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Biomedical subjects

A Coste

Publications and source records attributed to A Coste.

At least 37 records · Page 2Linked to original sources

Radiofrequency is a safe and effective treatment of turbinate hypertrophy.

OBJECTIVE: To evaluate the safety and efficacy of radiofrequency for reduction of inferior turbinate volume. STUDY DESIGN: Prospective before-and-after trial. METHODS: Fourteen patients complaining of chronic nasal obstruction and failing to respond to medical treatment were prospectively enrolled. All patients presented with inferior turbinate hypertrophy and no septal deformity. Radiofrequency inferior turbinate tissue reduction with three punctures in each turbinate (mean energy/puncture: 342 +/- 36 J, mean duration: 69 +/- 17 s, plateau tissue temperature: 75 +/- 6.4 degrees C). Patients were evaluated before and on days 3, 7, and 60 after intervention. RESULTS: No postoperative pain or complications were reported. Evaluation of nasal obstruction, quantified by visual analogue scale, showed a significant decrease of day time and nighttime obstruction after surgery. Acoustic rhinometry measurements showed that turbinate hypertrophy was significantly reduced in the sitting and supine positions on day 60 after surgery. Saccharin transit times decreased significantly on day 60 compared with preoperative measurements. Ciliary beat frequency, measured in vitro in nasal epithelial cells sampled from the inferior turbinate by brushing, was not significantly different before surgery and on day 60 after surgery. In the same samples, ciliated cells were the most abundant epithelial cell type before and after surgery, although in five cases, moderate numbers of squamous cells were detected on either day 7 or day 60 after surgery. CONCLUSION: Radiofrequency is a safe surgical procedure capable of reducing turbinate volume without altering the nasal mucosa, and causing minimal discomfort for the patient.

Catheter Ablation↗

First evidence of lysogeny in Propionibacterium freudenreichii subsp. shermanii.

Dairy propionic acid bacteria, particularly the species Propionibacterium freudenreichii, play a major role in the ripening of Swiss type cheese. Isometric and filamentous bacteriophages infecting P. freudenreichii have previously been isolated from cheese. In order to determine the origin of these bacteriophages, lysogeny of P. freudenreichii was determined by isometric bacteriophage type analysis. The genomic DNA of 76 strains were hybridized with the DNA of nine bacteriophages isolated from Swiss type cheeses, and the DNA of 25 strains exhibited strong hybridization. Three of these strains released bacteriophage particules following UV irradiation (254 nm) or treatment with low concentrations of mitomycin C. A prophage-cured derivative of P. freudenreichii was readily isolated and subsequently relysogenized. Lysogeny was therefore formally demonstrated in P. freudenreichii.

Bacteriophages↗

IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells.

In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration. We have thus investigated the effect of IL-13 on mucociliary differentiation of human nasal epithelial cells in primary culture. We show that IL-13 alters ciliated cell differentiation and increases the proportion of secretory cells. IL-13 downregulates the actin-binding protein ezrin and other cytoskeletal components. IL-13 also impairs lateral cell contacts and interferes with the apical localization of ezrin seen in differentiated ciliated cells. In addition, an IL-4 antagonistic mutant protein (Y124D), which binds to the IL-4 receptor alpha subunit, a common chain of IL-4 and IL-13 receptors, inhibits IL-13's effects. IL-13 also decreases ciliary beat frequency in a time- and dose-dependent manner. These results suggest that, in human allergic asthmatic responses, IL-13 affects both ciliated and secretory cell differentiation, leading to airway damage and obstruction.

Asthma↗

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance.

OBJECTIVE: Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters. MATERIAL AND METHODS: The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments. RESULTS: Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance. CONCLUSIONS: 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Administration, Intranasal↗

Inflammatory cells as well as epithelial cells in nasal polyps express vascular endothelial growth factor.

