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1.
Rhinology ; 48(3): 318-24, 2010 09.
Article in English | MEDLINE | ID: mdl-21038023

ABSTRACT

Evidence suggests IgE may play a role in chronic rhinosinusitis (CRS). We sought to determine if treatment with a monoclonal antibody against IgE (omalizumab) is effective in reducing CRS inflammation. We performed a randomized, double blind, placebo controlled clinical trial in subjects with CRS despite treatment (including surgery). Subjects were randomized to receive omalizumab or placebo for 6 months. The primary outcome was quantitative measurement of sinus inflammation on imaging. Secondary outcome measures included quality of life, symptoms, and cellular inflammation, nasal airflow (NPIF) and olfactory testing (UPSIT). Subjects on omalizumab showed reduced inflammation on imaging after treatment, whereas those on placebo showed no change. The net difference, however, was not different between treatments. Treatment with omalizumab was associated with improvement in the Sino-Nasal Outcome Test (SNOT-20) at 3, 5, and 6 months compared to baseline with no significant changes in the control group. Remaining measures showed no significant differences across treatments. We conclude that IgE plays, at most, a small role in the mucosal inflammation of CRS and the symptoms. Placebo controlled, blinded studies with larger enrollment are needed to determine the clinical significance of any potential change.


Subject(s)
Anti-Allergic Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Rhinitis/drug therapy , Sinusitis/drug therapy , Adult , Antibodies, Anti-Idiotypic , Antibodies, Monoclonal, Humanized , Chronic Disease , Double-Blind Method , Female , Health Status Indicators , Humans , Immunoglobulin E/physiology , Male , Middle Aged , Omalizumab , Quality of Life , Rhinitis/physiopathology , Sinusitis/physiopathology , Treatment Outcome
2.
Clin Exp Allergy ; 34(10): 1649-54, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15479283

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. RESULTS: Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction.


Subject(s)
Histamine H1 Antagonists, Non-Sedating/pharmacology , Loratadine/analogs & derivatives , Loratadine/pharmacology , Paranasal Sinuses/immunology , Pneumococcal Infections/immunology , Rhinitis, Allergic, Seasonal/immunology , Sinusitis/immunology , Animals , Antigens, CD/immunology , Cells, Cultured , Colony Count, Microbial , Female , Flow Cytometry/methods , Male , Mice , Mice, Inbred BALB C , Paranasal Sinuses/drug effects , T-Lymphocytes/immunology
3.
Clin Exp Allergy ; 31(12): 1913-22, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11737044

ABSTRACT

BACKGROUND: Inhalation of hot, humid air (HHA: 37 degrees C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. OBJECTIVE: To investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. METHODS: Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 degrees C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. RESULTS: Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. CONCLUSION: HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.


Subject(s)
Air , Antigens/immunology , Antigens/pharmacology , Histamine/immunology , Histamine/pharmacology , Humidity , Nasal Provocation Tests , Reaction Time/drug effects , Reaction Time/immunology , Ribonucleases , Adult , Atmosphere Exposure Chambers , Blood Proteins/drug effects , Blood Proteins/metabolism , Cross-Over Studies , Eosinophil Granule Proteins , Female , Hot Temperature , Humans , Leukocytes/drug effects , Leukocytes/immunology , Leukocytes/metabolism , Male , Nasal Lavage Fluid/chemistry , Nasal Lavage Fluid/cytology , Nasal Mucosa/chemistry , Nasal Mucosa/physiopathology , Rhinitis, Allergic, Seasonal/etiology , Rhinitis, Allergic, Seasonal/physiopathology , Serum Albumin/drug effects , Serum Albumin/immunology , Serum Albumin/metabolism , Time Factors
4.
Arch Intern Med ; 161(21): 2581-7, 2001 Nov 26.
Article in English | MEDLINE | ID: mdl-11718589

