K-Means Cluster Identification of Nutritional Phenotypes in Patients with Nontuberculous Mycobacterial Pulmonary Disease and Correlation Analysis with Runyon Classification

Background and Aims: To explore nutritional heterogeneity among patients with nontuberculous mycobacterial (NTM) pulmonary disease by identifying nutritional phenotypes using K-means clustering, and to compare nutritional and inflammatory markers, Runyon classification, and comorbidities across phenotypes. Methods: A retrospective analysis of 457 patients diagnosed with NTM pulmonary disease was conducted. Nine nutritional and inflammatory indicators were collected: body mass index (BMI), hemoglobin (HGB), lymphocyte count (LY), C-reactive protein (CRP), prealbumin (PAB), albumin (ALB), total protein (TP), triglycerides (TG), and total cholesterol (TC). The candidate clusters were initially evaluated using the elbow method and silhouette scores. In the absence of a distinct inflection point in the elbow method, the solution with the highest silhouette coefficient was regarded as the most compact candidate solution. An exploratory final clustering scheme was then determined by further incorporating bootstrap internal stability analysis and clinical interpretability. Subsequently, nutritional and inflammatory profiles, Runyon classification (Groups I and III), and comorbidity distributions were compared among phenotypes. Ordinal logistic regression analysis was employed to identify factors associated with nutritional phenotype grade. Results: Four nutritional phenotypes were identified: Healthy–Low Inflammation (24.5%), Hyperlipidemic–Well-nourished (18.8%), Lean–Moderate Inflammation (42.5%), and Severely Emaciated–High Inflammation (14.2%). Significant differences existed in nutritional and inflammatory markers (all P< 0.001). The Severely Emaciated–High Inflammation type exhibited the lowest BMI, HGB, ALB, and TP levels; highest CRP level; highest proportion of Runyon Group III mainly represented by the Mycobacterium avium complex (MAC) infections (67.7%, P=0.011); and more severe comorbidities (malignancy, renal insufficiency; P< 0.05). The Healthy–Low Inflammation type displayed optimal nutritional profiles, highest proportion of Runyon Group I (predominated by Mycobacterium kansasii and Mycobacterium marinum ) infections (44.6%, P=0.003), and few severe comorbidities. Ordinal logistic regression analysis demonstrated that age ≥ 60 years, malignant tumor, respiratory diseases, and renal diseases were significantly associated with an increased cumulative odds of progressing to a poorer nutritional phenotype grade (all P < 0.05). Conclusion: Nutritional status in patients with NTM pulmonary disease shows significant heterogeneity closely associated with inflammation, bacterial strain type, and comorbidities. The Severely Emaciated–High Inflammation type exhibited the most unfavorable nutritional-inflammatory profile, suggesting that early identification, nutritional assessment, and comprehensive intervention should be strengthened clinically for such patients. Keywords: nontuberculous mycobacterial pulmonary disease, nutritional phenotype, K-means clustering, Runyon classification, malnutrition, inflammatory response