The impact of inflammatory cells on lung function in asthmatics in a cross sectional retrospect study

doi:10.21203/rs.3.rs-3466867/v1

Background: Limited data exists on the impact of inflammatory cells and clinical characteristics on lung function in individuals with asthma.

Objective: The objective is to examine the correlation between increased inflammatory cells, asthma symptoms, and lung function in patients with asthma in a clinical setting.

Methods: A retrospective cohort study was conducted on 234 individuals suspected of having asthma in Xian, China between January 2008 and December 2021. Of those, 143 patients with complete clinical feature and lung function data were enrolled to examine the relationship between increased inflammatory cells, asthma symptoms, and lung function. Basic characteristics, blood eosinophil count, blood neutrophil count, blood platelet count, blood C-reactive protein (CRP), and comprehensive lung function analysis were evaluated at each inpatient for the 143 adult asthmatics. The association between inflammatory cells and clinical parameters with pulmonary function was compared.

Results: The results of the study showed that individuals in the alcohol intake group had elevated blood eosinophil count compared to those in the non-alcohol intake group (P=0.024). Long-acting inhaled beta 2 agonists and antibiotic therapy were associated with lower blood eosinophil count (P=0.021 and P=0.049, respectively) compared to other therapy.There was a independent association between blood eosinophil counts and FEV1 pre- and post-therapy in asthma but there was a markedly correlation between blood eosinophil counts and FEV1/FVC pre-and post-therapy in Asthma(P=0.007). Blood neutrophil counts were inversely correlated with FEV1/FVC after treatment (P=0.032). Night onset in asthma was positively correlated with blood neutrophil counts, while fever was negatively correlated with blood CRP (P=0.028). Platelet counts >300×109/L after treatment were significantly associated with a decline in FEV (<0.001) in patients with asthma. Elevated blood eosinophil count was independently associated with clinical features in asthma.

Conclusions: Based on the study's findings, there is a significant decline in FEV1/FVC among individuals with elevated blood eosinophil count, both pre- and post-bronchodilator while there was a independent relationship between blood eosinophil counts and FEV1 pre-and post-therapy in asthma. This suggests that increased levels of eosinophils may independently associated contribute to reduced lung function in asthma patients.

Asthma

Respiratory function tests

Forced expiratory volume in the first second (FEV1)

Forced vital capacity (FVC)

FEV1/FVC

Eosinophil

Asthma a heterogeneous disease characterized by the involvement of various cells including basophils, mast cells, neutrophils, T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), CD8⁺ T cells, B cells, and dendritic cells and cellular components in chronic airway inflammation of eosinophils[1] affecting an estimated 300 million people global, of all ages [2].In asthma patients,compared to healthy subjects,the decrease in lung function is greater over time[3], a subgroup of asthma patients lung function decline can progress into persistent airflow limitation [4]. Reduced lung function was associated with increased mortality in patients with Asthma[5]. Studies on the presence of eosinophils and neutrophils led to characterisation of subgroups that differed in their severity of disease (exacerbations) and response to therapy [6]. However, studies that asthma symptom and inflammatory cells with the decline of lung function remain performed.

FEV1 is often used as a primary endpoint in clinical studies [7]. Airway inflammation is closely associated with asthma, but the link is complex and indirect. Eosinophils mediated by Th2 derived cytokines are the most common inflammatory pattern in asthma. There is lots of evidence that eosinophils play an important role in causing severe exacerbations of asthma. Elevated blood eosinophil count are associated to an increased rate of asthma exacerbations and increased symptoms[8]. However, some studies have shown that elevated levels of eosinophils are associated with the severity of asthma and clinical symptoms in asthma patients, but how it affects lung function is unclear[9, 10]. Recent studies have shown that patients with asthma with a mixture of neutrophilic and eosinophilic inflammation had accelerated decline of respiratory function [11], but there are limited studies that examined the associations between inflammatory cells and clinic smptom and lung function, at least as measured by the number of eosinophils, neutrophils, platelet and the lung function in Asthma.

The aim of this study is to investigate whether there is an additive effect of increased systemic inflammation cells on asthma symptoms and lung function in patients with asthma, compared to those with normal levels of inflammatory cells. The study will examine the associations between eosinophils, neutrophils, platelets, and lung function in asthma and can delve deeper into the complex relationship between airway inflammation and lung function in asthma patients.

2.1 Study design

This study was a retrospective analysis of adult asthma patients who were enrolled in the Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi’an, China between 2008 and 2021 as show as Fig. 1. Flowchart. All subjects were at an uncontrolled stage of asthma and underwent imaging examination, pulmonary function test, airway hyperresponsiveness test or bronchodilator reversibility test, and sputum induction on the same day. The level of asthma control was defined by asthma symptom control and future risk of adverse outcomes based on the 2018 GINA guidelines of Asthma Management and Prevention. The subjects were divided into elevated blood eosinophil count group and low blood eosinophil count group based on their blood eosinophil count (≤ 0-0.45×10⁹ /L or > 0.45×10⁹ /L) on admission. The study was approved by Institutional Review Board,Tang Du Hospital, Air force Medical University (No. TDLL—202309-03) All study was performed according to the relevant guidelines and regulations.

2.2 Recorded data Study variables

The recorded data for this study included baseline clinical information such as age, sex, weight, height, lung function, sputum microbiology, medications, and respiratory symptoms are listed in Table 1. Blood eosinophil counts were also obtained from a post admission examination, and patients were categorized into high or low eosinophil count groups as Table 2. Other variables recorded included alcohol intake, race, education level, difficulty breathing, wheezing, cough with or without phlegm, palpitations, chest tightness and pain, fatigue, dizziness, allergic dermatitis, fever, allergic rhinitis, physical activity, exposure to dust and animals, emotional excitement, high altitude areas, foggy days, night-time symptoms, seasonal variation, waking up in the morning, getting cold, and glucocorticoid treatment etc are listed Table 1.

