Clinical correlates of rhinovirus infection in preschool asthma.

BACKGROUND: Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group. OBJECTIVES: To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome. METHODS: A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed for a 12-month period. Allergy tests and a standard health questionnaire were carried out at study entry. Respiratory virus presence in nasopharyngeal washes was studied at illness visits and at 3 scheduled visits. RESULTS: At study entry, mean age of the children was 5.3 years. Of 571 visits, 54% were positive for any virus and 39% for RV. Patient characteristics were only assessed with RV infection due to low number of other viruses. The use of supplementary vitamin D was inversely associated with RV infection (P < .05). RV infection was associated with more severe course of acute illness in terms of more severe nighttime coughing, more sleep disturbances, and more days with runny nose (all P < .05). RV infection was also associated with more severe disease course during the 12-month follow-up in terms of more nights with awakenings and more days of exercise-related symptoms (both P < .05). CONCLUSIONS: Vitamin D supplementation may have an anti-rhinovirus effect. Both short- and medium-term outcomes suggest RV infection to be an important clinical marker of instable preschool asthma.

Validation of the Global Allergy and Asthma European Network (GA2LEN) chamber for trials in allergy: Innovation of a mobile allergen exposure chamber.

BACKGROUND: Field clinical trials of pollen allergy are affected by the impossibility of predicting and determining individual allergen exposure because of many factors (eg, pollen season, atmospheric variations, pollutants, and lifestyles). Environmental exposure chambers, delivering a fixed amount of allergen in a controlled environmental setting, can overcome these limitations. Environmental exposure chambers are currently already used in phase 2, 3, and even 4 trials. Unfortunately, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinical trials. The new Global Allergy and Asthma European Network (GA2LEN) mobile exposure chamber is a step forward because the mobility of the chamber makes it convenient for patients to participate in clinical testing. OBJECTIVE: This study was made to validate the reproducibility, sensitivity, and specificity of the results obtained in the new GA2LEN chamber. METHODS: Seventy-two adult patients (19-61 years old) with allergic rhinitis with or without asthma caused by grass pollen were included in different clinical validation tests. Total symptom scores and total nasal symptom scores were recorded at time zero (0) and every 10 minutes during exposures, along with nasal and respiratory parameters. RESULTS: Exposure tests confirmed the reproducibility between subsequent runs and the sensitivity (P < .00001 vs patients exposed to placebo) and specificity (very low score in nonallergic subjects) in the GA2LEN chamber. No adverse reactions were recorded during the tests. CONCLUSIONS: The mobility of the GA2LEN chamber provides a new, potentially effective, and safe way of generating reliable data in allergy multicenter clinical trials.

Environmental factors affecting seasonality of ambulance emergency service visits for exacerbations of asthma and COPD.

OBJECTIVE: The aim of this study was to assess the association of severe exacerbations of asthma and Chronic Obstructive Pulmonary Disease (COPD) requiring ambulance emergency service (AES) visits with meteorological parameters and influenza outbreaks. METHODS: The records of patients calling the AES in 2007 and 2008 in the urban area of Lodz due to dyspnea were analyzed. Information on 25 daily reported meteorological parameters was obtained from the local meteorological service and data on influenza outbreaks obtained from the national surveillance service. RESULTS: During the winter months, a significantly higher mean daily number of AES visits for both COPD and asthma were noticed when compared to the summer. Interestingly, the number of daily AES visits correlated with several weather parameters, and the multiple regression analysis confirmed a negative correlation with minimum temperature, mean temperature and the dew point for both diseases (R = 0.526; p < 0.01; R = 0.577; p < 0.01 and R = 0.589; p < 0.01). Furthermore, the increased number of AES visits also correlated with a new number of cases of influenza infections as reported by local influenza surveillance system (rs = 77.6%; p < 0.001 and rs = 80.8%; p < 0.001 for asthma and COPD, respectively). CONCLUSION: Seasonality of AES visits for asthma and COPD are similar and seems to be related to specific weather conditions and to influenza outbreaks.

The statement of the Polish Society of Allergology experts on the treatment of difficult-to-treat asthma.

The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Mast cell and eosinophil activation during early phase of grass pollen-induced ocular allergic reaction.

Both mast cells and eosinophils were implicated in the pathophysiology of allergic conjunctivitis; however, the potential role of eosinophils in an early phase of allergic reaction has not been elucidated. The aim of this study was to assess the relation between clinical symptoms and sequence of mast cells and eosinophils specific mediators release into tear fluid during conjunctival allergen provocation. Patients with grass pollen rhinoconjunctivitis (n = 38) and healthy volunteers (n = 10) were challenged with increasing doses of allergen applied on the conjunctiva. The clinical symptoms were assessed by clinical score. Tear fluid was collected from 12 patients before provocation, at 20 and 40 minutes after positive response. Tryptase and eosinophil cationic protein (ECP) were measured using UniCap and 15-hydroxyeicosanoid acid (15-HETE) with a specific immunoassay. All allergic patients (but no control subjects) had a positive clinical response to the challenge. In 1 patient symptoms appeared after 50 BU/mL of grass allergen administration, in 3 patients symptoms appeared after 500 BU/mL (7.9% of patients), in 14 patients symptoms appeared after 1600 BU/mL (36.8%), and in 20 patients symptoms appeared after 5000 BU/mL (52.6%). The allergen dose was not correlated with the skin-prick test diameter. The mean tryptase concentration increased at 20 minutes from "nondetectable" to 5.89 ± 1.97 micrograms/L and then decreased to 1.77 ± 1.07 micrograms/L (n = 12; p < 0.05) at 40 minutes. ECP concentration was not changed at 20 minutes but increased at 40 minutes from 1.38 ± 0.98 micrograms/L before provocation to 10.61 ± 7.78 micrograms/L (n = 7; p < 0.05). There was no change in 15-HETE release. Both mast cells and eosinophils are activated during allergic reaction in conjunctiva and activation of eosinophils is preceded by activation of mast cells.

[Effects of parenteral lipid emulsions on immune system response]. / Wplyw mieszanek lipidowych stosowanych w zywieniu pozajelitowym na funkcje ukladu immunologicznego.

Lipid solutions used in parenteral nutrition (PN) are generally well tolerated. Recent studies reporting their effects on the immune system indicate that various compositions can modulate the immune response, thus affecting the response to pathogens and autoaggressive diseases. In this review, we discuss the compositions of various commercially available lipid solutions and their effects on the immune response to various pathologies. We conclude that: 1. Soybean oil-based emulsions are immunosuppressive and should be used with caution in inflammatory conditions, and are contraindicated in sepsis. 2. Mixtures of medium chain triglycerides and soybean oil are better tolerated. 3. Olive oil-based mixtures are neutral and are especially recommended for burned patients, premature infants and for long term PN. 4. Fish oil-based emulsions are beneficial in inflammatory conditions and in patients after major abdominal surgery.