phenylephrine-hydrochloride and Bronchial-Hyperreactivity

Perennial rhinitis and asthma are clinical syndromes representing a range of overlapping pathologies; accurate classification should therefore precede any comparison. Although the sinonasal cavities, trachea and bronchi have a common respiratory mucosa, there are also anatomical differences. For example, the nose has a capacitance vessel network and the lower airways possess smooth muscle, both of which are responsive to neurohumoral influences. The prevalence of rhinitis and asthma has increased over the last three decades. Rhinitis occurs in around 75% of allergic asthmatics while 20% of perennial allergic rhinitics develop asthma. Eosinophils, and their associated proteins and cytokines, may play a central role in both perennial rhinitis and asthma with and without atopy. The characteristic pathology of asthma can be summarized as a chronic, desquamating, eosinophilic bronchitis. Non-allergic rhinitis with eosinophilia is recognized, but without consistent evidence of epithelial damage. Eosinophils are also present in rhinosinusitis with polyposis, particularly in patients with aspirin sensitivity, in whom asthma also often occurs. Increased mast cell activation and mediator release is evident in both perennial rhinitis and asthma following allergen challenge. The importance of mast cells in non-atopic asthma and polyposis is also recognized. Adhesion molecules may also be upregulated, with an increased number and activation of TH2 lymphocytes. However, allergen-resultant T-cell activation may be less marked in the nose than in the lung. Autonomic imbalance also plays a role in both conditions via changes in neural tone to effector tissues, release of neuropeptides, and interplay with cellular recruitment. Pharmacological manipulation of rhinitis and asthma also illustrates the pathological similarities and differences.

Topics: Asthma; Autonomic Nervous System; Bronchi; Bronchial Hyperreactivity; Eosinophils; Glucocorticoids; Humans; Inflammation; Lung; Nose; Rhinitis, Allergic, Perennial; Sinusitis; Trachea

The response of asthmatic patients to exercise differs from that of healthy subjects, and the mechanisms responsible for the exercise-induced bronchoconstriction in the former group remain uncertain. The severity of bronchospasm may be related to water loss from the respiratory tree, but there are conflicting explanations for this. The response of the nose to exercise, in healthy subjects or in patients with asthma and rhinitis, has been the subject of few investigations, but a recent study found that the nose responds in a different fashion to the bronchi in patients with rhinitis and asthma. The bronchial tree responds by narrowing, while the nose becomes more patent. There is evidence that the bronchi are the main sites of airway narrowing in exercise-induced bronchoconstriction, while there can also be simultaneous tracheal dilatation. In addition, it now appears that the nasal response to exercise in all subjects parallels that of the trachea. In total, the results suggest that different mechanisms are responsible for regulating the patency of the upper and lower airways.

Topics: Asthma, Exercise-Induced; Bronchi; Bronchial Hyperreactivity; Exercise; Humans; Nose; Rhinitis

The incidence of rhinitis is on the increase, especially in towns and cities with high levels of pollution from motor traffic and industry. There is a growing body of evidence which links this increased incidence of rhinitis to chronic nasal irritation from industrial pollution. Studies on the mechanisms of nasal inflammation and the nasal immune response are now providing insights into the etiology of rhinitis. This knowledge will help in the development of therapies aimed at alleviating the symptoms of rhinitis and controlling the development of rhinitis in susceptible individuals. This review discusses some of the factors that may explain the increased incidence of rhinitis and examines basic mechanisms involved in the nasal response to infection and allergy.

Topics: Air Pollution; Bronchial Hyperreactivity; Humans; Nose; Nose Diseases; Respiratory Hypersensitivity; Rhinitis; Sneezing

This study compared the effects of 2-week administration of a topical steroid (fluticasone propionate [FP] 100 micrograms twice daily) with placebo in 28 patients with perennial nasal allergy who were allergic to house dust and mites in a double-blind randomized study. The number of inflammatory cells and decidual epithelial cells and concentrations of tryptase and eosinophil cationic protein in nasal lavages, and reactivity of the nasal mucosa to histamine and to antigen were investigated. The topical steroid, FP, significantly inhibited all of these assessments. The degree of improvement of nasal reactivity to histamine significantly correlated with the degree of decrease in eosinophil cationic protein levels.

