Chronic Obstructive Pulmonary Disease (COPD), a prevalent chronic condition characterized by persistent airflow limitation, represents a major global public health challenge due to its high prevalence, significant disability burden, and elevated mortality rates. The disease not only affects the lungs, leading to chronic cough, sputum production, and progressively worsening dyspnea, but also triggers various notable extrapulmonary effects and systemic comorbidities (1), contributing to its complex clinical profile. Among these, Acute Exacerbation of COPD (AECOPD) is a critical event in the disease trajectory, indicating a sudden deterioration of symptoms. It not only accelerates the decline of lung function but also stands as the primary factor driving increased rehospitalization risks and reduced survival (2).

Among the numerous systemic comorbidities associated with AECOPD, anemia—a frequently underestimated complication—has gained increasing clinical recognition in recent years (3). Anemia, fundamentally a pathological condition marked by diminished oxygen-carrying capacity of the blood, imposes a substantial global burden according to World Health Organization data (4). When anemia coexists with AECOPD, the two conditions can interact synergistically in detrimental ways. On one hand, the inherent chronic hypoxic state and systemic inflammatory milieu in AECOPD (5) are thought to contribute to anemia as a systemic comorbidity by suppressing erythropoietin activity and disrupting iron metabolism homeostasis, representing a pattern commonly classified as “anemia of chronic disease” (6). On the other hand, the presence of anemia further impairs tissue oxygen delivery, thereby aggravating pre-existing tissue hypoxia in AECOPD patients and creating a vicious cycle that unnecessarily increases respiratory load (7). Substantial clinical evidence indicates that AECOPD patients with comorbid anemia experience significantly prolonged hospital stays, consume more healthcare resources, and face a multiplied risk of long-term mortality (8). Therefore, early identification of anemia in AECOPD patients and timely optimization of underlying COPD management and comorbid conditions, together with systematic evaluation and treatment of reversible causes of anemia (such as iron deficiency and nutritional factors), may help reduce symptom burden, identify high-risk patients and potentially mitigate socioeconomic impact.

In clinical practice, complete blood count testing serves as the most direct and routine method for screening and diagnosing anemia. However, conventional diagnostic approaches often focus solely on whether hemoglobin (Hb) levels fall below a cutoff value, which inevitably limits the exploration of deeper insights into anemia. In reality, automated hematology analyzers provide a range of valuable red blood cell (RBC) parameters that collectively constitute a distinctive “identity fingerprint” of anemia. For instance, red cell distribution width (RDW), a key indicator reflecting heterogeneity in red blood cell volume, typically increases in response to impaired erythropoiesis or ineffective red cell production, and is closely associated with sustained inflammatory stress and oxidative damage in the body (9). Accumulating evidence indicates that elevated RDW is associated with more severe airflow limitation, higher risk of acute exacerbations, hospital readmission and increased mortality in patients with COPD and AECOPD (10, 11). In addition, RDW has been reported to be significantly increased in patients with obstructive sleep apnea syndrome (OSAS) and in overlap syndrome (COPD with OSAS), and higher RDW values correlate with apnea–hypopnea index and surrogate cardiovascular risk markers, further supporting its role as a simple, inexpensive marker of systemic hypoxia-inflammation burden (12, 13).

Meanwhile, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) are essential for the initial differentiation of anemia etiology (14) (e.g., microcytic hypochromic, normocytic, or macrocytic anemia). In recent years, cutting-edge research has begun to explore the prognostic value of these parameters in the field of COPD. Some scholars have identified RDW as an independent predictor of exacerbation risk in COPD patients (15), while other studies have reported that low MCH levels are closely linked to adverse outcomes in AECOPD patients (16).

Although existing studies have revealed associations between anemia and overall COPD prognosis, a key scientific question remains unresolved: within the specific AECOPD population, do these refined RBC parameters (such as RDW and MCH) exhibit regular, quantifiable changes as the severity of lung function impairment increases? Currently, there is a lack of comprehensive literature reporting systematic comparisons (17) and correlation analyses of RDW, MCH, and other indicators across AECOPD patients with different lung function grades (GOLD 1–4). This knowledge gap somewhat hinders clinicians from utilizing readily available complete blood count reports to more accurately assess disease severity in AECOPD patients (18).

