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Biomedical subjects

R Polosa

Publications and source records attributed to R Polosa.

At least 19 recordsLinked to original sources
PubMed2005

Effect of salbutamol on nasal symptoms and mast cell degranulation induced by adenosine 5' monophosphate nasal challenge.

BACKGROUND: In addition to its well-known functional agonism at the level of beta(2) adrenergic receptors on airways smooth muscle cells, salbutamol appears to have additional protective effects, possibly through an inhibition of mast cell activation. OBJECTIVE: The aim of this study is to provide the first evidence in vivo of inhibition of human mast cell activation by salbutamol. METHODS: Nine atopic subjects received placebo and salbutamol (5 mg/mL) 15 min before an adenosine 5' monophosphate (AMP) nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects prior to or 3, 5, 15 or 30 min after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. RESULTS: AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release with peak values achieved at 3 min after the challenge in all the subjects studied. Compared with placebo, salbutamol significantly attenuated the release of histamine and tryptase induced by AMP challenge (P=0.048 and 0.020, respectively). Moreover, the AMP-induced sneezing was also inhibited by pre-treatment with salbutamol (P=0.004). CONCLUSIONS: Intranasal salbutamol attenuates nasal symptoms and inhibits histamine and tryptase release caused by AMP nasal provocation thus supporting the hypothesis that salbutamol may play an additional protective role in the airways by inhibiting mast cell activation.

Adenosine Monophosphate↗
PubMed2004

Monitoring response to treatment in asthma management: food for thought.

Asthma is a chronic inflammatory disorder of the airways that is characterized by episodic symptoms. In this regard, asthma management has classically involved periodic re-assessment by the health-care provider, during which therapy is altered mainly based on clinical and physiological parameters, such as assessment of symptoms, spirometry and peak expiratory flow monitoring. In this context, various markers of airway inflammation (e.g. eosinophils in the induced sputum, nitric oxide in the exhaled air) have been proposed to assess the severity of asthma and to adjust the therapy accordingly. The evaluation of airway hyper-responsiveness with different stimuli has also been suggested as a new tool to monitor asthma. However, the lack of definite relationships between airway inflammation and asthmatic symptoms strongly limit the use of markers of asthma severity in the clinical setting. Therefore, the need of new tools to assess the severity of asthma is raised. The ideal measurement employed to establish the proper asthmatic therapy should be safe, non-invasive, easy to perform, reproducible and accurate, and have the capability to monitor the changes induced by the therapeutic interventions. A careful review of the available techniques, and the evaluation of their sensitivity and specificity in the clinical setting is warranted.

Asthma↗
PubMed2004

Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis.

BACKGROUND: Bronchial hyperresponsiveness (BHR) and airway inflammation are frequently associated with allergic rhinitis, and may be important risk factors for the development of asthma. Specific immunotherapy (SIT) reduces symptom in subjects with allergic rhinitis, but the mechanisms are not clear. AIMS OF THE STUDY: To assess the effect of Parietaria-SIT on asthma progression, rhinitic symptoms, BHR, and eosinophilic inflammation. METHODS: Nonasthmatic subjects with seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n = 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to methacholine, eosinophilia in sputum were collected throughout the 3-year study. RESULTS: By the end of the study, in the placebo group, symptoms and medication scores significantly increased by a median (interquartile range) of 121% (15-280) and 263% (0-4400) respectively (P < 0.01), whereas no significant difference was observed in the SIT group. We found no significant changes in sputum eosinophils and BHR to methacholine in both groups throughout the study. Nine of 29 participants developed asthma symptoms during the study; of these, only two subjects (14%) in the SIT-treated group (P = 0.056). CONCLUSIONS: Parietaria-SIT reduces symptom and rescue medication scores, but no changes in BHR to methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma, suggesting that SIT should be considered earlier in the management of subjects with allergic rhinitis.

Adult↗
PubMed2003

Monitoring of seasonal variability in bronchial hyper-responsiveness and sputum cell counts in non-asthmatic subjects with rhinitis and effect of specific immunotherapy.

Bronchial hyper-responsiveness (BHR) is documented in a proportion of non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double-blind, placebo-controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between-groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P=0.029), the median (inter-quartile range) AUC values being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and placebo-treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.

Adenosine Monophosphate↗
PubMed2003

Indirect airway challenges.

Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.

Asthma↗
PubMed2002

Nebulised morphine for severe interstitial lung disease.

BACKGROUND: The evidence to support the use of nebulized morphine to improve dyspnoea and exercise limitation in terminally ill patients with chronic lung disease is conflicting. OBJECTIVES: To assess the effectiveness of nebulized morphine in reducing dyspnoea in patients with end-stage interstitial lung disease SEARCH STRATEGY: RCTs and good quality CCTs were identified by searching Medline, Embase, Cinahl as well as the Cochrane controlled clinical trial register. The following search terms were used: (inhaled OR nebulised)/AND/morphine AND/Idiopathic pulmonary fibrosis/or/pulmonary fibrosis/or/idiopathic interstitial pneumonia/or/nonspecific interstitial pneumonia/or/non-specific interstitial pneumonia/or/usual interstitial pneumonia/or/desquamative interstitial pneumonia/or/cryptogenic fibrosing alveolitis/or/interstitial pneumonia/or/idiopathic interstitial lung disease/or/chronic interstitial pneumonia SELECTION CRITERIA: Any RCT and adequate quality CCT in adult patients with ILD that compared nebulized morphine with a control group. DATA COLLECTION AND ANALYSIS: Only one small RCT was identified. MAIN RESULTS: Compared to placebo (normal saline), administration of low-dose nebulized morphine (2.5 and 5.0 mg) to six patients with ILD did not improve maximal exercise performance, and did not reduce dyspnoea during exercise. REVIEWER'S CONCLUSIONS: The hypothesis that nebulized morphine may reduce dyspnoea in patients with interstitial lung disease has not been confirmed in the single small RCT identified.