ABSTRACT

BACKGROUND: The daily use of either intranasal corticosteroids or histamine(1) (H(1)) receptor antagonists has proved to be efficacious in the treatment of seasonal allergic rhinitis. Most patients, however, use these medications as needed. Our objective was to compare the effectiveness of as-needed use of H(1) receptor antagonists with that of intranasal corticosteroids in the treatment of seasonal allergic rhinitis. METHODS: We performed a randomized, open-label, parallel-group study comparing the as-needed use of an H(1) receptor antagonist (loratadine) with that of an intranasal corticosteroid (fluticasone propionate) in the management of fall seasonal allergic rhinitis in the fall of 1999. Subjects kept a diary of their daily symptoms and were examined at enrollment into the study and biweekly for 4 weeks during treatment. Outcome measures were the Rhinoconjunctivitis Quality of Life Questionnaire score, daily symptom diary scores, and the number of eosinophils and the levels of eosinophilic cationic protein in nasal lavage samples. RESULTS: Patients in the fluticasone-treated group reported significantly better scores in the activity, sleep, practical, nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life Questionnaire. The median total symptom score in the fluticasone-treated group was significantly lower than that in the loratadine-treated group (4.0 vs 7.0; P<.01). After treatment, the number of eosinophils was significantly smaller in the fluticasone-treated group compared with the loratadine-treated group (P =.001). Eosinophilic cationic protein levels followed the same pattern, with a significant correlation between the levels of eosinophilic cationic protein and the number of eosinophils (r(s) = 0.70, P<.01). CONCLUSION: As-needed intranasal corticosteroids reduce allergic inflammation and are more effective than as-needed H(1) receptor antagonists in the treatment of seasonal allergic rhinitis.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Histamine H1 Antagonists/administration & dosage , Rhinitis, Allergic, Seasonal/drug therapy , Administration, Intranasal , Administration, Oral , Adrenal Cortex Hormones/therapeutic use , Androstadienes/administration & dosage , Androstadienes/therapeutic use , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/therapeutic use , Eosinophils/drug effects , Fluticasone , Histamine H1 Antagonists/therapeutic use , Humans , Loratadine/administration & dosage , Loratadine/therapeutic use , Nasal Lavage Fluid/chemistry , Nasal Provocation Tests , Quality of Life , Treatment Outcome
5.
Arch Otolaryngol Head Neck Surg ; 127(10): 1181-4, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11587596

ABSTRACT

OBJECTIVE: To determine the attitude toward and the state of research within the field of otolaryngology-head and neck surgery. DESIGN: A questionnaire was sent to the chairpersons of departments of otolaryngology where residency training is provided. PARTICIPANTS AND SETTING: Program directors of academic otolaryngology training programs. MAIN OUTCOME MEASURE: Responses to questionnaire. RESULTS: Questionnaires were sent to 95 programs from which 86 responses were received. Respondents believed strongly that research was important to the specialty. Only two thirds of the full-time clinical faculty, however, do research, and on average they devote only 17% of their time to this activity. About a third of those doing research have funding, and the National Institutes of Health support only 12% of clinician-investigators. Although program directors believe that clinicians should do research, three fourths stated that clinicians were too busy to accomplish this goal. Surprisingly, half of the respondents were unaware of residency programs that offered 2 years of research training, aimed to develop clinician-investigators, who can become competitive for attainment of research funding. CONCLUSIONS: Although leaders within our specialty believe that research is important, clinicians are not provided with enough time to conduct research. Furthermore, pathways that would enhance their competitiveness to obtain research funding are not recommended to our future clinicians.


Subject(s)
Otolaryngology , Research , Attitude of Health Personnel , Faculty, Medical , Research Support as Topic/trends , Surveys and Questionnaires , United States , Workload
6.
Am J Respir Crit Care Med ; 164(9): 1640-6, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11719303

ABSTRACT

We previously showed that individuals with seasonal allergic rhinitis (SAR) had a reduced ability to condition air, which was improved by inflammation. We hypothesized that individuals with perennial allergic rhinitis (PAR) would condition air like SAR with inflammation. Because individuals with asthma usually have inflammation in the nose, we hypothesized that they would condition air like individuals with PAR. We performed a prospective, parallel study on 15 normal subjects, 15 subjects with SAR outside their allergy season, 15 subjects with PAR, and 15 subjects with asthma. Cold, dry air (CDA) was delivered to the nose and the temperature and humidity of the air were measured before entering and after exiting the nasal cavity. The total water gradient (TWG) was calculated and represents the nasal conditioning capacity. The TWG in the SAR group was significantly lower than that in normal subjects. There were no significant differences in TWG between the PAR and normal groups. Subjects with asthma had a significantly lower TWG than did normal subjects. There was a significant negative correlation between TWG and Aas score in the group with asthma (r(s) = -0.8, p = 0.0007). Our data show that subjects with asthma have a reduced ability of the nose to condition CDA compared with normal subjects, but which is similar to SAR out of season.


