scholarly journals Current Smoking With or Without Chronic Bronchitis is Independently Associated With Goblet Cell Hyperplasia in Healthy Smokers and COPD Subjects: an Analysis of the SPIROMICS Cohort

2020 ◽  
Author(s):  
Victor Kim ◽  
Stephanie Jeong ◽  
Huaqing Zhao ◽  
Jennifer Kraft ◽  
Mehmet Kesimer ◽  
...  
Keyword(s):  
Chronic Bronchitis ◽  
Goblet Cell ◽  
Clinical Symptoms ◽  
Periodic Acid ◽  
Airflow Obstruction ◽  
Active Smoking ◽  
Cell Hyperplasia ◽  
Current Smoking ◽  
Goblet Cell Hyperplasia ◽  
Former Smokers

Abstract Background: COPD, chronic bronchitis (CB) and active smoking have all been associated with large airway goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Methods: Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects] in which endobronchial mucosal biopsies were obtained during the SPIROMICS bronchoscopy substudy. Biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane by two independent observers in a blinded fashion. GCD was divided into tertiles (1=low, 2=medium, 3=high) based on log10 transformed values. Multivariable logistic and linear regressions were performed with CB and current smoking as the independent variables of interest and demographics and FEV1% predicted smoking as covariates.Results: Log10 GCD was greater in current smokers compared to former smokers (1.16±0.28 [n=31] vs. 0.85±0.42 [n=40], p=0.001). Those with classically defined CB had a greater log10 GCD compared to those without CB (1.21±0.31 [n=13] vs. 0.94±0.39 [n=58], p=0.024). Similarly, those with CB by the SGRQ definition had a greater log10 GCD compared to those without CB (1.13±0.39 [n=25] vs. 0.91±0.39 [n=43], p=0.028). Tertiles 2 and 3 had a greater percent of current smokers compared to tertile 1 (16.7, 50.0 and 63.6% in tertiles 1, 2 and 3, respectively, p=0.004). Current smoking was independently associated with tertile 3 (high GCD) (OR 4.15, 95% CI 1.17, 14.71) whereas CB was not in multivariable logistic regression. Similar results were found with multivariable linear regression for log10 GCD.Conclusions: GCD is higher in current smokers with and without airflow obstruction and in CB. However, current smoking, but not CB, is independently associated with GCD. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

scholarly journals Current smoking with or without chronic bronchitis is independently associated with goblet cell hyperplasia in healthy smokers and COPD subjects

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Victor Kim ◽  
Stephanie Jeong ◽  
Huaqing Zhao ◽  
Mehmet Kesimer ◽  
Richard C. Boucher ◽  
...  
Keyword(s):  
Chronic Bronchitis ◽  
Goblet Cell ◽  
Clinical Symptoms ◽  
Periodic Acid ◽  
Airflow Obstruction ◽  
Active Smoking ◽  
Cell Hyperplasia ◽  
Current Smoking ◽  
Goblet Cell Hyperplasia ◽  
Former Smokers

AbstractCOPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log10 transformed values. Log10GCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log10 GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high log10GCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

scholarly journals Guifu Dihuang Pills Ameliorated Mucus Hypersecretion by Suppressing Muc5ac Expression and Inactivating the ERK-SP1 Pathway in Lipopolysaccharide/Cigarette Smoke-Induced Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Huanhuan Zhang ◽  
Wenying Yu ◽  
Liting Ji ◽  
Yusen Zhong ◽  
Yiyou Lin ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Cigarette Smoke ◽  
Goblet Cell ◽  
Periodic Acid ◽  
Lung Damage ◽  
Pathological Changes ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Goblet Cell Hyperplasia ◽  
Expression Levels

Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease (COPD) and is associated with increasing sputum production and declining pulmonary function. Therefore, reducing mucus secretion can be a new therapeutic opportunity for preventing COPD. The Guifu Dihuang pill (GFDHP) is a classical Chinese medicine and has been used as an immunoregulator for treatment of kidney yang deficiency syndrome, including hypothyroidism, adrenocortical hypofunction, chronic bronchitis, and COPD, for more than 2000 years. However, the protective effects and mechanisms of GFDHP against mucus hypersecretion in COPD remain obscure. The aim of the present study was to explore the inhibitory effects of GFDHP on lipopolysaccharide/cigarette smoke- (LPS/CS-) induced Mucin5ac (Muc5ac) overproduction and airway goblet cell hyperplasia in mice. The mice were randomly assigned into 6 groups: control, model, GFDHP-L, GFDHP-M, GFDHP-H, and dexamethasone. The mice were given LPS twice through intranasal inhalation and then exposed to CS daily for 6 weeks. Three doses of GFDHP were orally administered daily during the last 3 weeks of the experiment. Pulmonary function was examined with an EMKA pulmonary system, and pulmonary hyperpermeability and lung damage were evaluated with an in vivo imaging system. Inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were detected with a cell count analyzer and though ELISA analysis, respectively. Lung pathological changes and airway goblet cell hyperplasia were analyzed with hematoxylin and eosin and Alcian blue periodic acid Schiff staining. The protein expression levels of Muc5ac and extracellular signal-regulated kinase (ERK)-specificity protein1 (SP1) signaling pathway were measured with Western blot and immunohistochemistry. The results demonstrated that GFDHP improved pulmonary function and suppressed mouse pulmonary hyperpermeability and edema. GFDHP suppressed inflammatory cell infiltration and cytokine release in BALF, thereby elevating pulmonary function. It ameliorated lung pathological changes and airway goblet cell hyperplasia, and suppressed expression levels of Muc5ac mRNA and protein and phospho-ERK and SP1 levels in the lung tissues of the COPD mice. In conclusion, GFDHP inhibited mucus hypersecretion induced by LPS/CS by suppressing the activation of the ERK-SP1 pathway.

scholarly journals The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures

2021 ◽  
Author(s):  
Linsey E. Haswell ◽  
David Smart ◽  
Tomasz Jaunky ◽  
Andrew Baxter ◽  
Simone Santopietro ◽  
...  
Keyword(s):  
Goblet Cell ◽  
3D Model ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia

scholarly journals Intermittent Oral Coadministration of a Gamma Secretase Inhibitor with Dexamethasone Mitigates Intestinal Goblet Cell Hyperplasia in Rats

2013 ◽  
Vol 42 (2) ◽  
pp. 422-434 ◽  
Author(s):  
Shirley A. Aguirre ◽  
Ling Liu ◽  
Natilie A. Hosea ◽  
Wesley Scott ◽  
Jeffrey R. May ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Gamma Secretase ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Secretase Inhibitor ◽  
Gamma Secretase Inhibitor

scholarly journals Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium

2011 ◽  
Vol 224 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Vasiliy V Polosukhin ◽  
Justin M Cates ◽  
William E Lawson ◽  
Aaron P Milstone ◽  
Anton G Matafonov ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Airway Epithelium ◽  
Hypoxia Inducible Factor ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Hypoxia Inducible Factor 1

Goblet Cell Hyperplasia is not Epithelial-Autonomous in the Cftr Knockout Intestine

2021 ◽  
Author(s):  
Nancy M Walker ◽  
Jinghua Liu ◽  
Sarah M Young ◽  
Rowena A Woode ◽  
Lane L. Clarke
Keyword(s):  
Cell Differentiation ◽  
Goblet Cell ◽  
Ex Vivo ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Cell Numbers ◽  
Markers Of Inflammation ◽  
Tlr4 Agonist ◽  
Goblet Cell Differentiation ◽  
Mucosal Morphology

Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2, Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum as compared to wild-type (WT). IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2 and Tlr4 protein expression was increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4 and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment.

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