Mary Lou Hayden

Design and baseline characteristics of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma

BACKGROUND Patients with severe and difficult-to-treat asthma represent a small percentage of asthma patients, yet they account for much of the morbidity, mortality, and cost of disease. The goal of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is to better understand the natural history of asthma in these patients. OBJECTIVE To describe the methods and baseline characteristics of the TENOR study cohort. METHODS The TENOR study is a 3-year, multicenter, observational study of patients with severe or difficult-to-treat asthma. From January through October 2001, more than 400 US pulmonologists and allergists enrolled patients. Patients 6 years or older who were considered to have severe or difficult-to-treat asthma by their physicians were eligible. Patients have been receiving care for 1 year or more, have a smoking history of 30 pack-years or less, and have current high medication or health care utilization in the past year. Data are collected semiannually. RESULTS A total of 4,756 patients enrolled and completed a baseline visit. Overall, 73% of the TENOR study patients are adults, 10% are adolescents, and 16% are children. According to physician evaluation, 48% of patients have severe asthma, 48% have moderate asthma, 3% have mild asthma, and 96% have difficult-to-treat asthma. Severe asthmatic patients have the highest health care utilization in the past 3 months (P < .001). CONCLUSIONS The TENOR study is the largest cohort of patients with severe or difficult-to-treat asthma. Although patients are equally divided into moderate or severe asthma categories, most are considered difficult-to-treat. The TENOR study highlights the lack of control in moderate-to-severe asthma and provides a unique opportunity to examine factors related to health outcomes in this understudied population.

Cross-reacting and species-specific determinants on a major allergen from Dermatophagoides pteronyssinus and D. farinae: Development of a radioimmunoassay for antigen P1 equivalent in house dust and dust mite extracts

Two species of mites of the genus Dermatophagoides are common in house dust and make a major contribution to the allergen content of house dust. As judged by skin tests and the radioallergosorbent test, these mites, D. pteronyssinus and D. farinae, demonstrate extensive cross-reactivity. When the major allergen from D. pteronyssinus, antigen P1, was compared with the equivalent allergen from D. farinae, these two proteins were found to have both species-specific and common antigenic determinants. With specifically purified antibodies directed against the common determinants, we developed a radioimmunoassay for these antigen P1 equivalent proteins in mite extracts as well as house dust extracts. The quantity of allergen in dust from 63 houses (255 samples) was measured, and values ranged from less than 100 to greater than 100,000 ng/gm of fine dust. The correlation between antigen P1 equivalent (ng/gm) and the number of mites per gram of dust (identified by microscopy) was very good (r = 0.74; p less than 0.001). Furthermore, this correlation was not affected by the species of mite in the dust sample. Of 9243 mites identified, 95% were of the genus Dermatophagoides, and of these, 16.4% and 18% could be positively identified as D. farinae and D. pteronyssinus, respectively. When the assay for antigen P1 equivalent was applied to isolated components of mite cultures of both species, significant allergen was found in the mite bodies, cuticles, and their excreta (fecal particles). For the house-dust samples, less than 10% of the allergen measured could be explained by the allergen content of mite bodies. Our results demonstrate that a radioimmunoassay for antigen P1 equivalent can provide an accurate and simple means of assessing the quantity of mite-derived allergen in dust-mite extracts, house-dust extracts, or house dust.

Chemical treatment of carpets to reduce allergen: A detailed study of the effects of tannic acid on indoor allergens

Tannic acid (TA), a protein-denaturing agent, has been reported to reduce allergen levels in house dust and is marketed for that purpose as 1% and 3% solutions. We investigated the effects of TA on dust allergens by using monoclonal antibody-based ELISAs for mite (Der p I, Der f I, and group II) and cat (Fel d I) allergens. Initial studies confirmed that TA reduced allergen levels in carpet dust. However, when dust samples from treated carpets are extracted in saline solution, residual TA redissolves and may interfere with the assessment of allergens. In the laboratory, concentrations of TA as low as 0.1% inhibited the assays, but this effect may be prevented by addition of 5% bovine serum albumin (BSA). After treatment of dust samples in the laboratory with 3% TA, the apparent reductions in Der p I and Der f I levels were 89% and 96%, respectively, but when the samples were extracted in 5% BSA the reductions were 74% and 92%. Similar effects were seen with dust samples from carpets treated with TA. In an extreme case in which a carpet had been repeatedly treated with TA, the apparent concentration of Der p I was < 0.05 microgram/gm without BSA and 2.1 and 8.4 microgram/gm when extracted in the presence of 1% and 5% BSA, respectively. Our testing of the ability of TA to denature Fel d I demonstrated an 80% reduction in allergen, but only in samples with an initial concentration of less than 200 micrograms Fel d I/gm dust.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessing Productivity Loss and Activity Impairment in Severe or Difficult-to-Treat Asthma