Table 1

Eosinophil counts were associated with baseline characteristics in 143 patients with Asthma
		Eosinophil counts ≤ 0-0.45×10⁹ /L	Eosinophil counts ༞0.45×10⁹ /L	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		95	48
Age, mean(SD)	Mean ± Sem	52.81 ± 14.27	50.79 ± 13.42	0.82	0.417	-2.88	6.92
	95%CI of the difference(minimum)	49.9	46.89
	95%CI of the difference(maximum)	55.72	54.69
Sex, n(%)	Male	47(49.47)	28(58.33)	1.00	0.316
Sex, n(%)	Female	48(50.53)	20(41.67)
Height, mean(SD)	Mean ± Sem	164.29 ± 8.15	166.38 ± 8.09	-1.45	0.151	-4.93	0.77
	95%CI of the mean(minimum)	162.63	164.02
	95%CI of the mean(maximum)	165.96	168.73
weight	Mean ± Sem	64.26 ± 12.01	67.38 ± 12.18	-1.46	0.147	-7.34	1.11
	95%CI of the mean(minimum)	61.81	63.84
	95%CI of the mean(maximum)	66.71	70.91
BMI in kg/m2 n(%)	Mean ± Sem	23.76 ± 3.81	24.21 ± 3.15	-0.69	0.489	-1.71	0.82
	95%CI of the mean(minimum)	22.99	23.29
	95%CI of the mean(maximum)	24.54	25.12
Smoking	Never n(%)	67(70.53)	33(68.75)	1.67	0.433
	Always n(%)	13(13.68)	4(8.33)
	Former n(%)	15(15.79)	11(22.92)
Alcohol intake	Never n(%)	89(93.68)	38(82.61)	7.44	0.024
	Always n(%)	6(6.32)	5(10.87)
	Former n(%)	0(0.00)	3(6.52)
Ethnicity	The Han nationality n(%)	94(98.95)	47(97.92)	0.25	0.620
Ethnicity	Other n(%)	1(1.05)	1(2.08)
Education	Illiteracy n(%)	2(2.78)	1(3.03)	6.23	0.101
	Primary school n(%)	16(22.22)	1(3.03)
	Junior high school n(%)	26(36.11)	14(42.42)
	High school or higher n(%)	28(38.89)	17(51.52)
Medication	SABA n(%)	30(31.58)	14(29.17)	0.09	0.768
	LABA, n(%)	42(44.21)	31(64.58)	5.30	0.021
	LAMA n(%)	47(49.47)	25(52.08)	0.09	0.768
	LABA, n(%)	0(0.00)	0(0.00)	——	——
	ICS n(%)	67(70.53)	36(75.00)	0.32	0.574
	VCS or OCS n(%)	49(51.58)	27(56.25)	0.28	0.597
	LABA + ICS n(%)	2(2.11)	1(2.08)	0.00	0.993
	Antibiotic therapy, n(%)	89(93.68)	40(83.33)	3.87	0.049
	LRA	37(38.95)	16(33.33)	0.43	0.512
	HRB	2(2.11)	1(2.08)	0.00	0.993
SABA short-acting beta-agonists,
LABA long-acting beta-agonists,
SAMA short-acting muscarinic antagonists,
LAMA long-acting β2-adrenergic antagonists,
ICS inhalation corticosteroids, VCS or OCS Intravenous or oral corticosteroids
LAMA Long acting muscarinic antagonist
LRA Leukotriene receptor antagonists
HRB H₂ receptor blockers

