RESUMEN
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Asunto(s)
Asma , Rinitis Alérgica , Rinitis , Humanos , Rinitis/diagnóstico , Rinitis/epidemiología , Rinitis/complicaciones , Asma/diagnóstico , Asma/epidemiología , Asma/etiología , Rinitis Alérgica/complicaciones , Alérgenos , MultimorbilidadRESUMEN
Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Asunto(s)
Asma/epidemiología , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Estacional/epidemiología , Animales , Asma/clasificación , Asma/complicaciones , Niño , Ensayos Clínicos como Asunto , Europa (Continente) , Humanos , Guías de Práctica Clínica como Asunto , Rinitis Alérgica Perenne/clasificación , Rinitis Alérgica Perenne/complicaciones , Rinitis Alérgica Estacional/clasificación , Rinitis Alérgica Estacional/complicaciones , Organización Mundial de la SaludRESUMEN
The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
Asunto(s)
Guías de Práctica Clínica como Asunto , Rinitis Alérgica Perenne/terapia , Asma/prevención & control , Asma/terapia , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Humanos , Técnicas de Planificación , Rinitis Alérgica Perenne/prevención & control , Rinitis Alérgica Estacional/prevención & control , Rinitis Alérgica Estacional/terapiaRESUMEN
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.
Asunto(s)
Antialérgicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Adulto , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Método Doble Ciego , Femenino , Indicadores de Salud , Humanos , Inmunoglobulina E/fisiología , Masculino , Persona de Mediana Edad , Omalizumab , Calidad de Vida , Rinitis/fisiopatología , Sinusitis/fisiopatología , Resultado del TratamientoRESUMEN
We have recently demonstrated that kinins are generated in vivo after nasal challenge with antigen of allergic, but not nonallergic, individuals. The present study was undertaken as a first step in determining the mechanism(s) of kinin formation during the allergic reaction and was directed towards establishing the availability and origin of kininogens in nasal secretions. Allergic individuals (n = 6) and nonallergic controls (n = 5) were challenged with antigen; and by using specific radioimmunoassays, nasal washes, obtained before and after challenge, were assayed for high molecular weight kininogen (HMWK), total kininogen (TK), albumin, and kinins. Dramatic increases in HMWK (1,730 +/- 510 ng/ml), TK (3,810 +/- 1035 ng/ml), kinin (9.46 +/- 1.75 ng/ml), and albumin (0.85 +/- 0.2 mg/ml) were observed after challenge of allergic individuals which correlated (P less than 0.001) with increases in histamine and N-alpha-tosyl-L-arginine methyl esterase activity and with the onset of clinical symptoms. For nonallergic individuals, levels of kininogens, albumin, and all mediators after antigen challenge were not different from base line. Linear regression analysis revealed excellent correlations (P less than 0.001 in each case) between increases in HMWK, TK, kinin, and albumin during antigen titration experiments and between the time courses of appearance and disappearance of HMWK, TK, kinin, and albumin after antigen challenge. Gel filtration revealed no evidence of degradation products of kininogens in nasal washes. For each allergic individual the ratio of HMWK/TK in postchallenge nasal washes was similar to the ratio of these two proteins in the same individual's plasma. These data suggest that, during the allergic reaction, there is an increase in vascular permeability and a transudation of kininogens from plasma into nasal secretions, where they can provide substrate for kinin-forming enzymes.
Asunto(s)
Hipersensibilidad/inmunología , Quininógenos/metabolismo , Mucosa Nasal/metabolismo , Adulto , Alérgenos , Antígenos , Humanos , Hipersensibilidad/metabolismo , Mastocitos/inmunología , Peso Molecular , Pruebas de Provocación Nasal , Albúmina Sérica/metabolismoRESUMEN
Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560 +/- 1,670 pg/ml) but in none of the controls (38 +/- 16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P less than 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100 +/- 4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.
