Flovent Inhaler

- Output about Loss of Asthma Control Following Inhaled Corticosteroid Withdrawal

Sputum IL-8

Patient Characteristics

Patient characteristics are shown in Table 1. Two patients in the budesonide treatment group were excluded from the analysis: one was unable to attend for all of the study visits, and the other provided induced-sputum specimens containing squamous cell counts > 80%.

Exacerbations

Eight of 12 patients had an exacerbation over the 10-week period of steroid withdrawal (Table 3). The remaining four subjects did not have an exacerbation during the 10 weeks of follow-up. Only 1 of 10 patients in the budesonide treatment group had an asthma exacerbation at week 2 (Table 2). Buy ventolin, flovent or advair to treat asthma effectively.


Sputum IL-8 and Neutrophils

Overall, the patients with an exacerbation after steroid cessation had significantly increasing levels of sputum IL-8, percentage of neutrophils, and sputum neutrophils 2 weeks prior to an exacerbation and at the onset of exacerbation (Fig 1, top left, A, top right, B, and bottom, C, respectively; Fig 2). The significant increase in IL-8 levels in induced sputum occurred at 2-week prior to an exacerbation and at the onset of exacerbation when compared with nonexacerbation (Table 4) [mean, 1,832.1 ± 151 ng/mL vs 1074.3 ± 111.0 ng/mL, p = 0.001; and 2.690.5 ± 154.7 ng/mL vs 1,420.7 ± 149.2 ng/mL, p < 0.0001, respectively]. The increase in percentage of neutrophils was also observed at the same period of time (Table 4) [mean, 42.0 ± 3.3% vs 23.6 ± 3.5%, p = 0.02; and 51.1 ± 1.9% vs 29.5 ± 4.2%, p = 0.0009, respectively]. Sputum neutrophilia correlated positively with changes in IL-8 levels (Fig 3) [r2 = 0.76, p = 0.01].

No significant differences were observed in baseline total sputum cell and differential cell counts between the budesonide treatment group and steroid withdrawal groups (Tables 2, 3). In contrast, there were significant differences in sputum lymphocyte counts (p = 0.01) and percentage of macrophages (p < 0.0001) at the onset of exacerbation (Table 4; Fig 2, center, right, D, and bottom, left, E).

Sputum Eosinophils

No significant differences in the percentages of eosinophils and absolute eosinophil number in sputum were observed either at the onset of exacerbation or 2 weeks before an exacerbation, compared with nonexacerbation data (Table 4, Fig 2, top, left, A, and top, right, B).

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Figure 1. Changes in sputum IL-8 (top left, A), percentage of neutrophils (top right, B), and number of neutrophils (bottom, C) in patients with or without an exacerbation (exac). Exacerbation data were derived from those who were treated with placebo (eight cases) and with budesonide (one case), and the nonexacerbation data included asthmatic subjects who were treated with budesonide (nine cases) and with placebo (four cases). Data are shown as mean ± SEM. Comparisons of concentrations of IL-8 and neutrophil numbers in sputum were made between the results 2 weeks prior to an exacerbation and those of nonexacerbation at week 8 and between data at the exacerbation visit and those of the week-10 nonexacerbation.

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Figure 2. Changes in percentage of eosinophils (top, left, A) and number of eosinophils (top, right, B), percentage of lymphocytes (center, left, C), number of lymphocytes (center, right, D), percentage of macrophages (bottom, left, E), and number of macrophages (bottom, right, F) in sputum collected from asthmatic subjects with and without an exacerbation. The exacerbation data were derived from those who were treated with placebo (eight cases) and with budesonide (one case), and the nonexacerbation data included asthmatic subjects who were treated with budesonide (nine cases) and with placebo (four cases). All data are shown as mean ± SEM. Comparisons of eosinophil numbers lymphocyte numbers and macrophage numbers in sputum were made between the results 2 weeks prior to an exacerbation and those of nonexacerbation at week 8 and between data on the exacerbation visit and those of the week-10 nonexacerbation. See Figure 1 legend for expansion of abbreviation not used in text.

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Figure 3. Relationship between changes in IL-8 concentrations and neutrophil numbers in sputum obtained from the asthmatic patients with severe exacerbations. Symbols represent individual asthmatic patients. IL-8 concentrations correlated positively and significantly with sputum neutrophilia.

