Airway Mucosa Of Patients Research Articles

A Quantitative Method for Assessing Treatment-Related Changes within the Airway Mucosa in Patients with Chronic Bronchitis

No standardized method has yet been established for evaluating airway mucosal aberrancies associated with chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB). While goblet cell hyperplasia (GCH) is an established pathognomonic hallmark of the CB disease process, no standardized method exists for acquiring mucosal biopsies and assessing morphologic airway mucosa alterations. Additionally, the impacts from interventions targeting the airway mucosa are not well defined. In this context, a reliable and robust measure for assessing airway mucosa at baseline and subsequent to an intervention is critical for characterizing treatment-related changes. Can standardizing airway biopsy tissue collection and histopathological assessment methods generate a robust and repeatable measure to assess airway mucosa tissue characteristics in the setting of COPD/CB? Initial tissue collection and histological assessment methods were designed by integrating various aspects from previously published evaluations, applied to an initial tissue sample cohort, and then iteratively refined by independent pathologists. A standardized metric for histologic airway mucosa assessments was developed that specified tissue collection methods, including re-sampling airways at multiple time points to enable evaluation of treatment-related effects by incorporating scores for GCH, eosinophilia, and chronic inflammation, and the degree of GCH heterogeneity present within each sample. This multi-center study generated a robust, reproducible approach for assessing airway mucosa aberrancies in the setting of COPD/CB. The iterative approach established consistent tissue specimen recovery and a granular scoring matrix that enabled quantitative scoring of the various tissue findings with substantial histopathologic interrater reliability. ClinicalTrials.gov; NCT03107494, NCT04677465; URL: www. gov Australian New Zealand Clinical Trials Registry (ANZCTR); ACTRN12617000330347; URL: anzctr.org.au.

Single-cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.

To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms. Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID, which was defined as persons with new or worsening respiratory symptoms following ≥12 weeks from their initial acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute coronavirus disease 2019 (COVID-19) (n=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced. A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the pulmonary long COVID group, which strikingly showed a unique cluster of neutrophils in the pulmonary long COVID group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the pulmonary long COVID and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters. A single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID.

Hydrogen regulated pyroptosis through NLRP3-GSDMD pathway to improve airway mucosal oxidative stress injury induced by endotracheal tube cuff compression

The cuff of endotracheal tube (ETT) is an indispensable device for establishing an artificial airway, yet cuff-induced compression often causes damage to the airway mucosa. The mechanism of this damage involves mucosal compression ischemia and the oxidative stress injury following reperfusion. Currently, there is a lack of effective strategies to protect the mucosa. Hydrogen, as a natural antioxidant, has demonstrated significant potential in the prevention and treatment of oxidative stress injuries. This study aimed to determine the protective effects of hydrogen on compressed airway mucosa. We found that the damage to the airway mucosa caused by ETT cuff compression was associated with oxidative stress-induced pyroptosis of airway epithelial cells. Inhalation of hydrogen effectively reduced the levels of reactive oxygen species, significantly ameliorating changes in epithelial cell pyroptosis, and this protective effect is linked to the inhibition of the NLRP3-GSDMD pathway. Further cellular studies, involving knockdown and overexpression of NLRP3, clarified that hydrogen exerts its protective effects on the airway mucosa by inhibiting epithelial cell pyroptosis. Additionally, we observed that using hydrogen-rich saline to inflate the ETT cuff in patients under general anesthesia significantly reduced postoperative sore throat. This study confirms that hydrogen effectively enhances tolerance of airway mucosa to oxidative stress injuries, offering a potential preventive and therapeutic strategy for protecting the airway mucosa in patients undergoing endotracheal intubation.

A Clinical Study on Video Bronchoscopy-guided Coblation for Benign Central Airway Stenosis.

Background: Benign central airway stenosis poses a significant challenge to respiratory and thoracic surgeons due to the high recurrence rate associated with current treatment methods, causing severe breathing difficulties and potentially life-threatening complications. This article aims to investigate the therapeutic efficacy and prospects of using coblation in the management of benign central airway stenosis in adults. Moreover, the pathogenesis of benign central airway stenosis was deeply explored to provide better guidance for future clinical treatments. Materials and Methods: This retrospective study examined patients with benign central airway stenosis who were treated at The Second Hospital of Hebei Medical University from 2017 to 2020. In addition, a comparative analysis of whole-genome sequencing was conducted between the aforementioned patient group and healthy populations to investigate the underlying etiology of this stenotic condition. Results: The present study encompassed 32 patients who underwent 43 treatments in total between 2017 and 2020. All patients exhibited alleviation of airway stenosis and an improvement in clinical symptoms following surgery, without any significant surgical or postoperative complications. Whole-genome analysis revealed significant changes in gene expression in the airway mucosa of patients with benign airway stenosis in comparison to healthy populations. A total of 91 differentially expressed genes were identified, among which 44 upregulated genes displayed characteristics of promoting inflammatory responses. Conclusion: Coblation demonstrates promise as an efficacious treatment modality for adults suffering from benign central airway stenosis, and its widespread application in clinical settings is anticipated. The direct pathogenesis of benign central airway stenosis involves airway lumen narrowing and obstruction resulting from excessive inflammation and proliferative granulation.

