Robert L. Jacobs

Responses to ragweed pollen in a pollen challenge chamber versus seasonal exposure identify allergic rhinoconjunctivitis endotypes

BACKGROUND The level of concordance between allergic symptoms induced on exposure to pollen in a pollen challenge chamber (PCC) versus the natural season is unknown. OBJECTIVE We sought to test the hypothesis that the symptom levels of allergic rhinoconjunctivitis elicited after out-of-season exposure to short ragweed in a PCC and during the natural season for giant ragweed pollen are highly correlated. METHODS Thirty-one ragweed-sensitive participants recorded symptoms for 15 days during the natural giant ragweed season in San Antonio, Texas. Twenty-six of these participants were challenged to short ragweed pollen in a PCC for 3 hours per day for up to 4 days. RESULTS In the PCC participants were dichotomized into those in whom low versus high levels of symptoms developed slowly or rapidly (ie, slow/low vs rapid/high). Each successive exposure visit associated with a progressive increase in symptom levels that approximated those experienced during the natural season. Hierarchic clustering identified 3 endotypes: endotypes I and II reflected concordantly low (n= 7) versus high (n = 14) total symptom scores (TSSs) in both the natural season and the PCC, respectively. Accordingly, the correlation between the TSSs recorded in the natural season and in the PCC for these 21 participants was very high. Although participants with endotype III (n = 5) had greater TSSs in the natural season than in the PCC, the degree of correlation between the TSSs remained high. CONCLUSIONS Our findings affirm our hypothesis, underscore the high cross-reactivity between distinct pollens, and highlight the utility of the PCC to identify novel allergy endotypes that might have contrasting mechanistic underpinnings and potentially therapeutic responses.

Comparative efficacy, safety, and effect on quality of life of triamcinolone acetonide and fluticasone propionate aqueous nasal sprays in patients with fall seasonal allergic rhinitis

BACKGROUND The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR). OBJECTIVE To compare the efficacy, safety, and effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal sprays in patients with SAR. METHODS Single-blind, parallel-group, active-controlled design. Patients were randomized to 3-week treatment with TAA 220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) were performed AM/PM, beginning at pretreatment baseline period. Incidences of specific treatment-related side effects were collected in daily questionnaires. HRQL was evaluated at baseline and end-of-treatment with a validated disease-specific, quality-of-life instrument. RESULTS TAA and FP produced similar improvement in daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P = 0.332) and at every weekly time point (P > 0.05). There were no significant differences between TAA and FP in any individual symptom score at any time point except week 2 (FP provided greater reduction in sneezing, P = 0.046). No significant difference was found between groups in overall occurrence of specific treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life Questionnaire scores were similar for TAA and FP at end-of-treatment. CONCLUSIONS Despite differing molecular potencies, FP and TAA demonstrated comparable efficacy in the treatment of SAR, and produced similar occurrences of specific treatment-related side effects and similar improvements in overall patient HRQL.

Organic antigen-induced interstitial lung disease: diagnosis and management

BACKGROUND Traditionally, chronic idiopathic interstitial pneumonia/fibrosis (IIP/F) had included usual interstitial pneumonia, desquamative interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). More recent classifications have included bronchiolitis obliterans-organizing pneumonia (BOOP), respiratory bronchiolitis-associated interstitial lung disease, and acute interstitial pneumonia. Some chronic eosinophilic pneumonias (CEP)/pulmonary infiltrate with eosinophilia (PIE) have obvious causes, but many lack an identifiable etiology. We felt that hypersensitivity pneumonitis (HP) was being underdiagnosed and was hidden within this large heterogeneous group of interstitial lung disorders of unrecognized cause. OBJECTIVE We sought to prove that detailed environmental histories and investigations would reveal causative contaminations in the home or workplace of some patients with idiopathic interstitial lung disease and remediation of the contamination would stabilize the disorder. METHODS Consecutive cases of IIP/F were investigated. Patients were identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and lung biopsies. They were further evaluated with detailed environmental histories, serologic tests, and investigation into the suspected causative environment. Environmental and specific antigen challenges were done in some cases. Remediation of contaminations or moving into another environment were the methods used as therapy. RESULTS Eighty-six consecutive patients with IIP/F were evaluated. Twelve patients were subsequently diagnosed with specific causes for interstitial lung disease. Fifty-seven of 74 patients were identified by clinical evaluation and lung biopsy with HP, CEP/PIE, NSIP, BOOP, UIP, and nonclassifiable morphologic patterns. Seventeen patients were not biopsied or had an inadequate transbronchial biopsy but had consistent findings radiographically and clinically of idiopathic interstitial lung disease. Contamination of the home was causative in 69 of 74 and the workplace in 3 of 74 cases. There were 9 positive and 33 negative environmental challenges with 4 positive and 1 negative specific challenges. Fifty of 74 (67%) patients are receiving no treatment and are free of active disease after remediation of the environmental contamination, with a mean survival of 8.2 years. CONCLUSIONS Our data show that UIP, BOOP, NSIP, CEP/PIE, and nonclassifiable morphologic patterns represent a spectrum of interstitial lung disease that may be caused by inhalation of organic dusts in the home or workplace as described with HP. Remediation of, or moving from the contamination, can lead to arrest of the active inflammatory process and stability of the lung disorder.

