Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Juliy M. Perelman; Aleksey B. Pirogov; Anna G. Prikhodko; Victor P. Kolosov

doi:10.2478/fzm-2022-0031

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

doi: 10.2478/fzm-2022-0031

Far Eastern Scientific Center of Physiology and Pathology of Respiration, 22 Kalinina Str., Blagoveshchensk 675000, Russia

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Corresponding author: Juliy M. Perelman, E-mail: jperelman@mail.ru

摘要

Abstract: Objective To evaluate the inflammatory pattern and the interferon (IFN) -γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = -0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.
- asthma /
- cold airway hyperresponsiveness /
- mixed pattern of bronchial inflammation /
- proinflammatory interferon-γ /
- T helper cells 1 immune response
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Figure 1. Cellular composition of sputum in asthma patients with different types of airway response to IHCA

IHCA, isocapnic hyperventilation with cold air.

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Figure 2. The correlation between baseline FEV₁ (% predicted) and baseline IFN-γ (pg/mL) in EBC

IHCA, isocapnic hyperventilation with cold air; IFN, interferon; EBC, exhaled breath condensate.

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Figure 3. The correlation between the ∆FEV₁ (%) in response to IHCA and the content of IFN-γ (pg/mL) in EBC after IHCA

FEV₁, forced expiratory volume in 1 sec; IHCA, isocapnic hyperventilation with cold air; IFN, interferon; EBC, exhaled breath condensate.

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Figure 4. The correlation between the content of IFN-γ (pg/mL) in EBC before and after IHCA (in group 1)

FEV₁, forced expiratory volume in 1 sec; IHCA, isocapnic hyperventilation with cold air; IFN, interferon; EBC, exhaled breath condensate.

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Table 1. Lung function and FEV₁ dynamics after administration of salbutamol in asthma patients with different types of airway response to IHCA

Indicators	Group 1 (n = 20)	Group 2 (n = 22)	P value
predicted FVC, %	106.9 ± 2.1	110.3 ± 1.8	> 0.05
predicted FEV₁, %	90.1 ± 2.1	98.0± 1.9	0.0019
FEV₁/VC, %	70.3 ± 1.3	74.1± 1.1	0.0057
predicted MEF_25-75, %	60.3 ± 3.0	70.7± 3.4	0.032
∆FEV_{1bronchodilator}, %	10.05 (4.00, 18.70)	7.28(3.37, 13.05)	> 0.05
Values are presented as mean ± SE and median (Q1, Q3). IHCA, isocapnic hyperventilation with cold air; IFN, interferon; FVC, forced vital capacity; MEF_25-75, the maximal midexpiratory flow at the level of 25%-75% FVC; ∆FEV_{1bronchodilator}, %, change in the index after inhalation of a short-acting β₂-agonist (salbutamol, 400 μg).

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Table 2. The concentration of IFN-γ in the exhaled breath condensate in asthma patients with different types of airway response to IHCA

Indicators	Group 1 (n = 20)	Group 2 (n = 22)	P Value
Initial	17.3± 2.8	21.2± 3.4	> 0.05
After IHCA	13.6± 3.2^#	48.7± 5.4^##	0.0024
Values are presented as mean ± SE. FVC, forced vital capacity; IHCA, isocapnic hyperventilation with cold air; IFN, interferon; P, significance level between groups 1 and 2 (unpaired t-test); ^#, P > 0.05; ^##, P = 0.022.

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