In nasal polyps (NPs), locally secreted growth factors are involved in the remodelling of the epithelium and extracellular matrix but little is known concerning vessel remodelling. The in situ expression of vascular endothelial growth factor (VEGF) in NPs and control nasal mucosa (CM) were evaluated and in vitro secretion of VEGF from primary human cultures of nasal epithelial cells (HNECs) was quantified. VEGF expression was evaluated in NP (n=14) and CM (n=6) after immunolabelling. In supernatants from HNECs cultured at air/liquid interface, VEGF was quantified by immunoassay, under baseline conditions and after transforming growth factor-beta1 (TGF-beta1) stimulation. In HNEC lysates, VEGF and VEGF messenger ribonucleic acid (mRNA) were detected using Western blot analysis and reverse transcriptase polymerase chain reaction respectively. VEGF positivity was more frequent in inflammatory cells in NPs (14 of 14) than in CM (three of six) (p<0.05) and in the epithelium in NPs (six of 14) than in CM (two of six) (nonsignificant). Under baseline conditions, the VEGF concentration in HNEC culture medium increased from day 2 to 4, then decreased and became undetectable. VEGF concentrations increased significantly after TGF-beta1 stimulation. In HNEC lysates, VEGF and VEGF mRNA were detected on days 4 and 14 of culture. It was concluded that vascular endothelial growth factor is intensely expressed in situ in nasal polyps, mainly in inflammatory cells but also in epithelial cells. Human nasal epithelial cells are able to secrete in vitro vascular endothelial growth factor. Transforming growth factor-beta1 upregulates this secretion. This suggests that vascular endothelial growth factor, inducing oedema and angiogenesis, could be involved in the pathogenesis of nasal polyps.

Endothelial Growth Factors↗

Nasal obstruction as a risk factor for sleep apnoea syndrome.

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.

Airway Resistance↗

Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps.

BACKGROUND: Because the epidermal growth factor receptor (EGFR) system regulates mucin production in airway epithelium, we hypothesized a role for this system in mucus hypersecretion that occurs in nasal polyposis. OBJECTIVE: We examined the relationship between goblet cell hyperplasia, EGFR expression, and inflammatory mediators produced by eosinophils and neutrophils in nasal polyp tissues. METHODS: Nasal polyp tissue samples from 8 patients and nasal turbinate biopsy specimens from 6 normal control subjects were examined for alcian blue/PAS staining, mucin MUC5AC (MUC5AC), and EGFR immunoreactivity and EGFR gene expression (in situ hybridization). We also examined the role of eosinophils and neutrophils in goblet cell hyperplasia. RESULTS: In control nasal mucosa alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 18.40% +/- 1.31% and 21.89% +/- 1.43%, respectively. In polyps the alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 51.30% +/- 5.85% and 52.07% +/- 6.58%, which was significantly larger than that found in control subjects (each comparison, P <.01). Four of 6 control specimens expressed EGFR messenger RNA and protein weakly in the epithelium. In polyps 4 of 8 specimens expressed EGFR gene and EGFR protein strongly; the EGFR-stained area was greater in hyperplastic than in pseudostratified epithelium. TNF-alpha immunoreactivity, expressed in eosinophils, was increased in EGFR-positive polyps compared with EGFR-negative polyps, suggesting a role for TNF-alpha in EGFR expression. Neutrophils were increased in the epithelium of EGFR-positive compared with EGFR-negative polyps, suggesting a role for these cells in mucin expression and in goblet cell degranulation. CONCLUSION: These data suggest a role for EGFR cascade in the regulation of goblet cell mucins in nasal polyps. Proof of concept will require clinical studies using selective EGFR inhibitors.

Cell Movement↗

Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea.

Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and/or lactation. Adult female mice were nasally immunized with virus-like particles (VLPs) made of viral proteins VP2 and 6 (VLP2/6) or VP 2, 6, and 7 (VLP2/6/7) derived from the RF rotavirus strain in the presence or absence of cholera toxin. Both vaccines elicited serum and milk antibodies against the respective VPs. Four days after parturition, suckling pups were challenged orally with RF rotavirus. Pups from mothers immunized with VLP2/6/7 but not VLP2/6 were protected against rotavirus diarrhea, indicating that VP7 plays a key role in protection. Protection was mediated by milk rather than serum antibodies, and mucosal adjuvants were not required. In conclusion, VLPs containing VP7 administered nasally to mothers represent a promising vaccine candidate for the protection of suckling newborns against rotavirus-induced diarrhea, even in the absence of a mucosal adjuvant.

Administration, Intranasal↗

Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell growth and permeability factor highly expressed in rodent alveolar epithelium after injury and repair. To investigate VEGF synthesis in human lung epithelial cells, we examined VEGF expression by cultured cells under basal conditions and after cytokine treatment or oxidative stress. Basal VEGF expression was detected in transformed human epithelial cell lines (A549 and 1HAEo-) and in primary human bronchial epithelial cells with RT-PCR, Western blot, and immunocytochemistry. Among the cytokines tested, only transforming growth factor-beta1 increased the levels of excreted VEGF(165) as measured by ELISA. Under hypoxia (0% O(2) for 24 h), the VEGF(165) level increased fivefold, and this effect was O(2) concentration dependent. VEGF concentrations in the medium of all the cell types studied reached values similar to those found in bronchoalveolar lavage fluids from normal patients. Endothelial cells (human umbilical vein endothelial cells) exposed to conditioned medium from primary bronchial epithelial cell cultures showed an increased growth rate, which was inhibited in the presence of a specific neutralizing antibody to VEGF. These results suggest that lung epithelial cells participate in the endothelial repair and angiogenesis that follow lung injury through the synthesis of VEGF.

