Nasopharyngeal isolates and their clinical impact on young children with asthma: a pilot study

Figures & data

Table 1 Nasopharyngeal isolates, airway resistance (R5), “common cold” symptoms (CCQ), and GINA assessment of asthma control in the 18 patients with asthma (33 pathogens of 10 types); December 2016–January 2017.

Patients, ID number (sex, age)	Isolates	CCQ score	GINA score	R5 z-score	Treatment modification
1 (M, 6.2 years)	HI, hRV	0	3	0.59	None
2 (F, 4.8 years)	SP	2	1	1.48	None
3 (M, 3.7 years)	hRV	2	4	Not done	Increased dose of ICS
4 (M, 4.8 years)	SP, HI, BPP, hRV	10	4	–0.14	Salmeterol added to ICS
5 (M, 4.4 years)	SP, hRV, hEV, AdV	0	4	1.40	None
6 (M, 6.2 years)	SP, HI, CoV 229E, CoV NL63	3	1	1.36	None
7 (M, 6.4 years)	None detected	2	2	0.46	None
8 (M, 4.9 years)	SP, CoV OC43	3	3	1.12	None
9 (M, 6.5 years)	SP	11	2	0.24	None
10 (M, 6.4 years)	hRV	0	4	–0.06	ICS started
11 (F, 4.9 years)	SP	2	Not done	1.69	None
12 (M, 4.4 years)	SP, HI, hRV	7	4	1.54	Montelukast added to ICS
13 (F, 4.2 years)	HI, hRV	16	3	0.20	Salmeterol added to ICS
14 (M, 4.2 years)	SP, HI, hEV, PIV3	4	1	3.05	None
15 (F, 4.9 years)	SP	1	Not done	1.34	None
16 (M, 3.6 years)	hRV	0	4	3.55	ICS started
17 (M, 6.1 years)	HI	8	3	–0.24	ICS started
18 (M, 3.2 years)	Not done	Not done	Not done	Not done	None

Notes: The treatment modifications were based on clinical findings at the discretion of the primary physician (pediatric pulmonologist).

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CCQ, common cold questionnaire; CoV 229E, coronavirus 229E; CoV NL63, coronavirus NL63; CoV OC43, coronavirus OC43; F, female; GINA, Global Initiative of Asthma; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; ICS, inhaled corticosteroid; M, male; SP, Streptococcus pneumoniae; PIV1, parainfluenza virus 1; PIV3, parainfluenza virus 3; R5, airway resistance at 5 Hz

Table 2 CCQ score, GINA assessment of asthma control score, R5 z-score, nasopharyngeal isolates, and escalation of asthma prophylaxis

CCQ score	GINA score	N*	R5 z-score	Isolates	Treatment escalated N (%)	P
0	0–1	5	–0.48 (1.22)	SP, HI, hRV, CoV 229E	0 (0)	0.4
	≥2	4	3.50 (0.54)	SP, HI, hRV, hEV, AdV, PIV1	2 (33)
1–7	0–1	11	1.42 (1.11)	SP, HI, hEV, PIV3, CoV 229E, CoV NL63, BP	2 (20)	1.0
	≥2	10	1.33 (1.96)	SP, HI, hRV, CoV OC43, AdV, MPV	2 (20)
8–16	0–1	4	–0.43 (1.76)	SP, HI, BP, PIV1	2 (50)	1.0
	≥2	4	0.03 (0.90)	SP, HI, hRV, BPP	2 (50)

Notes: P-values are Fisher’s exact test.

* N indicates the number of patients with the stated CCQ score and GINA score.

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CCQ, common cold questionnaire; CoV 229E, coronavirus 229E; CoV NL63, coronavirus NL63; CoV OC43, coronavirus OC43; GINA, Global Initiative of Asthma; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; MPV, metapneumovirus; SP, Streptococcus pneumoniae; PIV1, parainfluenza virus 1; PIV3, parainfluenza virus 3; R5, airway resistance at 5 Hz

Table 3 Nasopharyngeal isolates, airway resistance, and “common cold” symptoms in the 9 control children (23 isolates of 8 different types); December 2016–March 2017.

