Osteoporosis in the at-risk asthmatic.

The effect of inhaled glucocorticosteroids (ICS) on bone metabolism and subsequent osteoporosis is controversial. Explanations for this controversy include various study designs, duration of use, outcome measures, and population demographics of research studies with intranasal or inhalational ICS. Patients with poorly controlled asthma are at greatest risk of osteoporosis because they are commonly treated with intermittent or continuous systemic corticosteroids (SCS) or high-dose ICS. A 45-year-old Caucasian woman presents with moderate-to-severe asthma with frequent albuterol use and nighttime awakenings at least once weekly. She is on fluticasone/salmeterol 500/50 µg one inhalation twice daily and montelukast 10 mg/day. She requires prednisone 15 mg three times per day for 5 days up to three times a year. Is this patient at greater risk of osteopenia, characterized by a T-score between -1.0 and -2.5, and subsequent osteoporosis and an increased risk of fractures? If she has osteopenia, should she be treated with a bisphosphonate? The risk of osteoporosis and fracture increases significantly with frequent administration of SCS, and patients on such medications should undergo preventative measures and treatment. This study discuses factors that contribute to an increased risk of osteoporosis/osteopenia in patients with asthma and suggests recommendations based on the current literature.

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

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.

Intensive educational course in allergy and immunology.

A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile.

Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 40-75% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

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.

Drug-induced rhinitis.

BACKGROUND: Rhinitis is characterized by inflammation of the mucous membranes lining the nose and can be divided into two categories, allergic and non-allergic. Drug-induced is a type of non-allergic rhinitis. OBJECTIVE: A review of the literature was conducted. Very little is known about this topic and there are no publications to date solely devoted to drug-induced rhinitis. METHODS: A PubMed and Medline search was conducted using a combination of the keywords; drug, medication, rhinitis, congestion, rhinorrhea, sneezing, pruritus, vasomotor, reflex, neurogenic, allergic and non-allergic. Medications that were found in the search were then cross-referenced with the physicians desk reference and Epocrates. The final literature search was conducted in August 2009. RESULTS: Three categories of drug-induced rhinitis exist based on the mechanism of action. These include local inflammatory, neurogenic and idiopathic types. Rhinitis medicamentosa, a form of drug-induced rhinitis, has unique characteristics. CONCLUSION: When possible, the offending medication should be discontinued or substituted. Although there are no established treatment recommendations for drug-induced rhinitis other than avoidance, clinical experience suggests that it would be reasonable to initiate use of an intranasal corticosteroid spray to treat symptomatically. The addition of an intranasal antihistamine in combination with use of an intranasal corticosteroid may be considered as step-up therapy if the intranasal corticosteroid alone is not effective.

A new symptom-based questionnaire for predicting the presence of asthma.

BACKGROUND: Early diagnosis and treatment of asthma is important for improving health and minimizing the social and economic burden of the disease. A simple questionnaire would provide a convenient and timesaving tool to help physicians diagnose asthma. OBJECTIVE: The senior author developed a simple, pre-interview screening questionnaire--the Asthma Screening Questionnaire (ASQ)--consisting of 6 questions. The present report provides performance evidence that the ASQ is a reliable instrument for diagnosing asthma in adults. METHODS: Participants were asthmatics or controls, aged 18 to 65 years. All participants completed the questionnaire (self-administered and physician-administered), and underwent spirometry and a methacholine challenge test (if there was no reversibility during initial spirometry). Sensitivity, specificity, and positive and negative predictive values were calculated for each question, and the total scores of asthmatics were compared with those of controls. The degree of agreement between the self-administered and the physician-administered questionnaire was calculated. RESULTS: The main symptoms discriminating asthmatics from controls were cough more than average (88% vs 0%), cough from chest (72% vs 0%), shortness of breath with exercise (84% vs 16%), and chest tightness when lying down (72% vs 4%). A cutoff point of total score > or = 4 was associated with the highest combination of sensitivity (96%) and specificity (100%). Substantial agreement was observed between the self-administered and the physician-administered questionnaire (kappa statistic, 0.56-1.00; P<.0001). CONCLUSIONS: The ASQ is a simple, inexpensive, and efficient pre-interview screening tool to diagnose asthma.