OBJECTIVES Asthma can be associated with substantial productivity loss and activity impairment, particularly among those with the most severe disease. We sought to assess the performance characteristics of an asthma-specific adaptation of the Work Productivity and Activity Impairment Questionnaire (WPAI:Asthma) in patients with either severe or difficult-to-treat asthma. METHODS We analyzed 2529 subjects from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. The WPAI:Asthma was administered at baseline and at 12 months. Asthma control and quality-of-life were simultaneously assessed using the Asthma Therapy Assessment Questionnaire and Mini-Asthma Quality-of-Life Questionnaire, respectively. RESULTS Severe versus mild-to-moderate asthma was associated with a greater percentage of impairment at work (28% vs. 14%), at school (32% vs. 18%), and in daily activities (41% vs. 21%). At baseline, greater asthma control problems correlated with higher levels of impairment as measured by the WPAI (work: r = 0.54, school: r = 0.37, activity: r = 0.55). Over the 12-month follow-up period, improved quality-of-life correlated with decreased levels of impairment (work: r = -0.42, school: r = -0.36, activity: r = -0.48). In multivariate analyses, greater than 10% overall work impairment at baseline predicted emergency visits (OR 2.6 [1.6, 4.0]) and hospitalization (OR 4.9 [1.8, 13.1]) at 12 months. CONCLUSIONS The WPAI:Asthma correlates with other self-reported asthma outcomes in the expected manner and predicts health-care utilization at 12 months when administered to patients with severe or difficult-to-treat asthma.

Treatment of late-onset asthma with fluconazole

BACKGROUND Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton. OBJECTIVE We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial. METHODS Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements. RESULTS At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P =.012) and in oral steroid requirement (P =.01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment. CONCLUSION The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.

Chemical treatment of carpets to reduce allergen: Comparison of the effects of tannic acid and other treatments on proteins derived from dust mites and cats

BACKGROUND Several chemical treatments have been recommended for reducing mite and other allergen levels in carpets, including the protein-denaturing agent tannic acid (TA). OBJECTIVE We evaluated the efficacy of TA and other treatments on mite and cat allergens in carpets within houses. The effects of TA were assessed on Der p 1 and Der f 1, on group II mite allergens, and on the major cat allergen Fel d 1. METHOD Carpet treatments tested were benzyl benzoate moist powder, a 3% TA spray, and two carpet cleaners (Host and Capture). Carpets were treated twice and dust samples collected on a biweekly basis for 8 weeks: these samples were extracted in saline solution alone. Additional studies evaluated the effects of TA on 17 carpets. Carpets were treated twice (on days 0 and 28) and samples collected on days 0, 1, 7, 14, 28, and 42. Eighteen carpets were untreated controls. Dust samples were extracted separately in both saline solution and in the presence of 5% bovine serum albumin. RESULTS Benzyl benzoate and the two carpet cleaners reduced group 1 dust mite allergen concentrations in carpet dust. In addition, benzyl benzoate and TA reduced airborne group 1 mite allergens by more than 64%. Further studies showed that, in keeping with in vitro studies, TA inhibited the assay and bovine serum albumin abrogated this effect. Significant reductions after treatment occurred only for Der f 1 and group 2 dust mite allergens (p = 0.005 and p = 0.035, respectively). However, for all mite allergens the percentage changes after treatment were significant when compared with untreated carpets (p < 0.005 for Der f 1 and group 2 mite, p < 0.02 for Der p 1) but not for cat allergen (p > 0.3). The results suggested that repeated application of TA was necessary to maintain reduced allergen concentrations. CONCLUSION Carpet treatments can reduce mite-derived allergen levels in airborne and carpet dust. However, the effects do not appear to be maintained for long periods, are not dramatic, and are different for different allergens.

