BASE: Bronchiectasis Severity and Exacerbation Risk Study

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.