Efficacy and onset of action of fluticasone propionate aqueous nasal spray on nasal symptoms, eosinophil count, and mediator release after nasal allergen challenge in patients with seasonal allergic rhinitis

We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 μg, once daily) and matching placebo. NACs were performed before and at 6 h and 1. 2. 3. and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS. both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils; f=0.032; ECP; F=0.038). The onset became even more important at day 7 (eosinophils; P=0.001; ECP; P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (F=0.017) and for sneezing at day 7 (f=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.     

The Costello syndrome: Are nasal papillomata essential?

Summary Two patients with the Costello syndrome are presented. One was a 7-year-old girl with a history of infantile hypotonia and feeding difficulties. The other was a 3 5/12-year-old boy with a history of neonatal sepsis and respiratory problems. Both had relative macrocephaly at birth, curly hair, large ear lobes, epicanthic folds, a low nasal bridge, thick lips, a short and wide nose, a short neck, a barrel chest, redundant skin, tight Achilles tendons, and pes equinovarus. Nasal papillomata, as described in Costello's two patients, were absent in both patients. Borochowitzet al. (1992) described five patients with what we interpreted as the Costello syndrome but without nasal papillomata. In view of these findings, nasal papillomata are not likely to be essential in the diagnosis of the Costello syndrome.     

Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis

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Cat shedding of Fel d I is not reduced by washings, Allerpet-C spray, or acepromazine

Background: No published studies have compared the effectiveness of several treatments proposed to reduce cat allergenicity. Cat washing studies demonstrating efficacy involved very small sample sizes or infrequent washings. Allerpet-C (Allerpet, Inc., New York, N.Y.), a widely advertised topical spray, and acepromazine, a tranquilizer advocated as efficacious in subsedating doses, have never been scientifically studied. Objective: We compared the effects of cat washing, Allerpet-C spray, and acepromazine with that of no treatment on the shedding of the primary cat allergen, Felis domesticus I by cats. Methods: In a blinded, comparative, controlled study, we measured the amounts of Fel d I shed during an 8-week treatment period with a sample of 24 female mongrel cats randomly assigned to four groups; one group received weekly distilled water washings, one received weekly Allerpet-C spray applications, one received daily oral acepromazine, and one had no treatment (control). Thirty-minute, twice-weekly air samples were collected from each cat with a laminated plastic–acrylic chamber and air sampler. Results: One-sample, two-sided t tests comparing baseline to final-week measurements revealed no significant change in Fel d I within each group (mean change ±SD: washing; 487.6 ± 1896.4 mU per 30 minutes, p = 0.63; Allerpet-C spray, 429.2 ± 871.6 mU per 30 minutes, p = 0.46 acepromazine; −620.6 ± 1031.2, p = 0.52 per 30 minutes). Furthermore, analysis of covariance revealed no significant change in Fel d I levels between groups (p = 0.72). Conclusions: Our data do not show significant reductions in Fel d I shedding as a result of any of these treatments. Therefore we cannot recommend them to patients allergic to cats. (J ALLERGY CLIN IMMUNOL 1995;95:1164-71.)     

Identification of a voltage- and calcium-dependent non-selective cation channel in cultured adult and fetal human nasal epithelial cells

The apical membranes of cultured human nasal epithelial cells from adults and fetuses were investigated with the patch-clamp technique. Amiloride-insensitive, calcium- and voltage-dependent, non-selective cation channels were found in 4% of the cell-attached, and 18% of the inside-out and outside-out patches (n=412). Multiple functional channels were present in more than 90% of these patches, with a mean of 3.9 channels per patch (n=55). The current-voltage relationship can be described by the Goldman equations and the single channel conductance was 20.1±0.3 pS (n=29) in adult and 20.7±0.4 pS (n=44) in fetal cells in symmetrical 150mM NaCl solutions. The channels were highly selective for cations: P_Na/P_Cl was 30 in adult and 45 in fetal experiments. They were equally permeable for K⁺ and Na⁺, somewhat less for Cs⁺, and impermeable for choline⁺ and tetraethylammonium⁺. The open probability was voltage dependent: it increased approximately 2-fold with 30mV depolarization in the potential range from −60mV to +60mV. The channels were activated by Ca²⁺ concentrations of about 10⁻⁴M at the cytoplasmic side, but were insensitive to extracellular Ca²⁺ and amiloride (10⁻⁴M). The non-selective cation channels found in apical membranes of cultured fetal nasal epithelial cells were not different from the adult ones.     