Subject(s)
Asthma/physiopathology , Humidity , Nasal Cavity/physiopathology , Nasal Mucosa/physiopathology , Temperature , Adolescent , Adult , Analysis of Variance , Asthma/immunology , Case-Control Studies , Female , Humans , Male , Middle Aged , Nasal Cavity/immunology , Nasal Mucosa/immunology , Neutrophils/metabolism , Prospective Studies , Rhinitis, Allergic, Perennial/physiopathology , Rhinitis, Allergic, Seasonal/physiopathology , Statistics, Nonparametric
7.
J Appl Physiol (1985) ; 91(6): 2459-65, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11717205

ABSTRACT

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position (P < 0.01). TWG in supine position was significantly lower than that in upright position (P < 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position (P < 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.


Subject(s)
Air , Hot Temperature , Humidity , Nasal Cavity/physiology , Supine Position/physiology , Adult , Body Temperature , Female , Humans , Male , Nasal Mucosa/physiology
8.
J Allergy Clin Immunol ; 108(3): 424-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11544463

ABSTRACT

BACKGROUND: Although it is not proven, one factor considered important in the development of sinusitis is allergic rhinitis. OBJECTIVE: The purpose of this study was to determine whether ongoing allergic rhinitis enhances the infection and inflammation associated with Streptococcus pneumoniae acute sinus infection. METHODS: BALB/c mice were sensitized to ovalbumin by intraperitoneal injection. After infection of the sinuses by S pneumoniae, either with or without concomitant administration of ovalbumin to induce allergic inflammation, mice were killed at various times and their heads were prepared for histologic evaluation of the sinuses. RESULTS: Mice became allergic to ovalbumin and developed eosinophilia in the sinus and lung cavities in response to ovalbumin administration to each of the respective cavities. In comparison with controls, the mice with ongoing nasal allergic inflammation that were inoculated with S pneumoniae had significantly more bacteria recovered at sacrifice and had significantly more inflammation, as indicated by neutrophil, eosinophil, and mononuclear influx into the sinus mucosa. The percentage of the sinus area occupied by neutrophil clusters was also increased after infection in the allergic mice in comparison with the control mice. CONCLUSION: Our data demonstrate that mice can be sensitized to ovalbumin and develop a localized allergic reaction in the skin, nose, or lung. An ongoing local allergic response augments bacterial infection in these animals. We also demonstrate that allergic sensitization alone, allergen exposure alone, or an allergic response at a distal site, the lung, does not augment the sinus infection.


Subject(s)
Hypersensitivity/complications , Pneumococcal Infections/etiology , Sinusitis/etiology , Animals , Eosinophils/cytology , Female , Male , Mice , Mice, Inbred BALB C , Mucous Membrane/cytology , Neutrophils/cytology , Ovalbumin/immunology
9.
Arch Otolaryngol Head Neck Surg ; 127(8): 985-90, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11493211

ABSTRACT

BACKGROUND: Previous investigations have shown that mice with a tendency toward a T(H)1 or T(H)2 lymphocyte response manifest different reactions to inoculation with the parasite Leishmania major. BALB/c mice (with a tendency for a T(H)2 response) showed evidence of systemic infection, whereas C57Bl/6 mice (with a tendency for a T(H)1 response) showed only a local reaction. OBJECTIVE: To investigate whether BALB/c and C57Bl/6 mice respond differently to acute bacterial infection of the sinuses. METHODS: We inoculated the nasal cavities of C57Bl/6 and BALB/c mice with Streptococcus pneumoniae (type ATCC59), or with broth as a control. The mice were humanely killed 2, 5, 10, and 14 days after inoculation. Their heads were fixed, decalcified, and embedded in paraffin blocks. Sections were stained with hematoxylin and eosin, and the degree of inflammation was quantified by the number of neutrophils per square millimeter of the sinus mucosa and the percentage of the sinus cavity occupied by neutrophil clusters. RESULTS: Both groups of mice showed evidence of inflammation that was significantly greater than controls (P =.01), with no difference between groups. There was a correlation between the number of neutrophils per square millimeter in the sinus mucosa and the percentage of neutrophil clusters (C57Bl/6 mice, r = 0.37, P<.001; BALB/c mice, r = 0.20, P<.001). In the infected mice, the number of infiltrating neutrophils was significantly greater (P<.001) in anatomically lower (dependent) areas of the sinuses compared with the upper areas. CONCLUSION: Unlike leishmaniasis, acute bacterial sinusitis is not affected by the tendency of the host to favor either a T(H)1 or T(H)2 response.


