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- Ensayo clínico 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.
Descripción general del estudio
Estado
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Ahmad M Shaddad, MD
- Número de teléfono: +201111171930
- Correo electrónico: shaddad_ahmad@aun.edu.eg
Ubicaciones de estudio
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Asyut Egypt
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Asyut, Asyut Egypt, Egipto, 71515
- Reclutamiento
- Assiut university-Faculty of Medicine
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Contacto:
- Ahmad M Shaddad, MD
- Correo electrónico: shaddad_ahmad@aun.edu.eg
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Twelve-Month Bronchiectasis Exacerbation Risk Predicted by the BASE Prognostic Model (BASE-P)
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Current Bronchiectasis Severity Classification by the BASE Severity Model (BASE-S)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Discrimination Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework for Twelve-Month Bronchiectasis Exacerbation Risk
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Aliae A. Hussien, MD, Assiut University
- Investigador principal: Maiada K. Hashem, MD, Assiut University
- Investigador principal: Ahmad M Shaddad, MD, Assiut University
- Investigador principal: Alaa Sayed, MD, Assiut University
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2026-37-5
- 10.5281/zenodo.20143505 (Identificador de registro: Zenodo)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
Datos del estudio/Documentos
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Protocolo de estudio
Identificador de información: 10.5281/zenodo.20143505Comentarios de información: The locked BASE Version 1.0 protocol is included in the Zenodo methodological archive according to the record access conditions.
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Plan de Análisis Estadístico
Identificador de información: 10.5281/zenodo.20143505Comentarios de información: 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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Formulario de consentimiento informado
Identificador de información: 10.5281/zenodo.20143505Comentarios de información: The informed consent form may be made available through the Zenodo methodological archive or institutional request pathway according to ethics and institutional approval requirements.
Información sobre medicamentos y dispositivos, documentos del estudio
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