Table 2

Association between Eosinophilic count and lung function in asthmatic patients
		Eosinophil counts ≤ 0-0.45×10⁹ /L	Eosinophil counts ༞0.45×10⁹ /L	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		95	48
FVC(Before medication)	Mean ± Sem	2.61 ± 1.26	2.60 ± 0.86	0.05	0.957	-0.34	0.36
	95%CI of the mean(minimum)	2.29	2.31
	95%CI of the mean(maximum)	2.8	2.81
FVC(After taking the medication)	Mean ± Sem	2.72 ± 1.16	2.84 ± 0.80	-0.71	0.480	-0.46	0.22
	95%CI of the mean(minimum)	2.50	2.61
	95%CI of the mean(maximum)	3.00	3.11
FEV1(Before medication)	Mean ± Sem	67.72 ± 15.19	62.66 ± 13.00	1.95	0.053	-0.06	10.17
	95%CI of the mean(minimum)	64.56	58.05
	95%CI of the mean(maximum)	71.07	66.18
FEV1(After taking the medication)	Mean ± Sem	68.43 ± 14.24	64.02 ± 12.88	1.71	0.089	-0.68	9.50
	95%CI of the mean(minimum)	65.40	60.06
	95%CI of the mean(maximum)	71.46	67.98
FEV1/FVC(Before medication)	Mean ± Sem	31.17 ± 14.92	26.55 ± 8.55	2.34	0.021	0.72	8.53
	95%CI of the mean(minimum)	28.43	23.61
	95%CI of the mean(maximum)	34.84	28.98
FEV1/FVC(After taking the medication)	Mean ± Sem	28.94 ± 14.17	23.77 ± 7.18	2.76	0.007	1.47	8.88
	95%CI of the mean(minimum)	25.92	21.56
	95%CI of the mean(maximum)	31.96	25.98
Symptom
Dyspnea	No, n(%)	11(11.58)	5(10.42)	0.04	0.835
Dyspnea	Yes, n(%)	84(88.42)	43(89.58)
Gasp	No, n(%)	5(5.26)	2(4.17)	0.08	1.000
Gasp	Yes, n(%)	90(94.74)	46(95.83)
Cough + cough phlegm	No, n(%)	30(31.58)	12(25.00)	0.67	0.415
Cough + cough phlegm	Yes, n(%)	65(68.42)	36(75.00)
Cough + no cough phlegm	No, n(%)	71(74.74)	39(81.25)	0.76	0.383
Cough + no cough phlegm	Yes, n(%)	24(25.26)	9(18.75)
Palpitations of heart	No, n(%)	92(96.84)	48(100.00)	1.55	0.531
Palpitations of heart	Yes, n(%)	3(3.16)	0(0.00)
Chest distress	No, n(%)	92(96.84)	47(97.92)	0.14	1.000
Chest distress	Yes, n(%)	3(3.16)	1(2.08)
Thoracodynia	No, n(%)	94(98.95)	48(100.00)	0.51	1.000
Thoracodynia	Yes, n(%)	1(1.05)	0(0.00)
Chest tightness and chest pain	No, n(%)	91(95.79)	47(97.92)	0.43	0.864
Chest tightness and chest pain	Yes, n(%)	4(4.21)	1(2.08)
Fatigue	No, n(%)	94(98.95)	48(100.00)	0.51	1.000
Fatigue	Yes, n(%)	1(1.05)	0(0.00)
Giddy	No, n(%)	94(98.95)	48(100.00)	0.51	1.000
Giddy	Yes, n(%)	1(1.05)	0(0.00)
Fatigue and dizziness	No, n(%)	93(97.89)	48(100.00)	1.03	0.551
Fatigue and dizziness	Yes, n(%)	2(2.11)	0(0.00)
Atopic dermatitis	No, n(%)	93(97.89)	48(100.00)	1.03	0.551
Atopic dermatitis	Yes, n(%)	2(2.11)	0(0.00)
Fever	No, n(%)	92(96.84)	47(97.92)	0.14	1.000
Fever	Yes, n(%)	3(3.16)	1(2.08)
Allergic rhinitis	No, n(%)	95(100.00)	47(97.92)	1.99	0.336
Allergic rhinitis	Yes, n(%)	0(0.00)	1(2.08)
Under what circumstances the disease occurs
Physical activity	No, n(%)	76(80.00)	41(85.42)	0.63	0.428
Physical activity	Yes, n(%)	19(20.00)	7(14.58)
Exposure to dust and animals	No, n(%)	93(97.89)	43(89.58)	4.73	0.078
Exposure to dust and animals	Yes, n(%)	2(2.11)	5(10.42)
Get emotional	No, n(%)	94(98.95)	48(100.00)	0.51	1.000
Get emotional	Yes, n(%)	1(1.05)	0(0.00)
Inhabited plateau area	No, n(%)	95(100.00)	47(97.92)	1.99	0.336
Inhabited plateau area	Yes, n(%)	0(0.00)	1(2.08)
Foggy weather	No, n(%)	95(100.00)	47(97.92)	1.99	0.336
Foggy weather	Yes, n(%)	0(0.00)	1(2.08)
Night	No, n(%)	85(89.47)	42(87.50)	0.13	0.724
Night	Yes, n(%)	10(10.53)	6(12.50)
Springtime	No, n(%)	95(100.00)	47(97.92)	1.99	0.336
Springtime	Yes, n(%)	0(0.00)	1(2.08)
Autumn or winter	No, n(%)	95(100.00)	47(97.92)	1.99	0.336
Autumn or winter	Yes, n(%)	0(0.00)	1(2.08)
Alternation of seasons	No, n(%)	82(86.32)	44(91.67)	0.87	0.351
Alternation of seasons	Yes, n(%)	13(13.68)	4(8.33)
Spring or the change of seasons	No, n(%)	82(86.32)	43(89.58)	0.31	0.578
Spring or the change of seasons	Yes, n(%)	13(13.68)	5(10.42)
Autumn and winter or the change of seasons	No, n(%)	82(86.32)	44(91.67)	0.87	0.351
Autumn and winter or the change of seasons	Yes, n(%)	13(13.68)	4(8.33)
Get up in the morning	No, n(%)	94(98.95)	47(97.92)	0.25	1.000
Get up in the morning	Yes, n(%)	1(1.05)	1(2.08)
Catch a cold	No, n(%)	55(57.89)	34(70.83)	2.27	0.132
Catch a cold	Yes, n(%)	40(42.11)	14(29.17)
Glucocorticoid therapy	No, n(%)	91(95.79)	48(100.00)	2.08	0.365
Glucocorticoid therapy	Yes, n(%)	4(4.21)	0(0.00)

2.3 Statistical analysis

The objective of the statistical analysis was to determine the significance of the data obtained from the study. The data were analyzed using SPSS version 19.0 (USA), and a p-value less than 0.05 was considered statistically significant. Continuous variables were expressed as mean ± Sem (Standard error of mean value) for normal distribution or median (interquartile range) for non-normal distribution, while classification variables were analyzed using the chi-square test and expressed as number (percentage). Two groups of continuous variables were compared using t-test for normal distribution and Mann-Whitney U test for non-normal distribution.

The study evaluated the differences in basic features and pulmonary function between patients with elevated blood eosinophil count and low blood eosinophil count in asthma as show in Table 1. Elevated blood eosinophil count was associated with increased alcohol intake and decreased use of long-acting inhaled beta 2 agonists and antibiotics as show in Table 1 and Table 2. There was a negative correlation between blood eosinophil counts and FEV1/FVC in asthma, which became significant after treatment. Blood neutrophil counts were negatively correlated with FEV1/FVC after treatment and positively correlated with night onset in asthma as show as Table 3. No significant difference in lung function was found between the elevated blood lymphocyte counts and low blood lymphocyte counts group as shown Table 4, while platelet count > 300×10⁹/L was associated with significant differences in FVC and FEV1/FVC in patients with asthma as shown Table 5.There was no significant correlation between the level of CRP and lung function, but there was a positive correlation between the blood CRP and fever in asthma as shown in Table 6.

