Amado Carlos A, Ghadban Cristina, Agüero Juan, Lavín Bernardo A, Martín-Audera Paula, Guerra Armando R, Berja Ana, Aranda Nieves, Guzun Anastasia, Insua Ana Isabel, García-Unzueta Mayte
Department of Pulmonology, Hospital Universitario Marqués de Valdecilla, 39005 Santander, Spain.
Department of Medicine and Psychiatry, University of Cantabria, 39005 Santander, Spain.
J Clin Med. 2025 Jun 11;14(12):4154. doi: 10.3390/jcm14124154.
Non-anemic iron deficiency (NAID) has been increasingly recognized as a potential factor affecting chronic obstructive pulmonary disease (COPD) outcomes. However, its prognostic role in COPD exacerbations and hospitalizations remains poorly understood. This study aimed to evaluate the prevalence of NAID in COPD patients, its impact on functional parameters, and its predictive value for exacerbations and hospitalizations. This prospective observational study included 238 patients with stable COPD and 60 age- and sex-matched smokers without COPD as a control group. NAID was defined as serum ferritin < 100 ng/mL or serum ferritin between 100 and 299 ng/mL with transferrin saturation < 20%. Clinical assessments included pulmonary function tests, 6 min walk distance (6MWD), handgrip strength, and fat-free mass index (FFMI). Patients were followed for 12 months to record moderate and severe COPD exacerbations. Cox regression analysis was used to determine the predictive value of NAID for exacerbations and hospitalizations. NAID was present in 68.9% of COPD patients compared to 46.7% of smokers without COPD ( = 0.001). COPD patients with NAID had lower 6MWD (430 (330-500) m vs. 462 (390-510) m, = 0.029), reduced FFMI (17.9 (15.5-20.2) kg/m vs. 20.6 (17.6-22.6) kg/m, < 0.001), and weaker handgrip strength (26 (22-33) kg vs. 34 (27-40) kg, < 0.001) compared to non-NAID COPD patients. During the 12-month follow-up period, 140 patients developed moderate COPD exacerbations (107 in the NAID group), and 43 patients were hospitalized due to severe exacerbations (36 in the NAID group). Cox regression analysis showed that NAID was an independent predictor of moderate COPD exacerbations (HR 1.846, 95% CI 1.249-2.729, = 0.002) and hospitalization (HR 2.537, 95% CI 1.129-5.703, = 0.024) after adjusting for age, sex, lung function, and comorbidities. NAID is highly prevalent in COPD and is associated with worse exercise capacity, lower muscle mass, and increased exacerbation risk independently of sex and age. These findings suggest that NAID could be a valuable biomarker for risk stratification in COPD patients, warranting further research on potential therapeutic interventions targeting iron metabolism.
非贫血性缺铁（NAID）已日益被视为影响慢性阻塞性肺疾病（COPD）预后的一个潜在因素。然而，其在COPD急性加重和住院方面的预后作用仍知之甚少。本研究旨在评估COPD患者中NAID的患病率、其对功能参数的影响以及对急性加重和住院的预测价值。 这项前瞻性观察性研究纳入了238例稳定期COPD患者以及60例年龄和性别匹配的无COPD吸烟者作为对照组。NAID被定义为血清铁蛋白<100 ng/mL或血清铁蛋白在100至299 ng/mL之间且转铁蛋白饱和度<20%。临床评估包括肺功能测试、6分钟步行距离（6MWD）、握力和去脂体重指数（FFMI）。对患者进行了12个月的随访，以记录中度和重度COPD急性加重情况。采用Cox回归分析来确定NAID对急性加重和住院的预测价值。 68.9%的COPD患者存在NAID，而无COPD的吸烟者中这一比例为46.7%（P = 0.001）。与无NAID的COPD患者相比，有NAID的COPD患者6MWD更低（430（330 - 500）m对462（390 - 510）m，P = 0.029），FFMI降低（17.9（15.5 - 20.2）kg/m对20.6（17.6 - 22.6）kg/m，P < 0.001），握力更弱（26（22 - 33）kg对34（27 - 40）kg，P < 0.001）。在12个月的随访期内，140例患者发生了中度COPD急性加重（NAID组107例），43例患者因重度急性加重住院（NAID组36例）。Cox回归分析显示，在调整年龄、性别、肺功能和合并症后，NAID是中度COPD急性加重（HR 1.846，95%CI 1.249 - 2.729，P = 0.002）和住院（HR 2.537，95%CI 1.129 -