Based on the current research landscape, this study leverages in-depth collaboration between hospital laboratory medicine and respiratory departments, capitalizing on the strengths of multidisciplinary cooperation. We aim to conduct a retrospective analysis of 120 AECOPD patients admitted in the past 2 years to systematically investigate the following core aspects: first, to clarify the distribution characteristics of anemia and different types of anemia in the AECOPD population; second, to dynamically observe the trajectories of key RBC parameters such as RDW and MCH across patients with varying severities of lung function impairment; and finally, to evaluate the correlation of these parameters with FEV1% predicted values and their predictive efficacy for severe AECOPD. This study aims to provide a novel, economical, and efficient laboratory reference dimension for the clinical assessment of AECOPD (19), thereby contributing to individualized patient management and prognostic evaluation.

This study, through systematic analysis of clinical data from 120 hospitalized AECOPD patients, reveals a close association between anemia and related RBC parameters with disease severity and prognosis. Our findings indicate that the overall prevalence of anemia in AECOPD patients is as high as 26.7%, and this proportion increases sharply with worsening lung function grades, exceeding half in Grade IV patients (20). This trend coincides with increasing patient age, declining BMI, and decreasing serum albumin levels, collectively depicting a spectrum of “systemic pathophysiological disturbances” related to disease severity (21). This suggests that assessing AECOPD must not be confined solely to the lungs but must integrally include systemic factors such as anemia and nutritional status.

The most pivotal finding of this research lies in establishing a moderate but clinically meaningful association between two often-overlooked routine blood parameters- RDW and MCH-and the degree of lung function impairment in AECOPD. Elevated RDW, indicating increased heterogeneity in RBC volume, is a marker of ineffective erythropoiesis or heightened destruction. Within the chronic inflammatory milieu of AECOPD, persistently high levels of inflammatory cytokines (e.g., IL-6, TNF-α) (22) not only directly suppress the proliferation and differentiation of bone marrow erythroid progenitors but also disrupt iron metabolism homeostasis, leading to upregulated hepcidin levels, impaired intestinal iron absorption (23), and inhibited macrophage iron release, resulting in “functional iron deficiency.” Erythropoiesis under these conditions is inefficient and disordered, directly driving up RDW values Our data showing a significant negative correlation between RDW and FEV1%pred, and its role as an independent factor associated with worse lung function in multivariable regression, aligns with findings from researchers like Sara et al. (24), collectively elevating RDW’s value from a mere anemia differential indicator to a sensitive biomarker reflecting systemic inflammatory burden and oxidative stress levels in AECOPD.

Conversely, our finding that decreased MCH independently correlates with lung function severity holds more direct clinical significance. Low MCH is characteristic of microcytic hypochromic anemia, most commonly associated with iron deficiency. Our analysis of anemia type distribution revealed microcytic anemia accounting for over 50% (25), providing morphological support for the hypothesis that iron metabolism dysfunction may be an important component of AECOPD-related anemia; however, we were unable to verify this mechanism directly because iron metabolism indices were not measured and absolute and functional iron deficiency could not be distinguished. AECOPD patients are prone to absolute or functional iron deficiency due to factors like anorexia from chronic hypoxia and impaired iron utilization due to systemic inflammation (26). Low MCH signifies reduced Hb-carrying capacity per RBC, further compromising blood oxygen-carrying efficiency, exacerbating tissue hypoxia on top of the existing hypoxic physiology, and potentially contributing to lung function deterioration and pulmonary hypertension development (27). While research by Priya et al. (28) identified low MCH as a predictor of poor outcomes in AECOPD patients, our study further anchors this association to the specific dimension of lung function severity, deepening the understanding of its pathophysiological significance.