Table 3

Neutrophil count is associated with lung function in Asthmatic patients
		Neutrophil count < 1.6×10⁹ /L	Neutrophil count ༞7.3×10⁹ /L	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		3	31
FVC(Before medication)	Mean ± Sem	2.48 ± 0.44	2.37 ± 0.98	0.19	0.850	-1.06	1.28
	95%CI of the mean(minimum)	1.40	1.93
	95%CI of the mean(maximum)	3.57	2.66
FVC(After taking the medication)	Mean ± Sem	2.55 ± 0.62	2.58 ± 0.98	-0.05	0.962	-1.22	1.16
	95%CI of the mean(minimum)	1.02	2.21
	95%CI of the mean(maximum)	4.09	2.95
FEV1(Before medication)	Mean ± Sem	80.16 ± 9.39	64.71 ± 13.80	1.88	0.069	-1.26	32.16
	95%CI of the mean(minimum)	56.83	58.66
	95%CI of the mean(maximum)	103.49	69.28
FEV1(After taking the medication)	Mean ± Sem	80.93 ± 10.51	64.67 ± 12.04	2.25	0.032	1.47	31.05
	95%CI of the mean(minimum)	54.81	60.09
	95%CI of the mean(maximum)	107.05	69.25
FEV1/FVC(Before medication)	Mean ± Sem	33.47 ± 10.35	31.68 ± 13.87	0.22	0.830	-15.05	18.64
	95%CI of the mean(minimum)	7.76	27.01
	95%CI of the mean(maximum)	59.18	37.73
FEV1/FVC(After taking the medication)	Mean ± Sem	34.01 ± 14.33	28.08 ± 9.79	0.96	0.344	-6.66	18.50
	95%CI of the mean(minimum)	-1.59	24.36
	95%CI of the mean(maximum)	69.61	31.81
Symptom
Dyspnea	No, n(%)	0(0.00)	3(9.68)	0.32	1.000
Dyspnea	Yes, n(%)	3(100.00)	28(90.32)
Gasp	No, n(%)	0(0.00)	3(9.68)	0.32	1.000
Gasp	Yes, n(%)	3(100.00)	28(90.32)
Cough + cough phlegm	No, n(%)	0(0.00)	9(29.03)	1.19	0.549
Cough + cough phlegm	Yes, n(%)	3(100.00)	22(70.97)
Cough + no cough phlegm	No, n(%)	3(100.00)	26(83.87)	0.57	1.000
Cough + no cough phlegm	Yes, n(%)	0(0.00)	5(16.13)
Palpitations of heart	No, n(%)	3(100.00)	31(100.00)	——	——
Palpitations of heart	Yes, n(%)	0(0.00)	0(0.00)
Chest distress	No, n(%)	3(100.00)	31(100.00)	——	——
Chest distress	Yes, n(%)	0(0.00)	0(0.00)
Thoracodynia	No, n(%)	3(100.00)	31(100.00)	——	——
Thoracodynia	Yes, n(%)	0(0.00)	0(0.00)
Chest tightness and chest pain	No, n(%)	3(100.00)	31(100.00)	——	——
Chest tightness and chest pain	Yes, n(%)	0(0.00)	0(0.00)
Fatigue	No, n(%)	3(100.00)	31(100.00)	——	——
Fatigue	Yes, n(%)	0(0.00)	0(0.00)
Giddy	No, n(%)	3(100.00)	31(100.00)	——	——
Giddy	Yes, n(%)	0(0.00)	0(0.00)
Fatigue and dizziness	No, n(%)	3(100.00)	31(100.00)	——	——
Fatigue and dizziness	Yes, n(%)	0(0.00)	0(0.00)
Atopic dermatitis	No, n(%)	3(100.00)	31(100.00)	——	——
Atopic dermatitis	Yes, n(%)	0(0.00)	0(0.00)
Fever	No, n(%)	3(100.00)	29(93.55)	0.21	1.000
Fever	Yes, n(%)	0(0.00)	2(6.45)
Allergic rhinitis	No, n(%)	3(100.00)	30(96.77)	0.10	1.000
Allergic rhinitis	Yes, n(%)	0(0.00)	1(3.23)
Under what circumstances the disease occurs
Physical activity	No, n(%)	3(100.00)	26(83.87)	0.57	1.000
Physical activity	Yes, n(%)	0(0.00)	5(16.13)
Exposure to dust and animals	No, n(%)	3(100.00)	29(93.55)	0.21	1.000
Exposure to dust and animals	Yes, n(%)	0(0.00)	2(6.45)
Get emotional	No, n(%)	3(100.00)	31(100.00)	——	——
Get emotional	Yes, n(%)	0(0.00)	0(0.00)
Inhabited plateau area	No, n(%)	3(100.00)	31(100.00)	——	——
Inhabited plateau area	Yes, n(%)	0(0.00)	0(0.00)
Foggy weather	No, n(%)	3(100.00)	30(96.77)	0.10	1.000
Foggy weather	Yes, n(%)	0(0.00)	1(3.23)
Night	No, n(%)	1(33.33)	29(93.55)	9.55	0.031
Night	Yes, n(%)	2(66.67)	2(6.45)
Springtime	No, n(%)	3(100.00)	31(100.00)	——	——
Springtime	Yes, n(%)	0(0.00)	0(0.00)
Autumn or winter	No, n(%)	3(100.00)	31(100.00)	——	——
Autumn or winter	Yes, n(%)	0(0.00)	0(0.00)
Alternation of seasons	No, n(%)	3(100.00)	26(83.87)	0.57	1.000
Alternation of seasons	Yes, n(%)	0(0.00)	5(16.13)
Spring or the change of seasons	No, n(%)	3(100.00)	26(83.87)	0.57	1.000
Spring or the change of seasons	Yes, n(%)	0(0.00)	5(16.13)
Autumn and winter or the change of seasons	No, n(%)	3(100.00)	26(83.87)	0.57	1.000
Autumn and winter or the change of seasons	Yes, n(%)	0(0.00)	5(16.13)
Get up in the morning	No, n(%)	3(100.00)	31(100.00)	——	——
Get up in the morning	Yes, n(%)	0(0.00)	0(0.00)
Catch a cold	No, n(%)	1(33.33)	16(51.61)	0.37	1.000
Catch a cold	Yes, n(%)	2(66.67)	15(48.39)
Glucocorticoid therapy	No, n(%)	3(100.00)	31(100.00)	——	——
Glucocorticoid therapy	Yes, n(%)	0(0.00)	0(0.00)

