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Asthma is a common and burdensome chronic inflammatory airway disease that affects both children and adults. One of the main concerns with asthma is the manifestation of irreversible tissue remodelling of the airways due to the chronic inflammatory environment that eventually disrupts the whole structure of the airways. Most people with troublesome asthma are treated with inhaled corticosteroids. However, the development of steroid resistance is a commonly encountered issue, necessitating other treatment options for these patients. Biological therapies are a promising therapeutic approach for people with steroid‐resistant asthma. Interleukin 5 is recently gaining a lot of attention as a biological target relevant to the tissue remodelling process. Since IL‐5‐neutralizing monoclonal antibodies (mepolizumab, reslizumab and benralizumab) are currently available for clinical use, this review aims to revisit the role of IL‐5 in asthma pathogenesis at large and airway remodelling in particular, in addition to exploring its role as a target for biological treatments. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex‐related differences in the lungs. However, normal sex‐related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography‐derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never‐smokers. We analyzed full‐inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross‐sectional area >10, 5–10, and <5 mm2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p < 0.001). Females also had lower vessel volume >10 mm2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5–10 mm2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm2 (68 ± 18 vs. 82 ± 19 mL) (all p < 0.001). Normalized to total vessel volume, vessel volume >10 mm2 (11 ± 4 vs. 16 ± 4%, p < 0.001) and 5–10 mm2 (30 ± 6 vs. 34 ± 5%, p = 0.001) remained lower in females but vessel volume <5 mm2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males. [ABSTRACT FROM AUTHOR]

Airway fibroblasts, asthma, fibrosis, IL-5 receptor IL-5 receptor expression in lung fibroblasts: Potential role in airway remodeling in asthma Keywords: airway fibroblasts; asthma; fibrosis; IL-5 receptor EN airway fibroblasts asthma fibrosis IL-5 receptor 882 885 4 03/08/23 20230301 NES 230301 Tissue inflammation and airway structural changes, including sub-epithelial fibrosis are features of asthma pathogenesis. [Extracted from the article]

Sotrovimab, an anti‐severe acute respiratory syndrome‐coronavirus 2 monoclonal antibody is being utilized to prevent progression of coronavirus disease 2019 (COVID‐19). Therefore, to understand its benefits, we have conducted a retrospective analysis of all non‐hospitalized patients with symptomatic COVID‐19 who received a single infusion of sotrovimab and/or oral favipiravir at any Dubai COVID‐19 related healthcare center between July 1, 2021, and October 31, 2021. The main outcome was to evaluate the risk of hospitalization for patients with COVID‐19 or all‐cause death within 28 days of treatment initiation. In this analysis, which included 10,882 patients (1,135 in the sotrovimab group, 2,653 in the sotrovimab/favipiravir group, and 7,094 in the favipiravir group), sotrovimab or sotrovimab/favipiravir reduced the risk of hospitalization (13 patients (1.5%) in the sotrovimab group and 71 patients (2.9%) in the sotrovimab/favipiravir group vs. 251 patients (4%) in the favipiravir group; hazard ratio (HR) for sotrovimab: 0.16, 95% confidence interval (CI): 0.09–0.28, P < 0.001; and for sotrovimab/favipiravir, HR: 0.42, 95% CI: 0.32–0.56, P < 0.001), or death by day 28 from the start of treatment (no death in the sotrovimab group and 2 deaths in the the sotrovimab/favipiravir group vs. 10 deaths in the favipiravir group; odds ratio: 0.18, 95% CI: 0.04 to 0.81, P = 026). Safety was assessed in all the 3,788 patients in the sotrovimab and sotrovimab/favipiravir groups, and the reported adverse events were by 34 patients (<1%). In conclusion, sotrovimab was found to reduce the risk of progression of COVID‐19 when administrated early to non‐hospitalized patients with symptomatic COVID‐19. No safety concern was detected. [ABSTRACT FROM AUTHOR]