Abnormalities in these RBC parameters ultimately translate into poorer clinical outcomes. In this study, the anemia group had significantly prolonged hospital stays (29), and the high RDW group showed significantly reduced long-term survival (30), consistent with reports from Maurizio et al. (31). Prolonged hospitalization implies increased healthcare resource consumption and heightened family burden, while survival differences directly impact patient quality of life. Consequently, we advocate for mandatory anemia screening and in-depth interpretation of RBC parameters for AECOPD patients (32), particularly elderly, malnourished, severe cases. When persistent RDW elevation or progressive MCH decline is observed, clinicians should be alert to potential underlying, uncorrected iron metabolism disorders or ongoing inflammatory states, considering further investigations like ferritin and CRP, rather than dismissing them as insignificant comorbidities of chronic disease.

This study has several important limitations. First, it was designed as a single-center retrospective observational cohort of hospitalized AECOPD patients in a tertiary respiratory department. As such, the sample is prone to selection bias, the findings primarily reflect the case-mix and management patterns of this specific hospital, and the results cannot be generalized to broader AECOPD populations without confirmation in multi-center prospective studies. Second, the overall sample size was relatively small (n = 120), and the distribution of lung function grades was unbalanced, with only 15 patients in GOLD grade IV. This reduced the statistical power of subgroup and multivariable analyses, particularly for the most severe disease strata and for comparisons between anemia subtypes, so the corresponding estimates should be interpreted with caution and regarded as hypothesis-generating. Third, anemia types were inferred only from MCV and MCH, and systematic testing of iron metabolism indices (such as ferritin, transferrin saturation and serum iron), vitamin B12 and folate was not performed for all anemic patients. Therefore, we could not distinguish absolute from functional iron deficiency, and any mechanistic interpretation that iron metabolism disorders are involved in AECOPD-related anemia remains hypothetical and requires dedicated mechanistic studies. Fourth, because of the limited number of outcome events, only age, BMI and major RBC indices were included in the multivariable logistic regression models. Important potential confounders, including detailed smoking exposure (e.g., pack-years), prior exacerbation history, comorbid cardiovascular disease and systemic corticosteroid use, could not be fully adjusted for, and residual confounding is therefore unavoidable; the observed associations between RBC parameters and lung function severity should be regarded as exploratory rather than definitive. In addition, we used standard WHO hemoglobin cut-offs that do not account for secondary polycythemia in heavy smokers, which may have led to an underestimation of the true prevalence of anemia and should be considered when interpreting the reported anemia rates. Fifth, although C-reactive protein was recorded at baseline, we did not integrate CRP into the multivariable models or conduct formal correlation or mediation analyses. Consequently, the proposed inflammationaanemia–nemiaequently, the proposed ied in the manuscript is supported by existing literature but could not be empirically verified in our dataset. Furthermore, spirometry was only performed after patients had achieved clinical stabilization according to the criteria described in the Methods, which may have preferentially included individuals with relatively milder or improving exacerbations and excluded those who remained too unstable to undergo lung function testing, thereby introducing additional selection bias. Moreover, the median follow-up duration was approximately 12 months, which is relatively short for a chronic disease such as COPD; therefore, our survival analyses reflect only short-term prognosis and cannot address longer-term outcomes. In addition, we used all-cause mortality as the endpoint because reliable attribution of cause-specific death was often difficult in this real-world cohort, which may reduce the specificity of our findings for COPD-related mortality and should be taken into account when interpreting the prognostic implications.

This study concludes that in AECOPD patients, the prevalence of anemia is related to the severity of lung function impairment. Elevated RDW and decreased MCH are two key and independent RBC parameters reflecting AECOPD severity, respectively revealing core defects in ineffective/heterogeneous erythropoiesis and insufficient Hb synthesis under the disease state. Dynamically monitoring changes in RDW and MCH not only aids in the early identification of high-risk patients with comorbid anemia and iron metabolism disorders but also provides important, economical, and readily accessible laboratory evidence for clinically assessing disease severity, predicting hospitalization duration, and prognosis. Adopting a more comprehensive management strategy for AECOPD, integrating the management of anemia and related RBC parameters into routine assessment and intervention protocols, holds promise as a new breakthrough for improving patient clinical outcomes.