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Biomedical subjects

J Mullol

Publications and source records attributed to J Mullol.

At least 19 recordsLinked to original sources
PubMed2006

The impact of bronchiectasis associated to sinonasal disease on quality of life.

BACKGROUND: Bronchiectasis (BQs) is an uncommon disease with the potential to cause devastating complications. All patients with BQs have cough and chronic sputum production that may have a great impact on patient's quality of life. Upper airway symptoms are also frequent in patients with BQs. Associations between upper and lower airways diseases have been demonstrated in allergic rhinitis and asthma, nasal polyposis and asthma, chronic obstructive lung disease and chronic rhinosinusitis. OBJECTIVE: (1) To investigate the impact of bronchiectasis and nasal symptoms on quality of life. (2) To evaluate the added impact of nasal polyposis on quality of life in patients with BQs. METHODS: Sixty patients with bronchiectasis and upper airway symptoms were included. Patients were evaluated for nasal symptoms, nasal polyp size by endoscopy, and quality of life using the SF-36 generic questionnaire. RESULTS: In comparison with the Spanish general population, patients with BQs had worse scores in all SF-36 domains (P<0.05). Males reported significantly higher quality of life scores on physical functioning and social functioning than females did. Although the age, pulmonary function, presence of nasal polyps, upper airway symptoms, tobacco smoking history, and disease duration was similar between them. Males with BQs had worse quality of life than males from the Spanish general population on body pain, general health, and vitality (P<0.05). Females with BQs had worse quality of life than females from the Spanish general population on physical function, body pain, general health, vitality, social function, and emotional role (P<0.05). Nasal polyps were found in 25 (41.6%) of 60 patients with BQs. No significant differences were observed on quality of life outcomes between patients with BQs with and without nasal polyposis. CONCLUSION: These results suggest that BQs has a considerable impact on quality of life while nasal polyposis has no additional impact on the quality of life of patients with BQs.

Adult↗
PubMed2006

Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis.

BACKGROUND: The angiotensin system has a role in the pathogenesis of pulmonary fibrosis. This study examines the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in bleomycin induced lung fibrosis and its possible implication in the regulation of prostaglandin E(2) (PGE(2)) synthesis and cyclooxygenase-2 (COX-2) expression. METHODS: Rats were given a single intratracheal instillation of bleomycin (2.5 U/kg). Losartan (50 mg/kg/day) was administrated orally starting one day before induction of lung fibrosis and continuing to the conclusion of each experiment. RESULTS: Losartan reduced the inflammation induced by bleomycin, as indicated by lower myeloperoxidase activity and protein content in the bronchoalveolar lavage fluid. Collagen deposition induced by bleomycin was inhibited by losartan, as shown by a reduction in the hydroxyproline content and the amelioration of morphological changes. PGE(2) levels were lower in fibrotic lungs than in normal lungs. Losartan significantly increased PGE(2) levels at both 3 and 15 days. A reduction in COX-2 expression by bleomycin was seen at 3 days which was relieved by losartan. CONCLUSIONS: The antifibrotic effect of losartan appears to be mediated by its ability to stimulate the production of PGE(2). Losartan, which is already widely used clinically, could be assessed as a new treatment in lung fibrosis.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

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 10(6) cDNA molecules/mug total RNA and the densitometric ratio between protein and beta-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.

Adolescent↗
PubMed2006

[Sphenochoanal polyp. Diagnostic and therapeutic aspects].

INTRODUCTION: Sphenochoanal polyps (SCP) grow from the sphenoid sinus and occupy the nasopharynx. OBJECTIVE AND RESULTS: To describe the clinical and diagnostic features of SCP, reporting two cases. Epidemiological study of the series in the literature. 8 published series were found (22 cases). CONCLUSIONS: SCP is a rare lesion that is usually misdiagnosed for antrochoanal polyposis. A proper diagnosis and surgical treatment are the basis to prevent recurrence. We describe the first case of SCP with cacosmia.

Adult↗
PubMed2006

[Relation between rhinosinusitis and bronchiectasis].

The nose and lungs have both histological and functional similarities and differences. Sinonasal and bronchial involvement are associated in many diseases. Cystic fibrosis, primary ciliary dyskinesia, Young's syndrome, and alpha-1 antitrypsin deficiency are diseases in which bronchiectasis and rhinosinusitis are both present. This review considers the diseases in which bronchiectasis occurs along with sinonasal manifestations. We propose examining sinonasal disease from a new perspective by observing it in patients with bronchiectasis.

