Chronic obstructive pulmonary disease (COPD) involves irreversible airflow obstruction, often caused by cigarette smoke or air pollution. Chronic airway inflammation, dysfunctional alveolar macrophages, and impaired clearance of pathogens and apoptotic cells are characteristic of COPD. Key cell membrane phagocytosis-related surface proteins (cluster of differentiation factors [CD]206, CD36, CD38) are dysregulated, and macrophages are often enlarged with reduced function. Carbon deposits are commonly associated with exposure to smoke and pollution. Carbon deposits have been identified in both sputum and alveolar macrophages, correlating with increased exacerbations and decreased lung function. Previous studies lacked control groups or quantification.
A recent study published in ERJ Open Research aimed to compare the carbon content of alveolar macrophages in patients with COPD and smokers. The study also examined the impact of carbon accumulation on lung function and the phenotype of macrophages.
Lung samples were collected from 28 COPD patients (mean age = 68±8 years, male = 57) and 15 smokers (mean age = 67±7 years, male = 47) who underwent surgery for confirmed or suspected lung cancer. Peripheral blood from 8 healthy non-smokers was used to generate monocyte-derived macrophages (MDMs). Immunohistochemistry and quantification of carbon deposits were measured. Various analytical techniques, including quantitative polymerase chain reaction (qPCR), cell viability assays, MDMs microscopy, and enzyme-linked immunosorbent assay (ELISA), were employed in this study. Statistical analysis was performed using the Shapiro-Wilk normality test, the Kruskal-Wallis test, the Friedman test, the Mann-Whitney test, or the t-test, as determined by GraphPad InStat software.
Carbon deposits were found in alveolar macrophages from both COPD patients and smokers, with no significant difference in macrophage count or carbon positivity (52% vs 42%, P = 0.12) between the groups.  Both mean carbon area (5 µM2 vs 1.3 µM2, P = 0.04) and mean percentage carbon area (4.2 % vs 0.74 %, P = 0.04) were significantly raised in the COPD group compared to the smoker group. A negative association was observed between the percentage of forced expiratory volume in 1 second (FEV1) and both carbon areas (r = -0.39, P = 0.01) and percentage area (r = -0.45, P = 0.003). There was no significant association found between carbon deposit coverage and cigarette exposure (pack-years) or time since quitting smoking.
Carbon-positive alveolar macrophages were significantly larger compared to carbon-negative ones in COPD (Ve+: 15.8 µM, Ve-: 14.1 µM, P ≤ 0.0001) and smoker groups (Ve+: 16.28 µM, Ve-: 15.2 µM, P = 0.03). But the overall macrophage diameter did not significantly differ among COPD patients and smokers (14.9 µM vs 15.1 µM).
The MDM diameter increased dose-dependently with carbon, showing a 19% rise at 62 µg/mL (P = 0.01), regardless of the presence of visible carbon. Carbon exposure of ≥15 µg/mL significantly enhanced MDM expression of CD38, CD206, and CD80 with peak fold change of 1.5-1.8. CD36 and CD14 were unaffected. CXCL8 and TNF-α release was significantly enhanced after 24 hours at 62 and 31 µg/mL concentrations (p < 0.05). This indicated a dose-dependent inflammatory response.
Study limitations include a small sample size, a lack of indoor exposure data, the absence of health controls, and the unavailability of residential data.
In conclusion, this study found that increased alveolar macrophage carbon in COPD patients was associated with altered macrophage phenotype and reduced lung function. Future studies are needed to confirm findings using lung tissue and assess pollution exposure more precisely.
Reference: Baker J, Booth S, Dungwa J, et al. Alveolar macrophage carbon is associated with COPD severity. ERJ Open Res. 2025;In Press. doi:10.1183/23120541.00933-2024