Subject(s)
Neutrophils/immunology , Pneumococcal Infections/immunology , Sinusitis/immunology , Streptococcus pneumoniae , Acute Disease , Animals , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neutrophils/pathology , Pneumococcal Infections/pathology , Respiratory Mucosa/pathology , Sinusitis/pathology , Th1 Cells/immunology , Th2 Cells/immunology
10.
Am J Rhinol ; 15(1): 41-5, 2001.
Article in English | MEDLINE | ID: mdl-11258654

ABSTRACT

The nose functions to warm and humidify inspired air. The factors that influence these functions have been studied to a limited degree. We have developed a method for measuring the temperature and relative humidity of the air before and after nasal conditioning to study nasal function. In this experiment we studied the effects of raising the mucosal surface temperature by immersion of the feet in warm water. Six subjects (avg. age = 27.0 years) were randomized to immersion of the feet in 30 degrees C and 40 degrees C water. The nasal mucosal temperature increased significantly from the 32.2+/-1.3 degrees C during immersion in the 30 degrees C water to the 33.1+/-1.2 degrees C during immersion in 40 degrees water (p < 0.05). No significant difference in nasal volume was noted between the 30 degrees (17.8+/-4.5 cc) and the 40 degrees (17.7+/-5.3 cc) immersions. There was a significant increase in the conditioning capacity of the nose (as measured by total water content of inspired air) in response to cold-air challenge during the 40 degrees immersion (1669+/-312 mg water) when compared to the 30 degrees immersion (1324+/-152 mg water). From these data we deduce that warming of the nasal mucosa improves the ability of the nose to condition inspired air without a significant change in the volume of the nasal cavity.


Subject(s)
Air , Body Temperature , Hot Temperature , Humidity , Nasal Cavity/physiology , Nasal Mucosa/physiology , Acoustics , Adult , Air Conditioning , Analysis of Variance , Female , Foot/physiology , Humans , Immersion/adverse effects , Male , Nasal Cavity/anatomy & histology , Nasal Mucosa/anatomy & histology , Random Allocation
11.
Arch Otolaryngol Head Neck Surg ; 127(2): 193-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11177038

ABSTRACT

OBJECTIVE: To evaluate whether 1 year of continuous treatment with intranasal fluticasone propionate would lead to atrophy in the nasal mucosa compared with an active control, oral terfenadine. DESIGN: Prospective, randomized, multicenter, open-label, parallel-group study. SETTING: Two tertiary care academic institutions. PATIENTS: Seventy-five subjects older than 18 years with perennial allergic rhinitis. INTERVENTIONS: Patients received either fluticasone propionate aqueous nasal spray, 200 microg once daily, or terfenadine, 60 mg twice daily, for 1 year. Nasal biopsy specimens were obtained before and after 1 year of treatment and were evaluated for evidence of atrophy. MAIN OUTCOME MEASURES: Epithelial and collagen layer thickness of the nasal mucosa as assessed by light microscopy and the presence and degree of edema, and regularity of collagen fibrils as assessed by electron microscopy. Analyses were performed without knowledge of subject identity or treatment assignment. RESULTS: Neither fluticasone nor terfenadine treatment led to atrophy in the nasal mucosa by clinical or histologic observation. No significant changes from baseline were observed for any assessment of atrophy. In contrast to what would have been expected if atrophy were to occur, mean epithelial layer thickness in the fluticasone group significantly increased compared with terfenadine treatment (P = .03). CONCLUSIONS: Treatment with intranasal fluticasone for 1 year increases the thickness of the nasal epithelium as compared with a year's treatment with terfenadine and does not lead to atrophy in the nasal mucosa. The increased thickness in the fluticasone treatment may represent repair from epithelial damage caused by chronic allergic inflammation.