Background: Long‐term trajectories of asthma with fixed airflow obstruction (FAO) may reveal links to inflammatory endotypes. Objective: We investigated whether measures of asthma control and airway inflammation and remodelling differed by long‐term FAO status in moderate‐to‐severe asthma. Methods: Adults enrolled in the Difficult Asthma Study assessed initially using serial Asthma Control Questionnaire (ACQ), exacerbation history, spirometry and sputum cytology over 12 months, as well as endoscopic bronchial biopsy with airway smooth muscle (ASM) quantification, were revaluated three or more years later with questionnaires and spirometry. FAO was defined as a persistent post‐bronchodilator forced expired volume in one second (FEV1)‐to‐forced vital capacity ratio below 0.70. Results: Sixty‐two participants (mean ± SD age 48 ± 11 years; 50% female; 75% atopic; asthma duration 24 ± 14 years) returned for follow‐up assessment (median interval 7.9 years; IQR: 5.4‐8.8 years). Compared to participants without FAO (n = 28), those with FAO at baseline and long‐term follow‐up (n = 18) had higher baseline sputum neutrophil content and ASM, and a higher exacerbation frequency that persisted at long‐term follow‐up. Sputum eosinophils, ACQ and long‐term FEV1 decline did not differ. Participants with incident FAO at long‐term follow‐up (n = 16) had higher baseline exacerbation frequency, sputum eosinophil content, higher ACQ scores and greater decline in FEV1, whereas baseline ASM was similar to those without FAO. Conclusion: In moderate‐to‐severe asthma, long‐term FAO is characterized by neutrophilic sputum inflammation and airway remodelling, but FEV1 decline is similar to those without FAO. Long‐term incident FAO is preceded by higher exacerbation frequency, higher sputum eosinophil content and significant FEV1 decline. [ABSTRACT FROM AUTHOR]

Besides the respiratory system, severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS‐CoV‐2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS‐CoV‐2 receptor, angiotensin‐converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin‐angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS‐CoV‐2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2. [ABSTRACT FROM AUTHOR]

Increased airway smooth muscle (ASM) mass is a hallmark of airway remodeling in severe asthma. Th17-associated cytokines, particularly IL-17A, IL-17F, and IL-22, have been postulated to play a role in the pathogenesis of asthma. To investigate the in vitro effect of Th17 cytokines on the proliferation and survival of airway smooth muscle cells (ASMCs), human ASMCs from asthmatic and nonasthmatic subjects were incubated with IL-17A, IL-17F, or IL-22. The aforementioned cytokines demonstrated an ability to promote proliferation and survival of ASMCs from asthmatic and nonasthmatic subjects, which were mediated by selective activation of their corresponding receptors on ASMCs, including IL-17RA, IL-17RC, or IL-22R1, respectively. IL-17A and IL-17F-induced proliferation of ASMCs was dependent on ERK1/2 MAPK pathway, while IL-22-induced proliferation involved both ERK1/2 MAPK and NF-KB pathways. The involvement of signaling pathways was further confirmed by the inhibition of proliferation by knockdown of ERK1/2 MAPK or NF-KB p65 expression with pathway-specific siRNA. Together, our results show that Th17-associated cytokines promote proliferation and reduce the apoptotic rate of human ASMCs, raising the possibility that Th17 cytokines may contribute to increasing airway smooth muscle mass and airway remodeling in asthma. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease that is associated with airway remodeling, including hyperplasia of airway epithelial cells and airway smooth muscle cells, and goblet cell differentiation. We wished to address the potential role of histamine, a key biogenic amine involved in allergic reactions, in airway remodeling through the epidermal growth factor receptor (EGFR) pathway. Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF), from airway epithelial cells. Amphiregulin and HB-EGF were expressed in airway epithelium of patients with asthma. Histamine up-regulated their mRNA expression (amphiregulin 3.2-fold, P<0.001; HB-EGF 2.3-fold, P<0.05) and triggered their release (amphiregulin EC50 0.50 µM, 31.2±2.7 pg/ml with 10 µM histamine, P<0.01; HB-EGF EC50 0.54 µM, 78.5±1.8 pg/ml with 10 µM histamine, P<0.001) compared to vehicle control (amphiregulin 19.3±0.9 pg/ml; HB-EGF 60.2±1.0 pg/ml), in airway epithelial cells. Histamine increased EGFR phosphorylation (2.1-fold by Western blot analysis) and induced goblet cell differentiation (CLCA1 up-regulation by real-time qPCR) in normal human bronchial epithelial (NHBE) cells. Moreover, amphiregulin and HB-EGF caused proliferation and migration of both NHBE cells and human airway smooth muscle cells. These results suggest that histamine may induce airway remodeling via the epithelial-derived EGFR ligands amphiregulin and HB-EGF. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. [ABSTRACT FROM AUTHOR]

