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

Study drug and medical condition

No information provided.

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 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:; 1. To describe demographics of patients diagnosed with CLAD-BOS; 2. To describe clinical characteristics following lung transplantation for patients diagnosed with CLAD-BOS; 3. To evaluate the trajectory of other relevant spirometry parameters (i.e., FVC, FEV1/FVC, FEF25-75%); 4. To evaluate the OS of patients diagnosed with CLAD-BOS; 5. To evaluate the time to first CLAD-BOS progression; 6. To evaluate the cumulative incidence of CLAD-BOS progression; 7. To evaluate the rate of hospitalization due to respiratory failure after CLAD-BOS onset; 8. To evaluate the incidence of concomitant respiratory disease; 9. To evaluate the incidence of concomitant non-respiratory disease; 10. To describe the use of concomitant treatments and procedures for CLAD-BOS
• Data analysis plan:
  Descriptive summary statistics for continuous variables included the number of observations, mean, SD, median, Q1, Q3, minimum, and maximum values. Two-sided 95% confidence intervals (CIs) were presented where applicable.; Descriptive summary statistics for categorical variables included frequency and percentages.; The trajectories of FEV1, FVC, FEV1/FVC, and FEF25-75% over time were characterized using a linear mixed model (LMM) for repeated measurements with random coefficients and an unstructured covariance matrix.; For time-to-event outcomes, including overall survival (OS), cumulative event-free survival times were evaluated using the Kaplan-Meier (KM) method. The KM graphs were presented along with the number of patients-at-risk at specified timepoints. Patients who were free from the event were censored at the last available date.; Count data (CLAD-BOS progression, hospitalization rates) per patient-year and 95% CIs were estimated using negative binomial regression models, including an offset for patient follow-up time. ; ; Planned subgroup analyses of main outcomes were performed by region (EU/US), age (<55 years, ≥55 years), sex (male/female), race (White, Black or African American, Asian, Other, Not collected locally), FEV1/FVC ratio (<0.7, ≥0.7), rate of decline (<Q1, ≥Q1-<median, ≥median-<Q3, ≥Q3), Baseline Lung Allograft Dysfunction (yes/no), azithromycin use (yes/no), transplant type (single, bilateral). No multiplicity adjustments were applied due to the descriptive nature of the analyses.; Post-hoc analyses were conducted to further explore the disease trajectory and treatment effects in specific subpopulations and from the clinical diagnosis of BOS. The post-hoc analyses included alternative modeling approaches for FEV1 trajectory (linear spline mixed-effects models), alternative baseline definition using diagnosis date, and time-dependent Cox proportional hazards models for OS.; Analyses were performed using SAS, V. 9.4 or higher (SAS Institute, Cary, NC).>
• 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. Posthoc 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 versus single lung transplant 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 the diagnosis and provide a strong scientific rationale for initiating treatment in these patients as early as possible.