Asunto(s)
Alérgenos/inmunología , Cininas/biosíntesis , Rinitis Alérgica Estacional/metabolismo , Administración Intranasal , Adolescente , Adulto , Alérgenos/administración & dosificación , Relación Dosis-Respuesta Inmunológica , Femenino , Histamina/biosíntesis , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/metabolismo , Péptido Hidrolasas/biosíntesisRESUMEN
The effect of systemic glucocorticoid treatment on early- and late-phase nasal allergic reactions after allergen challenge was determined in a double-blind, cross-over study in 13 allergic individuals. The subjects were pretreated for 2 d before challenge with 60 mg prednisone per day or a matching placebo. A previously described model using repeated nasal lavages for measuring mediator release in vivo was utilized. Symptom scores obtained repeatedly before, during, and after the challenge and the number and timing of sneezes were recorded. The mediators measured were histamine. N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity, kinins, PGD2, and LTC4/D4. Albumin was also measured as a marker of plasma transudation. Blood samples were taken for determination of total number of white blood cells, differential count, and total blood histamine content. No effect of steroid therapy was found on the appearance of symptoms or any of the mediators, except a reduction in kinins, in the early phase of the allergic reaction. However, in the late phase, the prednisone reduced the number of sneezes (P less than 0.01), as well as the level of histamine (P less than 0.05), TAME-esterase activity (P less than 0.05), kinins (P less than 0.05), and albumin (P less than 0.05). Only low levels of leukotrienes were found in the late phase, but the quantities of these mediators seemed to be decreased by the glucocorticoid treatment (P = 0.06). PGD2 did not increase during the LPR and thus was not affected by glucocorticosteroids. The immediate response to a second challenge 11 h after the first was also evaluated. Whereas the appearance of mediators was enhanced over the initial response to the same challenge dose in placebo-treated subjects, this enhancement was abrogated after prednisone treatment. As this dose of drug is known to be clinically effective in treating hay fever, the present study confirms the earlier findings of others that short-term systemic glucocorticoid treatment inhibits the late phase but not the immediate phase of antigen challenge. Furthermore, secondary enhancement of immediate responses is inhibited. This study shows that glucocorticoids inhibit the generation or release of inflammatory mediators during the late reaction and the physiologic response.
Asunto(s)
Hipersensibilidad/tratamiento farmacológico , Mucosa Nasal/metabolismo , Prednisona/uso terapéutico , Administración Intranasal , Aerosoles , Cromatografía Líquida de Alta Presión , Método Doble Ciego , Histamina/análisis , Liberación de Histamina , Humanos , Cininas/análisis , Recuento de Leucocitos , Mucosa Nasal/efectos de los fármacos , Péptido Hidrolasas/análisis , Polen , Prostaglandina D2 , Prostaglandinas D/análisis , Distribución Aleatoria , SRS-A/análisis , Albúmina Sérica/análisis , Estornudo/efectos de los fármacosRESUMEN
Challenge of the nasal mucosa of allergic subjects with specific allergen induces not only the expected sneezing and rhinorrhea, but also the appearance in nasal secretions of mediators commonly associated with activation of mast cells or basophils: histamine, leukotrienes, prostaglandin D2 (PGD2), kinins, and TAME ([3H]-N-alpha-tosyl-L-arginine methyl ester)-esterase. To determine whether specific immunotherapy alters mediator release in vivo, nasal pollen challenge was used to compare 27 untreated highly sensitive ragweed (RW)-allergic subjects with 12 similarly sensitive patients receiving long-term immunotherapy (3-5 yr) with RW extract (median dose, 6 micrograms RW antigen E). The two groups were equally sensitive based on skin tests and basophil histamine release. The immunized group had a diminished response as demonstrated by (a) the treated group required higher pollen doses to excite sneezing or mediator release; (b) significantly fewer subjects in the treated group released mediators at any dose (TAME-esterase [P = 0.005], PGD2 [P = 0.04]), and (c) the treated group released 3-5-fold less mediator (TAME-esterase [P = 0.01], and histamine [P = 0.02]).