We have previously shown that CD8+γδ T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-γ (IFN-γ) expression. We hypothesized that the effects of CD8+γδ T cells were IFN-γ mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8+γδ T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 µmol/l) to inhibit IFN-γ synthesis or control oligodeoxynucleotide and 3·5 × 104 CD8+γδ T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated γδ T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered γδT cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8+γδ T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-γ. Defective or altered γδ T-cell function may account for some forms of allergic asthma. [ABSTRACT FROM AUTHOR]

To investigate the possible role of eosinophil peroxidase (EPO) in 3-nitrotyrosine (3NT) formation.Observational study employing immunocytochemistry to assess the presence of 3NT, inducible nitric oxide synthase (iNOS), eosinophils, mast cells, neutrophils, and lymphocytes in ethmoid sinus mucosal biopsies from normal controls and subjects with allergic and nonallergic chronic sinusitis and nasal polyposis.3NT was more evident in biopsies from sinusitis patients (2.67 ± 0.14, n = 21) than in healthy mucosa (0.43 ± 0.2, n = 7, P < 0.01), but scores in atopic and nonatopic subjects were similar. Colocalization studies confirmed that 3NT was largely confined to eosinophils. No relationship was found between 3NT and other immune cells. 3NT detection was not correlated with the amount of immunostaining for iNOS.Chronic sinusitis is accompanied by 3NT formation, which is largely restricted to the eosinophils, and likely driven by the action of eosinophil peroxidase, rather than by nitric oxide levels. EBM rating: B-2. [Copyright &y& Elsevier]

Objectives/hypothesis: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features.Study Design: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression.Methods: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means.Results: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance.Conclusion: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis The sinus mucosal inflammatory response in adult patients with chronic sinusitis is well documented in the literature. In contrast, little is known about the pathogenesis of this condition in children. The objective of the study was to compare the inflammatory cell profile and the extent of tissue remodeling in the sinus mucosa of children and adults with chronic sinusitis. Study Design Prospective design. Methods Children (n = 7) and adult patients (n = 7) with chronic sinusitis undergoing functional endoscopic sinus surgery were recruited for the study. Patients with no evidence of sinus disease (n = 6) were used as control subjects. Using immunohistochemical analysis, sinus mucosal specimens were assessed for the presence of T lymphocytes, eosinophils, basophils, mast cells, and neutrophils. The extent of submucosal collagen deposition was evaluated in histological sections using van Gieson stain. Results The number of T lymphocytes, eosinophils, and basophils and the amount of subepithelial collagen deposition are significantly higher in the mucosa of both adults and children with chronic sinusitis compared with normal control subjects ( P <.01). The number of mast cells is significantly higher in the mucosa of children with chronic sinusitis compared with normal control subjects ( P <.01). The number of eosinophils and neutrophils and the amount of subepithelial collagen deposition are significantly greater in adults compared with children with chronic sinusitis ( P <.01). Conclusions The sinus mucosal inflammatory profile is similar in adults and children with chronic sinusitis. However, the degree of tissue eosinophilia and remodeling is significantly greater in adult sinus specimens when compared with those of children with chronic sinusitis. [ABSTRACT FROM AUTHOR]

Objective Whether instillation into the maxillary sinus of topical budesonide affected the immune response and improved allergic patients with chronic rhinosinusitis that had persistence of symptoms despite appropriate surgical intervention was assessed. Study Design Double-blind placebo-controlled. Methods Twenty-six patients with allergy to house dust mites who had previously had surgery and who had persistent symptoms of disabling rhinorrhea or pressure-pain resistant to oral antibiotics and intranasal corticosteroids were recruited. During the double-blind study, patients instilled 256 μg budesonide daily or placebo through an intubation device (maxillary antrum sinusotomy tube) into one of the maxillary sinuses for 3 weeks before clinical assessment and a second biopsy. Results We found an improvement in the symptom scores in 11 of the 13 patients who received budesonide; we also found a decrease in CD-3 ( P = .02) and eosinophils ( P = .002), and a decrease in the density of cells expressing interleukin-4 ( P = .0001) and interleukin-5 messenger RNA ( P = .006) after treatment. Conclusion Topical budesonide delivered through a maxillary antrum sinusotomy tube can control chronic rhinosinusitis that persists after surgery. [ABSTRACT FROM AUTHOR]

