Showing papers in "Clinical allergy and immunology in 2007"

Epidemiology of rhinitis: allergic and nonallergic.

Abstract: In summary, the epidemiological data and characterization of allergic and nonallergic rhinitis has been reviewed. Chronic rhinitis symptoms are among the most common problems presenting to physicians. When approaching this problem the diagnostic challenge is to determine the etiology, specifically whether it is allergic, nonallergic, or perhaps an overlap of both conditions. Estimates of the prevalence of allergic rhinitis range from as low as 9% to as high as 42%. Although the prevalence of nonallergic rhinitis has not been studied definitively, it appears to be very common with an estimated prevalence in the United States of approximately 19 million. In comparison, the prevalence of mixed rhinitis is approximately 26 million, and allergic rhinitis ("pure" and "mixed" combined) 58 million. Challenges in the differential diagnosis of rhinitis result from two major factors. Not only are presenting symptoms of allergic, nonallergic, and mixed rhinitis often indistinguishable from one another, but also the differential diagnosis of nonallergic rhinitis is extensive. Nonallergic rhinitis is often characterized by onset after age 20, female predominance, nasal hyperactivity, perennial symptoms, and nasal eosinophilia in approximately one-third of the population. Positive tests for relevant specific IgE sensitivity in the setting of rhinitis do not rule out "mixed rhinitis" and may not rule out nonallergic rhinitis. The significance of symptom exacerbation by nonallergic triggers in the setting of allergic rhinitis remains to be determined. Goals for the future include reaching a consensus on the definitions of rhinitis and rhinitis subtypes including the establishment of mixed rhinitis, updating guidelines for the interpretation of nonrelevant positive tests for specific IgE sensitivity, and reaching agreement on the nonallergic triggers that best define VMR or VMR subtypes. Only then can the most applicable research results be obtained. The desired result is the delivery of the most appropriate treatment, specifically tailored to the accurate diagnosis of patients with rhinitis.

Chronic rhinosinusitis patterns of illness.

Abstract: Chronic rhinosinusitis is a complex, multifactorial illness that has genetic, infectious, immune, anatomic, allergic, and inflammatory components. The syndrome is defined based on imprecise symptoms that lack specificity for the condition. Nonetheless, certain relatively characteristic patterns of illness can be identified within the syndrome, and these provide some insight into the underlying cause(s) of CRS. Furthermore, they form a basis for the clinical assessment and management of patients. In general, CRS without NP is a more heterogeneous subgroup of patients more likely to have facial pain, headache, chronic recurrent infection, defects in systemic or local immune function, and more likely to experience local infectious complications, such as facial osteomyelitis. In contrast, CRS with NP patients are more likely to have male gender, anosmia/hyposmia, a history of prior sinus surgery, asthma and aspirin sensitivity, allergy to house dust mite, and AFRS. In the next 17 chapters, an in-depth discussion of factors contributing to the pathophysiology of CRS will be presented that will provide further insight into the clinical patterns of illness described herein. Armed with this information plus the clinical framework outlined in this chapter, a stepwise medical evaluation and treatment strategy will be presented in Chapter 19.

Mucociliary transport in chronic rhinosinusitis.

Abstract: In conclusion, this chapter provides a review of paranasal sinus anatomy and discusses the physiology of mucociliary transport and abnormalities observed in patients with CRS. Normal mucociliary transport is essential for the maintenance of healthy sinuses. This is well illustrated by PCD in which a congenital abnormality in ciliary function leads to, among other manifestations, CRS and bronchiectasis. A decrease in mucociliary clearance has been demonstrated in most studies of CRS, with the bulk of evidence suggesting that the decrease is secondary rather than a primary event. Mucostasis, hypoxia, microbial products, and mediators and toxic proteins generated during chronic inflammation probably all contribute to diminished mucociliary function. These factors decrease mucociliary function by direct toxic effects on cilia, ciliary loss, other ultrastructural alterations in the epithelium and changes in the viscoelastic properties of mucus. Studies of patients before and after surgical restoration of sinus ventilation have shown that mucociliary function improves gradually over 1-6 months postoperatively. The slower than normal rate of recovery of mucociliary clearance after surgery highlights the importance of careful postoperative medical and surgical management which is discussed in Chapters 19 and 20.

Role of mast cells and basophils in chronic rhinosinusitis.