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Antigens; Blood Proteins; Bronchial Hyperreactivity; Child; Chymases; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Glucocorticoids; Histamine; Humans; Hypersensitivity, Immediate; Male; Nasal Mucosa; Nose; Respiratory Hypersensitivity; Ribonucleases; Serine Endopeptidases; Therapeutic Irrigation; Time Factors; Tryptases

Ten rhinitic patients allergic to grass pollen were challenged with histamine intranasally 24 hours before and 24 hours after nasal provocation with grass pollen. Up to ten hours after allergen provocation nasal lavage fluid was obtained to characterize early and late phase reactions by measuring the levels of histamine and leukotrienes as indicators of mediator release, and albumin as a marker of increased vasopermeability. Ten minutes after allergen challenge with 10,000 BU grass pollen extract LTC4,D4, and albumin significantly increased from 62 to 576 pg/mL (P = .008) and from 15 to 81 micrograms/mL (P = .008), respectively, without significant changes after placebo challenge a week earlier. Although the patients showed increased responsiveness to histamine after allergen challenge compared with a placebo-challenged control group (P = .02), one patient only demonstrated a late phase nasal allergic reaction characterized by recurrence of clinical symptoms eight to ten hours after allergen challenge and recurrence of mediators in lavage fluid. It is concluded that an isolated early response after allergen challenge is sufficient to induce nasal hyperreactivity. A biochemically or clinically defined late phase allergic reaction does not necessarily accompany allergen-induced hyperreactivity.

Topics: Adolescent; Adult; Airway Resistance; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Female; Histamine; Humans; Male; Nasal Provocation Tests; Nose; Serum Albumin; SRS-A

The purpose of the study was to compare in vitro airway responses to neurokinin A & B (NKA and NKB) and expression of NK-2 receptors in airways of horses affected and unaffected with recurrent airway obstruction (RAO). Neurokinin-A, an inflammatory mediator belonging to the tachykinin family of neuropeptides, causes bronchoconstriction by binding to NK-2 receptors. Neurokinin-B is a lesser-known neuropeptide that acts on NK-3 receptors. Horses were placed into RAO-affected and RAO-unaffected groups based on their history, clinical scoring, and pulmonary function testing. Lung tissue from each lobe was collected for immunohistochemical staining for NK-2 receptors. Cumulative concentration-response relationships were determined on bronchial rings (4-mm wide) collected and prepared from the right diaphragmatic lung lobe to graded concentrations (half log molar concentrations 10(-7)M to 10(-4)M) of NKA and NKB. The results showed that NKA caused significantly greater contraction than NKB in both groups. In RAO-affected horses, both agents produced significantly greater bronchial contractions than those in the RAO-unaffected horses. Immunohistochemical staining showed that the overall NK-2 receptor distribution was significantly increased in bronchial epithelium and smooth muscles of bronchi and pulmonary vessels of RAO-affected than RAO-unaffected horses. The findings indicate that NK-2 receptors are up-regulated in RAO, suggesting that NK-2 receptor antagonists may have some therapeutic value in controlling the progression of airway hyperreactivity in horses affected with RAO.

Topics: Airway Obstruction; Animals; Antibodies; Bronchi; Bronchial Hyperreactivity; Horse Diseases; Horses; Immunohistochemistry; Muscle, Smooth; Neurokinin A; Neurokinin B; Nose; Receptors, Neurokinin-2; Recurrence; Respiratory Physiological Phenomena

Between the upper and the lower respiratory tracts exists a link. Numerous epidemiological, immunological studies and clinical observations suggest the pathogenic unity of the upper and lower airways. The most important observations regarding the nose-lung interaction is rhinitis and asthma. The inflammatory process in the nose is the same as in the bronchi, clinically defined as rhinosinusitis, nasal polyps, asthma, bronchial hyperreactivity, allergy, viral infections. The strict link between the rhinosinusitis and asthma implies new possibility of influencing one of the two complaints by treating the other one with an integrated therapy (pharmacotherapy, endonasal microsurgery).

Topics: Asthma; Bronchi; Bronchial Hyperreactivity; Humans; Nose; Respiratory System; Rhinitis

The decongestion test involves spraying an intranasal vasoconstrictor drug to evaluate the recovery of nasal airflow.. The aim of this study was to assess the relationship between pulmonary function (assessed by spirometry and methacholine challenge) and nasal airflow recovery after a topical vasoconstrictor had been administered in patients with allergic rhinitis (perennial, seasonal, or mixed allergic rhinitis).. A total of 150 subjects were studied. The total symptom score, sensitization, and pulmonary function were all assessed. All subjects underwent rhinomanometry and the decongestion test.. Univariate analysis revealed that nasal symptoms and spirometric parameters (except FEF(25-75) in subjects with seasonal allergic rhinitis) were not. Only bronchial hyperreactivity, assessed by methacholine challenge, proved to be significantly (and independently) associated with outcome (OR 1.45, P = 0.025).. This study provides the first evidence of an association between a positive response to the decongestion test and bronchial hyperreactivity, assessed by methacholine challenge, in patients with allergic rhinitis.