Bronchoalveolar Lavage Fluid↗

Predictive value of pulmonary function parameters for sleep apnea syndrome.

Nocturnal polysomnography is the standard diagnostic test for sleep apnea syndrome (SAS) but is both expensive and time-consuming. We developed a predictive index for SAS based on pulmonary function data, including respiratory resistance determined by the forced oscillation technique, from 168 obese snorers with suspected SAS. Our model used logistic regression to obtain case-by-case predictions of the probability of SAS, defined as an apnea-hypopnea index (AHI) > or = 15 during overnight polysomnography. We then tested our model in a prospective group of 101 similar patients. Specific respiratory conductance and daytime oxygen saturation contributed significantly to the model. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the index computed from these parameters were 98%, 86%, 90%, and 97%, respectively. In the prospective group, the model proved repeatable, with 100% sensitivity, 84% specificity, 86% PPV, and 100% NPV. The high NPV may help to identify obese snorers with a SAS risk that is so low as to make polysomnography unnecessary. Based on the 50% prevalence of SAS in our study and on the fact that polysomnography is required in all patients with daytime somnolence, we calculated that using our model would have obviated the need for polysomnography in 38% of our patients.

Female↗

Effects of mandibular advancement on respiratory resistance.

Mandibular advancing devices are proposed as nonsurgical treatment for certain patients with an obstructive sleep apnoea syndrome. Since they act by increasing the upper airway calibre, the aim of the present study was to investigate the changes in respiratory resistance (Rrs) resulting from mandibular advancement. Rrs was measured at the nose by the forced oscillation technique (4-32 Hz). Ten normal subjects were studied under three conditions: resting mandibular position, passive mandibular advancement steadied by a wax bite, and voluntary advancement, in random order. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. R0 (mean+/-SEM=3.5+/-0.2 cmH2O x L(-1) x s in the resting position) decreased significantly with passive advancement (2.9+/-0.2 cmH2O x L(-1) x s, p<0.001), but remained unchanged with voluntary mandibular advancement (3.6+/-0.2 cmH2O x L(-1) s). Similar results were obtained for R16. The results of this study demonstrate that the effects of mandibular advancement on upper airway resistance differ, depending on whether advancement is passive or active, and suggest that in order to simulate the actual effects of therapeutic devices, mandibular advancement should be passive.

Adult↗

Effects of nasal prongs on nasal airflow resistance.

STUDY OBJECTIVES: The aim of this study was to investigate whether nasal prongs, which have been proposed to assess nasal flow during sleep, affect nasal airflow resistance (NR). DESIGN: NR was estimated by posterior rhinomanometry at a 0.5 L/s flow, under eight conditions: in the basal state, and with seven different nasal prongs. PARTICIPANTS: The study was performed in 17 healthy supine subjects, 8 of whom had basal NR values within the normal range (< or = 2 cm H(2)O.L(-1).s, group 1), and 9 had increased basal NR values (> 2.5 cm H(2)O.L(-1).s, group 2), because of nare narrowness and/or deviated nasal septum. MEASUREMENTS AND RESULTS: NR increased significantly while breathing with nasal prongs (p < 0.0001 in both groups). The changes in NR (DeltaNR) induced by the different nasal prongs were characterized by large intersubject and intrasubject variability, with a maximum DeltaNR of 24.2 cm H(2)O.L(-1).s. Significant differences were found between the DeltaNR induced by the different nasal prongs (p < 0.001 in group 1, and p < 0.0003 in group 2), and for six of them, DeltaNR was significantly higher in group 1 than in group 2 (p < 0.02). CONCLUSIONS: This study demonstrates that nasal prongs can markedly increase NR in subjects presenting with nare narrowness and/or deviated nasal septum. Further investigations that would include nocturnal polysomnography are still required to evaluate the possible influence of nasal prongs on the diagnosis of obstructive sleep apnea syndrome and its severity.

Adult↗

Characterization of inflammatory reaction in upper airways of cystic fibrosis patients.