Bronchiectasis↗
PubMed2006

Effect of desloratadine on epithelial cell granulocyte-macrophage colony-stimulating factor secretion and eosinophil survival.

BACKGROUND: Second-generation antihistamines are H(1) receptor antagonists and may have additional anti-inflammatory effects. OBJECTIVE: The aims of the study were to evaluate the effect of desloratadine (DL) on cytokine secretion by epithelial cells from both nasal mucosa (NM) and polyps (NP), and on eosinophil survival primed by epithelial cell secretions. METHODS: Epithelial cells were cultured and stimulated with fetal bovine serum (FBS), IL-1beta or TNF-alpha with and without DL for 24 h. Culture supernatant cytokines concentration were measured by ELISA. Peripheral blood eosinophils were incubated with human epithelial cell conditioned media (HECM) and DL. Eosinophil survival was assessed by Trypan blue dye exclusion. Results are expressed as mean+/-SEM of cytokine concentration (pg/mL) or eosinophil survival index (%). RESULTS: FBS increased granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), IL-6, IL-8, and TGF-beta(1) secretion in epithelial cell cultures from both NM and NP. Only GM-CSF secretion was significantly (P<0.05) inhibited by a dose-response of DL compared with positive controls, in both NM (10(-5) m: 125+/-36 pg/mL, 10(-6) m: 95+/-22 pg/mL vs. control: 256+/-91 pg/mL, n=6) and NP (10(-5) m: 80+/-29 pg/mL, 10(-6) m: 109+/-45 pg/mL vs. control: 333+/-212 pg/mL, n=6). DL also showed an inhibitory effect on HECM-induced eosinophil survival from both NM and NP. At 72 h, DL significantly (P<0.01) inhibited eosinophil survival induced by HECM from NM (10(-5) m: 19.9+/-5.5%, n=9; 10(-6) m: 28.7+/-7.7%, n=9) and NP (10(-5) m: 6.2+/-2.8%, n=11) compared with HECM alone (NM: 42.1+/-7.3%; NP: 45.3+/-8.1%). CONCLUSION: The inhibitory effects of DL on epithelial cell GM-CSF secretion and on eosinophil survival induced by epithelial cell secretions, suggest that this H(1) antagonist may regulate eosinophil inflammation in upper airways.

Adolescent↗
PubMed2006

Mucin genes have different expression patterns in healthy and diseased upper airway mucosa.

BACKGROUND: Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy. OBJECTIVE: The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies. METHODS: Immunohistochemistry for MUC1, MUC2, and MUC4-MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral nasal polyps (NP; n=38), NP from CF patients (n=10), and antrochoanal (AC) polyps (n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in situ hybridization. RESULTS: MUC1, MUC4, and MUC5AC mucins were highly expressed in the epithelium and their expression pattern was similar in all NP types, MUC1 and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly detected at both epithelial and glandular levels with marked variability between groups. MUC5B was mainly detected in glands and the expression in all polyp types was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from CF patients than in bilateral NP and healthy NM. Although MUC2 expression was low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and MUC7 were scarcely detected and MUC7 expression was restricted to glands. CONCLUSIONS: These results suggest that NP have a different pattern of mucin expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps (decreased MUC2) have a different mucin expression pattern than bilateral NP.

Adolescent↗
PubMed2006

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗
PubMed2006

Tissue remodelling in upper airways: where is the link with lower airway remodelling?

Tissue remodelling reported in upper airways include epithelial hyperplasia, increased matrix deposition in the nasal or paranasal lining, matrix degradation and accumulation of plasma proteins. Genetic influences, foetal exposures and early life events may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of the disease and long-term uncontrolled inflammation. Structural changes may increase alteration of the protective functions of the upper airways namely by affecting mucociliary clearance and conditioning of inspired air. The sequences of tissue changes during wound repair of upper airway mucosa after surgery are illustrative of the complexicity of tissue modelling and remodelling and could be considered as an important source of information for a better understanding of the complex relationship between inflammatory reaction, of the subsequent tissue damages and fibroblast metabolism of upper airways.

Animals↗
PubMed2005

Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments.