Topics: Adult; Bronchial Hyperreactivity; Bronchial Provocation Tests; Humans; Male; Nose; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Spirometry

The relationship among inhaled allergen exposure, sensitization, and asthma severity is unknown.. To investigate the relationship among personal allergen exposure, reservoir dust allergen concentrations, and physiological measures of asthma severity; to examine the numbers of particles inspired that react with autologous IgE and IgG4.. A total of 117 patients with asthma wore 5 nasal air samplers (NASs) at home: 1 each for exposure to mite, cat and dog allergens, NAS-IgE, and NAS-IgG4. NASs were processed by HALOgen assay for allergen measurement and incubated with autologous serum for detection of NAS-IgE and NAS-IgG4. Reservoir allergen concentrations were measured by ELISA. Subjects' asthma severity was ascertained by measurement of lung function, exhaled nitric oxide, and nonspecific bronchial reactivity to histamine.. Nasal air sampler counts correlated with reservoir concentrations for cat (r=0.31; P=.001) and dog (r=0.20; P=.03) but not mite allergen (r=0.001; P=1.0). There was no significant relationship between sensitization with exposure measured by NAS to any allergen and PD20FEV1 (F[3,60]=1.60; P=.20); however, sensitization with exposure in dust reservoirs had significant effects on PD20FEV1 for any allergen (F[3,59]=3.12; P=.03), cat (F[3,59]=3.77; P=.01), and mite (F[3,59]=2.78; P=.05), but not dog (F[3,59]=1.06; P=.37). We repeated the analysis with separate variables for sensitization and exposure, controlling for the confounders; sensitization but not exposure conferred lower PD20FEV1 values. However, increasing cat allergen exposure was associated with improving bronchial reactivity in not cat-sensitized patients. NAS-IgE and NAS-IgG4 counts bore no relationship to any measure of asthma severity.. Nasal air samplers confer no advantage over reservoir dust analysis for studies of asthma severity.. In common with other measures of exposure, single nasal air samples do not provide a useful measure of home allergen exposure for the individual patient with allergic asthma.

Topics: Adolescent; Adult; Aged; Air Pollution, Indoor; Allergens; Animals; Asthma; Bronchial Hyperreactivity; Cats; Dogs; Dust; Environmental Monitoring; Female; Housing; Humans; Immunoglobulin E; Immunoglobulin G; Inhalation Exposure; Male; Middle Aged; Nose; Pyroglyphidae; Severity of Illness Index

Atopic individuals are predisposed to mounting vigorous T(H)2-type immune responses to environmental allergens. The skin is often the first organ that manifests allergic disease and may provide an early entry point for antigen sensitization.. We sought to determine whether epicutaneous exposure to the aeroallergen Aspergillus fumigatus induces nasal allergic responses. Furthermore, we aimed to examine the mechanism involved.. Wild-type and signal transducer and activator of transcription 6 (STAT6)-deficient mice were exposed to epicutaneous A fumigatus and control antigen ovalbumin. Nasal inflammation and responsiveness to methacholine were monitored.. Exposure to epicutaneous A fumigatus antigen induced a marked atopic dermatitis-like phenotype in a manner significantly more efficient than epicutaneous ovalbumin. A single A fumigatus intranasal challenge induced clinical nasal responses and hyperresponsiveness to methacholine in the nose as manifested by nasal symptoms, accompanied by allergic airway and nasal inflammation. Mechanistic analysis using gene-targeted mice revealed that the clinical nasal responses and hyperresponsiveness were STAT6-dependent. Although STAT6 was required for changes in nasal responses, it was not required for epicutaneous pathology except eosinophilia.. Epicutaneous exposure to the aeroallergen A fumigatus potently primes for STAT6-dependent nasal responses. These results draw attention to the cooperative interaction between the nasal tract and skin.. The skin is a potent site for antigen sensitization in the development of experimental allergic rhinitis.