Sunflower oil is not allergenic to sunflower seed-sensitive patients

The allergenicity of edible oils derived from sunflower seeds was investigated in two patients with anaphylactic sensitivity to sunflower seeds. Specific IgE-mediated hypersensitivity to sunflower seed was demonstrated by history, prick skin tests, positive passive transfer skin test, and RAST. Specific IgE directed toward sunflower oil, refined or cold pressed, could not be conclusively demonstrated. The Prausnitz-Küstner reaction with sunflower oils performed with one patients serum was negative. Although the cold-pressed sunflower oil was found to contain a minute amount of protein, open challenge with the derivative oils resulted in no immediate or delayed reaction in the two patients studied. Sunflower oil ingestion in these patients who were highly sensitive to the parent material proved safe. Nonallergenicity of derivative products needs to be proven for each case.

In vivo and in vitro comparison of fire ant venom and fire ant whole body extract

Thirty-four patients with a history of immediate hypersensitivity to the sting of the imported fire ant were evaluated in a study designed to compare the diagnostic usefulness of fire ant whole body extract (WBE) preparations with that of fire ant venom (IFAV). Ninety-one percent (31/34) of the hypersensitive patients skin tested with IFAV at a maximal concentration of 1:5 X 10(3), v/v, demonstrated a wheal equal to or greater than the histamine control. Fifty-three percent (18/34) of the group were skin test positive to a WBE preparation. When the criteria for a positive skin test were relaxed, 82% of the hypersensitive group could be identified with the IFAWBE. A comparison of skin test results in sensitive patients revealed variability in the sensitivity of the WBE preparations utilized in the study. Leukocyte histamine release demonstrated a dose-response release of histamine with both IFAV and SIWBEa preparations. Specific venom antisera produced in rabbits identified a precipitin line of common identity in a gel-diffusion system containing IFAWBE and IFAV. This finding was verified by the competitive inhibition of IFAWBE with IFAV in a solid-phase radioimmunoassay system. Fire ant WBEs contain venom constituents and are effective diagnostic agents in up to 82% of patients with hypersensitivity to the sting of the imported fire ant. Marked variability in the responsiveness of sensitive patients to different WBE preparations mandates standardization of these diagnostic preparations.

Hypersensitivity Pneumonitis Caused by Cladosporium in an Enclosed Hot-Tub Area

A 48-year-old woman had an 18-month history of malaise and chronic cough with intermittent episodes of fever, chills, and pneumonic infiltrates. Transbronchial biopsy findings were consistent with hypersensitivity pneumonitis. Cultures of fungus from a hot-tub room in her home were positive for Cladosporium species. Serum precipitins were weakly positive for Cladosporium cladosporioides. Removal of the patient from the home environment led to a resolution of symptoms within 1 week. Within 4 hours of re-exposure to the hot-tub room, symptoms and signs and changes in leukocyte count and spirometric values again occurred. Bronchial provocation with a commercial extract of C. cladosporioides led to a similar pattern 5 hours after the initial challenge. This case identifies a previously unreported etiologic agent and environmental site for hypersensitivity pneumonitis.