Abstract: Mast cells and basophils contribute to induction and/or maintenance of eosinophilic inflammation by a variety of mechanisms, including IgE-dependent and IgE-independent processes. The latter include a variety of stimuli that have only recently been elucidated, including mechanisms triggered by bacteria, virus, fungi, complement, or autoantibodies. MCs, and basophils contribute to inflammation both directly through the release of inflammatory mediators, cytokines and growth factors and indirectly through the activation of structural cells. Accumulating evidence places MCs (and most probably basophils) in a position of importance in the pathogenesis of CRS, particularly in the pathogenesis and progression of NP (Fig. 1). Mechanisms other than conventional IgE-dependent activation of MCs are intriguing as potential mechanisms of eosinophilic inflammation in non-allergic CRS/NP. Although it is not possible using current pharmacologic approaches to completely isolate the effects of MCs or basophils in CRS and NP pathogenesis, it seems most likely that such approaches will eventually be available. It might be expected that one or both of these cells will be shown to play important roles, particularly considering their potential for activation by IgE and non-IgE mechanisms, their production of a broad array of inflammatory mediators, cytokines and growth factors, and their unique assortment of proteases.

Nonallergic rhinitis with eosinophilia syndrome and related disorders.

Abstract: NARES is a clinical syndrome consisting of symptoms consistent with AR in which an absence of atopy has been demonstrated by allergen skin testing, with nasal cytology analysis showing greater than 20% eosinophils. Anosmia is a prominent feature not shared with AR. The pathophysiology of NARES is poorly understood, but a key component involves a self-perpetuating, chronic eosinophilic nasal inflammation with development of nasal micropolyposis and polyposis. Mast cells likely play an important role as well. NARES is a risk factor for the development of nasal polyposis and aspirin sensitivity, as well as obstructive sleep apnea. Treatment consists mainly of intranasal corticosteroids with or without the addition of second-generation antihistamines and/or LT receptor antagonists as an adjuvant.

Aspirin-sensitive rhinosinusitis and asthma.

Abstract: Although aspirin sensitive asthma has been recognized as a clinical entity since the beginning of this century, the mechanism for the production of this syndrome still remains obscure. Recent studies have indicated a higher than previously appreciated incidence of aspirin sensitive asthma, perhaps approaching 40% of steroid-dependent asthmatics. Challenge with both oral and bronchial instilled aspirin may be useful to identify aspirin-sensitive individuals. During aspirin-induced reactions, increased vascular permeability is noted. In addition, aspirin-sensitive individuals have altered levels of production of leukotriene E4 and enhanced sensitivity to inhaled leukotriene E4. However, nasal secretions of aspirin-sensitive individuals demonstrate enhanced leukotriene C4 concentration after aspirin challenge. It has also been noted that nonaspirin-sensitive patients have enhanced leukotriene C4 concentration. Thus, the specific defect leading to the pathogenesis of aspirin-sensitive asthma and rhinosinusitis in selected individuals remains obscure. Eosinophil activation has been noted in aspirin-sensitive rhinosinusitis patients; however, other cell types, including platelets and monocytes, have also been noted to exhibit metabolic abnormalities in this syndrome. Aspirin desensitization may be a useful option in selected patients with significant aspirin sensitive rhinosinusitis and asthma.

Vocal cord dysfunction, gastroesophageal reflux disease, and nonallergic rhinitis.

Abstract: VCD is often mistaken for asthma and can lead to treatment with corticosteroids and the development of significant side effects Early and correct diagnosis will avert significant iatrogenic complications For many individuals, the role of postnasal drip and GERD in the pathogenesis of VCD is central, as they are often associated with VCD and likely lead to increased laryngopharyngeal sensitivity and hyperreactivity Much needs to be further elucidated in terms of the underlying pathogenesis of VCD Management of VCD requires identification and treatment of underlying disorders and referral to speech therapists that can teach techniques of throat relaxation, cough suppression, and throat clearing suppression

Environmental nonallergic rhinitis.

