Distinctive clinical and radiological characteristics of persistent super-multiple ground-glass pulmonary nodules

The clinical characteristics and pathophysiological processes of super-multiple ground-glass nodules (GGNs) remain poorly understood due to their rare incidence. This retrospective-prospective study aimed to elucidate these aspects by analyzing 75 patients with "super-multiple GGNs," having more than five persistent nodules, each measuring at least 5 mm, identified from a larger cohort of 2589 patients. We compared these patients with those having solitary GGNs (N = 691) and 2-5 GGNs (N = 458) to evaluate clinical and radiological characteristics. All patients underwent a minimum 12-month follow-up with detailed documentation of nodule changes and treatments. Patients with super-multiple GGNs were significantly older, predominantly female, had lower smoking rates, and showed higher smog exposure and cough prevalence than other patients (p < .05). Radiologically, super-multiple GGNs appeared mostly unilaterally, predominantly in the right lung and upper lobes (p < .001). Progression occurred in 33.3% of these patients, of whom 44.0% exhibited simultaneous growth of multiple nodules. Compared with solitary GGNs (HR = 6.64, 95% CI = 3.18-13.84, p < .001) and 2-5 GGNs (HR = 3.26, 95% CI = 1.67-6.31, p < .001), super-multiple GGNs carried significantly higher progression risk. These findings highlight the distinct clinical characteristics and radiological evolutionary patterns of super-multiple GGNs, suggesting possible links to pulmonary inflammation.