John H. Krouse

Asthma and the unified airway

Inflammatory processes of the upper and lower airway commonly co-exist. Patients with upper respiratory illnesses such as allergic rhinitis and acute and chronic rhinosinusitis often present to both otolaryngologists and primary care physicians for treatment of their symptoms of nasal and sinus disease. These patients often have concurrent lower respiratory illnesses such as asthma that may be contributing to their overall symptoms and quality of life. Unfortunately, asthma frequently remains undiagnosed in this population. It was the objective of this paper to examine the relationship between upper respiratory illnesses such as rhinitis and rhinosinusitis and lower respiratory illnesses such as asthma, and to provide a framework for primary care and specialty physicians to approach these illnesses as a spectrum of inflammatory disease. The present manuscript was developed by a multidisciplinary workgroup sponsored by the American Academy of Otolaryngic Allergy. Health care providers in various specialties contributed to the manuscript through preparation of written materials and through participation in a panel discussion held in August 2006. Each author was tasked with reviewing a specific content area and preparing a written summary for inclusion in this final document. Respiratory inflammation commonly affects both the upper and lower respiratory tracts, often concurrently. Physicians who are treating patients with symptoms of allergic rhinitis and rhinosinusitis must be vigilant to the presence of asthma among these patients. Appropriate diagnostic methods should be used to identify individuals with concurrent respiratory illnesses, and comprehensive treatment should be instituted to reduce symptoms and improve quality of life.

Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class

OBJECTIVE To evaluate how well the medications currently approved in the United States for allergic rhinitis (AR) treat nasal symptoms when examined according to Food and Drug Administration-indicated uses and dosages. DATA SOURCES MEDLINE (1966 onward), EMBASE (1974 onward), and the Cochrane Library (2007) were systematically searched according to the following criteria defined at a roundtable meeting of the authors: randomized controlled trial, at least a 2-week duration, and approved indication and dosage in the United States. STUDY SELECTION Data from studies that met the inclusion criteria were extracted into evidence tables, which were reviewed twice by the full panel of authors. Individual panel members also were asked to comment on abstracts, articles, and summary tables based on their known expertise. The entire faculty approved the selection of studies included in this review. RESULTS Fifty-four randomized, placebo-controlled studies involving more than 14,000 adults and 1,580 children with AR met the criteria for review: 38 studies of seasonal allergic rhinitis (SAR; n = 11,980 adults and 946 children) and 12 studies of perennial allergic rhinitis (PAR; n = 3,800 adults and 366 children). The median percentage changes from baseline for total nasal symptom score for SAR were as follows: nasal antihistamines, -22.2%; oral antihistamines, -23.5%; intranasal steroids (INSs), -40.7%; and placebo, -15.0%. For PAR, the changes were as follows: oral antihistamines, -51.4%; INSs, -37.3%; and placebo, -24.8%. Data for mediator antagonists were limited. CONCLUSIONS The data, although limited, confirm that INSs produce the greatest improvements in nasal symptoms in patients with SAR. In addition, INSs are effective for PAR, but the data were of variable quality, and oral antihistamines may be equally effective for some patients. The reporting of published data should be standardized to permit better comparisons in future studies.

The Unified Airway—Conceptual Framework

Substantial evidence exists to support the concept that the respiratory system functions as an integrated unit. Pathophysiological processes that involve the upper airway generally occur in conjunction with lower airway diseases, and diffuse inflammation often affects mucosal surfaces of the middle ear, nose, sinuses, and tracheobronchial tree simultaneously. Support for this relationship can be found in epidemiological studies, in shared pathophysiological mechanisms, and in observed interactive treatment effects. This model and its implications are discussed.

Immune mediators in allergic rhinitis and sleep

OBJECTIVE: Our study goal was to examine polysomnography, indices of sleep and allergy, and serum and nasal cytokines in allergic and nonallergic subjects. STUDY DESIGN AND SETTING: In this descriptive, exploratory study, 4 allergic and 4 nonallergic subjects underwent 2 nights of polysomnographic recording with serial measurements of cytokines and completed measures of sleep quality and allergic symptoms. RESULTS: Three serum cytokines (interleukin (IL)-1β, IL-4, and IL-10) were higher in allergic subjects and were termed proallergic. Three serum cytokines (IL-1ra, IL-2, and IL-12) were higher in nonallergic subjects and were termed allergy inhibitory. Proallergic serum cytokines correlated with increased latency to rapid eye movement sleep, decreased time in rapid eye movement sleep, and decreased latency to sleep onset. Low levels of allergy-inhibitory serum cytokines were associated with increased allergic symptoms. CONCLUSIONS: Differences in serum cytokines between allergic and nonallergic individuals are associated with variations in polysomnography and allergic symptoms. SIGNIFICANCE: Understanding these mechanisms may suggest novel approaches to alleviating drowsiness and other symptoms in allergic patients.

Cancer as crisis: the critical elements of adjustment.

This study examined the course and duration of the crisis inherent in the diagnosis and treatment of cancer in women. Three groups of female patients, breast cancer, gynecological cancer, and breast biopsy patients, were compared on the variables of depression and body image. The women were assessed prior to surgery and at one- and two-month intervals in order to determine whether their crises had been resolved within the normal six-month framework. An additional follow-up was made after 20 months to evaluate any long-term effects of the diagnosis of cancer or its treatment. Results of the study revealed that only breast biopsy and mastectomy patients adapted appropriately and were able to resolve their crises. In examining the gynecological cancer patients, initial feelings of depression and body image continued to worsen even at 20 months following surgery. Implications for nursing practice are discussed, and suggestions for future research are presented.