Topics: Allergens; Animals; Aspergillus fumigatus; Bronchial Hyperreactivity; Hypersensitivity; Interleukin-13; Interleukin-18; Mice; Mice, Inbred BALB C; Nose; Skin; STAT6 Transcription Factor; Th2 Cells

The pathogenesis of allergic rhinitis and its link with asthma are well known. Nevertheless, a complete cross-sectional evaluation of the usually available clinical, functional and immunological parameters has never been made. We assessed nasal symptoms and flow, cytology, cytokines, pulmonary function and methacholine positivity in a large number of patients with pure pollinosis.. Young men presenting at a military hospital for routine follow-up were recruited for the study. They had to suffer from rhinitis alone (without asthma) for at least 2 years and had to have a positive skin prick test to pollens only. During the pollen season, they underwent symptom evaluation, measurement of nasal flow, nasal scraping and lavage (cell count and assay for IL-4, IL-5, IL-8 and IFNgamma), pulmonary function tests and methacholine challenge.. Fifty subjects (23.7+/-4.9 years old) were enrolled. All patients had high clinical scores (9.5+/-1.6) and inflammatory cells (eosinophils: 10.5+/-4 and neutrophils 21.3+/-6) and low nasal flow (482+/-111 ml/s). We found that the number of eosinophils in nasal scrapings highly correlated with all the above-mentioned parameters, including nasal flow, cytokines and spirometric values. A significant positive correlation was found between all inflammatory cells and all cytokines. IL-8, IL-4 and neutrophils displayed only a partial correlation with pulmonary parameters (FEV1, FVC and FEF25-75%), at variance wit IL-5 and eosinophils. Methacholine test positivity significantly correlated with the number of eosinophils in the nasal smear.. Eosinophils in the nasal smear display the best correlation with all the clinical and immunological parameters in allergic rhinitis and also correlate well with methacholine response.

Topics: Adolescent; Adult; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Cell Count; Cytokines; Eosinophils; Humans; Inflammation; Male; Methacholine Chloride; Nasal Lavage Fluid; Neutrophils; Nose; Pollen; Rhinitis, Allergic, Seasonal; Rhinomanometry; Skin Tests; Spirometry

Pollutants originating from the destruction of the World Trade Center (WTC) in New York City on 11 September 2001 have been reported to cause adverse respiratory responses in rescue workers and nearby residents. We examined whether WTC-derived fine particulate matter [particulate matter with a mass median aerodynamic diameter < 2.5 microm (PM2.5)] has detrimental respiratory effects in mice to contribute to the risk assessment of WTC-derived pollutants. Samples of WTC PM2.5 were derived from settled dust collected at several locations around Ground Zero on 12 and 13 September 2001. Aspirated samples of WTC PM2.5 induced mild to moderate degrees of pulmonary inflammation 1 day after exposure but only at a relatively high dose (100 microg). This response was not as great as that caused by 100 microg PM2.5 derived from residual oil fly ash (ROFA) or Washington, DC, ambient air PM [National Institute of Standards and Technology, Standard Reference Material (SRM) 1649a]. However, this same dose of WTC PM2.5 caused airway hyperresponsiveness to methacholine aerosol comparable to that from SRM 1649a and to a greater degree than that from ROFA. Mice exposed to lower doses by aspiration or inhalation exposure did not develop significant inflammation or hyperresponsiveness. These results show that exposure to high levels of WTC PM2.5 can promote mechanisms of airflow obstruction in mice. Airborne concentrations of WTC PM2.5 that would cause comparable doses in people are high (approximately 425 microg/m3 for 8 hr) but conceivable in the aftermath of the collapse of the towers when rescue and salvage efforts were in effect. We conclude that a high-level exposure to WTC PM2.5 could cause pulmonary inflammation and airway hyperresponsiveness in people. The effects of chronic exposures to lower levels of WTC PM2.5, the persistence of any respiratory effects, and the effects of coarser WTC PM are unknown and were not examined in these studies. Degree of exposure and respiratory protection, individual differences in sensitivity to WTC PM2.5, and species differences in responses must be considered in assessing the risks of exposure to WTC PM2.5.

Topics: Air Pollutants; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Dust; Explosions; Female; Lung; Mice; New York City; Nose; Plethysmography, Whole Body; Terrorism

