The Relation Between Peripheral Blood Leukocyte Counts and Respiratory Symptoms, Atopy, Lung Function, and Airway Responsiveness in Adults

doi:10.1378/chest.119.1.105

Chest

Volume 119, Issue 1, January 2001, Pages 105-114

https://doi.org/10.1378/chest.119.1.105 Get rights and content

Study objectives:

Eosinophils and neutrophils playmajor roles, respectively, in the pathogenesis of asthma and COPD, andit is well recognized that levels of these cells in peripheral bloodare increased in relation to their pulmonary involvement. However, therelation between peripheral blood cell counts of the other majorleukocyte groups and these lung diseases or markers of allergy orairflow obstruction is less clear. We have therefore investigated theassociation between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrenceof chronic respiratory symptoms, atopy, lung function, and bronchialhyperresponsiveness, and the modifying effect of age, in adults.

Design:

A cross-sectional general population study.

Setting:

Data on > 2,000 British adults, who originallyparticipated in a study of diet and lung health, were analyzed usingmultiple linear and logistic regression to adjust for potentialconfounders, including age, sex, and smoking history.

Results:

We found that, like eosinophils, the peripheralbasophil count was increased in relation to asthma and associatedsymptoms, and to airway hyperreactivity and increased total IgE, butdiffered from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative ofobstructive airway disease, in similar relation to neutrophils, butboth of these leukocyte counts were also increased in asthma patientsin older age groups. Lymphocyte counts were unrelated to any objectiveor subjective marker of disease.

Conclusions:

Ifperipheral blood cell counts reflect pulmonary involvement of theseleukocyte groups, basophils and monocytes may play a distinct role inthe pathogenesis of allergic and nonallergic respiratorydisease.

Section snippets

Materials and Methods

This study is based on data from adults aged 18 to 70 years froma Local Authority Area of Nottingham who participated in a survey ofdiet and lung disease in 1991, and have been described in detailelsewhere.¹⁵¹⁶ In summary, 7,016 adults > 18 years oldwere identified in a systematic sample from a random start point inlocal electoral registers and were invited to take part in the survey. Of these, 2,633 (representing between 48% and 59% of the initialsample subsequently ascertained to be alive and

Results

The age, sex, and smoking characteristics of the 2,369 subjectswho provided blood samples are shown in Table 1 and did not differ appreciably fromthose of the initial sample of 2,633 participants, describedelsewhere.¹⁶ All individual leukocyte counts wereapproximately log-normally distributed, with geometric means(interquartile ranges) for eosinophils of 151 cells/μL (range, 100 to230); neutrophils, 3,637 cells/μL (range 3,000 to 4,450);basophils, 64 cells/μL (range, 50 to 90); monocytes, 438

Discussion

In this analysis of peripheral blood leukocyte counts in a randomand representative adult population, we have observed the previouslywell-documented associations between asthma, IgE, and blood eosinophillevels, and have shown that peripheral blood eosinophil counts wereincreased in relation to symptoms of wheeze, cough, and dyspnea, and toobjective measures of allergen skin sensitization, reduced, FEV₁, airway hyperresponsiveness, and IgE levels. These findings reiterate the central role of