Table 4

Lymphocyte percentage and lung function are associated in Asthmatic patients
		Percentage of lymphocytes < 20%	Percentage of lymphocytes༞40%	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		22	19
FVC(Before medication)	Mean ± Sem	2.72 ± 1.17	3.19 ± 1.55	-1.12	0.271	-1.34	0.39
	95%CI of the mean(minimum)	2.20	2.28
	95%CI of the mean(maximum)	3.24	3.94
FVC(After taking the medication)	Mean ± Sem	2.99 ± 1.17	3.31 ± 1.62	-0.73	0.472	-1.23	0.58
	95%CI of the mean(minimum)	2.47	2.48
	95%CI of the mean(maximum)	3.50	4.14
FEV1(Before medication)	Mean ± Sem	67.09 ± 16.57	73.31 ± 13.14	-1.32	0.195	-15.78	3.33
	95%CI of the mean(minimum)	59.74	65.34
	95%CI of the mean(maximum)	74.44	79.13
FEV1(After taking the medication)	Mean ± Sem	67.46 ± 14.57	71.69 ± 13.04	-0.94	0.352	-13.35	4.88
	95%CI of the mean(minimum)	61.00	64.99
	95%CI of the mean(maximum)	73.92	78.40
FEV1/FVC(Before medication)	Mean ± Sem	29.34 ± 15.03	27.87 ± 12.53	0.34	0.739	-7.36	10.29
	95%CI of the mean(minimum)	22.67	21.95
	95%CI of the mean(maximum)	36.00	35.37
FEV1/FVC(After taking the medication)	Mean ± Sem	25.51 ± 10.06	26.11 ± 11.44	-0.17	0.863	-7.59	6.38
	95%CI of the mean(minimum)	21.05	20.23
	95%CI of the mean(maximum)	29.97	31.99
Symptom
Dyspnea	No, n(%)	3(13.64)	2(10.53)	0.00	1.000
Dyspnea	Yes, n(%)	19(86.36)	17(89.47)
Gasp	No, n(%)	1(4.55)	1(5.26)	0.01	1.000
Gasp	Yes, n(%)	21(95.45)	18(94.74)
Cough + cough phlegm	No, n(%)	10(45.45)	5(26.32)	1.61	0.205
Cough + cough phlegm	Yes, n(%)	12(54.55)	14(73.68)
Cough + no cough phlegm	No, n(%)	15(68.18)	14(73.68)	0.15	0.699
Cough + no cough phlegm	Yes, n(%)	7(31.82)	5(26.32)
Palpitations of heart	No, n(%)	21(95.45)	18(94.74)	0.01	1.000
Palpitations of heart	Yes, n(%)	1(4.55)	1(5.26)
Chest distress	No, n(%)	21(95.45)	19(100.00)	0.89	1.000
Chest distress	Yes, n(%)	1(4.55)	0(0.00)
Thoracodynia	No, n(%)	22(100.00)	18(94.74)	1.19	0.463
Thoracodynia	Yes, n(%)	0(0.00)	1(5.26)
Chest tightness and chest pain	No, n(%)	21(95.45)	18(94.74)	0.01	1.000
Chest tightness and chest pain	Yes, n(%)	1(4.55)	1(5.26)
Fatigue	No, n(%)	22(100.00)	19(100.00)	——	——
Fatigue	Yes, n(%)	0(0.00)	0(0.00)
Giddy	No, n(%)	21(95.45)	19(100.00)	0.89	1.000
Giddy	Yes, n(%)	1(4.55)	0(0.00)
Fatigue and dizziness	No, n(%)	21(95.45)	19(100.00)	0.89	1.000
Fatigue and dizziness	Yes, n(%)	1(4.55)	0(0.00)
Atopic dermatitis	No, n(%)	22(100.00)	19(100.00)	——	——
Atopic dermatitis	Yes, n(%)	0(0.00)	0(0.00)
Fever	No, n(%)	21(95.45)	18(94.74)	0.01	1.000
Fever	Yes, n(%)	1(4.55)	1(5.26)
Allergic rhinitis	No, n(%)	22(100.00)	19(100.00)	——	——
Allergic rhinitis	Yes, n(%)	0(0.00)	0(0.00)
Under what circumstances the disease occurs
Physical activity	No, n(%)	19(86.36)	18(94.74)	0.81	0.709
Physical activity	Yes, n(%)	3(13.64)	1(5.26)
Exposure to dust and animals	No, n(%)	22(100.00)	18(94.74)	1.19	0.463
Exposure to dust and animals	Yes, n(%)	0(0.00)	1(5.26)
Get emotional	No, n(%)	22(100.00)	18(94.74)	1.19	0.463
Get emotional	Yes, n(%)	0(0.00)	1(5.26)
Inhabited plateau area	No, n(%)	22(100.00)	19(100.00)	——	——
Inhabited plateau area	Yes, n(%)	0(0.00)	0(0.00)
Foggy weather	No, n(%)	22(100.00)	19(100.00)	——	——
Foggy weather	Yes, n(%)	0(0.00)	0(0.00)
Night	No, n(%)	18(81.82)	15(78.95)	0.05	1.000
Night	Yes, n(%)	4(18.18)	4(21.05)
Springtime	No, n(%)	22(100.00)	19(100.00)	——	——
Springtime	Yes, n(%)	0(0.00)	0(0.00)
Autumn or winter	No, n(%)	22(100.00)	19(100.00)	——	——
Autumn or winter	Yes, n(%)	0(0.00)	0(0.00)
Alternation of seasons	No, n(%)	18(81.82)	17(89.47)	0.48	0.804
Alternation of seasons	Yes, n(%)	4(18.18)	2(10.53)
Spring or the change of seasons	No, n(%)	18(81.82)	17(89.47)	0.48	0.804
Spring or the change of seasons	Yes, n(%)	4(18.18)	2(10.53)
Autumn and winter or the change of seasons	No, n(%)	18(81.82)	17(89.47)	0.48	0.804
Autumn and winter or the change of seasons	Yes, n(%)	4(18.18)	2(10.53)
Get up in the morning	No, n(%)	22(100.00)	19(100.00)	——	——
Get up in the morning	Yes, n(%)	0(0.00)	0(0.00)
Catch a cold	No, n(%)	12(54.55)	11(57.89)	0.05	0.829
Catch a cold	Yes, n(%)	10(45.45)	8(42.11)
Glucocorticoid therapy	No, n(%)	21(95.45)	18(94.74)	0.01	1.000
Glucocorticoid therapy	Yes, n(%)	1(4.55)	1(5.26)