Cysteinyl Leukotriene 1 Receptor Expression Associated With Bronchial Inflammation in Severe Exacerbations of COPD

Cysteinyl leukotriene 1 (CysLT1) receptor expression is known to be increased in the airway mucosa of patients with asthma, especially during exacerbations; however, nothing is known of its expression in COPD. We applied immunohistochemistry and in situ hybridization to endobronchial biopsies to determine inflammatory cell CysLT1 receptor protein and mRNA expression in the following: (1) 15 nonsmoker control subjects (NSC), (2) 16 smokers with moderate to severe COPD in its stable phase (S-COPD), and (3) 15 smokers with COPD hospitalized for a severe exacerbation (SE-COPD). The total number of bronchial mucosal inflammatory cells (CD45+) and those expressing CysLT1 receptor protein were significantly greater in SE-COPD (CysLT1 receptor protein: median [range] = 139 [31-634]) as compared with S-COPD (32 [6-114]) or NSC (16 [4-66]) (P < .001 for both). CysLT1 receptor gene expression showed similar differences. A greater proportion of CD451 cells expressed CysLT1 receptor protein in SE-COPD (median [range] = 22% [8-81]) compared with S-COPD (10% [4-32]) (P < .03) or NSC (7% [1-19]) (P < .002). In SE-COPD, the relative frequencies of CysLT1 receptor-expressing cells were as follows: tryptase1 mast cells > CD681 monocytes/macrophage > neutrophils > CD201 B lymphocytes = EG21 eosinophils. Moreover, there were positive correlations between the numbers of cells expressing CysLT1 receptor protein and the numbers of CD451 cells (r = 0.78; P < .003) and tryptase1 mast cells (r = 0.62; P < .02). Bronchial mucosal CysLT1 receptor-positive inflammatory cells are present in the bronchial mucosa in COPD in greatest number in those experiencing a severe exacerbation.

Leukotriene E 4–induced persistent eosinophilia and airway obstruction are reversed by zafirlukast in patients with asthma

We have shown that inhalation of leukotriene (LT) E 4 contributes to specific recruitment of eosinophils to the airway mucosa in patients with asthma at the time of maximal decrease in airway-specific conductance. We examined the ability of the cysteinyl LT 1 receptor antagonist, zafirlukast, to improve or prevent LT-mediated eosinophilia and airway obstruction in asthma. Bronchial biopsies were taken and pulmonary function was measured before and 4 to 6 hours after the dose of inhaled LTE 4 causing a > or =15% fall in FEV 1 at baseline both at week 0 and after 6-week randomly assigned treatment with a high dose of zafirlukast, 80 mg twice daily. Leukotriene E 4 inhalation at week 0 doubled the number of eosinophils in the airway mucosa in 21 of 25 patients with mild asthma, increased the numbers of neutrophils and lymphocytes, and decreased FEV 1 (-17%). Zafirlukast reduced both airway eosinophilia and obstruction in FEV 1 , whereas with a double-blind placebo treatment, the effect of LTE 4 on both parameters persisted for 6 weeks. On repeat LTE 4 inhalation challenge after 6 weeks, zafirlukast treatment prevented further airway eosinophilia and decrease in FEV 1 seen in the placebo group. Persistent LTE 4 -induced airway eosinophilia may form the basis of an amplification mechanism for further eosinophil recruitment. Zafirlukast prevents LTE 4 -induced eosinophilic airway inflammation in mild asthma.

Early interventions in asthma with inhaled corticosteroids

We have earlier shown epithelial damage in the airway mucosa in patients with asthma. Later other structural changes have been recognized in asthma, such as deposition of collagen and tenascin in the subepithelial basement membrane and changes in the laminin subchain composition. These processes are modified by an inflammatory process in the airways. Both the United States National Institutes of Health and the British Thoracic Society guidelines on the management of asthma emphasize the need for early use of anti-inflammatory drugs. Many clinical studies that used airway biopsy specimens have shown a decrease in airway inflammatory cell numbers after inhaled corticosteroid therapy. However, there is very little information on the effects of asthma medication on the structural components of the airways. Both the synthesis and degradation of many extracellular matrix components may be affected by the disease process and the drugs resulting in altered remodeling and gene expression in the airways. Because there are only a few studies that try to identify early changes in asthma, it is not known whether the anti-inflammatory treatment of asthma proposed by the guidelines is started early enough. (J Allergy Clin Immunol 2000;105:S582-5.)

