measure: Points.
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Baseline to 12 months follow-up.
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Discrimination Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework for Twelve-Month Bronchiectasis Exacerbation Risk
Časové okno: Baseline to 12 months follow-up.
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Evaluation of the discrimination performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework for prediction of bronchiectasis exacerbation during 12-month follow-up using area under the receiver operating characteristic curve analysis.
BASE is a novel baseline disease-signature model undergoing prospective derivation and validation in adults with non-cystic fibrosis bronchiectasis (NCFB).
Specific bedside thresholds and operational risk categories have not yet been established and will be derived in the development cohort before locked validation.
Unit of Measure: Area under the receiver operating characteristic curve (0-1 scale).
Higher values indicate better discrimination performance.
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Baseline to 12 months follow-up.
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Calibration Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework for Twelve-Month Bronchiectasis Exacerbation Risk
Časové okno: Baseline to 12 months follow-up.
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Assessment of calibration performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework for prediction of bronchiectasis exacerbation during 12-month follow-up.
Calibration performance will be assessed using calibration intercept and calibration slope where applicable.
BASE is a novel baseline disease-signature model undergoing prospective derivation and validation in adults with non-cystic fibrosis bronchiectasis (NCFB).
Unit of Measure: calibration slope values closer to 1 indicate better calibration performance.
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Baseline to 12 months follow-up.
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Clinical Utility of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework
Časové okno: Baseline to 12 months follow-up.
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Assessment of clinical utility of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework using decision curve analysis and net benefit across clinically relevant threshold probabilities for prediction of bronchiectasis exacerbation during 12-month follow-up.
BASE is a novel baseline disease-signature model undergoing prospective derivation and validation in adults with non-cystic fibrosis bronchiectasis (NCFB).
Unit of Measure: Net benefit (unitless).
Higher net benefit indicates greater clinical utility across the evaluated threshold probability range.
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Baseline to 12 months follow-up.
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Risk-Band Separation of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework
Časové okno: Baseline to 12 months follow-up.
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Assessment of separation between predefined Bronchiectasis Assessment of Severity and Exacerbations (BASE) risk categories for 12-month bronchiectasis exacerbation outcomes.
BASE risk categories will be derived in the development cohort before locked validation.
Outcome differences across risk categories will be assessed using exacerbation occurrence, exacerbation burden, and hospitalization-related outcomes where applicable.
Unit of Measure: Percentage of participants.
Higher observed event rates in higher BASE risk categories indicate better risk-band separation.
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Baseline to 12 months follow-up.
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Regression-Based Contribution Analysis of Bronchiectasis Assessment of Severity and Exacerbations (BASE) Candidate Variables
Časové okno: Baseline to 12 months follow-up.
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Assessment of the contribution of individual Bronchiectasis Assessment of Severity and Exacerbations (BASE) candidate variables to prediction of 12-month bronchiectasis exacerbation risk using regression coefficient analysis.
Candidate domains include functional assessment, radiological assessment, oxygenation assessment, and inflammatory assessment.
Unit of Measure: Regression coefficients (unitless).
Larger absolute coefficient values indicate greater contribution to the prediction model.
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Baseline to 12 months follow-up.
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Ablation Analysis of Bronchiectasis Assessment of Severity and Exacerbations (BASE) Model Components
Časové okno: Baseline to 12 months follow-up.
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Assessment of changes in predictive discrimination performance for 12-month bronchiectasis exacerbation risk following sequential removal of Bronchiectasis Assessment of Severity and Exacerbations (BASE) model components.
The analysis will evaluate the contribution of functional, radiological, oxygenation, and inflammatory domains to overall model performance.
Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale).
Larger changes indicate greater contribution of the removed component.
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Baseline to 12 months follow-up.
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Incremental Discrimination Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework Compared With Established Bronchiectasis Severity Tools
Časové okno: Baseline to 12 months follow-up.
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Assessment of the incremental discrimination performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework compared with established bronchiectasis severity tools, including the Bronchiectasis Severity Index (BSI), FACED score, and E-FACED score, for prediction of 12-month bronchiectasis exacerbation outcomes where complete data are available.
Unit of Measure: Area under the receiver operating characteristic curve difference (0-1 scale).
Higher positive values indicate greater incremental discrimination improvement.
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Baseline to 12 months follow-up.
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Incremental Calibration Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework Compared With Established Bronchiectasis Severity Tools
Časové okno: Baseline to 12 months follow-up.
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Assessment of the incremental calibration performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework compared with established bronchiectasis severity tools, including the Bronchiectasis Severity Index (BSI), FACED score, and E-FACED score, for prediction of 12-month bronchiectasis exacerbation outcomes where complete data are available.
Unit of Measure: Unitless calibration coefficients.
Calibration intercept values closer to 0 and calibration slope values closer to 1 indicate better calibration performance.
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Baseline to 12 months follow-up.
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Association Between Bronchiectasis Assessment of Severity and Exacerbations (BASE) Severity Categories and Twelve-Month Exacerbation Outcomes
Časové okno: Baseline to 12 months follow-up.
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Assessment of the association between Bronchiectasis Assessment of Severity and Exacerbations (BASE) baseline severity categories and bronchiectasis exacerbation outcomes during 12-month follow-up.
BASE severity categories will be derived in the development cohort and applied unchanged to the validation cohort.
Unit of Measure: Percentage of participants.
Higher exacerbation rates in higher BASE severity categories indicate stronger association between baseline disease severity and future clinical instability.
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Baseline to 12 months follow-up.
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Association Between Bronchiectasis Assessment of Severity and Exacerbations (BASE) Risk Categories and Hospitalization Outcomes
Časové okno: Baseline to 12 months follow-up.
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Assessment of the association between Bronchiectasis Assessment of Severity and Exacerbations (BASE) risk categories and bronchiectasis-related hospitalization during 12-month follow-up.
BASE risk categories will be derived in the development cohort and applied unchanged to the validation cohort.
Unit of Measure: Percentage of participants.
Higher hospitalization rates in higher BASE risk categories indicate stronger association between predicted risk category and clinically severe outcomes.
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Baseline to 12 months follow-up.
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Aliae A. Hussien, MD, Assiut University
- Vrchní vyšetřovatel: Maiada K. Hashem, MD, Assiut University
- Vrchní vyšetřovatel: Ahmad M Shaddad, MD, Assiut University
- Vrchní vyšetřovatel: Alaa Sayed, MD, Assiut University
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2026-37-5
- 10.5281/zenodo.20143505 (Identifikátor registru: Zenodo)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Časový rámec sdílení IPD
Kritéria přístupu pro sdílení IPD
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
Studijní data/dokumenty
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Protokol studie
Identifikátor informace: 10.5281/zenodo.20143505Komentáře k informacím: The locked BASE Version 1.0 protocol is included in the Zenodo methodological archive according to the record access conditions.
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Plán statistické analýzy
Identifikátor informace: 10.5281/zenodo.20143505Komentáře k informacím: The locked BASE Version 1.0 statistical analysis plan and supporting methodological materials are included in the Zenodo methodological archive according to the record access conditions.
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Formulář informovaného souhlasu
Identifikátor informace: 10.5281/zenodo.20143505Komentáře k informacím: The informed consent form may be made available through the Zenodo methodological archive or institutional request pathway according to ethics and institutional approval requirements.
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