Isatin down-regulates expression of atrial natriuretic peptide receptor A and inhibits airway inflammation in a mouse model of allergic asthma.

Isatin, an endogenous indole compound, prevents atrial natriuretic peptide (ANP) from signaling through its cell-surface receptor, NPRA. Allergic airway inflammation has been linked to natriuretic peptide signaling and blocking this signaling axis in the lung prevents allergen-induced pathology. In this study we encapsulated isatin in chitosan nanoparticles and tested them in a mouse model of allergic asthma by intranasal delivery to the lung. Isatin nanocapsules reduced lung pathology by blocking ANP signaling, but surprisingly also by reducing the expression of NPRA. Ovalbumin-allergic mice were treated intranasally with isatin-containing chitosan nanocapsules either before or after allergen challenge, and lung function, cytokine levels, histopathology and cellular infiltration were determined. ANP activity was quantitated by measuring changes in intracellular cyclic GMP and changes in NPRA levels were determined. For comparison with isatin's effects, the expression of the receptor was inhibited with small interfering RNA against NPRA mRNA. Isatin nanocapsules administered locally to the lung reduced cGMP production and NPRA expression and protected allergic mice from airway hyperreactivity and lung inflammation when given either before or after allergen challenge. Leukocyte infiltration was reduced and lung cytokine profiles showed a repolarization from a Th2-like to a Th1-like phenotype. Isatin nanocapsules administered locally to the lung inhibit NPRA signaling but also are capable of lowering the expression of NPRA, thus effectively reducing inflammation in a mouse model of allergic asthma. Pharmacological intervention to reduce NPRA activity through the inflammatory natriuretic peptide axis in the lung may be a useful adjunct therapy for treating lung disease.

Immunologic responses to therapeutic biologic agents.

Recombinant protein technology and the subsequent development of biologic agents for pharmacotherapy have greatly improved the treatment of a wide variety of diseases in humans. These products are subject to reactions not previously seen in other drug classes. Additionally, subtle alteration in the manufacture or administration of a biologic agent may cause reactions in subjects who previously tolerated it. This review highlights the unique immunologic reactions that are associated with the more commonly used biologic agents.

Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization.

Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. doses.

Curcumin prevents human dendritic cell response to immune stimulants.

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14(+) monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4(+) T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant.

Typical levels of airborne fungal spores in houses without obvious moisture problems during a rainy season in Florida, USA.

OBJECTIVE: The aim of this study was to determine types and levels of airborne fungal spores in air-conditioned homes built after 1980 without obvious moisture problems during the 2004 summer (rainy season) in central Florida, USA. METHODS: Eighteen single-family homes were selected based on protocol questionnaire and cursory inspection, which revealed no obvious moisture or visible fungal growth. Non-cultured spores were collected with Air-O-Cell cassettes. Three indoor air samples and 2 outdoor air samples were collected from each home. One indoor and 2 outdoor samples were not interpretable. Fifty-three indoor and 34 outdoor air samples were analyzed by optical microscopy. RESULTS: Several spore types were detected in the indoor samples, at levels generally lower than those detected in the outdoor samples. Spores from the Penicillium/Aspergillus group were the most prevalent types indoors, exceeding the absolute levels and relative percentages of these spores outdoors. Ascospores and basidiospores were the most prevalent spore types outdoors. The percentages of other spore types (Cladosporium and Curvularia) were similar in the indoor and outdoor samples. Moisture-indicator fungi (Chaetomium, Stachybotrys, and Ulocladium species) were nearly absent in both indoor and outdoor samples. CONCLUSION: Airborne fungal spores are present in average central Florida homes without obvious moisture problems during the summer, at levels that are lower than those found outdoors. Spores from the Penicillium/Aspergillus group are prevalent in these homes, and moisture-indicator fungi (Chaetomium, Stachybotrys, and Ulocladium species) are nearly absent. Despite climatic differences, airborne fungal spore types and levels in central Florida houses are similar to those found in other geographical locations.

Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce.