Abstract: The upper airway occupies a sentinel position with respect to the physical and chemical qualities of the inspired atmosphere. Responses of the upper airway can be acute or chronic, as well as primary (sensory) or secondary (physiologic). Olfaction and sensory irritation are cofactors in the perception of air quality. Secondary reflex responses to airborne irritants may include blockage (airflow obstruction), secretion (with or without associated inflammation), and alterations in mucociliary clearance. Of the above end points, obstruction has been documented in response to a variety of agents, including acetic acid vapor, ammonia, Cl2, ETS, mixed VOCs, vapors from carbonless copy paper, and (variably) SO2. Alterations in mucociliary clearance have been variably observed with SO2 and ETS exposure. A neutrophilic inflammatory response has been documented after acute exposure to either ozone or VOCs, and metaplastic mucosal changes after prolonged exposures to photochemical mixed air pollutants. Augmented reactivity to irritants is a phenotypic characteristic of both nonallergic and allergic rhinitis; however, understanding of underlying mechanisms remains elusive (75-78). Differential physiologic responsiveness to environmental irritant stimuli has been documented by allergic rhinitis status for acetic acid and Cl2 (objectively) and for mixed VOCs (subjectively only). Differential responsiveness by nonallergic rhinitis status has, to our knowledge, been documented for paper dust only, although a somewhat wider array of pollutants (including ETS and carbonless copy paper) has been studied in groups differing by self-reported pollutant reactivity. Interestingly, although the congestive response to allergens and irritants is similar, the underlying mechanisms appear to differ, with neither mast cell degranulation nor cholinergic parasympathetic reflexes appearing critical to the response (Fig. 3). Although neuropeptide release does not accompany Cl2-induced nasal obstruction, in one model system (hypertonic saline challenge), substance P release accompanied augmented secretions (80,81). In yet another hypertonic model (dry mannitol powder challenge), arachidonic acid metabolites characteristic of epithelial cell activation accompanied nasal obstruction (82). The relevance of these model systems to environmentally realistic (airborne) irritants remains unclear at this time. Overall, nonallergic rhinitis has received considerably less attention than has allergic rhinitis in the context of descriptive, pathophysiologic, and intervention studies. This statement applies equally in the context of environmental nonallergic rhinitis. As is hopefully evident from the above discussion, many potential research questions in this area remain to be addressed.

Innate and acquired immunity and epithelial cell function in chronic rhinosinusitis.

Abstract: We have outlined the myriad of roles, both proven and suspected, of epithelial cells in airway inflammation in general and CRS in particular. There is little doubt that these remarkable cells are essential for host defense, tissue responses to injury and threats, and inflammation that cause disease. We believe that many of these responses are likely to be amenable to the development of new therapies for CRS. As we acquire more information on the signaling processes that drive the protective responses in epithelial cells, we will improve our chances of developing approaches to enhance these responses without triggering deleterious inflammatory responses. Enhanced clearance of fungi and bacteria by local immune responses would likely be beneficial in reducing disease. As we better understand the signals that epithelial cells give and get from DCs, B and T lymphocytes, new opportunities for productive intervention will arise.

Rhinitis in the menstrual cycle, pregnancy, and some endocrine disorders.

Abstract: By clinical experience, rhinitis has been suggested as caused by some endocrine disorders, but the evidence for this is vague, and the few descriptions almost anecdotal. Rhinitis of the menstrual cycle has been more described, although a solid picture is still lacking. Pregnancy rhinitis is therefore so far the only clearly defined "hormonal rhinitis." However, the cause of pregnancy rhinitis is not simply estrogen or progesterone, but seems multifactorial, and may possibly be associated with the PGH. Treatment consists mainly of information, physiological measures, and nasal saline washings.

Quality of life in nonallergic rhinitis.

Abstract: Health-related quality-of-life questionnaires are instruments to assess the burden of a disease as perceived by the patient. Few data are available on the health-related quality of life of patients with nonallergic rhinitis, but data from studies of patients with allergic rhinitis show that rhinitis predominantly affects mental quality of life. This burden of rhinitis is associated with impaired sleep, excessive daytime sleepiness, concentration problems, and increased irritability.

Relationship between nonallergic upper airway disease and asthma.

Abstract: A growing body of scientific evidence supports the link between nonallergic upper airway disorders and asthma. Multiple studies have demonstrated that most patients with nonallergic asthma have chronic nasal symptoms as well as radiographic evidence of sinus mucosal disease. Equally important, preexisting symptoms of rhinitis place nonallergic patients at higher risk for developing asthma. Experimental studies demonstrate that the upper and lower airways may be connected via a number of paths, and that the systemic circulation may play a key role in amplifying inflammation in other portions of the respiratory tract. Finally, given this complex relationship between localized and systemic inflammation, it behooves all physicians to assess and treat rhinitis and sinusitis when they are present in patients with asthma.

Viral and bacterial rhinitis.