Objectives: Th-2 type cytokine production (Interleukin-4 [IL-4] and interleukin-5 [IL-5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-γR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors. Study Design: Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment. Methods: Immunocytochemistry (alkaline phosphatase-antialkaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, major basic protein (MBP), IL-4R, IL-5R, and IFN-γR. Results: Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P < .05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-γR; P < .05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R ( P < .05) and IL-4R ( P < .05) and increased expression of IFN-γR ( P < .05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues. Conclusions: We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-γ follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile. [ABSTRACT FROM AUTHOR]

Objectives: To assess the cellular and humoral effects of unilateral topical steroid application on the nasal mucosa of chronic sinusitis patients. Study Design: Cohort study with randomized grouping. Methods: Chronic sinusitis patients awaiting endonasal sinus surgery were randomly divided into a study group and a control group. All patients underwent allergy studies and categorized as allergic or nonallergic. Patients in the study group were exposed unilaterally to fluticasone propionate nasal spray, 100 μg/day for 4 to 6 weeks before the planned surgery. The control group was not exposed to steroids. At the time of surgery, anterior ethmoid mucosa specimens were obtained. The samples were immunostained for CD3, MBP, CD68, elastase, and tryptase. In situ hybridization was used for the detection of interleukin (IL)-4, IL-5, and interferon gamma (IFN-γ) mRNA. The results were compared between the treated and untreated sides of exposed patients, as well as with non-treated controls. Results: Twenty-one patients consented to participate in the study. The number of CD3-, MBP-, and tryptase-positive cells was significantly less in the treated and untreated sides of exposed patients, compared with unexposed controls. IL-4 and IL-5 mRNA were significantly downregulated in the treated side of allergic patients, as compared with nontreated patients. This effect could not be shown for IL-4 in nonallergic patients. Conclusions: Topical steroid therapy had an anti-inflammatory effect on both allergic and nonallergic chronic sinusitis patients. The unilateral application of the steroid spray affected the contralateral side as well. [ABSTRACT FROM AUTHOR]

Objectives: Th-2 type cytokine production (inter-leukin-4 [IL-4] and interleukin-5 [IL-5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-γR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors. Study Design: Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment. Methods: Immunocytochemistry (alkaline phosphatase-antial-kaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, MBP, IL-4R, IL-5R, and IFN-γR. Results: Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P < .05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-γR; P < .05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R ( P < .05) and IL-5R ( P < .05) and increased expression of IFN-γR ( P < .05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues. Conclusions: We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-γ follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile. Laryngoscope, 108:1528-1533,1998 [ABSTRACT FROM AUTHOR]

Objective: Fatigue is associated with obstructive sleep apnea (OSA). Increased inflammation in the pharyngeal tissues of OSA patients may further exacerbate the disease. This study evaluates the effects of intranasal corticosteroid (INCS) treatment on sleep parameters and airway inflammation in AR vs non‐AR OSA patients. Method: Allergic rhinitis (34), non‐AR (21) received mometasone. Before and after treatment, patients underwent polysomnography, MWT, Epworth assessment, and tissue biopsies from the turbinate, nasopharynx, uvula. The biopsies were processed for EG2, CD4, CD8, macrophages and neutrophils. Results: There were no differences in age, sex, BMI, or apnea‐hypopnea index (mean AHI = 28.4 vs 27.7/h) at baseline. After treatment, AR group showed significant improvements in: 1) supine AHI (55.85 vs 39.7/h), 2) oxygen saturation nadir (86.42 vs 88.8%), and 3) Epworth scores. This improvement was associated with reduction of eosinophils (P <. 0001), and to lesser extend CD4 positive cells (P <. 05) in the tissue obtained from the 3 sites, CD68 decreased at the uvula. Allergic subjects had a higher nasal symptoms score before treatment, not statistically significant, nor was there evidence that change over time differed by allergy status. Conclusion: This study confirmed the implication of inflammation in sleep apnea and showed that controlling inflammation in the upper airways is very useful in improving clinical symptoms associated with this disease. [ABSTRACT FROM AUTHOR]

