Significantly , genes regulated by both formoterol and budesonide were overrepresented in the genome ; moreover , budesonide-plus-formoterol induced and repressed 609 and 577 mRNAs , respectively , of which ~1/3 failed the cut-off criterion for either treatment alone .
Transcriptome-level interactions between budesonide and formoterol provide insight into the mechanism of action of ICS/LABA combination therapy in asthma. In 2019, the Global Initiative for Asthma treatment guidelines were updated to recommend that inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy should be a first-in-line treatment option for asthma. Although clinically superior to ICS, mechanisms underlying the efficacy of this combination therapy remain unclear. We hypothesised the existence of transcriptomic interactions, an effect that was tested in BEAS-2B and primary human bronchial epithelial cells (pHBECs) using formoterol and budesonide as representative LABA and ICS, respectively. In BEAS-2B cells, formoterol produced 267 (212 induced; 55 repressed) gene expression changes (>=2/<=0.5-fold) that were dominated by rapidly (1-2h) upregulated transcripts. Conversely, budesonide induced 370 and repressed 413 mRNAs, which occurred predominantly at 6-18h and were preceded by transcripts enriched in transcriptional regulators. Significantly , genes regulated by both formoterol and budesonide were overrepresented in the genome ; moreover , budesonide-plus-formoterol induced and repressed 609 and 577 mRNAs , respectively , of which ~1/3 failed the cut-off criterion for either treatment alone . While induction of many mRNAs by budesonide-plus-formoterol was supra-additive, the dominant (and potentially beneficial) effect of budesonide on formoterol-induced transcripts, including those encoding many pro-inflammatory proteins, was repression. Gene ontology analysis of the budesonide-modulated transcriptome returned enriched terms for transcription, apoptosis, proliferation, differentiation, development and migration. This "functional" ICS signature was augmented in presence of formoterol. Thus, LABAs modulate glucocorticoid action and comparable transcriptome-wide interactions in pHBECs imply that such effects may be extrapolated to asthmatics taking combination therapy. While repression of formoterol-induced pro-inflammatory mRNAs should be beneficial, the pathophysiological consequences of other interactions require investigation.
### Instruction:
            Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds 
            that can co-occur for the mentioned treatment

            ### Input:
            Transcriptome-level interactions between budesonide and formoterol provide insight into the mechanism of action of ICS/LABA combination therapy in asthma. In 2019, the Global Initiative for Asthma treatment guidelines were updated to recommend that inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy should be a first-in-line treatment option for asthma. Although clinically superior to ICS, mechanisms underlying the efficacy of this combination therapy remain unclear. We hypothesised the existence of transcriptomic interactions, an effect that was tested in BEAS-2B and primary human bronchial epithelial cells (pHBECs) using formoterol and budesonide as representative LABA and ICS, respectively. In BEAS-2B cells, formoterol produced 267 (212 induced; 55 repressed) gene expression changes (>=2/<=0.5-fold) that were dominated by rapidly (1-2h) upregulated transcripts. Conversely, budesonide induced 370 and repressed 413 mRNAs, which occurred predominantly at 6-18h and were preceded by transcripts enriched in transcriptional regulators. Significantly , genes regulated by both formoterol and budesonide were overrepresented in the genome ; moreover , budesonide-plus-formoterol induced and repressed 609 and 577 mRNAs , respectively , of which ~1/3 failed the cut-off criterion for either treatment alone . While induction of many mRNAs by budesonide-plus-formoterol was supra-additive, the dominant (and potentially beneficial) effect of budesonide on formoterol-induced transcripts, including those encoding many pro-inflammatory proteins, was repression. Gene ontology analysis of the budesonide-modulated transcriptome returned enriched terms for transcription, apoptosis, proliferation, differentiation, development and migration. This "functional" ICS signature was augmented in presence of formoterol. Thus, LABAs modulate glucocorticoid action and comparable transcriptome-wide interactions in pHBECs imply that such effects may be extrapolated to asthmatics taking combination therapy. While repression of formoterol-induced pro-inflammatory mRNAs should be beneficial, the pathophysiological consequences of other interactions require investigation.

            ### Response:
            formoterol, budesonide
            