Specific Immunotherapy for respiratory allergy is used since about one century and there is now solid documentation of its efficacy. Nevertheless, the methods and experimental designs used in clinical trials are quite heterogeneous and there is no unanimously accepted methodological standard. Many studies are planned with study designs that may not confirm the clinical value of SIT as an effective treatment to reduce disease severity. To ensure that patients are treated based on sound scientific evidence and to minimize the risk of misusing limited financial resources for scientific studies, the World Allergy Organization (WAO) convened a group of experts to provide guidelines for the methodology of future immunotherapy studies. This document summarizes the recommendations for study design, patients' selection, appropriate outcomes and statistical treatment to be used in planning and performing clinical trials with specific immunotherapy.

Rhinitis medicamentosa.

Rhinitis medicamentosa (RM) is a condition induced by overuse of nasal decongestants. The term RM, also called rebound or chemical rhinitis, is also used to describe the adverse nasal congestion that develops after using medications other than topical decongestants. Such medications include oral beta-adrenoceptor antagonists, antipsychotics, oral contraceptives, and antihypertensives. However, there are differences in the mechanism through which congestion is caused by topical nasal decongestants and oral medications. Very few prospective studies of RM have been performed and most of the knowledge about the condition comes from case reports and histologic studies. Histologic changes consistent with RM include nasociliary loss, squamous cell metaplasia, epithelial edema, epithelial cell denudation, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, and inflammatory cell infiltration. Since the cumulative dose of nasal decongestants or time period needed to initiate RM has not been conclusively determined, these medications should only be used for the shortest period necessary. Validated criteria need to be developed for better diagnosis of the condition. Stopping the nasal decongestant is the first-line treatment for RM. If necessary, intranasal glucocorticosteroids should be used to speed recovery.

Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo.

The potential of cationic SiO2 nanoparticles was investigated for in vivo gene transfer in this study. Cationic SiO2 nanoparticles with surface modification were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA at the nanoparticle surface was achieved at a particle ratio of 80 (w/w nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm with a distribution from 10-100 nm. The ability of these particles to transfect pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were obtained in the presence of FCS and chloroquine at a particle ratio of 80. These nanoparticles were tested for their ability to transfer genes in vivo in the mouse lung, and a two-times increase in the expression levels was found with silica particles in comparison to EGFP alone. Very low or no cell toxicity was observed, suggesting silica nanoparticles as potential alternatives for gene transfection.

Allergenicity of varieties of soybean.

BACKGROUND: Soybean hulls (SHs) cause respiratory allergies. This study investigates the allergenicity of soybean varieties (SVs) by in vivo and in vitro tests. METHODS: Ten SVs were studied: (a) five with a proved clinical relevance (SVs 1, 2, 3, 4, 5), the last four with a 'dull' phenotype; (b) five of undetermined relevance, three of them (SVs 6, 7, 8) with a 'shiny' phenotype, and two (SVs 9 and 10) with a 'dull' phenotype. Extracts from all 10 SVs were used to skin prick test (SPT) 21 subjects sensitized to SHs. Positive and negative sera pools prepared from sera of subjects sensitized or not to SHs, respectively, were utilized to perform in vitro experiments (specific IgE and IgG4 determinations, SDS-PAGE/IgE-Western blot, and IgE-inhibition). RESULTS: In this study, it was found that 52.4, 52.4, 57.1, 71.4, 80.9, 42.9, 57.1, 71.4, 52.4, and 38.1% subjects had a positive SPT with SVs 1-10, respectively (P NS). Specific IgE values to SVs 1-10 obtained with the positive pool are 28.3, 26.4, 29.9, 28.3, 26.8, 4.8, 13.4, 6.7, 24.7, and 17.5% total counts bound, respectively; and specific IgG4 values 0.851, 0.818, 0.721, 1.609, 0.789, 0.617, 0.662, 0.0, 1.127, and 0.934 OD units, respectively; the microgram of protein required to produce 50% inhibition are 2.5, 3.7, 4.5, 2.4, 5, 39.8, 25.2, 25.1, 4.5, and 8.9, respectively. A 7-kDa band is present in all SVs except in those with a 'shiny' phenotype. CONCLUSIONS: The SVs with a 'shiny' phenotype contain less allergens than the other SVs studied, as determined by in vitro tests. However, SPT results with the SVs do not differ. Genetic screens should be devised to select plants with reduced, preferably absent, allergenicity, but with a high nutritional value, and this allergenicity should be studied utilizing in vivo and in vitro tests.