Table 5

Association between platelet count and lung function in Asthmatic patients
		Platelet count < 100×10⁹ /L	Platelet count ༞300×10⁹ /L	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		2	14
FVC(Before medication)	Mean ± Sem	1.57 ± 0.11	2.99 ± 0.79	-2.45	0.028	-2.66	-0.18
	95%CI of the mean(minimum)	——	2.39
	95%CI of the mean(maximum)	——	3.17
FVC(After taking the medication)	Mean ± Sem	1.92 ± 0.06	3.02 ± 0.80	-4.71	< 0.001	-1.62	-0.59
	95%CI of the mean(minimum)	——	2.51
	95%CI of the mean(maximum)	——	3.53
FEV1(Before medication)	Mean ± Sem	65.50 ± 26.16	58.27 ± 17.61	0.52	0.614	-22.99	37.44
	95%CI of the mean(minimum)	——	45.62
	95%CI of the mean(maximum)	——	67.64
FEV1(After taking the medication)	Mean ± Sem	76.00(Only 1 case)	58.66 ± 17.99	0.93	0.374	-23.86	58.55
	95%CI of the mean(minimum)	——	47.23
	95%CI of the mean(maximum)	——	70.08
FEV1/FVC(Before medication)	Mean ± Sem	41.23 ± 13.69	21.19 ± 7.30	3.31	0.006	6.94	33.13
	95%CI of the mean(minimum)	——	16.45
	95%CI of the mean(maximum)	——	26.13
FEV1/FVC(After taking the medication)	Mean ± Sem	38.78(Only 1 case)	20.90 ± 8.49	2.02	0.068	-1.58	37.33
	95%CI of the mean(minimum)	——	15.51
	95%CI of the mean(maximum)	——	26.30
Symptom
Dyspnea	No, n(%)	0(0.00)	1(7.14)	0.15	1.000
Dyspnea	Yes, n(%)	2(100.00)	13(92.86)
Gasp	No, n(%)	0(0.00)	0(0.00)	——	——
Gasp	Yes, n(%)	2(100.00)	14(100.00)
Cough + cough phlegm	No, n(%)	0(0.00)	4(28.57)	0.76	1.000
Cough + cough phlegm	Yes, n(%)	2(100.00)	10(71.43)
Cough + no cough phlegm	No, n(%)	2(100.00)	11(78.57)	0.53	1.000
Cough + no cough phlegm	Yes, n(%)	0(0.00)	3(21.43)
Palpitations of heart	No, n(%)	2(100.00)	14(100.00)	——	——
Palpitations of heart	Yes, n(%)	0(0.00)	0(0.00)
Chest distress	No, n(%)	2(100.00)	13(92.86)	0.15	1.000
Chest distress	Yes, n(%)	0(0.00)	1(7.14)
Thoracodynia	No, n(%)	2(100.00)	14(100.00)	——	——
Thoracodynia	Yes, n(%)	0(0.00)	0(0.00)
Chest tightness and chest pain	No, n(%)	2(100.00)	13(92.86)	0.15	1.000
Chest tightness and chest pain	Yes, n(%)	0(0.00)	1(7.14)
Fatigue	No, n(%)	2(100.00)	14(100.00)	——	——
Fatigue	Yes, n(%)	0(0.00)	0(0.00)
Giddy	No, n(%)	2(100.00)	14(100.00)	——	——
Giddy	Yes, n(%)	0(0.00)	0(0.00)
Fatigue and dizziness	No, n(%)	2(100.00)	14(100.00)	——	——
Fatigue and dizziness	Yes, n(%)	0(0.00)	0(0.00)
Atopic dermatitis	No, n(%)	2(100.00)	13(92.86)	0.15	1.000
Atopic dermatitis	Yes, n(%)	0(0.00)	1(7.14)
Fever	No, n(%)	2(100.00)	13(92.86)	0.15	1.000
Fever	Yes, n(%)	0(0.00)	1(7.14)
Allergic rhinitis	No, n(%)	2(100.00)	14(100.00)	——	——
Allergic rhinitis	Yes, n(%)	0(0.00)	0(0.00)
Under what circumstances the disease occurs
Physical activity	No, n(%)	1(50.00)	12(85.71)	1.47	0.350
Physical activity	Yes, n(%)	1(50.00)	2(14.29)
Exposure to dust and animals	No, n(%)	2(100.00)	12(85.71)	0.33	1.000
Exposure to dust and animals	Yes, n(%)	0(0.00)	2(14.29)
Get emotional	No, n(%)	2(100.00)	14(100.00)	——	——
Get emotional	Yes, n(%)	0(0.00)	0(0.00)
Inhabited plateau area	No, n(%)	2(100.00)	14(100.00)	——	——
Inhabited plateau area	Yes, n(%)	0(0.00)	0(0.00)
Foggy weather	No, n(%)	2(100.00)	14(100.00)	——	——
Foggy weather	Yes, n(%)	0(0.00)	0(0.00)
Night	No, n(%)	2(100.00)	12(85.71)	0.33	1.000
Night	Yes, n(%)	0(0.00)	2(14.29)
Springtime	No, n(%)	2(100.00)	14(100.00)	——	——
Springtime	Yes, n(%)	0(0.00)	0(0.00)
Autumn or winter	No, n(%)	2(100.00)	14(100.00)	——	——
Autumn or winter	Yes, n(%)	0(0.00)	0(0.00)
Alternation of seasons	No, n(%)	1(50.00)	11(78.57)	0.76	0.450
Alternation of seasons	Yes, n(%)	1(50.00)	3(21.43)
Spring or the change of seasons	No, n(%)	1(50.00)	11(78.57)	0.76	0.450
Spring or the change of seasons	Yes, n(%)	1(50.00)	3(21.43)
Autumn and winter or the change of seasons	No, n(%)	1(50.00)	11(78.57)	0.76	0.450
Autumn and winter or the change of seasons	Yes, n(%)	1(50.00)	3(21.43)
Get up in the morning	No, n(%)	2(100.00)	14(100.00)	——	——
Get up in the morning	Yes, n(%)	0(0.00)	0(0.00)
Catch a cold	No, n(%)	1(50.00)	10(71.43)	0.37	1.000
Catch a cold	Yes, n(%)	1(50.00)	4(28.57)
Glucocorticoid therapy	No, n(%)	2(100.00)	13(92.86)	0.15	1.000
Glucocorticoid therapy	Yes, n(%)	0(0.00)	1(7.14)