Assessment of asthma control and asthma exacerbations in the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) observational cohort.

Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.

Serum IgE antibodies to Trichophyton in patients with urticaria, angioedema, asthma, and rhinitis: Development of a radioallergosorbent test

A series of patients was identified who demonstrated immediate positive skin tests to intradermal Trichophyton extract. These skin responses did not correlate with other fungal skin tests and were present both in atopic and nonatopic patients. The individuals demonstrating positive immediate skin tests included patients with urticaria, angioedema, asthma, and/or rhinitis, as well as five of 34 normal control subjects. Most skin test positive individuals had a history of local fungal infection and clinical signs suggestive of fungal infection. By use of Trichophyton tonsurans extract linked to Sepharose as the immunosorbent, it was possible to measure IgE antibodies in 26/30 sera from skin test positive individuals. With strongly positive sera, RAST bound up to 30% of the radiolabeled anti-IgE added. The results confirm that most skin test positive individuals have IgE-mediated hypersensitivity to Trichophyton. These observations support the older view that absorption of dermatophyte allergen through the skin should be considered as a possible cause of allergic disease.

Dust Mite Allergen Avoidance in the Treatment of Hospitalized Children with Asthma

BACKGROUND Asthma is a leading cause of hospital admission in children. The majority of children with asthma are sensitized and exposed to inhalant allergens that may contribute to chronic airway inflammation. OBJECTIVE To evaluate the practicality and effects of dust mite (D. farinae and D. pteronyssinus) allergen avoidance in homes of children hospitalized with acute asthma. METHODS Children 5 to 18 years of age who were admitted with asthma to a suburban Atlanta hospital were randomly assigned, without knowledge of allergen sensitization or exposure in their houses, to active (n = 13) or placebo (n = 10) treatment group. Active treatment included encasing mattress, box springs, and pillows in allergen impermeable covers; weekly hot water wash of bed linens; replacement of bedroom carpet with polished flooring; and 3% tannic acid spray to living room carpet. Placebo treatment included permeable encasing for bedding, cold water wash, and water spray for carpet. Dust samples were analyzed for dust mite, cockroach, and cat allergens, while serum samples were analyzed for IgE antibodies to the same allergens. Outcome measures included daily peak expiratory flow rates, spirometry, methacholine inhalation challenge, and hospital readmission. RESULTS Children in both groups were similar by demographics, sensitization, and exposure to dust mite allergen. Allergen levels fell > 3-fold in many active and placebo homes. Children in the active group had improved PEFR at 3 and 6 months after intervention (P < .04, P < .05, respectively). Six of seven children in the study who were sensitized and exposed to dust mite allergen demonstrated improved PEFR at 3 months when allergen levels fell in both bedding and bedroom floor. There was no difference in FEV1 or methacholine challenge, although a few children in either group could tolerate methacholine because of bronchial hyperreactivity. Six children (four active and two placebo) were readmitted to hospital during the study. CONCLUSION Increases in PEFR were recorded among children in the active treatment group and also among sensitized patients whose dust mite allergens fell. These results support the hypothesis that avoidance can be effective even among children admitted to hospital. The study was complicated by insufficient numbers of mite-allergic children and poor compliance with diaries and the protocol. Recruitment from the hospital resulted in participants with more severe asthma than anticipated. The results also suggest that many of the patients in this group will continue to have exacerbations triggered by upper or lower respiratory tract infections.

Allergic Rhinitis: A Growing Primary Care Challenge

Purpose To describe the growing problem of allergic rhinitis (AR) and the latest recommendations on its diagnosis and management for the nurse practitioner (NP) in primary care settings. Data Sources Recent clinical research, review articles and consensus guidelines, and the authors clinical experience. Conclusions The prevalence of AR is increasing, possibly due to increased airborne pollutants, poor ven‐tilation, and rising levels of indoor allergens. Allergic disease is systemic and rarely involves a single symptom. Treatments include reducing exposure to allergens as well as pharma‐cotherapy. Implications for Practice Patient education is crucial for successful management and includes understanding the aller‐gic basis of symptoms, reducing allergen expo‐sure, understanding proper use of medications, and reassessing the plan on a regular basis.