BACKGROUND: Nasal polyposis (NP) is not a life-threatening disorder but may have a great impact on the quality of life (QoL). The objective of this study: (i) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form-36 Health Survey (SF-36) questionnaire; (ii) to compare the QoL outcome after medical or surgical treatment; and (iii) to assess and compare the effect of medical and surgical treatment on nasal symptoms. METHODS: About 109 patients with nasal polyps were included. Fifty-three patients were randomly allocated to receive oral prednisone for 2 weeks and 56 to undergo endoscopic sinus surgery. All patients administered intranasal budesonide for 12 months. Patients were evaluated for nasal symptoms, polyp size, and QoL. RESULTS: In comparison with the Spanish general population, patients with NP had worse scores on all SF-36 domains except for physical functioning. Nonasthmatic patients with NP had better QoL than asthmatic patients with NP on role physical functioning, body pain, and vitality (P <0.05). At 6 and 12 months, a significant improvement on all of SF-36 domains was observed after both medical and surgical treatment reaching the levels of general population (P <0.05). Nasal symptoms and polyp size improved after both medical and surgical treatment at 6 and 12 months (P <0.05). CONCLUSION: These results suggest that NP has considerable impact on a patient's QoL and that both medical and surgical treatment led to similar effects in improving QoL.

Asthma↗
PubMed2005

Costs associated with persistent allergic rhinitis are reduced by levocetirizine.

BACKGROUND: Allergic rhinitis was recently classified by the ARIA guidelines as persistent or intermittent. Levocetirizine was shown to improve symptoms and health-related quality of life of patients with persistent allergic rhinitis in the XPERT study, a 6-month randomized double blind placebo-controlled trial. OBJECTIVE: To assess the total costs of persistent allergic rhinitis, and the effect of long-term treatment with levocetirizine on these costs from several perspectives (societal, social security system, and employers). METHODS: Direct medical cost parameters (medications, physician visits and hospitalizations) and time lost parameters (workdays and Usual Daily Activities (UDA) lost) related to persistent allergic rhinitis and its comorbidities (asthma, sinusitis, otitis and upper respiratory infection) were measured. A cost analysis was performed using 2002 French costing data. RESULTS: From a societal perspective, the total cost of persistent allergic rhinitis without long-term treatment was estimated at 355.06/patient/month. From a social security perspective, levocetirizine treatment yielded an additional cost of 2.78/patient/month, compared to no-treatment. However, levocetirizine reduced the total cost of persistent allergic rhinitis and its comorbidities by 152.93/patient/month from a societal perspective and by 64.70/patient/month from an employer perspective. Most gains resulted from a decrease in the lost workdays and UDA in the levocetirizine group. CONCLUSION: The cost of persistent allergic rhinitis is substantial. Treatment with levocetirizine reduces the cost of persistent allergic rhinitis and its comorbidities to the society by 152.93/patient/month while improving symptoms and health-related quality of life.

Cetirizine↗
PubMed2005

Nasal and bronchial response to exercise in patients with asthma and rhinitis: the role of nitric oxide.

BACKGROUND: Physical exercise is associated with a decrease in nasal resistance in rhinitis and an increase in bronchial resistance in asthma. The objective was to evaluate the relationship between the levels of nasal nitric oxide (nNO) and exhaled bronchial nitric oxide (eNO) with bronchial responses to exercise in patients with rhinitis and asthma. METHODS: We submitted 24 subjects with asthma and rhinitis to an exercise test. A decrease in FEV(1)> or =15% was considered positive. The volume of the nasal cavity and the minimal cross-sectional area (MCA) was evaluated by means of acoustic rhinometry (AR), and nNO and eNO were evaluated by chemoluminiscence. The measurements were recorded at baseline, 15 and 50 min after the end of the exercise test. RESULTS: The exercise test was positive in 17 cases. Fifteen minutes after exercise test, the nasal volume increased by 57% (P < 0.0001) and was still increased by 30% after 50 min (P < 0.0001). There was no correlation between decrease in FEV(1) and increase in nasal volume. The baseline value of nNO was 1185 +/- 439 ppb, and the value at 15 and 50 min was 1165 +/- 413 and 1020 +/- 368 ppb, the latter value being significantly lower (P < 0.01) than the baseline. The baseline value of eNO was 21 +/- 19 ppb, with no significant differences at 15 and 50 min. There was no significant correlation between either the decrease in FEV(1) and the nasal response, or the baseline eNO and nNO values. CONCLUSIONS: The nasal and bronchial response to exercise is completely different in rhinitis and asthma; in the former, an increase in nasal volume occurs, while in the latter there is a drop in FEV(1). There is no relationship between the values of nasal or exhaled NO and the nasal and bronchial response after exercise.

