Clinical Utility of the BACES Score in Predicting Outcomes and Guiding Treatment Strategies in NTM-PD = 비결핵항산균 폐질환 환자에서 BACES 점수의 임상적 유용성과 치료 전략 결정에 대한 분석

다국어 초록 (Multilingual Abstract)

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic and heterogeneous infection with variable clinical course and treatment response. Although the BACES score (comprising Body mass index, Age, Cavity, Erythrocyte sedimentation rate, and Sex) has been proposed as a simple prognostic index for mortality, its broader clinical utility across diverse outcomes and treatment decisions remains unclear. This dissertation aimed to evaluate the BACES score as an integrated tool for predicting multiple outcomes, to explore the biological significance of its inflammatory component, and to assess whether BACES-based stratification can inform therapeutic decision-making in patients with NTM-PD.
Methods: Three complementary retrospective and prospective cohort studies were conducted at Seoul National University Bundang Hospital and Seoul National University Hospital. The first cohort (The BACES validation cohort, n = 681) examined associations between baseline BACES scores and clinical outcomes, including disease progression, culture conversion, and cause-specific mortality. The second cohort (The ESR/CRP discrepancy cohort, n = 1,057) compared the clinical characteristics and prognostic implications of patients showing discordant inflammatory markers—elevated ESR with normal CRP versus elevated CRP with normal ESR. The third cohort (The treatment strategy cohort, n = 592) evaluated outcomes of immediate treatment versus watchful waiting in Mycobacterium avium complex pulmonary disease (MAC-PD), applying propensity score matching to balance baseline severity. Primary endpoints included progression-free survival, culture conversion, and mortality from respiratory or infectious causes.
Results: Higher BACES scores were strongly associated with worse outcomes across multiple domains, including higher rates of disease progression, lower rates of culture conversion after treatment, and all-cause mortality. Respiratory and infection-associated mortality rates increased with the higher BACES score, with adjusted hazard ratios of 5.13 (95% CI 2.48–10.59) for BACES 2-3 and 18.29 (7.92–42.2) for BACES 4-5 compared to BACES 0-1. Discrepancy rate between ESR and CRP was 34.4%, which was mostly due to elevation of ESR with normal CRP (90.4%). Patients with elevated ESR but normal CRP were typically older, leaner, and bronchiectasis-predominant, whereas those with high CRP showed higher BMI and more frequent diabetes or malignancy. However, ESR/CRP discrepancy was not an independent predictor of mortality after adjustment, indicating that ESR reflects chronic, disease-related inflammation, whereas CRP elevation represents transient systemic stress. In the treatment strategy analysis, immediate antibiotic initiation achieved higher and faster culture conversion (HR 3.07, 95% CI 1.68–5.61, p < 0.001) but did not improve overall or cause-specific survival, while adverse events—particularly gastrointestinal intolerance and visual disturbance—were significantly more frequent with early therapy. Subgroup analyses according to various disease severity revealed comparable results.
Conclusions: The BACES score is a robust, multidimensional index that integrates systemic, radiologic, and demographic determinants of disease severity in NTM-PD. Elevated ESR remains a valid marker of chronic inflammation within this framework. Although early antimicrobial therapy enhances microbiologic response, it does not translate into a survival benefit once baseline severity is balanced. These findings support the incorporation of BACES into routine clinical assessment and individualized treatment planning. Further research is warranted to refine risk-adapted decision-making between immediate therapy and watchful waiting in NTM-PD.

국문 초록 (Abstract)