Children, ID number (sex)	Age (years)	Isolates	CCQ score	R5 z-score
1 (F)	3.5	SP, HI, hRV, hBoV	0	2.45a
2 (M)	5.5	SP, Flu A-H3	5	0.85
3 (F)	4.0	SP, HI, hEV	4	–0.60
4 (M)	5.9	SP, AdV	0	–0.82
5 (M)	5.1	SP, HI, hRV	0	–1.99
6 (F)	5.5	SP, Flu A-H3	6	2.45
7 (M)	5.1	hRV, hEV	Not done	0.25
8 (M)	4.2	SP, hRV, hBoV, PIV4	11	2.09
9 (F)	3.3	HI	Not done	1.57

Note:

a Child 1 was found subsequently to have symptoms of allergic rhinitis and mild night cough.

Abbreviations: AdV, adenovirus; CCQ, common cold questionnaire; F, female; Flu A-H3, influenza A virus-H3; hBoV, human bocavirus; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; M, male; SP, Streptococcus pneumoniae; R5, airway resistance at 5 Hz

Figure 1 Nasopharyngeal pathogens isolated from the 18 patients with asthma and the 9 healthy children during the studied winter periods.

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CoV, coronavirus; Flu A-H3, influenza A virus-H3; hBoV, human bocavirus; hEV, human enterovirus; hRV, human rhinovirus; HI, Haemophilus influenzae; PIV, parainfluenza virus; SP, Streptococcus pneumoniae.

Figure 2 The horizontal lines are mean values. The P-values are Mann–Whitney (2-tailed) between CCQ score =0 and the other groups. Kruskal–Wallis test that compared 3 CCQ groups revealed an asymptotic significance (2-tailed) of 0.013. Panel (A): R5 z-scores in the patients with asthma as function of CCQ score. Panels (B–D): R5 z-scores as function of Global Initiative of Asthma assessment of asthma control score in the patients with asthma grouped by their CCQ score.

Abbreviations: ACT, asthma control test; CCQ, Common Cold Questionnaire; R5, airway resistance at 5 Hz.

Figure S1 Percent positive nasopharyngeal pathogens isolated from the 18 patients with asthma (A) and the 9 healthy children (B) during the studied winter periods.

Note: “x”, not detected.

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CoV coronavirus; Flu A-H3, influenza A virus-H3; hBoV, human bocavirus; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; PIV1, parainfluenza virus 1; PIV3, parainfluenza virus 3; SP, Streptococcus pneumoniae.

Table S1 Nasopharyngeal isolates, airway resistance (R5), “common cold” symptoms (CCQ), and GINA score in the 18 patients with asthma

Patients, ID number (sex, age)	February 2017 (34 pathogens of five different types)
	Isolates	CCQ scores	GINA scores	R5 z-scores
1 (M, 6.2 years)	SP, HI, PIV1	0	3	Not successful
2 (F, 4.8 years)	SP, HI	7	1	0.94
3 (M, 3.7 years)	HI, BP	5	0	1.67
4 (M, 4.8 years)	HI, hRV	0	0	−0.02
5 (M, 4.4 years)	SP, HI, hRV	4	2	4.45
6 (M, 6.2 years)	SP, HI, hRV	4	0	Not done
7 (M, 6.4 years)	SP, HI, hRV	2	1	Not done
8 (M, 4.9 years)	SP	1	2	3.14
9 (M, 6.5 years)	SP	9	3	−1.06
10 (M, 6.4 years)	Not done	Not done	Not done	Not done
11 (F, 4.9 years)	SP	0	Not done	Not done
12 (M, 4.4 years)	SP, HI	0	0	−0.14
13 (F, 4.2 years)	SP, hRV	0	3	Not done
14 (M, 4.2 years)	SP, hRV	7	2	0.94
15 (F, 4.9 years)	SP, HI, hRV	5	0	Not done
16 (M, 3.6 years)	hRV	0	0	−3.00
17 (M, 6.1 years)	SP	9	0	Not done
18 (M, 3.2 years)	SP, HI	0	Not done	5.29

Note: Patients 2 and 3 had treatment modifications, which included increased inhaled corticosteroid dosing.

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CCQ, common cold questionnaire; CoV 229E, coronavirus 229E; CoV NL63, coronavirus NL63; CoV OC43, coronavirus OC43; F, female; GINA, Global Initiative of Asthma; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; M, male; SP, Streptococcus pneumoniae; PIV1, parainfluenza virus 1; PIV3, parainfluenza virus 3; R5, airway resistance at 5 Hz.