Table 6

CRP and lung function are associated in Asthmatic patients
		CRP < 10mg/L	CRP ༞10mg/L	t or c²	p	95%CI of the difference(minimum)	95%CI of the difference(maximum)
n		56	15
FVC(Before medication)	Mean ± Sem	2.26 ± 0.84	1.93 ± 0.68	1.40	0.166	-0.14	0.80
	95%CI of the mean(minimum)	2.02	1.56
	95%CI of the mean(maximum)	2.48	2.36
FVC(After taking the medication)	Mean ± Sem	2.49 ± 0.83	2.19 ± 0.60	1.32	0.192	-0.16	0.76
	95%CI of the mean(minimum)	2.26	1.84
	95%CI of the mean(maximum)	2.72	2.56
FEV1(Before medication)	Mean ± Sem	64.58 ± 15.07	64.85 ± 12.68	-0.06	0.949	-8.75	8.20
	95%CI of the mean(minimum)	60.17	56.79
	95%CI of the mean(maximum)	68.47	71.74
FEV1(After taking the medication)	Mean ± Sem	65.55 ± 13.94	63.21 ± 12.32	0.57	0.569	-5.82	10.51
	95%CI of the mean(minimum)	61.75	56.10
	95%CI of the mean(maximum)	69.36	70.32
FEV1/FVC(Before medication)	Mean ± Sem	32.24 ± 14.38	36.59 ± 11.41	-1.08	0.282	-12.38	3.66
	95%CI of the mean(minimum)	28.35	29.17
	95%CI of the mean(maximum)	36.31	42.10
FEV1/FVC(After taking the medication)	Mean ± Sem	29.48 ± 15.06	30.25 ± 7.82	-0.19	0.854	-9.12	7.57
	95%CI of the mean(minimum)	25.37	25.73
	95%CI of the mean(maximum)	33.59	34.77
Symptom
Dyspnea	No, n(%)	3(5.36)	0(0.00)	0.84	1.000
Dyspnea	Yes, n(%)	53(94.64)	15(100.00)
Gasp	No, n(%)	2(3.57)	0(0.00)	0.55	1.000
Gasp	Yes, n(%)	54(96.43)	15(100.00)
Cough + cough phlegm	No, n(%)	19(33.93)	3(20.00)	1.07	0.300
Cough + cough phlegm	Yes, n(%)	37(66.07)	12(80.00)
Cough + no cough phlegm	No, n(%)	42(75.00)	12(80.00)	0.16	0.950
Cough + no cough phlegm	Yes, n(%)	14(25.00)	3(20.00)
Palpitations of heart	No, n(%)	54(96.43)	15(100.00)	0.55	1.000
Palpitations of heart	Yes, n(%)	2(3.57)	0(0.00)
Chest distress	No, n(%)	56(100.00)	15(100.00)	——	——
Chest distress	Yes, n(%)	0(0.00)	0(0.00)
Thoracodynia	No, n(%)	55(98.21)	15(100.00)	0.27	1.000
Thoracodynia	Yes, n(%)	1(1.79)	0(0.00)
Chest tightness and chest pain	No, n(%)	55(98.21)	15(100.00)	0.27	1.000
Chest tightness and chest pain	Yes, n(%)	1(1.79)	0(0.00)
Fatigue	No, n(%)	56(100.00)	15(100.00)	——	——
Fatigue	Yes, n(%)	0(0.00)	0(0.00)
Giddy	No, n(%)	56(100.00)	15(100.00)	——	——
Giddy	Yes, n(%)	0(0.00)	0(0.00)
Fatigue and dizziness	No, n(%)	56(100.00)	15(100.00)	——	——
Fatigue and dizziness	Yes, n(%)	0(0.00)	0(0.00)
Atopic dermatitis	No, n(%)	56(100.00)	15(100.00)	——	——
Atopic dermatitis	Yes, n(%)	0(0.00)	0(0.00)
Fever	No, n(%)	55(98.21)	12(80.00)	7.38	0.028
Fever	Yes, n(%)	1(1.79)	3(20.00)
Allergic rhinitis	No, n(%)	55(98.21)	15(100.00)	0.27	1.000
Allergic rhinitis	Yes, n(%)	1(1.79)	0(0.00)
Under what circumstances the disease occurs
Physical activity	No, n(%)	46(82.14)	10(66.67)	1.70	0.343
Physical activity	Yes, n(%)	10(17.86)	5(33.33)
Exposure to dust and animals	No, n(%)	52(92.86)	13(86.67)	0.59	0.808
Exposure to dust and animals	Yes, n(%)	4(7.14)	2(13.33)
Get emotional	No, n(%)	56(100.00)	15(100.00)	——	——
Get emotional	Yes, n(%)	0(0.00)	0(0.00)
Inhabited plateau area	No, n(%)	56(100.00)	15(100.00)	——	——
Inhabited plateau area	Yes, n(%)	0(0.00)	0(0.00)
Foggy weather	No, n(%)	56(100.00)	14(93.33)	3.79	0.211
Foggy weather	Yes, n(%)	0(0.00)	1(6.67)
Night	No, n(%)	48(85.71)	15(100.00)	2.42	0.274
Night	Yes, n(%)	8(14.29)	0(0.00)
Springtime	No, n(%)	55(98.21)	15(100.00)	0.27	1.000
Springtime	Yes, n(%)	1(1.79)	0(0.00)
Autumn or winter	No, n(%)	56(100.00)	15(100.00)	——	——
Autumn or winter	Yes, n(%)	0(0.00)	0(0.00)
Alternation of seasons	No, n(%)	47(83.93)	13(86.67)	0.07	1.000
Alternation of seasons	Yes, n(%)	9(16.07)	2(13.33)
Spring or the change of seasons	No, n(%)	46(82.14)	13(86.67)	0.17	0.978
Spring or the change of seasons	Yes, n(%)	10(17.86)	2(13.33)
Autumn and winter or the change of seasons	No, n(%)	47(83.93)	13(86.67)	0.07	1.000
Autumn and winter or the change of seasons	Yes, n(%)	9(16.07)	2(13.33)
Get up in the morning	No, n(%)	56(100.00)	15(100.00)	——	——
Get up in the morning	Yes, n(%)	0(0.00)	0(0.00)
Catch a cold	No, n(%)	32(57.14)	5(33.33)	2.69	0.101
Catch a cold	Yes, n(%)	24(42.86)	10(66.67)
Glucocorticoid therapy	No, n(%)	55(98.21)	15(100.00)	0.27	1.000
Glucocorticoid therapy	Yes, n(%)	1(1.79)	0(0.00)