Table 3—Changes in Clinical Parameters and Sputum Neutrophils in Asthmatic Subjects Following Inhaled Corticosteroid Withdrawal

Variables Weeks
I
0
2 4 6 8 10
Patients, No. 12 12 8 7 6 4
FEVb % predicted 73.5 ± 0.9 66.9 ± 1.1 67.5 ± 1.6 67.7 ± 1.7 67.9 ± 1.7 71.1 ± 0.4
Exacerbations, No. 0 4 1 1 2 0
Total cells, 106/mL 3.7 ± 0.3 6.0 ± 0.8 5.7 ± 0.8 6.9 ± 0.9 7.7 ± 0.7 6.4 ± 0.4
Neutrophils, % 31.0 ± 2.6 39.7 ± 2.3 40.8 ± 3.6 35.6 ± 5.9 28.2 ± 8.4 14.3 ± 1.3
Neutrophils, 106/mL 1.1 ± 0.1 2.5 ± 0.4 2.5 ± 0.5 2.7 ± 0.7 2.4 ± 0.8 0.9 ± 0.1
Eosinophils, % 3.8 ± 0.5 4.2 ± 0.7 5.3 ± 0.9 6.4 ± 1.3 6.4 ± 1.3 8.1 ± 1.1
Eosinophils, 106/mL 0.1 ± 0.02 0.2 ± 0.04 0.3 ± 0.04 0.4 ± 0.06 0.4 ± 0.07 0.5 ± 0.06
Macrophages, % 60.6 ± 2.7 50.9 ± 2.6 50.2 ± 2.9 51.8 ± 5.7 60.9 ± 7.1 73.6 ± 3.0
Macrophages, 106/mL 2.3 ± 0.3 2.9 ± 0.4 2.7 ± 0.3 3.3 ± 0.3 4.5 ± 0.6 4.7 ± 0.5
Lymphocytes, % 4.2 ± 0.7 4.5 ± 0.7 3.8 ± 0.9 4.9 ± 0.8 4.7 ± 0.5 4.5 ± 1.7
Lymphocytes, 106/mL 0.1 ± 0.02 0.2 ± 0.04 0.2 ± 0.05 0.3 ± 0.05 0.4 ± 0.05 0.3 ± 0.1

Table 4—Measurements of Sputum Indices of Exacerbation and Nonexacerbation Groups

Variables Exacerbation (n = 9) Nonexacerbation (n = 13) p Value 95% Confidence Interval of Difference
IL-8, ng/mL
2 wk before visit
1,832.1 ± 151 1,074.3 ± 111.0 0.001 – 1,159.4 to – 356.3
Last visit 2,690.5 ± 154.7 1,420.7 ± 149.2 < 0.0001 – 1,753 to – 786.8
Total cell counts, 106
2 wk before visit 5.1 ± 0.9 4.65 ± 0.5 0.69 – 1.77 to 2.61
Last visit 8.5 ± 0.8 4.63 ± 0.5 0.0007 1.84 to 5.89
Neutrophils, %
2 wk before visit
42.0 ± 3.3 23.6 ± 3.5 0.02 – 29.2 to – 7.4
Last visit 51.1 ± 1.9 29.5 ± 4.2 0.0009 – 33.2 to – 9.99
Eosinophils, %
2 wk before visit
4.3 ± 0.4 2.8 ± 1.1 0.24 – 4.1 to 1.1
Last visit 2.7 ± 0.6 2.7 ± 1.0 0.99 – 2.96 to 2.99
Lymphocytes, %
2 wk before visit
5.1 ± 0.7 3.1 ± 0.8 0.09 – 4.5 to 0.36
Last visit 3.6 ± 0.7 1.5 ± 0.8 0.08 – 4.48 to 0.29
Macrophages, %
2 wk before visit
50.3 ± 3.8 70.1 ± 3.5 0.0003 11.2 to 32.0
Last visit 41.6 ± 2.2 68.2 ± 3.2 < 0.0001 17.6 to 35.7
March 4, 2016 Asthma
Tags: Asthma exacerbation interleukin-8 neutrophil