배경: 비결핵항산균 폐질환은 만성적이고 임상 경과가 다양한 감염성 질환으로, 예후 예측과 치료 결정이 어렵다. BACES 점수(체질량지수, 연령, 공동, 적혈구침강속도, 성별)는 사망률을 예측하는 간단한 지표로 제시되었으나, 다양한 임상 결과와 치료 전략 전반에 걸친 임상적 활용성은 명확히 규명되지 않았다. 본 연구는 BACES 점수의 다면적 예후 예측 능력을 평가하고, 염증 지표로서 ESR의 임상적 의미를 규명하며, BACES 기반 위험도 분류가 치료 결정에 기여할 수 있는지를 확인하고자 하였다.
방법: 서울대학교병원과 분당서울대학교병원에서 후향적·전향적 세 코호트를 구축하였다. 첫 번째 코호트(BACES 검증 코호트, n=681)는 진단 시 BACES 점수와 질병 진행, 배양 전환, 사망 원인 간의 관련성을 분석하였다. 두 번째 코호트(ESR/CRP 불일치 코호트, n=1,057)는 ESR 상승-CRP 정상형과 CRP 상승-ESR 정상형 간의 임상 특성과 예후를 비교하였다. 세 번째 코호트(치료 전략 코호트, n=592)는 Mycobacterium avium complex 폐질환 환자에서 즉시 치료군과 경과관찰군을 비교하였으며, 성향점수매칭을 통해 기저 중증도를 보정하였다. 주요 평가변수는 무진행 생존, 배양 전환, 호흡기 또는 감염 관련 사망이었다.
결과: BACES 점수가 높을수록 질병 진행률은 증가하고 치료 후 배양 전환율과 생존율은 감소하였다. 호흡기 또는 감염 관련 사망의 보정된 위험비는 BACES 2–3군 5.13(95% CI 2.48–10.59), BACES 4–5군 18.29(7.92–42.2)로 점수에 따라 단계적으로 상승하였다. ESR과 CRP의 불일치율은 34.4%였으며, 대부분(90.4%)은 ESR 단독 상승형이었다. ESR 상승-CRP 정상형 환자는 고령·저체중·기관지확장증 우세형이었고, CRP 상승형은 당뇨병·악성종양 동반이 많았다. 그러나 ESR/CRP 불일치는 다변량 분석에서 독립적인 사망 예측인자가 아니었다. 치료 전략 분석에서 즉시 항균치료는 배양 전환을 유의하게 촉진하였으나(위험비 3.07, p<0.001), 전체 및 원인별 생존에는 유의한 차이가 없었고, 위장장애 및 시력 이상 등 이상반응은 즉시치료군에서 더 많았다.
결론: BACES 점수는 비결핵항산균 폐질환의 임상적 중증도를 통합적으로 반영하는 다차원적 예후 지표로서, ESR은 만성 염증의 안정된 지표로 유효함을 확인하였다. 조기 항균치료는 미생물학적 반응을 향상시키지만, 중증도가 보정된 후에는 생존 이득이 없었다. 본 연구는 BACES 점수를 활용한 개별화된 치료 결정과 위험도 기반 경과관찰 전략의 임상적 근거를 제시하며, 향후 이를 최적화하기 위한 추가 연구가 필요하다.

목차 (Table of Contents)

• Introduction 1
• Section 1: Background of the Study 1
• Section 2: Purpose of Research 4
• Methods 6
• Section 1: Study Subjects 6
• Section 1-1: BACES Validation Cohort 6
• Section 1-2: ESR/CRP Discrepancy Cohort 6
• Section 1-3: Treatment Strategy Cohort 7
• Section 2: Data Collection 7
• Section 2-1: BACES Validation Cohort 7
• Section 2-2: ESR/CRP Discrepancy Cohort 8
• Section 2-3: Treatment Strategy Cohort 9
• Section 3: Definition of Variables 10
• Section 4: Definition of Outcomes 10
• Section 5: Statistical Analysis 13
• Results 15
• Section 1: Validation of the BACES score for various clinical outcomes 15
• Section 1-1: Patient selection process and baseline characteristics 15
• Section 1-2: Baseline symptoms according to BACES severity 19
• Section 1-3: Clinical outcomes according to BACES severity 20
• Section 1-4: Factors associated with respiratory or infection-related mortality 21
• Section 2: Comparative analysis of ESR and CRP using their discrepancy 23
• Section 2-1: Patient selection process according to the discrepancy of ESR and CRP 23
• Section 2-2: Patient characteristics according to the discrepancy of ESR and CRP 24
• Section 2-3: Patient outcomes according to the discrepancy of ESR and CRP 28
• Section 3: Treatment strategies in MAC-PD considering the BACES score 30
• Section 3-1: Patient selection and propensity score matching according to immediate treatment and watchful waiting strategies 30
• Section 3-2: Treatment outcomes according to the treatment strategies 34
• Section 3-3: Survival outcomes according to the treatment strategies 38
• Section 3-4: Exploratory analysis using a different waiting period 41
• Discussion 45
• Section 1: Key findings 45
• Section 2: Comparison with similar research 47
• Section 3: Strengths of this study 50
• Section 4: Limitations 52
• Section 5: Conclusions 54
• References 56
• Abstract in Korean 61