Table 2.
Summary of transcriptomic analyses in adult asthmatics.
| Population | Methods | Purpose | Findings | Ref. |
|---|---|---|---|---|
| Blood | ||||
| Exacerbation sample in adult asthmatics (n = 118) | Microarray and qPCR with pathway analysis |
To identify the exacerbation-associated gene expression patterns in PBMC | TLR activation pathway with elevations in type 1 interferon and IL-15 genes is associated with asthma exacerbation. | [149] |
| Nonsmoking SA/smoking SA/nonsmoking mild to moderate asthma/nonsmoking controls (n = 246/88/77/87) | Microarray with WGCNA | To find the transcriptional differences between subgroups of asthmatics and non-asthmatics in whole blood | Differentially expressed genes in immune cells of severe asthmatics. Gene sets related to chemotaxis, mobilization, migration, and infiltration of myeloid cells contribute to asthma severity. |
[150] |
| Airway epithelial cell | ||||
| nonsmoking asthma/nonsmoking HCs/smoking controls (n = 42/28/16) |
Microarray and qPCR | To explore the distinct gene expression related to airway dysfunction and corticosteroid treatment in epithelial cells of asthmatics | Identification of 22 differentially expressed genes in asthmatics. IL-13-derived asthma-associated genes (CLCA1, periostin, and serpinB2) are decreased by corticosteroid treatment with an improvement in lung function. |
[151] |
| Asthmatics/HCs (n = 42/28) |
Microarray and qPCR | To define the molecular phenotypes based on type 2 cytokines-induced gene expression in epithelial brushings of asthmatics | Phenotyping of asthma as Th2-high and Th2-low based on CLCA1, periostin, and sepinB2 gene expression. Th2-high asthma has worse clinical outcomes (lower lung function, higher serum IgE, and blood/airway eosinophilia) and inflammatory features (subepithelial fibrosis and increase of mucin stores). |
[152] |
| Nonsmoking SA/smoking SA/mild-to-moderate asthma/HCs (n = 46/16/34/41) |
Microarray | To investigate the pathogenesis of severe asthma and the influences of blood, sputum, and submucosal eosinophils or neutrophils on the gene expression in bronchial brushing | 7 genes (COX-2, ADAM-7, SLCO1A2, TMEFF2, TRPM-1, and 2 unnamed genes) are positively correlated with blood and submucosal eosinophilia with thick lamina reticularis and elevated FENO. | [153] |
| SA/moderate asthma with ICS/mild asthma with ICS/mild-to-moderate asthma with no ICS/HCs (n = 51/19/22/37/26) |
Microarray with WGCNA, LIMMA, and pathway analysis | To identify specific genetic networks to be associated with asthma severity | Asthma severity has a positive correlation with a network related to mitosis/cell division and T2 inflammation, but a negative correlation with a network related to epithelial growth/repair, cell integrity/remodeling, and neuronal function/development. | [154] |
| Sputum | ||||
| Asthmatics/HCs (n = 59/13) |
Microarray and qPCR with GO and pathway analysis | To establish 3 distinct transcriptional asthma phenotypes (TAPs) considering clinical status and gene expression in the sputum of asthmatics | Classification of asthma phenotypes as eosinophilic, neutrophilic, or paucigranulocytic asthma based on the predominance of immune cells in sputum. IL-1 and TNF-α/NF-κB pathways are involved in the pathogenesis of neutrophilic asthma. |
[155] |
| Asthmatics/HCs (n = 37/15) |
qPCR | To determine genetic profiling related to Th2 cytokines in the sputum cells of asthmatics for the categorization of asthma phenotypes | Standardization of IL-4, IL-5, and IL-13 gene expression for classification as Th2-high and Th2-low subtypes (Th2 gene mean). Th2-high asthma has poor clinical outcomes (low lung function and blood eosinophilia) with elevation in mast cell/eosinophil-related genes. |
[156] |
| Asthmatics/HCs (n = 106/20) |
