Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma

2022 ◽  
pp. 2101865
Author(s):  
Taha Al-Shaikhly ◽  
Ryan C. Murphy ◽  
Andrew Parker ◽  
Ying Lai ◽  
Matthew C. Altman ◽  
...  

Eosinophils are implicated as effector cells in asthma but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation.In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation.Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type of AHR that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type-2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that IL-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile.We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018010 ◽  
Author(s):  
Ji Eun Soh ◽  
Kyung-Moon Kim ◽  
Ji-Won Kwon ◽  
Hyung Young Kim ◽  
Ju-Hee Seo ◽  
...  

BackgroundRelationship between recurrent wheeze and airway function and inflammation in preschool children is not fully known.ObjectiveTo investigate the relationship between recurrent wheeze and airway inflammation, lung function, airway hyper-reactivity (AHR) and atopy in preschool children.DesignObservational study, comparing forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid-forced expiratory flow (FEF25%–75%), dose–response slope (DRS), exhaled nitric oxide (eNO) and atopic sensitisation between children with recurrent wheeze and those without.SettingPopulation-based, cross-sectional study in Seoul and the Gyeonggi province of Korea conducted as a government-funded programme to perform standardised measurement of the prevalence of allergic diseases, and related factors, in preschool children.Participants900 children aged 4–6 years.Primary and secondary outcome measureseNO, FEV1/FVC, FEF25%–75%, DRS, atopic sensitisation and allergic diseases.MethodsChildren completed the modified International Study of Asthma and Allergies in Childhood questionnaire and underwent eNO assessments, spirometry, methacholine bronchial provocation tests and skin prick tests. Recurrent wheeze was defined as having a lifetime wheeze of more than three episodes, based on the questionnaire. The frequency of hospitalisation and emergency room visits was also obtained by means of the questionnaire. ‘Current’ wheeze was defined as having symptoms or treatments within the past 12 months.ResultsThe prevalence of recurrent wheeze was 13.4%. Children with recurrent wheeze showed a higher prevalence of lifetime or current allergic rhinitis (p=0.01 and p=0.002, respectively) and lifetime atopic dermatitis (p=0.007). Children with recurrent wheeze showed lower FEV1/FVC (p=0.033) and FEF25%–75%(p=0.004), and higher eNO levels (p=0.013) than those without recurrent wheeze. However, the DRS, prevalence of atopic sensitisation and serum IgE levels were not significantly different between the two groups.ConclusionsRecurrent wheeze in preschool children may be associated with airway inflammation and diminished airway function, but not with AHR or atopy.


2005 ◽  
Vol 98 (3) ◽  
pp. 850-855 ◽  
Author(s):  
Joseph C. Anderson ◽  
Albert L. Babb ◽  
Michael P. Hlastala

We analyzed published measurements of the bronchial circulation and airway wall (Anderson JC, Bernard SL, Luchtel DL, Babb AL, and Hlastala MP. Respir Physiol Neurobiol 132: 329–339, 2002) and determined that the radial distribution of bronchial capillary cross-sectional area was fractal. We limited our analysis to bronchial capillaries, diameter ≤10 μm, that resided between the epithelial basement membrane and adventitia-alveolar boundary, the airway wall tissue. Thirteen different radial distributions of capillary-to-tissue area were constructed simply by changing the number of annuli (i.e., the annular size) used to form each distribution. For the 13 distributions created, these annuli ranged in size from to of the size of the airway wall area. Radial distributions were excluded from the fractal analysis if the sectioning procedure resulted in an annulus with a radial thickness less than the diameter of a capillary. To determine the fractal dimension for a given airway, the coefficient of variation (CV) for each distribution was calculated, and ln(CV) was plotted against the logarithm of the relative piece area. For airways with diameter >2.4 mm, this relationship was linear, which indicated the radial distribution of bronchial capillary cross-sectional area was fractal with an average fractal dimension of 1.27. The radial distribution of bronchial capillary cross-sectional area was not fractal around airways with diameter <1.5 mm. We speculated on how the fractal nature of this circulation impacts the distribution of bronchial blood flow and the efficiency of mass transport during health and disease. A fractal analysis can be used as a tool to quantify and summarize investigations of the bronchial circulation.


2014 ◽  
Vol 116 (6) ◽  
pp. 668-673 ◽  
Author(s):  
G. R. Washko ◽  
A. A. Diaz ◽  
V. Kim ◽  
R. G. Barr ◽  
M. T. Dransfield ◽  
...  

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% ( P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.


2015 ◽  
Vol 72 (6) ◽  
pp. 428-434 ◽  
Author(s):  
Maysaa Nemer ◽  
Liv I B Sikkeland ◽  
Mayes Kasem ◽  
Petter Kristensen ◽  
Khaldoun Nijem ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 295 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ya-Ling Chen ◽  
Ming-Chin Yu ◽  
Kuo-Wei Yeh ◽  
Szu-Chuan Shen ◽  
...  

Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.


2006 ◽  
Vol 7 (1) ◽  
Author(s):  
Jiska B Snoeck-Stroband ◽  
Dirkje S Postma ◽  
Thérèse S Lapperre ◽  
Margot ME Gosman ◽  
Henk A Thiadens ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eline Lauwers ◽  
Annemiek Snoeckx ◽  
Kris Ides ◽  
Kim Van Hoorenbeeck ◽  
Maarten Lanclus ◽  
...  

Abstract Background Functional Respiratory Imaging (FRI) combines HRCT scans with computational fluid dynamics to provide objective and quantitative information about lung structure and function. FRI has proven its value in pulmonary diseases such as COPD and asthma, but limited studies have focused on cystic fibrosis (CF). This study aims to investigate the relation of multiple FRI parameters to validated imaging parameters and classical respiratory outcomes in a CF population. Methods CF patients aged > 5 years scheduled for a chest CT were recruited in a cross-sectional study. FRI outcomes included regional airway volume, airway wall volume, airway resistance, lobar volume, air trapping and pulmonary blood distribution. Besides FRI, CT scans were independently evaluated by 2 readers using the CF-CT score. Spirometry and the 6-Minute Walk Test (6MWT) were also performed. Statistical tests included linear mixed-effects models, repeated measures correlations, Pearson and Spearman correlations. Results 39 CT scans of 24 (17M/7F) subjects were analyzed. Patients were 24 ± 9 years old and had a ppFEV1 of 71 ± 25% at the time of the first CT. All FRI parameters showed significant low-to-moderate correlations with the total CF-CT score, except for lobar volume. When considering the relation between FRI parameters and similar CF-CT subscores, significant correlations were found between parameters related to airway volume, air trapping and airway wall thickening. Air trapping, lobar volume after normal expiration and pulmonary blood distribution showed significant associations with all spirometric parameters and oxygen saturation at the end of 6MWT. In addition, air trapping was the only parameter related to the distance covered during 6MWT. A subgroup analysis showed considerably higher correlations in patients with mild lung disease (ppFEV1 ≥ 70%) compared to patients with moderate to severe lung disease (ppFEV1 < 70%) when comparing FRI to CF-CT scores. Conclusions Multiple structural characteristics determined by FRI were associated with abnormalities determined by CF-CT score. Air trapping and pulmonary blood distribution appeared to be the most clinically relevant FRI parameters for CF patients due to their associations with classical outcome measures. The FRI methodology could particularly be of interest for patients with mild lung disease, although this should be confirmed in future research.


2021 ◽  
Author(s):  
Edineia Rosa da Paz ◽  
Cynthia Mafra Fonseca de Lima ◽  
Soraia Nogueira Felix ◽  
Bruna Schaeffer ◽  
Clóvis Eduardo Santos Galvão ◽  
...  

Abstract Background: Cleaning workers represent a significant proportion of the active population worldwide, with poor remuneration, particularly in developing countries. Despite this, they remain a relatively poorly studied occupational group. They are constantly exposed to agents that can cause symptoms and respiratory problems.Objective: To investigate the airway inflammation and respiratory symptoms of cleaning workers from different workplaces. Methods We performed a cross-sectional study on the prevalence of upper airway inflammation and symptoms of asthma/rhinitis related to cleaning work, according to workplace.167 participants were divided into four groups: Hospital (H), University (U), Housekeeper (Ho) and Control (C). A nasal swab was collected for upper airway inflammation evaluation. Clinical profiles and respiratory symptom employee evaluations were performed using specific questionnaires (ECRHS and ISAAC).Results: Cleaning workers showed increased neutrophils and lymphocytes; Hospital and University showed increased macrophages compared to the Housekeeper and Control. Hospital and Housekeeper showed increased eosinophils when they performed cleaning services for up to one year and also reported having more asthma symptoms than the Control. Cleaning workers showed increased rhinitis symptoms. The University group showed increased rhinitis symptoms aggravated by the workplace compared with the Hospital and Housekeeper. Cleaning workers showed an increased affirmative response when direct asked about rhinitis symptoms compared to Control.Conclusions: Cleaning workers showed airway inflammation, asthma symptoms and rhinitis, regardless of the occupational environment to which they were exposed and also showed increased rhinitis and asthma symptoms. Hospital cleaning workers showed increased macrophages, lymphocytes and eosinophils compared to the others. The length of time spent performing cleaning work was not related to nasal inflammation or respiratory symptoms in this population. However, there are differences in workplaces. Clinical Trial registration number NCT03311048, October 16, 2017. Availble at: https://clinicaltrials.gov/ct2/show/NCT03311048 (retrospectively registered).


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