This study retrospectively compared the baseline pulmonary function and inflammatory cells and asthma symptom in asthma patients. we found a positive association between alcohol intake with blood eosinophil count; a inversely association between long-acting inhaled beta 2 agonists and antibiotic therapy group with blood eosinophi count in treatment group; a week inverse correlation between blood eosinophil counts and FEV1/FVC in asthma pre-treatment; a significanlt inversely correlation between blood eosinophil counts and FEV1/FVC in asthma post-treatment; There was a positive correlation between the blood neutrophil counts and night onset in asthma; a inversely association between the blood neutrophil counts and FEV1/FVC in asthma post-treatment. There was a positive correlation between the blood CRP and fever in asthma.

Blood eosinophil levels are being used to identify patients with type 2 asthma, may become a candidate for new biotherapy. Eosinophilic inflammation is evident in about half of asthma patients and is associated with increased disease severity, frequency of exacerbations and burden of symptoms, and decreased lung function[10], but in this study, elevated blood eosinophil count was independently associated to clinical feature in asthma preceding as shown as Table 1 and Table 2, this means that clinical characteristics could not be used to identify patients with values consistently elevated level or low level of blood eosinophil count. No gender differences were observed between inflammation markers and lung function as shown in Table 1. Blood eosinophil count is one of the predictive biomarkers of eosinophilic asthma. Although we did not find a correlation between blood eosinophil counts and FEV1, we showed that a significant inversely correlation between blood eosinophil counts and FEV1/FVC in asthma post-treatment as shown in Table 2; previous study showed that eosinophil blood counts had an opposite relation to lung function[12]. Previous study indicated that blood eosinophils are related to severe asthma exacerbations[13], and it is possible that severe exacerbations contribute to excess FEV1 decline. Our study showed there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma as shown as Table 2, consistent with previous report[14]. This can be explained by report[15] that in mice, absolute neutrophil counts increased significantly after consuming large amounts of alcohol. However, in the alcohol-treated animals, the absolute count of lymphocytes decreased significantly. Alcohol toxicity did not lead to markedly change of eosinophils and basophils. Oldenburg et al reported that alcohol-induced reduction of allergic inflammatory cells in a mouse model of allergic asthma[16]. But we found a significant correlation between alcohol intake and an increase in blood eosinophils count as shown as Table 1, our data is consistent with recent study in which ethanol impairs CD4⁺ T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4⁺ T cell differentiation to a pro-inflammatory phenotype[17]. This also indicates that the actual situation of the patient is much more complex compared to the mouse model.

Neutrophils are the most abundant inflammatory cells known in the lungs of patients with chronic lung disease, we showed that a inversely association between the blood neutrophil counts and FEV1/FVC in asthma post-treatment as shown in Table 4, this result is consistent with previous report that white blood cell (WBC) subtypes were negatively associated with lung function level except lymphocytes in the observational studies[18]. Neutrophils are central to the prevention and control of infections as they have an armamentarium of responses necessary to kill organisms and amplify the inflammatory response[19].

CRP has been used routinely for the past 30. In our data,CRP is positively correlated with fever as shown in Table 6, indicating the degree of inflammation, which is consistent with previous research findings, although it cannot be confirmed whether it is caused by pathogens or autoimmune inflammation.It has been well known that the clinically frequently-used CRP is part of an intrinsically, non-specific acute phase reaction and is therefore not sensitive or specific to identify different causes of fever(Limper et al 2010).

The main limitation of our study is the fact that it was a single center retrospective study with relatively small number of patients.

Elevated Blood Eosinophil count patients showed independent parameter values of baseline pulmonary function and airway eosinophilic inflammation in contrast to low blood eosinophil count, which may correlate with the pathogenesis of asthma symptom in elevated blood eosinophil count.

CRP C-reactive protein

FEV1 Forced expiratory volume in the first second

FVC Forced vital capacity

Th2 T helper 2 cells

ILC2 Type 2 innate lymphoid cells

Sem Standard error of mean value

WBC White blood cell

Ethics approval and consent to participate

This study was reviewed and approved by the Institutional Review Board of the Second Affiliated Hospital of Air Force Medical University（No. TDLL—202309-03）. The written informed consent for this retrospective study was waived by the Institutional Review Board of the Second Affiliated Hospital of Air Force Medical University.

Consent for publication

The Author confirms:that the work described has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis);that it is not under consideration for publication elsewhere;that its publication has been approved by all co-authors, if any;that its publication has been approved (tacitly or explicitly) by the responsible authorities at the institution where the work is carried out.The Author agrees to publication in the Journal indicated below and also to publication of the article in English by Springer in Springer's corresponding English-language journal.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable reques

Competing interests

None of the funding agencies or industry partners had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding

This work was supported by the Natural Science Foundation of China (Grant Nos. NSFC82070061). Social Talent Fund Project of Tangdu Hospital and The Fourth Military Medical University (Grant Nos. 2021SHRC008);

Authors' contributions

YJL, YWC, QZ and JFG analysed the data. GL wrote the first draft of the manuscript.

FGJ supervised the study and contributed to the design of present data analyses. YJL, YWC contributed to drafting the manuscript and all co-authors revised it critically. All authors conceived and designed the study, acquired the data, and accessed, analyzed, and interpreted the data. All authors participated in the development and critical review of the manuscript. All authors provided final approval for publication submission and are accountable for the accuracy and integrity of the work.

Acknowledgements

We would like to thank all members of Department of Respiratory and Critical Care Medicine of Tangdu Hospital of Air Force military Medical University lab for helpful discussions.

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No competing interests reported.

The impact of inflammatory cells on lung function in asthmatics in a cross sectional retrospect study

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Journal Publication

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Abstract

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Status:

Journal Publication

Version 1