A Retrospective Chart Review Study of Patients With Chronic Lung Allograft Dysfunction-Bronchiolitis Obliterans Syndrome (CLAD-BOS) Post Lung Transplantation – "BOSTON EVOLUTION"

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Other
• If ‘other’, further details on the scope of the study:
  Study to describe natural disease evolution and clinical outcomes. Data collection methods: The study data sources consisted of medical records (including electronic and/or paper) and patient notes for the study patients.
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Retrospective chart review study

Population studied

• Short description of the study population:
  Adult patients aged ≥ 18 years who are recipients of a lung transplant and diagnosed with CLAD-BOS following transplantation.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  284

Study design details

• Study design:
  This was a retrospective, multinational, multicenter chart review study of adult patients with clinically diagnosed CLAD BOS after lung transplantation. All data were retrospectively collected from patient records, starting from the lung transplantation date through the last date of available data;
• Main study objective:
  The primary objective of this study was to evaluate the FEV1 trajectory of patients diagnosed with CLAD BOS.
• Setting:
  The study was conducted at approximately 6 sites located in the US and EU regions, with patient enrollment distributed nearly equally between the 2 regions. Eligible patients were identified through retrospective chart reviews of medical records at the participating study sites. The records were screened chronologically, starting with patients diagnosed with CLAD BOS from 01 January 2013. Patients who met the eligibility criteria were included in the study.
• Comparators:
  Not applicable
• Outcomes:
  Primary Outcome: To evaluate the FEV1 trajectory of patients diagnosed with CLAD-BOS; Secondary Outcomes: To describe demographics of patients diagnosed with CLAD-BOS, Lung Transplant History, Best Post-transplant Spirometry Parameters, CLAD-BOS Characteristics, Clinical Characteristics Following Lung Transplantation, Signs, Symptoms, or Other Clinical Findings, Trajectory of Other Relevant Spirometry Parameters, Overall Survival, Time to First CLAD-BOS Progression, Cumulative Incidence of CLAD-BOS Progression, Rate of Hospitalization due to Respiratory Failure After CLAD-BOS Onset, Incidence of Concomitant Respiratory and Non-Respiratory Disease, Use of Concomitant Treatments and Procedures for CLAD-BOS.
• Data analysis plan:
  Descriptive summary statistics for continuous variables will include the number of patients, mean, standard deviation, median, interquartile range, and range. Descriptive summary statistics for categorical variables will include frequency counts and percentages. Confidence intervals around mean or proportion will be presented where applicable. The trajectories of FEV1 and other longitudinal parameters will be characterized using a Linear Mixed Model for repeated measurements, using all observed available FEV1 measurements up to the last date of data available. ; Overall survival and time to first CLAD-BOS progression will be assessed using Kaplan-Meier methods. Rates at yearly intervals will be reported along with the estimated medians and the corresponding CIs, whenever estimable. Kaplan-Meier curves will be presented along with the number of patients at risk at exact time points. Incidence rates will be evaluated using negative binomial or Poisson (in case of lack of convergence) regression, including an offset for patient follow-up time. Estimations will be provided along with their 95% CIs. ; Subgroup analyses of main outcomes will be performed by age class, gender, race, region, and severity of disease. Statistical details and potential new subgroup definitions will be reported in the Statistical Analysis Plan (SAP). ; The SAP will be issued before starting the collection of data with more technical and detailed elaboration of the principal features of statistical analyses. ; Additional post-hoc analyses may be produced to further explore data according to the results obtained. Any deviations from the original SAP (including unplanned analyses) will be documented in the Clinical Study Report.
• Summary results:
  This study provides the most comprehensive description to date of the natural history and progression of CLAD-BOS following lung transplantation. It highlights a significant decline in lung function among patients with CLAD-BOS over a 3-year period, with spirometry parameters such as FEV₁, FVC, FEV₁/FVC, and FEF₂₅-₇₅% showing progressive deterioration. The analysis confirms that, after disease onset, patients experience a rapid initial decline in lung function during the first 24 weeks, followed by a slower, progressive deterioration over subsequent years. This pattern was consistent across analytical approaches. Sensitivity analyses further supported the robustness of these findings. Post-hoc analyses using the clinically diagnosed date of CLAD-BOS as the starting point, instead of the pre-specified algorithmic onset date, confirmed the same disease trajectory, an initial steep decline followed by slower progression, with only minor differences in estimated values. This consistency reinforces the reliability of the overall disease course characterization. Slight variations were observed, including a marginally greater FEV₁ decline at early timepoints and a shorter median OS (approx. 10 months less), when analyses were anchored to the clinical diagnosis date. Survival analyses demonstrated a clear difference by transplant type, with markedly longer median OS in bilateral lung transplant recipients compared to single lung recipients. The overall median survival from CLAD-BOS onset was 77.5 months, consistent with previously reported outcomes in this population. In summary, the study delineates a consistent pattern of disease progression characterized by an early, steep decline in lung function followed by stabilization or gradual deterioration over time. These data clearly indicate that the optimal therapeutic window for treating CLAD-BOS is at the early stage of disease diagnosis and provide a strong scientific rationale for in these patients as early as possible.