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Treadmill exercise ameliorates memory deficits and hippocampal inflammation in ovalbumin-sensitized juvenile rats
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Citation Excerpt :
Measurement of blood total and differential WBC counts are commonly used for the examination the systemic inflammation status in asthmatic animals (James et al., 1999) as WBC count is a marker of inflammation and an immune system indicator (Gillum et al., 1993). Several ongoing studies have demonstrated that WBC count strongly is associated with inflammation in asthma (Eftekhar et al., 2018a, 2018b; Lewis et al., 2001; Navratil et al., 2009). Furthermore, in asthmatic individuals, airway inflammation is linked to systemic inflammation, which was documented by enhanced circulating levels of IL-6 and C-reactive protein (CRP) (Fujita et al., 2007; Peters et al., 2016).
The behavioral changes, including spatial learning and memory impairment as well as depressive- and anxiety-like behaviors in an animal model of asthma were demonstrated previously. On the other hand, there is increasing evidence that the anti-inflammatory actions of exercise are related to their neuroprotective properties against different insults in the brain. This study was aimed to explore the effects of moderate treadmill exercise on cognitive deficits and possible anti-inflammatory mechanisms in ovalbumin (OVA)-sensitized rats. The exercise groups were trained to run on the treadmill 30 min/day with an intensity of 12 m/min, 5 days/week for 4 weeks. Animals in the OVA groups were sensitized by two intraperitoneal (i.p.) injections of OVA (10 μg/injection) and challenged with OVA by inhalation during the treadmill running exercise period. Passive avoidance (PA) memory, levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in the hippocampus, total and differential white blood cell (WBC) count in the blood as well as pathological changes of the lung were then evaluated. OVA-sensitization was resulted in cognitive deficits in the PA task, along with increased total and differential WBC in blood and TNF-α in the hippocampus. However, exercise ameliorated these changes and increased the IL-10 level in the hippocampus, suggesting that moderate treadmill exercise can improve memory impairment in OVA-sensitized rats due to its anti-inflammatory properties.
A profile of TNFR2<sup>+</sup> regulatory T cells and CD103<sup>+</sup> dendritic cells in the peripheral blood of patients with asthma
2020, Human Immunology
The interaction of tolerogenic CD103⁺ dendritic cells (DCs) with regulatory T (Tregs) cells modulates immune responses by inducing immune tolerance. Hence, we determined the proportion of these cells in the peripheral blood mononuclear cells (PBMC) of asthmatic patients. We observed lower trends of CD11b^-CD103⁺ DCs and CD86 within CD11b^-CD103⁺ DCs, while increased levels of Foxp3 expressing CD25^+/-TNFR2⁺ cells in asthmatics. There was a positive correlation in the expression of Foxp3 within CD3⁺CD4⁺CD25⁺TNFR2⁺ Tregs and CD11b^-CD103⁺ as well as the expression of CD86 within HLA-DR⁺CD11c⁺CD11b^-CD103⁺ DCs. In conclusion, we suggest that the increased levels of Tregs in blood could continuously suppress the T helper 2 (Th2) cells activation in the circulation which is also supported by the increase of anti-inflammatory cytokines IL-10 and TNF. Overall, functional immunoregulation of the regulatory cells, particularly Tregs, exhibit immune suppression and induce immune tolerance linked with the immune activation by the antigen presenting cells (APC).
Increase in blood eosinophils during follow-up is associated with lung function decline in adult asthma
2019, Respiratory Medicine
Citation Excerpt :
We found a linear relationship between blood eosinophilia increasing over time and FEV1 decline. Until now, several groups including ours have shown pretty consistently that high blood eosinophils are associated with low FEV1 [33–36]. However, confirming the results of most previous longitudinal studies, we show no association between blood eosinophils at baseline and FEV1 decline [15,35,37–39].
Asthma is associated with accelerated rate of lung function (FEV₁) decline.
To determine predictive factors associated with FEV₁ decline in adult asthma.
A retrospective study was conducted in 229 asthmatics recruited from the University Asthma Clinic of Liege. Subjects had at least two visits with post-bronchodilation (post-BD) FEV₁ and minimum one year between them. A multivariable linear regression analysis was conducted in order to come up with factors associated with lung function decline.
Post-BD FEV₁ decline in % predicted. y⁻¹ was 0.2 (95%CI -2.0 to 2.8) in the overall population. Our population was made up of mild to moderate asthmatics [1] for 58%, aged 50 (41–60) years old, 62% were female and 59% were atopic. Median ICS dose was 1000 μg beclomethasone equivalent (CFC)/day with 81% treated at baseline. Time between visits was 46.8 ± 32.1 months. The univariate linear regression analysis revealed a negative association between % predicted FEV₁ decline and baseline ACQ (p < 0.0001) and blood eosinophils (% and/mm³) (p < 0.0001 and p < 0.0001). A positive association was found between % predicted FEV₁ decline and baseline pre-BD FEV1 (mL) values (p = 0.001), blood neutrophils (%) (p = 0.02), change in blood eosinophils (%) (p < 0.0001), time between visits (months) (p < 0.0001). The predictive variables for accelerated decline highlighted by the multivariable analysis (r² = 0.39) were change in blood eosinophils (%) over time (p = 0.002) and time between visits (months) (p < 0.0001).
These findings highlight a new value for blood eosinophil counts as their increase over time predicts greater lung function decline in asthma.
Systemic inflammatory markers in relation to lung function in NHANES. 2007–2010
2018, Respiratory Medicine
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Previous studies have shown an association between CRP levels and reduced lung function and the levels probably reflect both the inflammatory activity in the lungs and an underlying low-grade systemic inflammation [8–11]. Blood eosinophil count (B-Eos) and blood neutrophil count (B-Neu) are both markers of local and systemic inflammation, and important in asthma [12–14] and COPD [15]. Eosinophils release proteins that are cytotoxic and can cause airflow obstruction and bronchial epithelial damage [12,16].
Low-grade systemic inflammation, mainly assessed by C-reactive protein (CRP), has been associated with impaired lung function. Few studies have studied if CRP, blood eosinophils, and blood neutrophils offer additive information in relation to lung function.
To analyse associations between lung function and CRP, blood eosinophils, and blood neutrophils, with special regard to additive information of combining the inflammatory markers.
Cross-sectional study on 7753 participants, 20–80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, blood eosinophils, and blood neutrophils were analysed in relation to the following lung function parameters: forced expiratory volume in 1 s (FEV₁% predicted), forced vital capacity (FVC % predicted), and FEV₁/FVC ratio.
CRP, blood eosinophils, and blood neutrophils levels were inversely related to FEV₁ and FVC. Only blood eosinophils and blood neutrophils were inversely related to FEV₁/FVC ratio. Further, lower lung function was found with increased number of elevated inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV₁ (β-coeff., −2.20, −4.43, and −6.43, p < 0.001) and FVC (β-coeff., −1.70, −3.15 and −5.33, p < 0.001), respectively.
CRP, blood eosinophils, and blood neutrophils offer independent and additive information in relation to lower FEV₁ and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually.
Long-Term Efficacy and Clinical Remission After Benralizumab Treatment in Patients with Severe Eosinophilic Asthma: A Retrospective Study
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View all citing articles on Scopus