Adult↗
PubMed2004

The ARIA/EAACI criteria for antihistamines: an assessment of the efficacy, safety and pharmacology of desloratadine.

BACKGROUND: The definition of allergic rhinitis and the classification of its severity and treatment have advanced in recent years following the publication of the Allergic Rhinitis and its Impact of Asthma (ARIA) document. The ARIA and the European Academy of Allergology and Clinical Immunology (ARIA/EAACI) have published a set of recommendations that outline the pharmacological and clinical criteria to be met by medications commonly used in the treatment of allergic rhinitis. METHODS: An international group of experts met to assess the profile of the antihistamine, desloratadine, under the ARIA/EAACI criteria. Data on desloratadine were collected from peer-reviewed clinical studies and review articles, which were corroborated and augmented by comprehensive public access documents from the European Medicines Evaluation Agency (EMEA). RESULTS AND CONCLUSION: Based on this systematic review, it was concluded that the efficacy, safety and pharmacology of desloratadine broadly meet the ARIA/EAACI criteria for antihistamines.

Animals↗
PubMed2004

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 GRalpha and GRbeta, as well as their alterations in pathological states. GRalpha 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. GRbeta has been found to act as a dominant negative inhibitor of GRalpha-mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRalpha-mediated transrepression. In addition, for most tissues the expression of GRbeta, at least at the mRNA level, is extremely low compared with that of GRalpha. Some pro-inflammatory cytokines appear to upregulate the expression of GRbeta, and increased GRbeta 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 GRbeta in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.

Asthma↗
PubMed2004

Expression of glucocorticoid receptors alpha and beta in steroid sensitive and steroid insensitive interstitial lung diseases.

BACKGROUND: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors alpha (GRalpha) and beta (GRbeta). A study was undertaken to assess GRalpha and GRbeta 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. GRalpha and GRbeta expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25-75th percentile. RESULTS: GRalpha mRNA expression (10(5) cDNA copies/ micro g 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). GRbeta expression was at least 1000 times lower than that of GRalpha and did not differ between the three groups. A negative correlation was found between GRalpha mRNA levels and the fibrotic pathology score of the tissue (r = -0.484, p<0.01) and a positive correlation was found between GRalpha 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 GRalpha.

Adult↗
PubMed2003

Nuclear factor-kappaB activity is down-regulated in nasal polyps from aspirin-sensitive asthmatics.

BACKGROUND: We examined whether a decreased activity of nuclear factor(NF)-kappaB), a transcriptional regulator of cyclooxygenase-2 (COX-2), could account for down-regulation of COX-2 in nasal polyps of aspirin-sensitive asthmatics. METHODS: Nasal polyps were obtained from 17 aspirin-intolerant asthma/rhinitis patients (AIAR; 7 men, mean age 48 +/- 12 years) and 23 aspirin-tolerant asthma/rhinitis patients (ATAR; 12 men, mean age 65 +/- 11 years). COX-2 mRNA expression was measured using semiquantitative reverse transcriptase competitive polymerase chain reaction (RT-PCR), and the results were expressed as mean +/- standard error of 106 molecules of mRNA/ micro g of total RNA. NF-kappaB binding was measured with 32P-labeled oligonucleotides and electrophoretic mobility shift assay (EMSA), and the results were expressed as a percentage with respect to the mean EMSA obtained in 19 healthy nasal mucosa. RESULTS: The mean levels of COX-2 mRNA expression (0.25 +/- 0.06) and NF-kappaB activity (89 +/- 13) in nasal polyps from AIAR were significantly lower than in polyps from ATAR (COX-2 = 1.58 +/- 0.50, and NF-kappaB = 143 +/- 12, P < 0.01 and P < 0.05, respectively). Levels of COX-2 mRNA and NF-kappaB activity in polyps from patients on corticosteroid therapy did not differ statistically from those who were not on this therapy before polypectomy. CONCLUSION: This study shows that the low expression of COX-2 mRNA in nasal polyps from aspirin-sensitive patients is associated with a down-regulation of NF-kappaB activity.

Adrenal Cortex Hormones↗