Nasal histamine challenge in nonallergic and allergic subjects evaluated by acoustic rhinometry

Nasal patency shows spontaneous variations but is influenced by a number of factors like exercise and allergic conditions. Nasal histamine challenge has been used to define nasal hypersensitivity. We have applied acoustic rhinometry as a new objective method to study the spontaneous variations of the nasal mucosa and its response to histamine challenge in 12 nonallergic subjects and 12 subjects with nasal allergy to pollen, but out of the pollen season. Measurements of the minimum cross-sectional area and the volume of the nasal cavities were done every 15 min for 6 h. More pronounced spontaneous variations, defined by the coefficient of variation of the measurements, were encountered in the allergic than in the nonallergic subjects, especially with regard to the minimum cross-sectional areas in the nasal cavities (P < 0.02). Allergic subjects showed increased sensitivity to histamine, as compared with nonallergic subjects, during low-concentration (0.1%) challenge (P < 0.05) and a prolonged effect of histamine challenge (P = 0.01). Antihistamine (cetirizine) had a significant effect on the histamine-induced symptoms and decrease of nasal dimensions during histamine challenge, but no significant effect on pollen-induced changes. In the allergic group, the decrease in minimum area during allergen provocation correlated with the level of specific IgE (r = 0.81; P = 0.0015).     

Human lung cancer cell lines express cell membrane complement inhibitory proteins and are extremely resistant to complement-mediated lysis; a comparison with normal human respiratory epithelium in vitro,and an insight into mechanism(s) of resistance

Human lung cancer expresses cell membrane complement inhibitory proteins (CIP). We investigated whether human lung cancer cell lines also express cell-membrane CIP molecules and whether the biology of CIP molecules in these cell lines differs from that of CIP in normal human respiratory epithelium in culture. The cell lines ChaGo K-1 and NCI-H596 were compared with normal human nasal epithelium in primary cultures in respect to the level of cell membrane CIP expression of membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and CD59, in respect to the level of cell resistance to complement-mediated lysis, and in respect to the contribution of cell membrane CIP to cell resistance against complement-mediated lysis. We found, using flow cytometry, that both human lung cancer cell lines expressed MCP, DAF and CD59, as did normal nasal epithelial cells. However, normal cells showed a large subpopulation of low DAF-expressing cells (60% of all cells) and a smaller subpopulation of high DAF-expressing cells (40%), while the lung cancer cell lines showed only one cell population, of high DAF expression. In addition, both lung cancer cell lines expressed higher MCP levels, and NCI-H596 cells showed higher levels of CD59. Cell resistance to complement-mediated lysis of both lung cancer cell lines was much higher than that of normal cells. Fifty percent normal human serum, under the same concentrations of complement activators, induced lysis of less than a mean of 10% of lung cancer cells, while lysing up to a mean of 50% of nasal epithelial cells. Lung cancer cell resistance to complement was due to its ability to prevent significant activation of complement upon its cell membrane, as manifested by a failure of complement activators to increase cell membrane deposition of C3-related fragments. The exact mechanism for this resistance remains obscure. Unexpectedly, neutralizing antibodies, anti-MCP and anti-DAF were entirely ineffective and anti-CD59 was only slightly effective (18% mean cell lysis) in increasing the susceptibility of the lung cancer cell lines to complement, while the same antibodies were very effective in facilitating complement-mediated lysis of the normal nasal epithelial cells (50% mean cell lysis with CD59 MoAb). On the other hand, detachment of DAF and CD59 by phosphatidylinositol-specific phospholipase C (PIPLC) from the lung cancer cell lines abrogated their resistance to lysis. We suggest that the biology of cell membrane CIP molecules in human lung cancer cell lines is different from that of CIP in normal respiratory epithelial cells. Human lung cancer cell lines are able to prevent significant complement activation upon its cell membrane and are therefore especially resistant to complement-mediated lysis. Complement resistance may serve this common and highly lethal human cancer as an escape mechanism from the body's immunosurveillance and prevent effective immunotherapy with tumour-specific MoAbs.