Laura Pujols

A short course of oral prednisone followed by intranasal budesonide is an effective treatment of severe nasal polyps.

Background: Nasal polyposis is an inflammatory disease of unknown etiology. This study aimed to evaluate the effect of a short course of oral prednisone followed by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed tomography scan.

Glucocorticoid receptors in human airways

Inhaled and intranasal glucocorticoids are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma, allergic rhinitis, and nasal polyposis. The last few years have seen a growing understanding of the mechanisms of glucocorticoid action and, in particular, the receptor that mediates glucocorticoid actions, the glucocorticoid receptor (GR). In this revision we present an update on the GR gene, the expression and regulation of its gene products, namely GRα and GRβ, as well as their alterations in pathological states. GRα is responsible for the induction and repression of target genes, it is expressed in virtually all human cells and tissues, and its expression is known to be downregulated by glucocorticoids. GRβ has been found to act as a dominant negative inhibitor of GRα‐mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRα‐mediated transrepression. In addition, for most tissues the expression of GRβ, at least at the mRNA level, is extremely low compared with that of GRα. Some pro‐inflammatory cytokines appear to upregulate the expression of GRβ, and increased GRβ expression has been reported in diseases associated with glucocorticoid resistance or insensitivity, such as bronchial asthma, nasal polyposis, and ulcerative colitis. However, the possible role of GRβ in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.

Corticosteroid Treatment in Chronic Rhinosinusitis: The Possibilities and the Limits

Chronic rhinosinusitis, including nasal polyps, is an inflammatory disease of the nose and sinuses. The medical treatment, mainly topical intranasal and oral corticosteroids, constitutes its first line of therapy. Long-term treatment with corticosteroid nasal spray reduces inflammation and nasal polyp size, and improves nasal symptoms such as nasal blockage, rhinorrea, and the loss of smell. Corticosteroid intranasal drops may be used when intranasal spray fails to demonstrate efficacy. Short courses of oral steroids are recommended in severe chronic rhinosinusitis with nasal polyps or when a rapid symptomatic improvement is needed. Endoscopic sinus surgery is only recommended when the medical treatment fails. Intranasal corticosteroids should be continued postoperatively. When using intranasal corticosteroids, care should be taken in selected populations such as children, pregnant women, and elderly patients; especially in those patients with comorbid conditions such as asthma, in which the overall steroid intake can be high due to the administration of both intranasal and inhaled corticosteroids.

Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion

Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p<0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.

Nuclear factor‐κB activity is down‐regulated in nasal polyps from aspirin‐sensitive asthmatics

Background: We examined whether a decreased activity of nuclear factor(NF)‐κB), a transcriptional regulator of cyclooxygenase‐2 (COX‐2), could account for down‐regulation of COX‐2 in nasal polyps of aspirin‐sensitive asthmatics.

United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis

Background:  Although various relationships between the lower and upper airways have been found, the association of bronchiectasis with chronic rhinosinusitis and nasal polyps has not been thoroughly evaluated. This study was undertaken to examine the association of idiopathic and postinfective bronchiectasis with chronic rhinosinusitis and nasal polyposis.

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids

Background:  Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC‐treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels.

Effects of topical anti‐inflammatory drugs on eosinophil survival primed by epithelial cells. Additive effect of glucocorticoids and nedocromil sodium

Background Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polypcsis.

Upregulation of COX‐1 and COX‐2 in nasal polyps in cystic fibrosis

Background: Since abnormalities in prostanoid metabolism occur in the lower airway of patients with cystic fibrosis (CF), it is likely that they could also be detected in the nose. Methods: The degree of mRNA and protein expression of cyclo-oxygenase (COX) enzymes 1 (COX-1) and 2 (COX-2) was examined using quantitative reverse competitive polymerase chain reaction (RT-PCR) and Western blot analysis in the nasal polyps from 10 patients with CF, nasal polyps from 10 non-CF patients and 11 nasal mucosa specimens. The results are presented as 106 cDNA molecules/μg total RNA and the densitometric ratio between protein and β-actin. Results: COX-1 mRNA levels were significantly higher in CF nasal polyps (median 2.34, 25–75th percentiles 1.6–3.2) than in the nasal mucosa (0.78, 0.11–1.21), while there was no difference with non-CF nasal polyps (1.11, 0.80–3.15). COX-1 protein levels were significantly higher in CF nasal polyps (3.63, 2.71–4.27) than in nasal mucosa (1.55, 0.66–2.33) and non-CF nasal polyps (2.19, 1.72–3.68). COX-2 mRNA was significantly higher in CF nasal polyps (3.34, 2.42–7.05) than in nasal mucosa (1.69, 0.19–3.50). No differences were found in COX-2 mRNA expression between CF and non-CF polyps (1.38, 0.12–6.07). COX-2 protein levels were also significantly higher in CF nasal polyps (0.23, 0.04–0.34) than in non-CF nasal polyps (0.011, 0.009–0.016) or nasal mucosa (0.014, 0.014–0.016). Conclusions: Upregulation in the expression of COX-1 and COX-2 could explain the high production of prostanoids reported in CF. These findings raise questions regarding the potential use of selective or non-selective COX-2 non-steroidal anti-inflammatory treatment in CF.

Expression of glucocorticoid receptors α and β in steroid sensitive and steroid insensitive interstitial lung diseases

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors α (GRα) and β (GRβ). A study was undertaken to assess GRα and GRβ expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)). Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GRα and GRβ expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25–75th percentile. Results: GRα mRNA expression (105 cDNA copies/µg total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.8–14.9; n = 11) than in patients with IPF (4.4; 3.2–6.6; n = 19; p<0.001). GRβ expression was at least 1000 times lower than that of GRα and did not differ between the three groups. A negative correlation was found between GRα mRNA levels and the fibrotic pathology score of the tissue (r = −0.484, p<0.01) and a positive correlation was found between GRα mRNA levels and improvement in forced vital capacity (r = 0.633; p<0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF. Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GRα.