Subject(s)
Androstadienes/administration & dosage , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/adverse effects , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Nasal Mucosa/drug effects , Rhinitis, Allergic, Perennial/drug therapy , Rhinitis, Allergic, Seasonal/drug therapy , Administration, Intranasal , Administration, Oral , Adult , Androstadienes/adverse effects , Atrophy , Female , Fluticasone , Glucocorticoids , Humans , Male , Middle Aged , Nasal Mucosa/pathology , Prospective Studies , Rhinitis, Allergic, Perennial/pathology , Rhinitis, Allergic, Seasonal/pathology , Terfenadine/administration & dosage
13.
J Allergy Clin Immunol ; 106(6): 1045-52, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11112885

ABSTRACT

BACKGROUND: We have previously shown that subjects with seasonal allergic rhinitis out of season had a reduced ability to warm and humidify air compared with normal subjects. OBJECTIVE: We sought to investigate whether allergic reactions induced by either seasonal exposure or nasal challenge with antigen would decrease the capacity of the nose to condition cold, dry air. METHODS: We performed two prospective studies comparing the effects of allergic inflammation, induced by either seasonal exposure or nasal challenge with antigen, on nasal conditioning capacity (NCC). The total water gradient (WG) across the nose was used to represent the NCC. In the first study, the NCC was measured and compared before and during the allergy season in 10 subjects with seasonal allergic rhinitis. In the second study, 20 subjects with seasonal allergic rhinitis were recruited outside of the allergy season. NCC was measured and compared before and 24 hours after challenge with antigen. RESULTS: In the first study, seasonal allergic subjects in season showed a significant increase in NCC when compared with their preseason baseline (total WG in season: 2050 +/- 138 mg vs total WG preseason: 1524 +/- 100 mg; P <.01). In the second study, antigen challenge led to early-phase and late-phase responses. There was a statistically significant increase in NCC 24 hours after antigen challenge compared with that before antigen challenge (total WG after antigen challenge: 1938 +/- 101 mg vs total WG before antigen challenge: 1648 +/- 84 mg; P =.01). CONCLUSION: Allergic reactions induced by either seasonal exposure or antigen challenge increase the ability of the nose to condition inspired air. We speculate that allergic inflammation increases this ability by changing the perimeter of the nasal cavity.


Subject(s)
Nose/physiology , Rhinitis, Allergic, Perennial/epidemiology , Rhinitis, Allergic, Seasonal/epidemiology , Adult , Allergens/pharmacology , Female , Hot Temperature , Humans , Humidity , Male , Nasal Provocation Tests , Prevalence , Prospective Studies , Respiration/immunology , Rhinitis, Allergic, Perennial/physiopathology , Rhinitis, Allergic, Seasonal/physiopathology
15.
Am J Respir Crit Care Med ; 162(3 Pt 1): 1031-7, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10988126

ABSTRACT

We have developed a method for measuring the temperature and relative humidity of air prior to and after nasal conditioning and used it to study the effect of treatment with ipratropium bromide on the ability of the nose to condition cold, dry air. We performed randomized, double-blind, placebo-controlled, two-way crossover studies and an open study in nonallergic subjects. The subjects were treated with ipratropium bromide (84 microgram) or normal saline solution sprayed into the nasal cavity 15 min before the measurement of nasal conditioning capacity. Cold, dry air was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before entering and after exiting the nasal cavity. The total water gradient across the nose was calculated and represents nasal conditioning capacity. Ipratropium bromide treatment significantly increased nasal conditioning capacity when compared with saline. Ipratropium bromide led to less reduction in the cold, dry air-induced decrease in the nasal volume (p < 0.05) without affecting the decrease in nasal surface temperature during cold, dry air exposure (p = 0.3). Our data show that ipratropium bromide increases the ability of the nose to condition cold, dry air. Thus, treating rhinitis with ipratropium bromide should not increase the burden for inspired air conditioning on the conducting pulmonary airways.


Subject(s)
Body Temperature Regulation/drug effects , Bronchodilator Agents/pharmacology , Humidity , Ipratropium/pharmacology , Nasal Mucosa/drug effects , Administration, Intranasal , Adult , Body Temperature Regulation/physiology , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle Aged , Nasal Mucosa/physiology
16.
Arch Otolaryngol Head Neck Surg ; 126(6): 749-54, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10864113