Inflammatory cell populations have not been yet precisely evaluated in cystic fibrosis (CF) airways. We intended to characterize morphological modifications, inflammatory cell infiltration and cell proliferation in nasal tissues obtained from 15 CF patients and from 6 non-CF patients with nasal polyposis. Morphological analysis showed an intense inflammatory infiltration in CF and non-CF tissues with only few modifications in the epithelium from CF tissues. Inflammatory cell populations characterized by specific immunolabeling were quantified, showing a predominance of macrophages and T- and B-lymphocytes and only moderate numbers of neutrophils in CF tissues; in non-CF polyps, lymphocytes and eosinophils were abundant. Proliferating cell percentages quantified after proliferating cell nuclear antigen immunolabeling were 5.3+/-4.1% (mean +/- SD) in CF polyps and 3.1+/-1.2% in non-CF polyps in epithelium but were very low in lamina propria. Intense inflammation in nasal tissues from CF patients is therefore dominated by macrophages and lymphocytes rather than by neutrophils. While morphology is preserved, proliferation is high in epithelium from CF polyps. These findings should be regarded in the future for a better understanding of inflammation in CF airway disease.

Adolescent↗

[ENT diseases associated with allergic rhinitis: a review of the literature].

Various diseases of the upper airway, such as acute or chronic sinusitis, otitis media, pharyngitis or laryngitis, snoring and sleep apnea syndrom, may be associated with allergic rhinitis. The relationship between these pathologies and the allergic rhinitis has been well established from a clinical and epidemiological point of view, but the pathophysiological mechanisms remain uncertain. A good knowledge of symptoms and the performance of explorations, such as nasal endoscopy for sinusitis, are important in order to take care of these associated diseases. When upper airway diseases are associated with allergic rhinitis, treatment of rhinitis must generally be reinforced. Treament of associated disease will be specific to each disease, and sometimes surgery is required, specially in case of chronic sinusitis. In all cases, the pneumologist, allergologist and ENT physician should work in close collaboration.

Acute Disease↗

Pharmacological characterization of muscarinic receptors implicated in rabbit detrusor muscle contraction and activation of inositol phospholipid hydrolysis in rabbit detrusor and parotid gland.

In the present study, we evaluated the pharmacological characteristics of the functional muscarinic receptors implicated in rabbit detrusor contraction and coupled to inositol phospholipid turnover in rabbit detrusor and parotid gland. The selectivity of several muscarinic antagonists for detrusor vs. salivary gland muscarinic receptors was also examined. The affinities for the muscarinic m1-, m2- and m3-receptor subtypes were determined using membranes from human cloned receptors expressed in CHO-K1 cells using [3H]-N-methyl scopolamine as a radioligand. Anti-muscarinic activity was determined in isolated rabbit detrusor by measuring the displacement of the contractile response to carbachol, and in rabbit detrusor and rabbit parotid by measuring the displacement of inositol phospholipid hydrolysis (total inositol phosphate accumulation) to carbachol. A significant correlation was found between the potencies to antagonize carbachol-induced rabbit detrusor contraction (pK(B)) and the affinities (pKi) for the m3-receptor subtype (r = 0.93, P = 5 x 10(-6)). Lower, but significant, correlations [0.88 (P = 6.3 x 10(-5)), 0.72 (P = 4.6 x 10(-3))] were obtained with m1- or m2-receptor subtypes, respectively. Each muscarinic antagonist tested displayed similar potency to antagonize carbachol-stimulated inositol phospholipid hydrolysis in rabbit detrusor and parotid (r = 0.96, P = 8 x 10(-3)). A significant correlation was found between the potencies to antagonize carbachol-stimulated inositol phospholipid hydrolysis (pK(B)), determined in rabbit detrusor and rabbit parotid, and the affinities (pK(i)) for the m3-receptor subtype [r = 0.96 (P = 0.01), 0.99 (P = 5 x 10(-5)), respectively] and for the m1-receptor subtype [r = 0.98 (P = 3.5 x 10(-3)), 0.94 (P = 0.02), respectively] but not for the m2-receptor subtype [r = 0.33, 0.57, ns, respectively]. In each in vitro assay, methoctramine (preferential M2 selective antagonist) and pirenzepine (preferential M1 selective antagonist) were slightly potent. We suggest that the muscarinic receptor implicated in the response to carbachol in rabbit detrusor and parotid gland corresponds to the M3-subtype. None of the muscarinic antagonists studied in rabbit tissues displayed preferential affinity for the detrusor.

Animals↗

Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production.