Rhinitis patients may have abnormal airway function as demonstrated by an obstruction in large or small airways and increased bronchial reactivity to inhaled nonspecific provocating agents. The nonspecific bronchial hyperreactivity (BHR) is particularly important in patients with rhinitis because they are more prone to develop asthma. However, the factors associated with BHR in rhinitis patients have not yet been explained. Therefore, we performed this study to determine the differences in airflow rates, and bronchial and nasal resistance between nonasthmatic rhinitis patients with or without BHR, and to evaluate the relationship between these parameters and bronchial reactivity to methacholine. A total of 66 patients with allergic rhinitis but not asthma were selected for the study and divided into two groups; Group 1 (40 patients with allergic rhinitis and negative mechacholine provocation test) and Group 2 (26 patients with allergic rhinitis and positive methacholine provocation test). Pulmonary function tests, methacholine provocation tests, anterior rhinomanometry, and skin prick tests were performed on the patients. The study groups were homogeneous with regard to gender, age, duration of illness, and smoking ratio. Expiratory airflow parameters including FVC, FEV1, PEFR, and FEF25 were similar in both groups, however FEV1/FVC, FEF25-75, FEF50, and FEF75 were significantly lower in Group 2. Additionally, sRaw was significantly higher in Group 2 and negatively correlated with the expiratory airflow parameters for small airways. Total nasal resistance was not different between the groups. There was no correlation between nasal resistance and BHR to methacholine or airway resistance. The present study suggests that nonasthmatic rhinitis patients with BHR may have mild but significant changes in the small airways. Clinical and functional follow-up of these patients should assess the long-term consequences of these parameters and their clinical importance.

Topics: Adolescent; Adult; Bronchial Hyperreactivity; Female; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Male; Manometry; Methacholine Chloride; Middle Aged; Nose; Peak Expiratory Flow Rate; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Skin Tests; Vital Capacity

Very little information is available on the acute histopathological bronchial alterations caused by reactive airways dysfunction syndrome (RADS). We had the opportunity to carry out sequential bronchial biopsies in a subject with RADS due to chlorine (60 h, 15 days, 2 and 5 months after the acute exposure), and also to assess spirometry and bronchial responsiveness to methacholine. A 36 year old worker in a water-filtration plant (nonsmoker) abruptly inhaled high concentrations of chlorine on September 12, 1994. He experienced immediate nasal and throat burning, retrosternal burning and wheezing, and these symptoms persisted during and after the workshift. Two days later, he complained of retrosternal burning, dyspnoea and wheezing. Inspiratory wheezing was documented. His forced expiratory volume in one second (FEV1) was 66% of predicted and the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was slightly abnormal (2.5 mg.mL-1). On the following day, the patient underwent bronchial biopsies, which showed almost complete replacement of the epithelium by a fibrinohaemorhagic exsudate. The subject was prescribed inhaled steroids. Fifteen days after the accident, the PC20 was improved to 6 mg.mL-1. Bronchial biopsies showed considerable epithelial desquamation with an inflammatory exudate and swelling of the subepithelial space. Five weeks after the accident, the PC20 was normal (57 mg.mL-1). Inhaled steroids were stopped. Two months after the accident, the PC20 deteriorated to 4 mg.mL-1. Biopsies then showed regeneration of the epithelium by basal cells and there was still a pronounced inflammatory infiltrate. Inhaled steroids were restarted. Three and five months later, the PC20 was normal (24 mg.mL-1). Bronchial biopsies showed a greatly improved epithelium and reduction of the inflammatory infiltrate. This case report shows that reactive airways dysfunction syndrome can cause acute, marked, though partially reversible, histological abnormalities. Inhaled steroids may modulate changes in bronchial responsiveness in this condition.

Topics: Adult; Aerosols; Anti-Infective Agents; Biopsy; Bronchi; Bronchial Hyperreactivity; Chest Pain; Chlorine; Dyspnea; Epithelium; Follow-Up Studies; Forced Expiratory Volume; Humans; Inflammation; Male; Nose; Occupational Diseases; Pharynx; Regeneration; Respiratory Sounds; Spirometry; Syndrome; Water Purification

The objective of the present study was to investigate nasal function by active anterior rhinomanometry with respect to spirometric data and bronchial hyperresponsiveness to methacholine in 9-year-old children. The study population consisted of 300 children (ages 8 to 11 years; mean, 9.3 years; 161 male, 139 female), who underwent basal rhinomanometry followed by a decongestion test and a lung function test consisting of spirometry and a methacholine provocation test. The flow values of the basal rhinomanometry showed a significant correlation with height and bronchial hyperresponsiveness. The consecutive decongestion test showed a marked increase in flow rates at each level, which was found to be significantly higher in children with bronchial hyperresponsiveness (p < 0.01). The spirometric data showed no influence on rhinomanometric values. These results suggest that nasal dysfunction and reactivity in terms of the decongestion test may be associated with bronchial hyperresponsiveness in children.

Topics: Airway Resistance; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Female; Humans; Male; Methacholine Chloride; Nose; Reference Values

Topics: Anaphylaxis; Bronchial Hyperreactivity; Hypersensitivity; Immune System Diseases; Nose; Tripelennamine

Topics: Anaphylaxis; Bronchial Hyperreactivity; Hypersensitivity; Immune System Diseases; Nose; Tripelennamine