Six‐minute walk distance (6MWD) assessment is recommended for pulmonary arterial hypertension multidimensional risk stratification. However, current 6MWD cut‐off values were mainly derived from North American and European pulmonary arterial hypertension registries. Therefore, it is unknown if such cut‐off values broadly apply to other geographical populations. In this study, we aimed to identify 6MWD cut‐off values for Brazilian pulmonary arterial hypertension patients and to contrast our findings to current international Pulmonary Hypertension guidelines recommendations. One‐hundred four consecutive pulmonary arterial hypertension patients were allocated in groups according to their 6MWD, considering 50 m as a clinically relevant 6MWD difference. Next, patients were categorized into different 6MWD ranges based on similar survival rates in each group: < 250 m, 250–400 m, and >400 m. The study outcome was all‐cause mortality and transplantation according to the 6MWD range. Survival was truncated at five years. Median follow‐up period was 4.35 years (0.48–5.00). Survival rates at 1, 2, 3, and 5 years were 96%, 89%, 81%, and 73%, respectively. Cox analyses adjusted for age, sex, and pulmonary arterial hypertension etiology showed that 6MWD < 250 m and >400 m were associated with higher and lower risk of all‐cause mortality and transplantation. According to Harrell's c‐statistic, the prognostic discrimination of the 6MWD cut‐off value identified by the current study was 0.70 while international Pulmonary Hypertension guidelines 6MWD cut‐offs value was 0.61. In conclusion, our findings suggest that 6MWD geographical variations should be considered when assessing risk stratification in pulmonary arterial hypertension.

Dendritic cells (DCs) are key sentinels in the lung mucosa that interpret environmental signals to either promote tolerance or trigger inflammation, influencing the development of chronic lung diseases. This review highlights recent mechanistic insights showing that metabolic checkpoints serve as upstream regulators of DC fate and activity: inflammatory stimuli activate HIF-1α/mTOR-linked glycolytic pathways that drive maturation, cytokine secretion, antigen presentation, and migration. In contrast, AMPK-related oxidative and lipid metabolism pathways support tolerogenic states that encourage regulatory T-cell responses and inhibit checkpoints like PD-1/PD-L1. We also present evidence that DC subset specialization (cDC1 vs. cDC2) and their tissue location interact with these metabolic pathways to regulate lymphoid tissue formation, including the development and persistence of tertiary lymphoid structures in chronically inflamed lungs. These ectopic lymphoid tissues enhance local immune responses through DC–stromal interactions and ongoing T follicular helper–B cell communication, contributing to persistent inflammation and tissue remodeling in conditions such as COPD, asthma, pulmonary hypertension, and fibrotic interstitial lung disease. Finally, we discuss the translational potential of targeting this immunometabolic–lymphoid pathway, suggesting that modulating metabolic regulators, migratory circuits, and tolerogenic programs could restore immune balance while maintaining host defense—a promising framework for developing advanced therapies for chronic lung inflammation.