Table S2 Nasopharyngeal isolates, airway resistance (R5), “common cold” symptoms (CCQ), and GINA in the 18 patients with asthma

Patients, ID number (sex, age)	March 2017 (28 pathogens of 9 different types)
	Isolates	CCQ scores	GINA scores	R5 z-scores
1 (M, 6.2 years)	Not done	Not done	Not done	Not done
2 (F, 4.8 years)	SP, BP	9	1	−3.02
3 (M, 3.7 years)	CoV 229E	0	0	−0.75
4 (M, 4.8 years)	None detected	0	0	−0.48
5 (M, 4.4 years)	SP, HI, hRV	5	3	5.04
6 (M, 6.2 years)	SP, HI, hRV	4	0	2.43
7 (M, 6.4 years)	SP, HI, HEV, Adv	1	2	−0.41
8 (M, 4.9 years)	SP, HI, MPV	4	2	Not done
9 (M, 6.5 years)	SP, HI	3	0	0.85
10 (M, 6.4 years)	None detected	Not done	Not done	Not done
11 (F, 4.9 years)	SP, PIV1	8	1	−0.43
12 (M, 4.4 years)	HI, hRV, PIV4	9	1	Not done
13 (F, 4.2 years)	None detected	Not done	Not done	Not done
14 (M, 4.2 years)	SP, HI	13	4	1.68
15 (F, 4.9 years)	HI, hRV	3	0	−0.67
16 (M, 3.6 years)	None detected	Not done	Not done	Not done
17 (M, 6.1 years)	HI	8	0	0.35
18 (M, 3.2 years)	Not done	Not done	Not done	Not done

Note: Patient 2 had increased inhaled corticosteroid dosing.

Abbreviations: AdV, adenovirus; BP, Bordetella pertussis; BPP, Bordetella parapertussis; CCQ, common cold questionnaire; CoV 229E, coronavirus 229E; CoV NL63, coronavirus NL63; CoV OC43, coronavirus OC43; F, female; GINA, Global Initiative of Asthma; hEV, human enterovirus; HI, Haemophilus influenzae; hRV, human rhinovirus; M, male; SP, Streptococcus pneumoniae; PIV1, parainfluenza virus 1; PIV3, parainfluenza virus 3; R5, airway resistance at 5 Hz.

Table S3 Responses to the Global Asthma Network Questionnaire (based on symptoms in the past 12 months) in the 18 patients with asthma

Patients ID	Number of wheezing episodes	Wheezing disturbing night sleep	Wheezing limiting speech	Emergency wheezinga	Days missed school	Exercise- induced wheezing	Rhinitis	Eczema	Chest infection in infancy	Use of SABA	Use of LABA/ICS
1	?	?	?	>2	0	No	Yes	Yes	≥6	Every day	Every day
2	4–12	Never	No	2	0	No	No	No	?	As needed	?
3	1–3	≥1/wk	no	1		No	Yes	Yes	1	As needed	?
4	>12	≥1/wk	Yes	1	4–12	Yes	Yes	No	2–5	?	?
5	1–3	≥1/wk	No	1	4–12	Yes	No	Yes	0	As needed	Courses
6	4–12	≥1/wk	Yes	1	0	Yes	Yes	No	1	?	?
7	?	?	?	0	0	No	Yes	Yes	0	Courses	Every day
8	4–12	≥1/wk	No	2	>12	No	Yes	Yes	2–5	As needed	Every day
9	1–3	<1/wk	No	2	1–3	No	Yes	No	2–5	Courses	?
10	1–3	≥1/wk	No	1	0	Yes	Yes	No	1	As needed	?
11	1–3	<1/wk	No	1	0	Yes	Yes	Yes	1	As needed	Courses
12	1–3	≥1/wk	No	1	1–3	Yes	Yes	Yes	1	Courses	?
13	?	?	?	2	1–3	Yes	Yes	No	2–5	?	?
14	1–3	<1/wk	No	2	0	No	Yes	No	0	?	Every day
15	?	?	?	0	0	Yes	Yes	No	0	As needed	As needed
16	4–12	≥1/wk	No	1	4–12	Yes	No	Yes	0	As needed	Every day
17	1–3	<1/wk	No	1	4–12	Yes	Yes	No	1	As needed	Every day
18	4–12	≥1/wk	No	0	0	?	?	?	?	?	?

Note:

a Wheezing requiring urgent doctor or emergency department visit or hospitalization; “?”, skipped responses.

Abbreviations: ICS, inhaled corticosteroid; LABA, long acting β-agonist; SABA, short acting β-agonist; wk, week.