Asunto(s)
Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Adulto , Basófilos/fisiopatología , Liberación de Histamina , Humanos , Inmunoterapia , Persona de Mediana Edad , Pruebas de Provocación Nasal , Péptido Hidrolasas/metabolismo , Prostaglandina D2 , Prostaglandinas D/metabolismo , Rinitis Alérgica Estacional/fisiopatología , Rinitis Alérgica Estacional/terapia , SRS-A/metabolismo , EstornudoRESUMEN
The purpose of our study was to assess the effect of cold, dry air (CDA) on the nasal mucosa of selected individuals in relation to the release of inflammatory mediators associated with mast cells. 12 subjects with a history of nasal symptoms of rhinorrhea and congestion upon cold or dry environmental exposure were challenged by nasal breathing of CDA and warm, moist air (WMA). Each subject was tested on two occasions with the order of the challenges reversed. Symptom scores were recorded, and the levels of histamine, prostaglandin (PG) D2, kinins, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity in nasal lavage fluids were measured. CDA caused a significant increase in mediator levels and in symptom scores as compared to baseline or to WMA. No significant increase in symptom scores or mediators was noted after WMA challenge, with the exception of a marginal increase in kinins. The response to CDA was similar, regardless of challenge order. Changes in mediators correlated with one another, and symptom scores correlated significantly with the levels of histamine, kinins, and PGD2. Five subjects without a history of nasal symptoms on cold air exposure had no change in mediators or symptom scores after CDA or WMA challenge. We conclude that CDA causes the release of inflammatory mediators possibly associated with mast cells and speculate that such a mechanism may be involved in the bronchospasm induced by CDA in asthmatics.
Asunto(s)
Aire , Frío , Humedad , Mastocitos/metabolismo , Mucosa Nasal/metabolismo , Rinitis/fisiopatología , Adolescente , Adulto , Liberación de Histamina , Humanos , Inflamación , Cininas/metabolismo , Persona de Mediana Edad , Pruebas de Provocación Nasal , Péptido Hidrolasas/metabolismo , Prostaglandina D2 , Prostaglandinas D/metabolismo , Rinitis/etiologíaRESUMEN
The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
RESUMEN
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.
Asunto(s)
Corticoesteroides/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Rinitis Alérgica Estacional/tratamiento farmacológico , Administración Intranasal , Administración Oral , Corticoesteroides/uso terapéutico , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Antialérgicos/administración & dosificación , Antialérgicos/uso terapéutico , Eosinófilos/efectos de los fármacos , Fluticasona , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Líquido del Lavado Nasal/química , Pruebas de Provocación Nasal , Calidad de Vida , Resultado del TratamientoRESUMEN
The pathogenesis of rhinitis was investigated using a model of nasal provocation with different types of stimuli. Allergic subjects had an immediate response to antigenic challenge with symptoms of rhinitis highly correlated with increments in the concentrations of histamine, prostaglandin D2, kinins and kininogens, leukotrienes, and toluene sulfonyl arginine methyl ester esterase activity in their nasal secretions. This reaction was abated by a tricyclic antihistamine also capable of inhibiting mediator release from human mast cells in vitro and, in some subjects, by disodium cromoglycate. In a number of patients, symptoms reappeared three to 12 hours after nasal provocation. This late reaction also involves release of all of the aforementioned mediators except for prostaglandin D2, and preliminary data suggest that it can be inhibited by oral or topical steroids. Cold, dry air can induce rhinitis with mast cell mediator release from selected subjects. The pathogenesis of this reaction is unclear, but there are indications that osmolarity changes are responsible for mast cell activation. Thus, mast cells can be induced to release mediators and cause nasal symptoms by both immunologic and physical mechanisms, which may account for the pathophysiology of several types of rhinitis.