Reduced airway absorption in seasonal allergic rhinitis.

The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.

Permeability of the respiratory membrane in healthy, non-smoking controls and patients with sarcoidosis and chronic obstructive lung disease

I n pulmonary and/or bronchial circulatory systems the exudation of plasma proteins to lung compartments may be due to increased pcrnieatiility of the respiratory membrane[ 1,2]. Epithelial and endothelial cells DI !lie alveolar lcvcl arc joined by tight junctions in the lungs of normal healthy people. These tight junctions form a barrier to prevent protein cxudation[3]. The permeability of the epithelial layer to proteins is less than that of the endothel layer]3]. In pathologic cases, high nioleculer weight proteins can pass the endothelial barrier easily through the intcrcndothelial gaps[3,4\. Biopsy material taken from the airway mucosa of patients with asthma showed increased epithel obstruction, enlargement of the basal nienibranc, protein exudation and increased permeability of respiratory membrane[S]. There is a strong correlation between respiratory membranc permeability and airway hypcrresponsiveness and airway inflammation[5-7]. Airway hyperresponsiveness is the obstructive reaction of the bronchioles to cold, allergens. dangerous respiratory irritants, fog, dust and occupational exposures[X]. On the other hand the unbalance between the contracting and relaxing effects of adrenergic and cholinergic systems on muscle tonus constitutes another factor[6,9]. The activation of parasympathetic nervous system leads to a release of mediators from mast cells and leukocytes[7-9]. Hypercholinergic response plays an important role in the local bronchial inflammatory reaction. Increased airway epithelial destruction and increased permeability of respiratory membrane occur as a result of neurogenic inflammation[9, lo]. In the recent years the permeability of the respiratory membrane is determined by the concentration gradient of proteins between the serum and the bronchoalveolar lavage fluid (BALF) to understand the pathogenesis of various pulmonary diseases[l1-13]. High molecular weight proteins not formed in the lungs are specially chosen for determination1 11-13]. We examined in this study the permeability of the respiratory membrane in healthy, non-smoking controls (n= l l ) , patients with sarcoidosis (n = 19), and patients with chronic obstructive pulmonary disease (COPD) (n= 12). Venous blood was obtained from each individual and BALF was taken from the right nicdiuni lobe by means of a fiber optic broncoscope. Serum and BALF saniplcs were analyzed for albumin (alb), total protein (Tpr) and urea. Albumin and lotal protein analyses were done by the Fulin-Lowry methodl 141 and urea by the enzymatic methodllS]. From the biochemical data: The concentration gradient across the respiratory membrane (protcinl in BALF [protcinl in serum 0 protein = IlHNl x and

Allergen exposure induces the activation of allergen-specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders.

Biopsy specimens were obtained from the bronchial or the nasal mucosa of three patients with grass pollen-induced bronchial asthma or rhinitis 48 h after positive bronchial or nasal provocation test with grass pollen extract. T cell clones (TCC), derived from these and control specimens, were then assessed for their phenotype, allergen-specificity, profile of cytokine secretion and ability to provide B cell help for IgE synthesis. Out of 50 and 61 CD4+ TCC derived from the bronchial mucosa of the two patient with atopic asthma 11 (22%) and 19 (31%), respectively, showed both proliferation and cytokine production in response to grass pollen allergens under major histocompatibility complex-restricted conditions. Of these 21 (70%) exhibited a clear-cut type 2 T helper (Th2) profile and induced IgE synthesis in autologous peripheral blood B cells in the presence of grass allergens. All the other 9 grass-specific clones showed a Th0 pattern of cytokine secretion, but only 1 provided moderate help for IgE synthesis. In contrast, the majority of TCC, derived under the same experimental conditions from the bronchial mucosa of two nonatopic patients with toluene diisocyanate-induced asthma, were CD8+ and most of them produced interferon-gamma or interferon-gamma and interleukin-5, but not interleukin-4, in response to nonspecific stimulation. Of 22 CD4+ TCC3 (14%) derived from the grass-stimulated mucosa of the patient with allergic rhinitis, but none of those derived from the unstimulated nostril of the same patient, exhibited proliferation and cytokine production in response to grass allergens. All had a clear-cut Th2 profile and provided help for IgE synthesis by autologous B cells. These data indicate that inhalation of the relevant allergen results in the activation of allergen-specific Th2 lymphocytes in the airway mucosa of patients with allergic respiratory disorders. These cells may play a central role in determining the nature of the inflammatory response in the airways of atopic patients.