Imported fire ant hypersensitivity. Studies of human reactions to fire ant venom

It is now apparent that venom and venom components of the Hymenoptera superfamilies of Apida (honeybee) and Vespida (wasps, yellow jackets, and hornets) are becoming increasingly important in the diagnosis and treatment of hypersensitivity reactions. Stings from fire ants (superfamily Formicidae, family Myrmicinae) have also been recognized as causes of systemic reactions in man. Fire ant venom is unique in its composition, consisting mainly of alkaloids in aqueous suspension with only trace amounts of protein. This study compares the skin reactivity of fire ant venom and synthesized alkaloid components with the whole body extract (WBE) of fire ants and other Hymenoptera. The venom as well as the WBE of fire ants was found useful for skin test diagnosis of sensitive individuals. There appear to be cross-reactive or shared antigens between fire ant venom, WBE, and WBE of other Hymenoptera. Successful passive transfer of skin reactivity to nonsensitive individuals was accomplished with sera from sensitive individuals. Loss of this passive transfer by heating sera at 56 degrees C for 4 hr is evidence in favor of IgE mediating the positive skin test to the venom.

Hypersensitivity pneumonitis: beyond classic occupational disease–changing concepts of diagnosis and management

OBJECTIVE To review inhaled antigens in home environments that cause hypersensitivity pneumonitis (HP) of varied clinical expressions and histopathologic patterns. DATA SOURCES Computer-assisted MEDLINE and manual searches for articles concerning HP, interstitial lung disease (ILD), epidemiology of HP and ILD, challenge procedures of HP, and indoor fungi. STUDY SELECTION Published articles concerning inhaled antigens in home environments and HP were selected. RESULTS Current criteria for the diagnosis of HP are too restrictive, because most apply only to the classic acute presentation and are of limited value in the subacute and insidious forms. Clinical expressions vary across the gamut of respiratory tract signs and symptoms. Patterns on lung biopsy may include all histopathologic descriptions of idiopathic ILD. The home is the likely causative environment rather than the workplace. Exposures may be occult and require in-depth environmental histories and on-site investigations to detect antigens and sources. CONCLUSIONS Natural or environmental challenges have become an important tool for diagnosing HP and determining effectiveness of remediation. Early diagnosis and effective remediation of the cause lead to a high survival rate, whereas diagnosis in advanced stages leads to disability and/or premature death.

Response of the nonaliergic rhinitis with eosinophilia (HARES) syndrome to 4% cromolyn sodium nasal solution

Abstract A double-blind, parallel, multiple-dose drug trial was perforated on 23 adult patients with nonallergic rhinitis with eosinophilia (HARES) syndrome. All patients were characterized clinically as having perennial nasal symptoms of sneezing paroxysms, profuse watery rhinorrhea, and pruritus of the nasopharyngeal and conjunctiva( mucosa, with minimal nasal obstruction to airflow. They had nasal secretion eosinophilia, negative prick or intradermal immediate skin tests, negative serum RAST results to common inhalant allergens, negative methacholine bronchoprovocation challenges, and normal total eosinophil counts and total serum IgE levels. Twelve patients received a 4% cromolyn sodium nasal solution and/I patients received a matching placebo administered six times daily. for 8 wk. Daily symptom scores for itchy nose, runny nose, stuffy nose, itchy eyes, itchy throat, mouth breathing, postnasal drainage, sneezing, and nose blowing were recorded by the patients. Eye, ear, nose, and throat (SENT) examinations were performed weekly by one of the investigators, and blood samples for CBC and chemistries were obtained at the start and termination of the study. Chemistries and blood counts showed no adverse effects of the drug. No important differences between the drug and placebo groups were noted in either the .symptom scores or SENT examinations of the two groups. We conclude that 4% cromolyn sodium nasal solution is of no benefit in the treatment of patients with the HARES syndrome.

Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p <or= 0.001) in study 1 and more effective than both placebo and fexofenadine (p <or= 0.034) in study 2 with respect to the mean changes from baseline in the nighttime reflective total ocular symptom score and predose instantaneous total ocular symptom score. In these double-dummy studies, fexofenadine did not separate from placebo in comparisons of the nighttime symptoms score or the nighttime nasal or ocular symptom measures. The incidence of adverse events was similar among groups. FFNS once daily was more effective than fexofenadine and placebo with respect to nighttime sleep disturbance caused by seasonal allergy symptoms.