Microarray and qPCR | To validate genetic biomarkers for inflammatory phenotypes of asthma and prediction of ICS treatment response | Identification of 23 differentially expressed genes across eosinophilic, neutrophilic, and paucigranulocytic phenotypes. The 3 genes for eosinophilic asthma (CLC, CPA3, and DNASE1L3) and 3 for neutrophilic asthma (IL1B, ALPL, and CXCR2) are validated with distinct alterations after ICS treatments. |
[157] |
| Asthmatics/HCs (n = 84/27) |
RNA seq with WGCNA and pathway analysis | To identify genetic networks in sputum immune cells of asthmatics for clustering them into T2-high and T2-low subgroups | High T2-network gene expression in the T2-high asthma comes from the interaction of various immune cells (eosinophils, mast cells, basophils, and dendritic cells), leading to severe airway dysfunction. CD8+T cell network gene expression is lower in T2-low asthma and negatively correlated with body mass index. |
[158] |
| Elderly asthmatics/HCs (n = 55/10) |
Microarray with GSEA and cluster analysis | To find distinct biological mechanisms with genetic profiling in sputum cells for clustering of elderly asthmatics | Identification of 2 molecular clusters in elderly asthmatics with increased OXPHOS and EMT gene sets, respectively. The OXPHOS/UPR system related to oxidative stress leads to inflammatory response and immune function dysregulation in the airways of elderly asthmatics. The EMT gene sets contribute to airway remodeling with lower lung function in elderly asthmatics. |
[159] |
| Nasal brushings | ||||
| Mild-to-moderate asthmatics/HCs (n = 66/124) |
Microarray and RNA seq with pathway and classification analysis | To validate nasal brush-based classifier genes for the diagnosis of asthma | Identification of 90 genes as a nasal classifier for mild-to-moderate asthma | [160] |
| BALF | ||||
| SA/moderate asthma with ICS/mild asthma with ICS/mild-to-moderate asthma with no ICS/HCs (n = 44/15/18/40/37) |
LIMMA, WGCNA, GO and pathway analysis | To determine severity-related genes and influence of β-agonist use on gene expression in BAL immune cells | Higher BAL neutrophils with increased gene expression related to TNF-α and type 1 interferon pathway in SA. Several severity-related genes are within or close to asthma susceptibility loci (5q, 17q, 1p). A specific gene network related to cAMP signaling is associated with asthma severity and β-agonist exposure. |
[161] |
| Mixed | ||||
| Adult/childhood-onset SA (n = 253/158) |
Microarray with GSVA | To identify gene signatures in adult-onset compared to childhood-onset SA using diverse samples (nasal brushings, bronchial brushings, and sputum) | Identification of 5 differentially expressed gene signatures in nasal brushings, 6 in bronchial brushings, and 3 in sputum. Specific genes related to immune cells (eosinophils, mast cell, ILC3) and type 2 inflammation are up-regulated in adult-onset SA. |
[162] |
HCs, healthy controls; SA, severe asthma; ICS, inhaled corticosteroid; qPCR; quantitative PCR; WGCNA, weighted gene co-expression network analysis; LIMMA, linear models for microarray data; GO, gene ontology; GSCA, gene set co-expression analysis; PBMC, peripheral blood mononuclear cell; BALF, bronchoalveolar lavage fluid; TLR, toll-like receptor; CLCA1, chloride accessory 1; COX-2, cyclooxygenease-2; ADAM-7, a disintegrin and metalloproteinase domain-containing protein 7; SLCO1A2, solute carrier organic anion transporter family member 1A2; TMEFF2, transmembrane protein with epidermal growth factor like and two follistatin like domains 2; TRPM-1, transient receptor potential cation channel subfamily M member 1; CLC. Charcot-leydon crystal protein; CPA3, carboxypeptidase A3; DNASE1L3, deoxyribonuclease 1-like 3; ALPL, alkaline phosphatase, tissue-nonspecific isozyme; CXCR2, chemokine (C-X-C motif) receptor 2; OXPHOS, oxidative phosphorylation; UPR, unfolded protein response; EMT, epithelial-mesenchymal transition; cAMP, cyclic adenosine 3′,5′-monophosphate; ILC3, innate lymphoid cell 3.