Marked Goblet Cell Hyperplasia with Mucus Accumulation in the Airways of Patients Who Died of Severe Acute Asthma Attack

Aikawa, Tadao; Shimura, Sanae; Sasaki, Hidetada; Ebina, Masahito; Takishima, Tainotsu

doi:10.1378/chest.101.4.916

Cited by 472 publications

(320 citation statements)

References 26 publications

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“…One of the consequences of chronic airway inflammation in asthma is remodelling of the airways, which consists of increases in airway smooth muscle (ASM) mass (Dunnill et al, 1969), goblet cell hyperplasia (Laitinen et al, 1985;Aikawa, 2001) and subepithelial fibrosis (Roche et al, 1989). ASM thickening in chronic asthma involves both hyperplasia and hypertrophy of ASM cells (Ebina et al, 1993) and compared with other structural abnormalities in the airways of asthmatics, increased ASM mass is a most important determinant of excessive airway lumen narrowing (James et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Eynott

Nath

Leung

et al. 2003

British J Pharmacology

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1 Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. 2 We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. 3 Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg À1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. 4 SP600125 significantly reduced the number of eosinophils (Po0.05) and lymphocytes (Po0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (Po0.05) and CD 2 þ T-cell (Po0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (Po0.05) and epithelial cell incorporation (Po0.05). 5 SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. 6 Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

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Section: Introductionmentioning

confidence: 99%

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Eynott

Nath

Leung

et al. 2003

British J Pharmacology

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“…Airways of severe acute asthmatics showed 30-fold increases in GC area in peripheral airways with marked accumulation of mucus in airway lumens. However, in nonacute asthmatics, the GC areas and amounts of mucus in the lumens was small and not different from one another [7]. Similarly, SAETTA et al [6] reported that asthmatics who died suddenly showed airway luminal occlusion with mucous plugs.…”

Section: Discussionmentioning

confidence: 95%

“…Thus, some patients may have massive overgrowth of peripheral airways by goblet cells, as seen in the airways of patients with mucous plugging who died of acute, severe asthma [7]. It is reasonable to assume that asthmatic individuals with marked goblet cell hyperplasia may be most at risk from stimuli (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Hypersecretion is a more neglected component of asthma, but airway hypersecretion also plays a significant role in its pathogenesis, especially in acute asthma. Post mortem studies reported mucous obstruction in small airways [5], and subsequent studies have reported that goblet cell (GC) hyperplasia and mucous plugging are important findings in patients who die of acute asthma [6,7].…”

mentioning

confidence: 99%

“…In healthy subjects [8] and in pathogen-free animals [9], airways generally contain few GCs, but airways of asthmatics and of individuals with other hypersecretory diseases airways show GC hyperplasia [1±4, 6,7]. Thus, GC hypersecretion is presumed to be an important factor in hypersecretory diseases, especially in peripheral airways where prolific GCs could easily cause plugging.…”

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confidence: 99%

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Role of neutrophil elastase in hypersecretion in asthma

Takamatsu

Agustı́

1999

Eur Respir J

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Goblet cell (GC) hyperplasia and mucous plugging are common in patients with acute asthma. These patients also show neutrophil recruitment into the airways. Neutrophils contain elastase, a potent secretagogue in airways. Therefore, it was reasoned that neutrophil recruitment, by releasing elastase, could result in GC hypersecretion. When neutrophil chemoattractants were instilled in the airways of guinea-pigs, time-dependent neutrophil recruitment and GC degranulation occurred. An inhibitor of leukocyte infiltration (NP15669) prevented both responses, implicating neutrophils. An inhibitor of neutrophil elastase (ICI 200,355) abolished GC degranulation, implicating elastase. Further studies implicate movement of elastase from cytoplasmic granules to the neutrophil surface, and they suggest a role for adhesion molecules on neutrophils and on GCs in neutrophil-dependent GC degranulation. Similarly, instillation of ovalbumin (OVA) into airways of OVA-sensitized guinea-pigs caused early recruitment of neutrophils and GC degranulation. GC degranulation was prevented by pretreatment with NP15669 or ICI 200,355. These results implicate neutrophil release of elastase in allergen-induced hypersecretion. The results suggest a mechanism for the mucous plugging that occurs in acute asthma; prevention of neutrophil recruitment, prevention of neutrophil-GC adhesion, or inhibition of elastase activity could provide effective therapy for this serious pathophysiological abnormality. Eur Respir J 1999; 13: 190±196.

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Up-regulation of the Mucosal Epidermal Growth Factor Receptor Gene in Chronic Rhinosinusitis and Nasal Polyposis

Ding

Zheng²,

Bagga³

2007

Arch Otolaryngol Head Neck Surg

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To investigate the expression of epidermal growth factor receptor (EGFR) messenger RNA (mRNA) in human sinus mucosa and to compare the expression of EGFR and EGF among patients with chronic rhinosinusitis (CRS), patients with CRS and nasal polyposis (CRS/NP), and a healthy control group.Design: Maxillary sinus ostia mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS or CRS/NP and from patients undergoing surgery for non-CRS pathologic conditions (control group). The samples were analyzed using semiquantitative reverse transcription-polymerase chain reaction to detect mRNA of EGFR. Hematoxylin-eosin staining and immunofluorescent staining were used to localize EGFR and EGF in the sinus mucosa.Setting: Academic research.Participants: Three groups (CRS, CRS/NP, and control), each with 10 subjects, were enrolled in the present study.Main Outcome Measures: Area ratios of positive cells in the epithelia were compared among the CRS, CRS/NP, and control groups. In addition, eosinophils were counted in the subepithelial connective tissue in the 3 groups.Results: The level of EGFR mRNAs in the sinus mucosa of the CRS and CRS/NP groups was statistically sig-

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Marked Goblet Cell Hyperplasia with Mucus Accumulation in the Airways of Patients Who Died of Severe Acute Asthma Attack

Cited by 472 publications

References 26 publications

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Role of neutrophil elastase in hypersecretion in asthma

Up-regulation of the Mucosal Epidermal Growth Factor Receptor Gene in Chronic Rhinosinusitis and Nasal Polyposis

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