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.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis; Non-cystic Fibrosis Bronchiectasis; Bronchiectasis With Acute Exacerbation

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

• Study Contact: Name: Ahmad M Shaddad, MD; Phone Number: +201111171930; Email: shaddad_ahmad@aun.edu.eg

Study Locations

• Egypt
  • Asyut Egypt
    • Asyut, Asyut Egypt, Egypt, 71515
      • Recruiting
      • Assiut university-Faculty of Medicine
      • Contact: Ahmad M Shaddad, MD; Email: shaddad_ahmad@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with non-cystic fibrosis bronchiectasis (NCFB) attending outpatient clinics, inpatient wards, or respiratory follow-up services at Assiut University Hospitals during the study enrollment period will be prospectively screened for eligibility. Eligible participants will have clinically and radiologically confirmed non-cystic fibrosis bronchiectasis (NCFB) and will undergo baseline assessment using the Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework, followed by 12-month follow-up for bronchiectasis exacerbations, hospitalization, functional change, inflammatory marker change, and clinical outcomes. Participants will receive routine clinical care, and no treatment or intervention will be assigned by the study protocol.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Twelve-Month Bronchiectasis Exacerbation Risk Predicted by the BASE Prognostic Model (BASE-P)	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 to 12 months follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Current Bronchiectasis Severity Classification by the BASE Severity Model (BASE-S)	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.	Baseline Day 1
Time to First Bronchiectasis Exacerbation	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.	Baseline to 12 months follow-up.
Number of Bronchiectasis Exacerbations During Follow-Up	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.	Baseline to 12 months follow-up.
Severe Bronchiectasis Exacerbation Requiring Hospitalization	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.	Baseline to 12 months follow-up.
Change in Forced Expiratory Volume in One Second Percent Predicted (FEV1% Predicted)	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.	Baseline to 12 months follow-up.
Change in Resting Room-Air Oxygen Saturation Measured by Pulse Oximetry (SpO₂)	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.	Baseline to 12 months follow-up.
Change in Neutrophil-to-Lymphocyte Ratio (NLR)	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.	Baseline to 12 months follow-up.
Change in C-Reactive Protein (CRP)	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).	Baseline to 12 months follow-up.
Bronchiectasis-Related Hospital Admission	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.	Baseline to 12 months follow-up.
Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the Bronchiectasis Severity Index (BSI)	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).	Baseline to 12 months follow-up.
Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the FACED Score	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).	Baseline to 12 months follow-up.
Comparison of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework With the E-FACED Score	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).	Baseline to 12 months follow-up.
Change in Modified Reiff Score	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.	Baseline to 12 months follow-up.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discrimination Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework for Twelve-Month Bronchiectasis Exacerbation Risk	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.	Baseline to 12 months follow-up.
Calibration Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework for Twelve-Month Bronchiectasis Exacerbation Risk	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.	Baseline to 12 months follow-up.
Clinical Utility of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework	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.	Baseline to 12 months follow-up.
Risk-Band Separation of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework	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.	Baseline to 12 months follow-up.
Regression-Based Contribution Analysis of Bronchiectasis Assessment of Severity and Exacerbations (BASE) Candidate Variables	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.	Baseline to 12 months follow-up.
Ablation Analysis of Bronchiectasis Assessment of Severity and Exacerbations (BASE) Model Components	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.	Baseline to 12 months follow-up.
Incremental Discrimination Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework Compared With Established Bronchiectasis Severity Tools	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.	Baseline to 12 months follow-up.
Incremental Calibration Performance of the Bronchiectasis Assessment of Severity and Exacerbations (BASE) Framework Compared With Established Bronchiectasis Severity Tools	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.	Baseline to 12 months follow-up.
Association Between Bronchiectasis Assessment of Severity and Exacerbations (BASE) Severity Categories and Twelve-Month Exacerbation Outcomes	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.	Baseline to 12 months follow-up.
Association Between Bronchiectasis Assessment of Severity and Exacerbations (BASE) Risk Categories and Hospitalization Outcomes	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.	Baseline to 12 months follow-up.

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Aliae A. Hussien, MD, Assiut University; Principal Investigator: Maiada K. Hashem, MD, Assiut University; Principal Investigator: Ahmad M Shaddad, MD, Assiut University; Principal Investigator: Alaa Sayed, MD, Assiut University

Publications and helpful links

Helpful Links

• Locked BASE Version 1.0 methodological archive including protocol, statistical analysis plan, disclosure materials, baseline severity-classification framework, 12-month exacerbation-risk prediction framework, and development-validation governance.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: May 15, 2026
• First Submitted That Met QC Criteria: May 15, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Bronchiectasis; Non-cystic fibrosis bronchiectasis (NCFB); Bronchiectasis exacerbation; Exacerbation risk; One-year exacerbation risk; Baseline risk prediction; Disease-signature model; Prospective observational cohort; Bronchiectasis severity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 2026-37-5; 10.5281/zenodo.20143505 (Registry Identifier: Zenodo)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data may be made available only upon reasonable scientific request and after approval by the principal investigator, the institutional authority, and the relevant ethics committee when applicable. Data sharing will be restricted to approved research purposes and will require a formal data use agreement. No directly identifiable participant information will be shared. The Bronchiectasis Assessment of Severity and Exacerbations (BASE) framework, scoring architecture, analytic code, model coefficients, and related intellectual materials remain under the authority of the investigators and Assiut University unless separately released by formal written authorization.
• IPD Sharing Time Frame: Beginning 12 months after publication of the primary study results and for 3 years thereafter.
• IPD Sharing Access Criteria: Access may be granted to qualified researchers submitting a methodologically sound proposal for scientific purposes related to non-cystic fibrosis bronchiectasis (NCFB). Requests must be reviewed and approved by the principal investigator and institutional authority. Approved requesters must sign a data use agreement covering confidentiality, restricted use, data security, no re-identification attempts, no unauthorized redistribution, and acknowledgement of the investigators and Assiut University.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Study Data/Documents

1. Study Protocol
   Information identifier: 10.5281/zenodo.20143505
   Information comments: The locked BASE Version 1.0 protocol is included in the Zenodo methodological archive according to the record access conditions.
2. Statistical Analysis Plan
   Information identifier: 10.5281/zenodo.20143505
   Information comments: 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.
3. Informed Consent Form
   Information identifier: 10.5281/zenodo.20143505
   Information comments: The informed consent form may be made available through the Zenodo methodological archive or institutional request pathway according to ethics and institutional approval requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No