Sputum Neurturin Levels in Adult Asthmatic Subjects

Figures & data

Table 1 Characteristics of Asthmatic Subjects

Characteristics	Findings
Number of subjects	64
Age, mean (SD), years	64 (12)
Gender, male/ female	32 / 32
BMI, mean (SD)	24.7 (5.1)
Smoking status, never / former / current	32 / 29 / 3
Duration of asthma treatment, mean (SD), years	12.9 (12.9)
Atopic subjects	47 (73)
Allergic rhinitis	35 (55)
Chronic sinusitis	19 (30)
Severity of asthma, mild intermittent and mild persistent / moderate persistent / severe persistent	13 / 26 / 25
Blood eosinophil in white blood cell count, mean (SD), %	6.3 (5.6)
Serum total IgE, mean (SD), IU/mL	457 (532)
Dose of ICS (equivalent to fluticasone propionate), mean (SD), µg/day	639 (384)
Use of LABA	52 (81)
Use of LTRA	40 (63)
Use of theophylline	25 (39)
Use of LAMA	18 (28)
Use of biological agents	9 (14)
Regular use of oral corticosteroids	10 (16)

Note: Data are presented as number (percentage) of participants unless otherwise indicated.

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by square of height in meters); ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; LTRA, leukotriene receptor antagonist; LAMA, long-acting muscarinic antagonist.

Table 2 Summary of Asthma Control-Related Parameters

Asthma Related Parameter	Finding
% Predicted FEV1, %	81.5 (22.2)
FEV1 / FVC, %	68.6 (13.8)
FeNO, ppb	78 (62)
ACT global score, points	18.9 (5.0)
Controlled subjects in ACT score (≥ 20 points), N (%)	32 (50)
Subjects with occasional use of systemic corticosteroids in the previous year, N (%)	24 (38)
Subjects with unscheduled visit to outpatient clinic or emergency department for asthma deteriorations in the previous year, N (%)	17 (27)

Note: Data are presented as mean (SD) unless otherwise indicated.

Abbreviations: FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; ACT, asthma control test.

Figure 1 Relationship between sputum NRTN levels and serum NRTN levels in asthmatic subjects (n = 15). Open circles indicate levels below the lower limit of the measurement range.

Table 3 Summary of Sputum Analyses Data

	Number of Participants	Finding
NRTN level in sputum supernatant, ng/mL	64	2.03 (1.29)
Total inflammatory cell count, x10^6 /mL	64	2.81 (5.25)
Differentiation of sputum inflammatory cell	64
Macrophages, %		21.4 (13.0)
Neutrophils, %		49.5 (25.8)
Lymphocytes, %		1.5 (1.2)
Eosinophils, %		27.7 (28.4)
Cytokine and extra cellular matrix levels in sputum supernatant
IL-4, ng/mL	44	9.5 (8.0)
IL-5, ng/mL	44	32.3 (7.4)
IL-13, ng/mL	51	12.1 (1.7)
IL-6, ng/mL	36	17.8 (19.6)
IFN-γ, ng/mL	38	19.9 (7.5)
MMP-2, pg/mL	33	398 (298)
MMP-9, pg/mL	37	327 (705)

Note: Data are presented as mean (standard deviation) of subjects.

Abbreviations: NRTN, neurturin; IL-, interleukin-; IFN-γ, interferon-gamma; MMP-, matrix metalloproteinase-.

Figure 2 Comparisons of sputum NRTN levels between asthmatic subjects by atopic status (A), by different asthma severities (B), by asthma control status (C), with or without a fixed airflow obstruction (D), with or without asthma exacerbations with unscheduled visits the outpatient clinic in the previous year (E), and with or without asthma exacerbations with occasional uses of systemic corticosteroids in the previous year (F). The box signifies the 25th and 75th percentiles, and the median is represented by a short line within the box. The open circle indicates sputum NRTN level in asthmatic subjects. *p < 0.05.

Abbreviations: Mild, mild intermittent or mild persistent asthma; Moderate, moderate persistent asthma; Severe, severe persistent asthma; ACT, asthma control test; AO, fixed airway obstruction; w/o, without; AEUV, asthma exacerbation with unscheduled visits the outpatient clinic; AECS, asthma exacerbation with occasional uses of systemic corticosteroids.

Figure 3 Relationships between sputum NRTN level and FeNO level (A), ACT score (B), and % predicted FEV₁ (C). A comparison of sputum NRTN levels between asthmatic subjects with FeNO < 20 ppb and those with FeNO ≥ 20 ppb (D). The result of linear regression analysis of the data that reveal a significant correlation is represented by the solid line. The box signifies the 25th and 75th percentiles, and the median is represented by a short line within the box. The open circle indicates sputum NRTN level in asthmatic subjects.

Abbreviations: FeNO, fractional exhaled nitric oxide; ACT, Asthma Control Test; FEV₁, forced expiratory volume in one second.

Figure 4 Receiver operating characteristic (ROC) analysis of sputum NRTN level and FeNO as predictors of sputum eosinophilia (eosinophils ≥ 2%). The area under the curves of sputum NRTN and FeNO were 0.578 and 0.945, respectively.

Figure 5 Correlations between sputum NRTN level and sputum eosinophils (A), sputum neutrophils (B), sputum macrophages (C), and sputum lymphocytes (D) in asthmatic subjects.

Figure 6 Comparisons of sputum NRTN levels between asthmatic subjects by airway inflammatory phenotypes. *p < 0.05.

Figure 7 Correlations between sputum NRTN level and IL-4 (A), IL-5 (B), IL-13 (C), IFN-γ (D), IL-6 (E), MMP-2 (F), and MMP-9 (G) levels in sputum supernatant. The results of linear regression analysis of the data that reveal significant correlations are represented by the solid line. Dashed lines indicate the limit of each measurement, and open circles indicate levels outside the measurement range.