Analgesics, Opioid↗
PubMed2002

Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease.

Adenosine is a purine nucleoside which mediates a variety of cellular responses relevant to asthma and COPD through interaction with specific receptors. Administration of adenosine by inhalation to patients with asthma and COPD is known to cause concentration related bronchoconstriction. Responses elicited by this purine derivative in asthma and COPD should not be considered as a mere reflection of non-specific airways hyperresponsiveness. Evaluation of airways responsiveness by adenosine induced bronchoconstriction may be valuable in differentiating asthma from COPD, monitoring of anti-inflammatory treatment in asthma, surveying disease progression, and assessing disease activity in relation to allergic airways inflammation.

Adenosine↗
PubMed2002

Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease.

Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important roles in the exacerbation of these conditions express adenosine receptors and demonstrate relevant effects through stimulation of these receptors. Therefore, blockade of these receptors may be a valuable approach to the treatment of asthma and chronic obstructive pulmonary disease. Promising adenosine-receptor targets for novel therapeutics of asthma and chronic obstructive pulmonary disease have recently been identified in a number of inflammatory cell types, including mast cells, eosinophils, lymphocytes, neutrophils, and macrophages. The recent characterisation of the A2B receptors indicates the human lung mast cell as one of the most strategic cellular targets.

Asthma↗
PubMed2002

Making, disseminating and using clinical guidelines.

Clinical guidelines are statements designed to help physicians make decisions about appropriate health care for specific circumstances. The constant rise in the number of published guidelines has been accelerated by the need of healthcare organizations to integrate evidence from clinical research with rational health policy, with the prospect of improving the quality and reducing the costs of health care at a local level. The best guidelines are developed from a systematic examination and appraisal of good evidence from well conducted trials, supported by appropriate clinical expertise, and leading to unambiguous recommendations. Great care needs to be taken both to maximize the validity of guidelines and to ensure their use within clinical practice. Moreover, the evidence on which clinical guidelines are based can change with time and therefore they should be reviewed regularly. The critical approaches to making high-quality guidelines, the value of implementation strategies, and how healthcare organizations and individual physicians can use medical guidelines to enhance clinical effectiveness will be discussed.

Delivery of Health Care↗
PubMed2001

The interaction between particulate air pollution and allergens in enhancing allergic and airway responses.

Although the detrimental effects of air pollution on human health have been brought widely to public notice, it appears that less attention has been given to the potential role of toxic air pollutants in the induction of allergic conditions such as asthma, rhinoconjunctivitis, and atopic eczema. A number of large epidemiologic studies have shown that people exposed to intense motor vehicle traffic and its associated emissions are at major risk for allergic symptoms, reduced lung function, and increased sensitization to common airborne allergens. Several laboratory-based studies have demonstrated that particulate air pollutants emitted from motor vehicles can induce allergic inflammation, enhance IgE responses, and increase airway hyperresponsiveness, which could provide an underlying mechanism for the increasing prevalence of allergic diseases. This article reviews the evidence that supports the causative link between particulate air pollution and the sharp increase in the prevalence of type I allergies in developed countries.

Air Pollution↗
PubMed2000

Expression of c-erbB receptors and ligands in human nasal epithelium.

BACKGROUND: The epidermal growth factor (EGF) family of growth factors plays an important role in maintenance and repair in a variety of epithelial tissues. However, very little is known about coexpression of these factors and their receptors, the c-erbB family of receptor tyrosine kinases, in human nasal epithelium. OBJECTIVE: We sought to investigate the expression of these molecules in cultured nasal epithelial cells and nasal mucosa from healthy individuals. METHODS: Identification of c-erbB receptors and their ligands was sought by using reverse transcription PCR, Western blotting, and immunohistochemistry. RESULTS: Messenger RNA encoding the EGF receptors (EGFR) c-erbB2 and c-erbB3, but not c-erbB4, was detected in primary cultures of human nasal epithelial cells. Transcripts encoding EGF, heparin-binding EGF, transforming growth factor (TGF) alpha, and amphiregulin were also detected. Receptor and ligand expression was confirmed by using immunocytochemical staining of the cells and Western blotting of the cell lysates. Immunohistochemical analysis of tissue sections obtained from biopsy specimens of nasal mucosa revealed intense membrane staining for the EGFR within the respiratory nasal epithelium, which was predominantly localized at the level of the columnar epithelial layers. Similar staining patterns were observed for c-erbB2 and c-erbB3 in the respiratory nasal epithelium. Evidence for EGF, transforming growth factor alpha, heparin-binding EGF, amphiregulin, and betacellulin immunostaining in the nasal epithelium was also obtained; their staining patterns paralleled that of EGFR immunostaining. CONCLUSION: Colocalization of c-erbB receptors and ligands establishes a basis on which to investigate c-erbB receptor- mediated effects in human nasal epithelium.

Cells, Cultured↗
PubMed2000

Involvement of the epidermal growth factor receptor in epithelial repair in asthma.

Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c-erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1-20.4) in normal subjects (n=10) to 18.4 (9.3-28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4-31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o- bronchial epithelial cells, we found that EGF accelerated repair of scrape-wounded monolayers and that the EGFR-selective inhibitor, tyrphostin AG1478, inhibited both EGF-stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage-induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR-mediated repair and tissue remodeling, release of the profibrogenic mediator TGF-beta2 was also measured. Scrape wounding increased release of TGF-beta2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF-beta2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling.

Adult↗