Abstract: In contradistinction to the poetically inspired disjunction between the name and quality of a rose recited by Juliet in the famous quote from Shakespeare's play, disease labels used in the medical sciences need to have exact meaning to ensure that they communicate an accurate diagnosis and a valid treatment approach. Above, we presented a consistent nosology for rhinitis consequent to infection. There, we argued that the term "rhinitis" should be used to describe the condition of nasal mucosal pathology and that the rSSC be used to describe the appreciated expression of that pathology. In discussing viral and bacterial rhinitis, we conclude that former is consistent with a strict application of our nosology where the accompanying rSSC is usually referred to as cold or flu, but that the latter is not. Lacking direct evidence for bacterial infection of the nasal mucosa, bacterial rhinitis is better referred to as an acute bacterial infection of an adjacent compartment complicated by rhinitis (e.g., sinusitis complicated by rhinitis) or as "toxic rhinitis" complicated by bacterial infection. Interestingly, bacterial infection of the adjacent compartments is a frequent complication of viral rhinitis making "bacterial" rhinitis a complication of a complication of viral rhinitis. The antiviral and antibacterial host-defense mechanisms available to the nasal mucosa are multilayered and formidable. For this reason, nasal mucosal infection with extracellular bacterial pathogens is rarely established and infection with a broad range of upper respiratory viruses is self-limited with short duration morbidity and no mortality. However, in select subpopulations, those infections predispose to more serious complications associated with secondary bacterial, and perhaps viral, infection of the sinuses, middle ears, and lungs. The morbidity and mortality of these complications remains a concern, and strategies to decrease their frequency need to be formulated and tested in clinical trials. Because the viruses causing rhinitis are spread by interpersonal contact, the most appropriate and least expensive prophylactic measures are good hygiene and contact avoidance. Prophylactic efficacy for vaccination and passive immunoglobulin therapy was demonstrated for influenza and RSV infections, respectively. However, these approaches hold little promise for other viruses and are associated with some risks, making them less acceptable for populations "at low risk" for the more serious complications of viral rhinitis. Existing pharmacological treatments for viral rhinitis target the effector chemicals of the rSSC and therefore are largely palliative, whereas antiviral treatment has limited theoretical and realized efficacy, and no treatment has been shown to decrease the risk of complications. Indeed, given the small treatment window available (time between rSSC onset and typical resolution) and the poor understanding of the immune/inflammatory pathways of host defense, it is doubtful that the general population's demand for a cure will be satisfied in the near future, but then, viral rhinitis by any other name is still just a cold.

Approach to the evaluation and medical management of chronic rhinosinusitis.

Abstract: Despite the many frustrations involved in the care of CRS, there are many "successes," and most patients experience at least moderate benefit from medical treatment. I cannot emphasize enough the importance of breaking down the evaluation into component parts and addressing each one. Often, successful treatment is only achieved after all elements of the treatment program are in place. Patients are typically desperate for improvement and understand that several different strategies may need to be tried before a successful program is found. Given the high impact of CRS on patients' quality of life, it is not surprising that some of the most grateful patients are the ones in whom a successful medical program has been discovered.

Allergic fungal sinusitis.

Abstract: Many common chronic inflammatory rhinosinusitis conditions (hypertrophic sinus disease [HSD]) have the histopathological profile of allergic or asthmatic inflammation. Allergic fungal sinusitis (AFS) is both a type of noninvasive fungal rhinosinusitis and a type of HSD. AFS has clinicopathological features that make it similar, but not identical, to allergic bronchopulmonary aspergillosis (ABPA). Allergic mucin is a defined pathological entity occurring in ABPA, AFS, and in the HSD "eosinophilic mucin rhinosinusitis (EMRS)." Diagnosis of AFS requires a careful review of surgical reports, histopathology, and culture results. Treatment includes surgery and aggressive postoperative medical management of allergic inflammatory disease. Prognosis is good with integrated medical-surgical follow-up, but recurrence remains problematic. The association of ABPA, AFS, and HSD with class II genes of the major histocompatibility complex places the initiation of these inflammatory diseases within the context of antigen presentation and the acquired immune response. Pathological immunomanipulation of this response by local microbial superantigens may be a common mechanism for disease pathogenesis. Future research into the molecular biology of these related conditions may offer insight into the pathogenesis of other chronic inflammatory diseases.

Interfacing medical and surgical management for chronic rhinosinusitis with and without nasal polyps.

Abstract: The development of FESS provided the otolaryngologist with an approach for restoring sinus ostial patency while simultaneously maximizing the restoration of normal mucociliary function. While minor modifications to the basic procedure continue to be discussed, FESS is widely accepted as the standard of care for surgical management of CRS. Image-guided surgery offers further promise of allowing more precise surgery with fewer intraoperative complications. Most patients with CRS who fail medical therapy will benefit from FESS with improved outcomes and possibly improvement in comorbidities, especially asthma. Postoperative medical management and attention to contributive factors for disease, such as the presence of allergies and aspirin intolerance, are key factors toward assuring successful surgical outcomes. The surgical approach and outcomes vary somewhat based on whether the patient has CRS without NP, CRS with NP, or classic AFRS. Furthermore, the goals of surgery depend on whether other underlying conditions, such as cystic fibrosis, are present. The last section in this chapter provides guidance as to the combined medical and surgical management of various forms of CRS based on existing evidence from the literature.