Table 5.

Main findings and characteristics of miRNA studies in the context of AEs.

Biological sample	miRNA profiling	Subjects	Phenotype	Main findings	PMID [reference]
Whole blood	Human MicroRNA v2.0 Assay Pool (Illumina).	Children with (n=100) and without asthma (n=100) recruited at a Turkish hospital	Asthma severity (GINA, 2008) and AEs severity	Increased expression of 10 miRNAs was associated with asthma severity and exacerbations severity: HS_108.1, HS_112, HS_182.1, HS_240, HS_261.1, HS_3, HS_55.1, HS_91.1, hsa-mir-604, and hsa-mir-638.	26422695 [104]
Peripheral blood	q-PCR	Children with acute-stage asthma (n=100) and healthy children (n=100) recruited at a Chinese hospital	Acute asthma attacks (not defined)	miR-1 expression levels were reduced in acute-stage asthma compared with controls. miR-1 expression levels improved prediction of acute asthma attacks compared with IL-4, IL-5, IL-8, and TNF-α in the same population.	30046607 [105]
Serum	q-PCR	Subjects with (n=59) and without asthma (n=11) recruited in the United States	Lifetime and past 12 months frequency of asthma-related hospitalizations	miR-1 levels were inversely correlated with sputum eosinophilia and asthma-related hospitalization frequency, and positively correlated with lung function and ACT scores.	32035607 [106]
Serum	q-PCR	European children with asthma from CAMP: 38 with and 115 without exacerbations	OCS bursts in the past 12 months following randomization with ICS	Increased expression of 12 miRNAs was associated with OCS bursts: miR-206, miR-146b-5p, miR-222–3p, miR-409–3p, miR-223–5p, miR-126–5p, miR-339–3p, miR-30e-3p, miR-126–3p, miR-342–3p, miR-454–3p, and miR-720. A clinical and 3-miRNA model (miR-146b, miR-206, and miR-720) showed higher AUC for prediction of OCS use compared with the clinical model in the same population (AUC: 0.81 vs 0.67).	29940952 [107]
Serum	q-PCR	6-week longitudinal study of 21 adults with asthma recruited at a Polish hospital	Admission for an unplanned visit due to worsened symptoms of asthma accompanied by a decrease in ventilatory parameters	Reduced levels of miRNA-126a, miRNA-16, and miRNA-21 during the exacerbation compared with the follow-up visit.	31743969 [108]
Induced sputum	Nanostring nCounter array v3.0a	Subjects with (n=62) and without asthma (n=9) recruited in the United States	Asthma-related hospitalizations in the past 12 months	A 12 miRNA.WGCNA module was directly correlated with asthma hospitalizations. Ten of these miRNA correlated significantly and consistently with sputum neutrophils, longer duration of asthma, decreased quality of life, impaired lung function, and/or increased BDR. The miRNA module correlated with a mRNA module enriched in genes participating in TLR/Th17 signalling and endoplasmic reticulum stress.	32255668 [109]
Whole blood	Small-RNA sequencing	Costa Rican children with asthma (nFE=183; nIF=168) from GARCS	≥3 events of asthma-related ER/AC visits and/or hospitalizations in the last 12 months (frequent exacerbations, FE) compared with no or infrequent exacerbation (IF)	5 miRNA (miR-451b, hsa-miR-142–5p, hsa-miR-6739–3p, hsa-miR-7–5p, and hsa-miR-4433b-5p) were downregulated in FE compared with IF. 15 mIRNA (hsa-miR-93–3p, hsa-miR-766–3p, hsa-miR-331–3p, hsa-miR-532–3p, hsa-miR-664b-3p, hsa-miR-296–5p, hsa-miR-6515–3p, hsa-miR-4286, hsa-miR-1296–5p, hsa-miR-29b-2–5p, hsa-miR-500b-5p, hsa-miR-500a-5p, hsa-miR-642a-5p, hsa-miR-103a-2–5p, and hsa-miR-550a-3p) were upregulated in FE compared with IF. miR-532–3p, miR-296–5p, miR-766–3p, miR-7–5p, and miR-451b also showed significant association with COPD exacerbations.	35447890 [110]

Abbreviations: AC: Acute care; AUC: Area under the curve; CAMP: Childhood Asthma Management Program; COPD: Chronic obstructive pulmonary disease; ER: Emergency room; FE: Frequent exacerbations; GARCS: Genetics of Asthma in Costa Rica Study; GINA: Global Initiative for Asthma; ICS: Inhaled corticosteroids; IF: No or infrequent exacerbations; mRNA: Messenger RNA; OCS: Oral corticosteroids; q-PCR: Real-time quantitative polymerase chain reaction; RNA: Ribonucleic acid; Th17: T helper 17 cells; TLR: Toll-like receptor; WGCNA: Weighted gene co-expression network analysis.