ABSTRACT

BACKGROUND: We have previously reported that preconditioning allergic subjects with hot, humid air (HHA) (temperature, 37 degrees C; relative humidity >95%) in an environmental chamber resulted in partial inhibition of the early response to nasal allergen challenge. OBJECTIVE: To investigate whether this inhibitory effect could be achieved by inhalation of HHA via a face mask. DESIGN: Randomized, 4-way crossover study. SUBJECTS: Eighteen subjects with seasonal allergic rhinitis participated in the study outside of their allergy season. INTERVENTIONS: Subjects underwent preconditioning with room air (RA) (temperature, 25 degrees C; relative humidity <20%) or HHA either in a chamber or delivered via a face mask for 1 hour prior to and during nasal challenge with diluent for the allergen extract followed by 2 increasing doses of allergen. RESULTS: Net changes from diluent challenge for all parameters were compared between HHA and RA in each delivery method. Hot, humid air delivered by mask significantly inhibited the mean+/-SEM number of allergen-induced sneezes (HHA, 2.7+/-0.6; RA, 6.6+/-2.1; P=.03), congestion score (HHA, 2.3+/-0.5; RA, 3.4+/-0.5; P=.01), and secretion weights (HHA, 26.9+/-4.4 mg; RA, 38.6+/-5.0 mg; P=.048). However, HHA inhaled in a chamber significantly inhibited only the mean+/-SEM allergen-induced congestion (HHA, 1.2+/-0.4; RA, 3.6+/-0.6; P=.002) and pruritus (HHA, 0.7+/-0.3; RA, 2.3+/-0.5; P=.002) scores. CONCLUSIONS: Preconditioning the nasal mucosa with HHA partially decreases the early response to nasal challenge with antigen irrespective of the administration technique. The secretory response, however, is only inhibited by localized delivery of HHA to the nose. The inhibitory effects of HHA are therefore probably related to local changes in the nasal mucosa and are not dependent on total body exposure to HHA.


Subject(s)
Atmosphere Exposure Chambers , Bronchial Provocation Tests , Nasal Mucosa , Rhinitis, Allergic, Seasonal/prevention & control , Adult , Allergens , Cross-Over Studies , Female , Humans , Humidity , Male , Masks , Serum Albumin/analysis , Temperature
17.
Allergy ; 55 Suppl 64: 17-27, 2000.
Article in English | MEDLINE | ID: mdl-11291777

ABSTRACT

The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the allergic response. In animal models, mizolastine inhibits antigen-induced eosinophil infiltration into mouse skin and into the nasal cavity of guinea-pigs. Mizolastine also significantly inhibits antigen-induced neutrophil infiltration into the bronchoalveolar lavage fluids of guinea-pigs. In addition, it inhibits arachidonic acid-induced paw oedema in rats without affecting carrageenin-induced rat paw oedema, suggesting an effect on LT generation. In man, mizolastine inhibits early and late antigen-induced soluble intercellular adhesion molecule 1 (ICAM-1) levels in skin blisters. It also inhibits anaphylactic release of histamine from rodent mast cells, LTC4 and LTB4 release from mouse bone-marrow-derived mast cells, LTC4 release from rat intestinal mast cells, and 5-lipoxygenase activity of polymorphonuclear neutrophils of guinea-pig intestines and rat basophilic leukaemia cells. It is clear that a number of H1-antihistamines have multiple effects on the allergic inflammatory response. It is equally clear that these antiallergic effects are not uniformly shared among all drugs of this class. The assessment of the clinical significance of these results and research regarding the parts of the molecules responsible for these activities are underway.


Subject(s)
Anti-Allergic Agents/immunology , Histamine H1 Antagonists/immunology , Histamine H1 Antagonists/therapeutic use , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Animals , Anti-Allergic Agents/therapeutic use , Benzimidazoles/immunology , Benzimidazoles/therapeutic use , Disease Models, Animal , Humans , Receptors, Histamine H1/immunology , Rhinitis/drug therapy , Rhinitis/immunology
18.
Otolaryngol Head Neck Surg ; 121(5): 585-90, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10547475

ABSTRACT

In this in vivo prospective, controlled study, we have examined the capsaicin-induced levels and secretion patterns of the colocalized neuropeptides substance P, calcitonin gene-related peptide (CGRP), and neurokinin A in nasal secretions of subjects with nasal polyps, and we compared these with secretion patterns from healthy subjects and from subjects with allergic rhinitis. Capsaicin was used to elicit neuropeptide release. The neuropeptide levels were measured by an ELISA technique. For substance P, subjects with nasal polyps responded very poorly to capsaicin stimulation. The atopic group was more reactive to capsaicin stimulation than control subjects. For CGRP the increase was immediate in all groups. Atopic subjects and subjects with polyps had a less pronounced but sustained response to capsaicin stimulation. CGRP levels in atopic subjects and those with polyps were restored rapidly. Atopic subjects had higher neurokinin A levels with an immediate and sustained response to capsaicin. Control subjects had higher levels than those with polyps, but both groups were nonresponsive to capsaicin stimulation.