: Dr. Lewis is funded by the Medical Research Council.

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Chest

Clinical InvestigationsASTHMAThe Relation Between Peripheral Blood Leukocyte Counts and Respiratory Symptoms, Atopy, Lung Function, and Airway Responsiveness in Adults

Study objectives:

Design:

Setting:

Results:

Conclusions:

Section snippets

Materials and Methods

Results

Discussion

Chest

Lancet

J Allergy Clin Immunol

Lancet

Ann Epidemiol

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

The effect of cigarette smoking on neutrophil kinetics in human lungs

N Engl J Med

Macrophages and polymorphonuclear neutrophils in lung defense and injury

Am Rev Respir Dis

Neutrophils and emphysema

N Engl J Med

Activated neutrophils secrete stored α1-antitrypsin

Am J Respir Crit Care Med

Airflow limitation in chronic bronchitis is associated with T-lymphocyte and macrophage infiltration of the bronchial mucosa

Am J Respir Crit Care Med

Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8(+) T lymphocytes with FEV 1

Am J Respir Crit Care Med

Inflammatory cells in the bronchial glands of smokers with chronic bronchitis

Am J Respir Crit Care Med

T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis

Am Rev Respir Dis

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma

Am Rev Respir Dis

Clinical Investigations
ASTHMA
The Relation Between Peripheral Blood Leukocyte Counts and Respiratory Symptoms, Atopy, Lung Function, and Airway Responsiveness in Adults

Activated neutrophils secrete stored α₁-antitrypsin