Table 1. Summary of studies investigating the association between upper airway microbiota and childhood asthma.

Study	Country	Participant (n)	Asthma definition	Wheezing & asthma rate	Age at sample collection	Sample	Bacterial sequence, region	Method	Confounding factors	Changes in diversity and richness
Powell et al., 2019 [17]	UK	98	Physician diagnosed wheeze	26.5% wheeze at 24 mo	6 wk, 6, 9, 12, 18, and 24 mo	Oropharyngeal swab	16S rRNA V3-V5	Roche 454 pyrosequencing	Ethnicity, family history of atopy, presence of fever, use of antibiotics in the 4 wk prior to visit	Increased α-diversity (p < 0.001)
Ta et al., 2018 [19]	Singapore	122	Symptom-based wheeze	27.8% rhinitis with wheezing at first 18 mo	3 wks, 3, 6, 9, 12, 15, and 18 mo	Nasal swab	16S rRNA V3-V6	Illumina HiSeq	Gender, family history of respiratory disease, presence of siblings, mode of delivery, use of intrapartum antibiotic prophylaxis, postnatal antibiotics and breastfeeding pattern	Decreased α-diversity (p = 0.025) in rhinitis with wheeze
Cardenas et al., 2012 [25]	Ecuador	48	Physician diagnosed	50% early-onset wheezing	Once at age 10.2 mo (mean)	Oropharyngeal swab	16S rRNA V3-V5	Roche 454 pyrosequencing	NA	No changes in diversity and richness
Teo et al., 2018 [26]	Australia	244	Questionnaire based	10.6% early-sensitized children with wheezing at 5 yr	2, 6, and 12 mo	Nasopharyngeal sample	16S rRNA V4	Illumina MiSeq	Gender and lower respiratory infection	NA
Teo et al., 2015 [28]	Australia	234	Symptom-based	28% wheezing at 5 yr	7, 8 and 9 wks, and 2, 6, and 12 mo	Nasopharyngeal sample	16S rRNA V4	Illumina MiSeq	Gender, maternal and paternal history of atopic disease	NA
Thorsen et al., 2019 [18]	Denmark	644	Symptoms-based	22.7% asthma in the first 6 yr	1 wk, 1, and 3 mo	Hypopharyngeal aspirate	16S rRNA V4	Illumina MiSeq	NA	At age 1 month: increased Shannon index p = 0.0046, Richness p = 0.0017 and Bray-Curtis p = 0.016
Toivonen et al., 2020 [22]	Finland	704	Physician diagnosed and medication	8% at age 7 yr	2, 13 and 24 mo	Nasal swab	16S rRNA V4	Illumina MiSeq	Gender, siblings, parental asthma and child’s eczema by age 13 mo	No changes in α and β-diversity measures.
Tang et al., 2021 [27]	USA	285	Physician diagnosed and medication	6–63% asthma at age 6, 8, 11, 13, and 18 yr	2, 4, 6, 9, 12, 18, and 24 mo	Nasopharyngeal sample	16S rRNA V4	Illumina MiSeq	Age, gender, and season	NA
Chiu et al., 2017 [20]	Taiwan	87	Questionnaire based	36.7% asthma	Once at ages 3–5 yr	Throat swab	16S rRNA V3-V4	Illumina MiSeq	Age, gender, maternal atopy, passive smoking, older siblings, and household income OR FDR-adjusted	Lower Chao1 (p = 0.014) and Shannon (p = 0.023) indeces in mite sensitized asthma
Kim et al., 2017 [21]	Korea	92	Physician diagnosed	33.6% asthma	Once at ages 7.1–8 (mean)	Nasopharyngeal swab	16S rRNA V1-V3, whole metagenome	Roche 454 pyrosequencing, Illumina HiSeq	NA	No change in α-diversity. Increased β-diversity (p < 0.001)
Birzele et al., 2017 [31]	Austria	86	Physician diagnosed, symptom and questionnaire based	22.9% asthma	Once at ages 6–12 yr	Nasal swab	16S rRNA V3-V5	Roche 454 pyrosequencing	Farming	Decreased richness OR=0.63, p = 0.087 and Shannon index OR=0.66, p = 0.129
Depner et al., 2017 [29]	Germany	68	Physician diagnosed, symptom and questionnaire based	57.3% asthma	Once at ages 7–12 yr	Nasal swab	16S rRNA V3-V5	Roche 454 pyrosequencing	Farming	Lowered richness p = 0.052
Castro-Nallar et al., 2015 [30]	USA	14	Physician diagnosed	57.1% asthma	Once at 11–15 years (mean)	Nasal brush	Whole metagenome	HiSeq metagenome sequencing	NA	High richness and low evenness

NA, not applicable; V, variable regions.