Subject(s)
Nasal Polyps/physiopathology , Neuropeptides/metabolism , Nose Neoplasms/physiopathology , Adolescent , Adult , Calcitonin Gene-Related Peptide/metabolism , Capsaicin , Female , Humans , Male , Middle Aged , Nasal Mucosa/metabolism , Nasal Polyps/diagnosis , Neurokinin A/metabolism , Nose Neoplasms/diagnosis , Prospective Studies , Reference Values , Respiratory Hypersensitivity/diagnosis , Respiratory Hypersensitivity/physiopathology , Substance P/metabolism
19.
J Appl Physiol (1985) ; 87(3): 1038-47, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10484575

ABSTRACT

To study the response of the maxillary sinus to histamine provocation, we performed a double-blind, randomized, crossover trial during which nonallergic subjects without symptoms of rhinitis (n = 25) received either 10 mg loratadine or placebo once daily for a week and then underwent nasal challenge with histamine (3, 10, and 30 mg/ml) followed, 24 h later, by a maxillary sinus challenge while still receiving the medication. Nasal challenge with histamine led to significant increases in vascular permeability, reflex nasal secretions, sneezing, and other nasal symptoms. Sinus challenge resulted in significant increases in vascular permeability within the sinus cavity (P < 0.01) and some nasal symptoms but no significant change in reflex nasal secretions. The response of the sinus mucosa to histamine was lower in magnitude than that of the nose. Treatment with loratadine resulted in a significant inhibition of the histamine-induced changes in both nasal and sinus cavities. Our data suggest the lack of a sinonasal reflex response to histamine provocation of the maxillary sinus of nonallergic individuals.


Subject(s)
Histamine H1 Antagonists/pharmacology , Histamine , Loratadine/pharmacology , Maxillary Sinus/physiology , Nose/physiology , Adult , Cross-Over Studies , Double-Blind Method , Female , Humans , Hypersensitivity/physiopathology , Male , Maxillary Sinus/drug effects , Nose/drug effects , Pilot Projects , Reflex/drug effects , Reflex/physiology , Serum Albumin/metabolism , Sneezing/physiology
20.
J Allergy Clin Immunol ; 104(2 Pt 1): 285-93, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10452746

ABSTRACT

BACKGROUND: We have previously shown that hot, humid air partially reduces the early allergic response. Mechanisms for this effect have been suggested, but none has gained universal acceptance. The most likely explanations are a modification of mucosal temperature or a reduction in nasal secretion osmolality. OBJECTIVE: We sought to investigate whether increasing the nasal mucosal surface temperature by immersing feet in warm water (WW) could decrease the immediate nasal response to challenge with allergen. METHODS: We performed a randomized, 2-way crossover study on 14 subjects with seasonal allergic rhinitis outside of their allergy season. They immersed their feet in either WW (42 degrees C) or room-temperature water (RW; 30 degrees C) for 5 minutes before and during nasal challenge with diluent for the allergen extract, followed by 2 increasing doses of allergen. RESULTS: There was a statistically significant increase in nasal mucosal temperature from baseline after warming of feet (WW, 1.9 +/- 0.1 degrees C, vs RW, 0.2 +/- 0.1 degrees C; P =. 001), but there were no significant differences in body temperature (WW, 0.1 +/- 0.1 degrees C, vs RW, 0.4 +/- 0.1 degrees C; P =.1). Net changes from diluent challenge for all parameters were compared between immersion of feet in WW and RW. Immersion of feet in WW significantly inhibited allergen-induced sneezes (WW, 5.7 +/- 1.1, vs RW, 11.6 +/- 3.2; P <.01), human serum albumin levels (WW, 941.7 +/- 172.2 microg/mL vs RW, 1524.8 +/- 220.6 microg/mL; P <.01), and secretion weights (WW, 30.5 +/- 7.2 mg, vs RW, 41.8 +/- 6.8 mg; P <. 01). CONCLUSION: Our data show that warming of feet decreases the early response to nasal challenge with antigen. This inhibitory effect is probably related to the increase in the nasal mucosal temperature.


Subject(s)
Nasal Mucosa , Nasal Provocation Tests , Skin Temperature , Adolescent , Adult , Cross-Over Studies , Female , Foot , Hot Temperature , Humans , Male , Rhinitis, Allergic, Seasonal/immunology
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