Skin Testing for Inhalant Allergy 2003: Current Strategies:

Skin testing has been in common use for the diagnosis of inhalant allergy since the 19th century. With the identification of pollen sensitivity as the causative factor for fall hay fever in 1872,1 physicians could begin to approach specific methods to diagnose and treat this common condition. Within 1 year, Blackley2 performed the first skin tests with pollen extracts, noting that a wheal would quickly develop at the site of pollen placement on excoriated skin in sensitized individuals. From these early experiences with cutaneous testing for inhalant allergy, many methods and systems have been developed over the past 130 years to provide an accurate diagnosis of inhalant allergy among symptomatic patients. For many years, the primary approach that has been practiced by the majority of otolaryngic allergists and taught by the American Academy of Otolaryngic Allergy (AAOA) has been skin endpoint titration (SET)—a quantitative method for the diagnosis of inhalant allergy. SET has been demonstrated to be an extremely safe method of skin testing,3 allowing immunotherapy to be administered both in the office and at home with adverse reactions occurring only rarely. In SET, various dilutions of antigenic concentrates are applied in a sequential manner to not only demonstrate the presence of allergy but to quantitate the degree of sensitivity and determine the safe initial starting dose for desensitization immunotherapy. The broadly accepted approach to SET embraced by the majority of otolaryngic allergists was formalized by Rinkel,4 who observed that 1:5 dilutions of antigen applied in sequentially increasing concentrations provided reliable and clinically useful information in guiding successful immunotherapy. Over the past decade, a number of forces have led otolaryngic allergists to alter their approach to practice. Broadly, these complementary forces can be described as scientific and socioeconomic. The profession of medicine and the provision of medical care are becoming increasingly directed by evidence-based practice, the reliance on objective data from prospective clinical research to justify the use of a specific procedure or treatment. With the influence of governmental oversight and thirdparty payers, physicians must demonstrate that the techniques they use to approach a clinical problem are both safe and effective. Examination of scientific factors in the testing and treatment of patients for inhalant allergy demonstrates that although SET continues to be a useful technique for otolaryngic allergists in diagnosing and treating inhalant allergy, there is little controlled research documenting its effectiveness. Although scientific support has been demonstrated in at least three articles,5-7 there remains only limited experimental evidence supporting the efficacy of SET-based immunotherapy. Despite From the Department of Otolaryngology, Wayne State University (Dr Krouse), and Department of Otolaryngology, University of Texas Southwestern Medical Center, Department of Otolaryngology, University of Texas Medical Branch, and Department of Otolaryngology, University of Texas Health Science Center (Dr Mabry). Reprint requests: John H. Krouse, MD, PhD, 540 E Canfield, 5E-UHC, Detroit, MI 48201, USA; email, jkrouse@med. wayne.edu. Copyright

Rhinogenic Laryngitis, Cough, and the Unified Airway

Over the past 10 years, there has been increasing recognition of the interaction between the upper and lower airways in patients with a variety of infectious and inflammatory illnesses, including allergic rhinitis, rhinosinusitis, and asthma. Epidemiologic and mechanistic links have been proposed to demonstrate these relationships and to offer possible etiologic explanations to account for these observations. Among patients with upper respiratory illnesses, cough can be seen as a common symptom, both from the direct influences of upper airway inflammation, which incite reflex changes and bronchospasm, and from the exacerbation of associated pulmonary processes, such as asthma. Despite this increasing awareness of interaction between the upper and lower airways, the influence of both upstream and downstream respiratory inflammatory processes on laryngeal pathophysiology has not been extensively studied. Research suggests, however, that both direct stimulatory effects on the larynx and secondary effects of mucus production and mucus trafficking can create a range of laryngeal symptoms, including cough. This review discusses the interaction of the upper and lower airway in respiratory disease, and focuses on the effect of these respiratory processes on laryngeal inflammation, function, and symptoms.

Sensitivity and Specificity of Prick and Intradermal Testing in Predicting Response to Nasal Provocation with Timothy Grass Antigen

OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with timothy antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with Multi-Test II (MT). Subjects with negative wheals were tested with a 1:500 intradermal injection of timothy. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing timothy concentrations. CSA was assessed and nasal visual analog scale (VAS) completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to provocation were 87% and 86%. Intradermal testing increased sensitivity to 93%. Hierarchical linear modeling (HLM) demonstrated that subjects positive to skin testing had significant reductions in CSA and worsening VAS scores with increasing concentrations of nasally delivered antigen. CONCLUSION AND SIGNIFICANCE: Epicutaneous testing with the Multi-Test II offers 87% sensitivity and 86% specificity in assessing timothy grass reactivity.

Skin Testing in Predicting Response to Nasal Provocation with Alternaria

Objective: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with Alternaria antigen.

Executive Summary: Asthma and the Unified Airway

Asthma is a common comorbid disorder that will be seen by otolaryngologists in their treatment of patients with rhinitis, rhinosinusitis, and otitis media. Among otolaryngologists, however, a diagnosis of asthma is infrequently considered in this patient population. Otolaryngologists, however, may be in an important position to recognize this potential diagnosis and provide treatment or appropriate referral. To further develop this relationship among upper and lower airway inflammation, and to provide important information to otolaryngologists regarding this relationship, a multidisciplinary workgroup was impaneled by the American Academy of Otolaryngic Allergy in August 2006. The full report of this meeting is published separately as a Supplement to Otolaryngology-Head and Neck Surgery. This Executive Summary provides a brief synopsis of that document, with a focus on comorbid respiratory inflammation for otolaryngologists. In the treatment of their patients with allergic rhinitis and rhinosinusitis, otolaryngologists must be aware of the possible presence of asthma so that appropriate treatment and/or referral can be initiated. The impact of this practice will allow more comprehensive treatment of patients with upper and lower airway disease, and will improve patient symptoms, function, and quality of life.