Objective: To study the role of superantigen (SAg) in inducing glucocorticoid (GC) receptor beta and steroid resistance in an explant model of nasal tissue., Methods: Nasal tissue was obtained from inferior turbinates of controls and ragweed (RW)-sensitive patients. Tissue samples were incubated with SAg of staphylococcal enterotoxin B. In addition, tissue samples from RW-sensitive patients were incubated with RW allergen in the presence and absence of both SAg and dexamethasone (DEX). The expression of GC receptor beta was assessed by immunocytochemistry. The expression of interleukin (IL)-2 and IL-4 mRNA was assessed by in situ hybridization., Results: SAg induced an increase in the expression of GC receptor beta in atopic tissue and to a lesser extent in nonatopic tissue. The most significant induction of GC receptor beta was observed in response to SAg and RW in atopic tissue. Stimulation of atopic tissue with RW alone and SAg alone induced IL-4 and IL-2 mRNA, respectively. Incubation of atopic tissue with both SAg and RW induced both IL-2 and IL-4 mRNA. The increase in IL-4 mRNA expression was blunted by the addition of DEX to atopic tissue stimulated with RW alone but not to tissue stimulated by both RW and SAg., Conclusion: Our results demonstrate that SAgs induce steroid resistance in atopic nasal explant tissue by up-regulating the expression of GC receptor beta. Furthermore, we have shown that the up-regulation of GC receptor beta is a local event that is associated with the coexpression of IL-2 and IL-4 mRNA.

Objectives/hypothesis: Mucus overproduction is commonly found in airway disease in patients with cystic fibrosis. Interleukin-9 (IL-9) has been shown to mediate airway hyper-responsiveness and mucus overproduction. Recently, the calcium-activated chloride channel hCLCA1 has been described to be upregulated by IL-9 and has been thought to regulate the expression of soluble gel-forming mucins. We sought to examine the expression of IL-9, interleukin-9 receptor (IL-9R), and hCLCA1 in the upper airway of patients with cystic fibrosis in comparison to healthy control subjects and to demonstrate the relationship of IL-9, IL-9R, and hCLCA1 expression with mucus production., Study Design: Prospective design., Methods: Biopsy samples from nasal polyps of four patients with cystic fibrosis, nasal mucosa of six patients with cystic fibrosis, sinus mucosa of eight patients with cystic fibrosis, and nasal mucosa of six healthy control subjects were stained with periodic acid-Schiff (PAS) to identify mucus glycoconjugates. IL-9, IL-9R, and hCLCA1 expression was determined by immunocytochemical study., Results: We demonstrated significant increases in IL-9, IL-9R, and hCLCA1 immunoreactivity in the mucosa of patients with cystic fibrosis compared with that found in control subjects (P <.05). There were no significant differences between the different locations (nasal polyps, nasal mucosa, and sinus mucosa) in the patient group (P >.05). We also observed a significant increase in the number of mucus-producing cells in biopsy specimens from patients with cystic fibrosis in comparison to control subjects. A positive correlation was found between hCLCA1-positive cells and IL-9-positive cells (correlation coefficient [r] = 0.79, P <.05) or IL-9R-positive cells (r = 0.92, P <.05). Moreover, a positive correlation was also present between PAS-positive (mucus-producing) cells and hCLCA1-positive cells (r = 0.64, P <.05) or IL-9R-positive cells (r = 0.64, P <.05)., Conclusions: Increased expression of IL-9 and IL-9R, as well as upregulation of hCLCA1, in mucus-overproducing epithelium of patients with cystic fibrosis supports the hypothesis that IL-9 contributes to mucus overproduction in cystic fibrosis. Expression of hCLCA1 may also be responsible, in part, for the overproduction of mucus. These preliminary findings suggest that hCLCA1 might be an interesting new therapeutic target to control mucus overproduction in airway disease in patients with cystic fibrosis.