Asunto(s)
Pruebas de Provocación Bronquial , Rinitis/fisiopatología , Aire , Basófilos/efectos de los fármacos , Frío , Ciproheptadina/análogos & derivados , Ciproheptadina/farmacología , Histamina/farmacología , Humanos , Mastocitos/efectos de los fármacos , Factores de TiempoRESUMEN
A nasal challenge model of allergic rhinitis was used to determine if pretreatment with oral theophylline reduces histamine release in vivo. Ten subjects were entered into a double-blind, cross-over trial. The results showed that both the physiologic response (sneezing) (p = 0.02) and the amount of mediators (histamine, kinins, toluene sulfonyl arginine methyl ester esterase activity) (p less than 0.01 for all) released into nasal secretions were significantly reduced after one week of pretreatment with theophylline. At the time of challenge, the serum concentrations of theophylline were between 8 and 22 micrograms/ml. It is speculated that the ability of theophylline to block the clinical response to antigen challenge and to decrease the release of mast cell mediators contributes to its clinical efficacy in the treatment of asthma.
Asunto(s)
Pruebas de Provocación Bronquial , Teofilina/farmacología , Adolescente , Adulto , Método Doble Ciego , Femenino , Liberación de Histamina/efectos de los fármacos , Humanos , Cininas/análisis , Masculino , Péptido Hidrolasas/análisis , Rinitis/fisiopatología , Estornudo/efectos de los fármacosRESUMEN
Choanal atresia is a congenital anomaly usually diagnosed at birth. This case involves bilateral choanal atresia in a newborn with respiratory difficulties in whom there is an inability to pass a #8 French catheter through the nose. In contrast, unilateral choanal atresia causes a variable degree of nasal obstruction that may delay the diagnosis. We report a case of unilateral choanal atresia in a 9-year-old boy diagnosed as having chronic sinusitis with allergic rhinitus. Initial interpretation of a computerized, tomographic (CT) examination confirmed the diagnosis of chronic sinusitis. The definitive diagnosis, however, was made by endoscopic evaluation. A review is presented of the epidemiology, clinical presentation, differential diagnosis, and contemporary surgical management for unilateral choanal atresia.
Asunto(s)
Atresia de las Coanas/diagnóstico , Sinusitis/diagnóstico , Niño , Enfermedad Crónica , Diagnóstico Diferencial , Humanos , Masculino , Cavidad Nasal/diagnóstico por imagen , Senos Paranasales/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
In an attempt to identify inflammatory mediators that may contribute to rhinorrhea, nasal congestion and other cold symptoms, we recruited 40 healthy young adults (median age, 20) for provocative rhinovirus challenge. Mediators measured included histamine, kinins and enzymes with arginine esterase activity. Volunteers were inoculated with rhinovirus or a sham inoculum. Nasal secretions for viral culture were obtained daily, and volunteers were deemed infected if they shed virus or had a 4-fold or greater increase in serum antibody titer. The virus-infected group was subdivided using the Jackson criteria into an ill or non-ill group; each group was compared to the control group. Of the 27 virus-inoculated subjects, 25 had positive cultures for the challenge virus, and 15 became ill. None of the controls had a positive culture. All variables measured--except histamine--grew stronger in direct relationship with the symptoms as the cold increased in severity. In the infected-ill group, the mean kinin level increased more than 10-fold over baseline. The kinin level remained relatively unchanged in the control and non-ill groups. Similar results were found for levels of albumin and enzymes with arginine esterase activity. Histamine levels remained constant in both the infected-ill and non-ill groups, which suggests that mast cells and basophils do not participate in the pathophysiology of rhinovirus infections and that antihistamines should be ineffective in treating rhinovirus colds. Since volunteers who developed cold symptoms exhibited a notable increase in kinin, a potent inflammatory mediator, we recommend further study of a kinin antagonist in reducing nasal symptoms.
Asunto(s)
Resfriado Común/metabolismo , Histamina/metabolismo , Cininas/metabolismo , Adulto , Albúminas/metabolismo , Anticuerpos Antivirales/biosíntesis , Hidrolasas de Éster Carboxílico/metabolismo , Resfriado Común/inmunología , Humanos , Recuento de Leucocitos , NeutrófilosRESUMEN
To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine-induced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation.
