The objective of the study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO materials exacerbated the existing allergic airway inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes in lungs with and without the pre-existing condition. In contrast, CuO PEG had a significantly lower potential in triggering pulmonary changes revealing that surface PEGylation suppresses the effects triggered by the pristine material. Overall design: Pristine CuO (CuO) and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivates were investigated in a murine asthma model. In the used model, each mouse (eight per group) received intraperitoneally a mixture of 50 mg of OVA and 2 mg of aluminum/magnesium hydroxide in 100 ml of PBS on day 1 and 10. After 10-day recovery, mice were exposed to 50 ml of PBS or 50 mg of OVA in 50 ml of PBS with or without dispersed CuO nanomaterials via oropharyngeal aspiration in isoflurane anaesthesia on four consecutive days. CuO materials were tested at three doses – 2.5, 10 and 40 mg/mouse/administration. Bronchoalveolar lavage was collected for cytological analysis and lung tissue samples for histological assessment and Agilent microarrays.