The involvement of diesel exhaust particles (DEPs) in respiratory diseases was evaluated by studying their effects on two in vitro models of human airway epithelial cells. The cytotoxicity of DEPs, their phagocytosis, and the resulting immune response were investigated in a human bronchial epithelial cell line (16HBE14o-) as well as in human nasal epithelial cells in primary culture. DEP exposure induced a time- and dose-dependent membrane damage. Transmission electron microscopy showed that DEPs underwent endocytosis by epithelial cells and translocated through the epithelial cell sheet. Flow cytometric measurements allowed establishment of the time and dose dependency of this phagocytosis and its nonspecificity with different particles (DEPs, carbon black, and latex particles). DEPs also induced a time-dependent increase in interleukin-8, granulocyte-macrophage colony-stimulating factor, and interleukin-1beta release. This inflammatory response occurred later than phagocytosis, and its extent seems to depend on the content of adsorbed organic compounds because carbon black had no effect on cytokine release. Furthermore, exhaust gas posttreatments, which diminished the adsorbed organic compounds, reduced the DEP-induced increase in granulocyte-macrophage colony-stimulating factor release. These results suggest that DEPs could 1) be phagocytosed by airway epithelial cells and 2) induce a specific inflammatory response.

Biological Transport↗

Protruding the tongue improves posterior rhinomanometry in obstructive sleep apnoea syndrome.

In posterior rhinomanometry (PRM), oropharyngeal pressure is measured using a tube placed between the tongue and the hard palate. For valid results the patient must position the tongue and soft palate so that both the oropharynx and nasopharynx remain open. A high rate of failure of conventional PRM has been reported in normal individuals. In patients with obstructive sleep apnoea syndrome (OSAS), upper airway abnormalities may further increase the failure rate. This study proposes a modification of the technique in which protrusion of the tongue enhances pressure transmission between the nasopharynx and the mouth. In eight normal subjects, resistance was similar when measured by both methods. Of 24 OSAS patients, conventional PRM was unsuccessful in 11. In the remaining 13 patients, a significant correlation between the two methods was found, but resistance was lower by "tongue-out" than by conventional PRM, consistent with a decrease, during tongue protrusion, in retropalatal resistance, which is a component of the "nasal" resistance measured by PRM. In 26 OSAS patients, unilateral nasal resistance values measured by "tongue-out" PRM were similar to those measured by anterior rhinomanometry. When the "tongue-out" method was used routinely in 541 snorers, failure rates were 1.1% in the 272 non-OSAS patients and 3.7% in the 269 OSAS patients. These results indicate that posterior rhinomanometry with tongue protrusion is a highly effective tool for measuring nasal resistance in snorers.

Adolescent↗

Combined effects of a mechanical nasal dilator and a topical decongestant on nasal airflow resistance.

The goal of this study was to compare the isolated and combined effects of two treatments being used to reduce nasal airflow resistance (NR): an internal nasal mechanical dilator (Nozovent; Prevancure; Sté Pouret, Paris, France) and a topical decongestant, fenoxazoline hydrochloride (Aturgyl; Synthelabo; Le Plessis-Robinson, France). The study was performed in 17 healthy subjects. NR was estimated by active posterior rhinometry at a 0.5 L/s flow under four conditions: in the basal state, with the internal nasal mechanical dilator, after treatment with fenoxazoline hydrochloride, and with both fenoxazoline hydrochloride and the mechanical dilator. The mean NR (+/- SD) decreased from 1.65+/-0.54 cm H2O/L/s in the basal state to 1.02+/-0.27 cm H2O/L/s with the mechanical dilator (p < 0.001), 1.03+/-0.47 cm H2O/L/s with fenoxazoline hydrochloride (p < 0.001), and 0.48+/-0.15 cm H2O/L/s with both the mechanical dilator and fenoxazoline hydrochloride (p < 0.001). The decreases in NR observed after using either the mechanical dilator (deltaNR(N)) or fenoxazoline hydrochloride (deltaNR(A)) were not significantly different. The decrease in NR observed with both (deltaNR(N + A)) was not significantly different from the sum deltaNR(N) + deltaNR(A): 1.16+/-0.53 cm H2O/L/s vs 1.25+/-0.63 cm H2O/L/s, respectively (p > 0.05). deltaNR(N + A) strongly correlated with deltaNR(N) + deltaNR(A): deltaNR(N + A) = 0.80 (deltaNR(N) + deltaNR(A)) + 0.15 (r = 0.96; p < 0.0001). However, the slope of the regression line of deltaNR(N + A) vs deltaNR(N) + deltaNR(A) was significantly lower than unity (p < 0.003). These results demonstrate that, although not totally additive, the effects of using the mechanical dilator and fenoxazoline hydrochloride are cumulative. Further studies that include patients with nasal obstruction would allow us to better evaluate the benefit of a therapy combining both treatments.

Administration, Topical↗