Asunto(s)
Histamina/farmacología , Cloruro de Metacolina/farmacología , Mucosa Nasal/efectos de los fármacos , Adulto , Atropina/farmacología , Difenhidramina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Histamina/administración & dosificación , Humanos , Cinética , Lidocaína/farmacología , Masculino , Cloruro de Metacolina/administración & dosificación , Mucosa Nasal/metabolismo , Receptores Colinérgicos/efectos de los fármacos , Receptores Colinérgicos/fisiología , Receptores Histamínicos H1/efectos de los fármacos , Receptores Histamínicos H1/fisiología , Reflejo/efectos de los fármacos , Reflejo/fisiología , Taquifilaxis/fisiología , Terfenadina/farmacologíaRESUMEN
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.
Asunto(s)
Aire , Calor , Humedad , Cavidad Nasal/fisiología , Posición Supina/fisiología , Adulto , Temperatura Corporal , Femenino , Humanos , Masculino , Mucosa Nasal/fisiologíaRESUMEN
Ten subjects with a history of cold air-induced nasal symptoms participated in a randomized two-period crossover study to evaluate the occurrence and magnitude of the reaction induced by inhalation and exhalation of cold dry air through the nose. The protocol involved breathing of either warm moist or cold dry air for 45 min at resting breathing rates. The nasal response was quantified by determining the amount of produced secretions as well as by measuring histamine and N-alpha-p-tosyl-L-arginine methyl (TAME) esterase activities in recovered nasal lavage fluids. Symptom scores were obtained. Warm moist air did not increase symptoms nor did it result in any significant changes in secretions or mediator levels. Compared with baseline, cold dry air induced significant rhinorrhea and increased both secretion weights (9.6 +/- 1.3 vs. 28.1 +/- 6.5 mg; P = 0.01) and the levels of histamine (3.9 +/- 1.2 vs. 10.6 +/- 2.7 ng/ml; P = 0.02) and TAME esterase activity (3.1 +/- 0.8 vs. 7.0 +/- 2.0 counts.min-1.10(-3); P = 0.01). We conclude that bidirectional nasal breathing of cold dry air results in a reaction that is qualitatively similar to that induced when air is only inhaled through the nose and exhaled through the mouth.
Asunto(s)
Frío/efectos adversos , Nariz/fisiología , Mecánica Respiratoria/fisiología , Rinitis/fisiopatología , Adulto , Biomarcadores , Estudios Cruzados , Femenino , Histamina/metabolismo , Humanos , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/fisiopatología , Pruebas de Provocación Nasal , Péptido Hidrolasas/metabolismo , Rinitis/metabolismo , TemperaturaRESUMEN
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.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1/farmacología , Histamina , Loratadina/farmacología , Seno Maxilar/fisiología , Nariz/fisiología , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipersensibilidad/fisiopatología , Masculino , Seno Maxilar/efectos de los fármacos , Nariz/efectos de los fármacos , Proyectos Piloto , Reflejo/efectos de los fármacos , Reflejo/fisiología , Albúmina Sérica/metabolismo , Estornudo/fisiologíaRESUMEN
To assess the ability of the nose to warm and humidify inhaled air, we developed a nasopharyngeal probe and measured the temperature and humidity of air exiting the nasal cavity. We delivered cold, dry air (19-1 degrees C, <10% relative humidity) or hot, humid air (37 degrees C, >90% relative humidity) to the nose via a nasal mask at flow rates of 5, 10, and 20 l/min. We used a water gradient across the nose (water content in nasopharynx minus water content of delivered air) to assess nasal function. We studied the characteristics of nasal air conditioning in 22 asymptomatic, seasonally allergic subjects (out of their allergy season) and 11 nonallergic normal subjects. Inhalation of hot, humid air at increasingly higher flow rates had little effect on both the relative humidity and the temperature of air in the nasopharynx. In both groups, increasing the flow of cold, dry air lowered both the temperature and the water content of the inspired air measured in the nasopharynx, although the relative humidity remained at 100%. Water gradient values obtained during cold dry air challenges on separate days showed reproducibility in both allergic and nonallergic subjects. After exposure to cold, dry air, the water gradient was significantly lower in allergic than in nonallergic subjects (1,430 +/- 45 vs. 1,718 +/- 141 mg; P = 0.02), suggesting an impairment in their ability to warm and humidify inhaled air.