Treatment with azelastine hydrochloride and fluticasone propionate in a single delivery device of young children and adolescents with allergic rhinitis.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

Objective approach for fending off the sublingual immunotherapy placebo effect in subjects with pollenosis: double-blinded, placebo-controlled trial.

BACKGROUND: Symptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect. OBJECTIVE: To assess the ability of exhaled breath temperature (EBT), a putative marker of airway inflammation, to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study. METHODS: This was a double-blinded, placebo-controlled clinical trial in 56 subjects (mean ± SD 30 ± 12 years old, 33 men) sensitized to grass pollen. The objective measurements were EBT, spirometry, and periostin and high-sensitivity C-reactive protein in blood. Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms. Evaluations were performed before, during, and after the grass pollen season. RESULTS: Fifty-one subjects (25 and 26 in the active treatment and placebo groups, respectively) were assessed before and during the pollen season. The mean pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the active treatment than in the placebo group (P = .030). Of the other objective markers, only the blood periostin level increased significantly during the pollen season (P = .047), but without intergroup differences. Subjectively, the mean pre- vs in-season increase in the visual analog scale score was 32.3% smaller in the active treatment than in the placebo group, although this difference did not reach statistical significance (P = .116). CONCLUSION: These results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a putative quantitative measurement of airway inflammation, which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785394.

Characteristics of a patient population seeking medical advice for nasal symptoms in Bulgaria.

BACKGROUND: The proportion of patients visiting general practitioners (GPs), otorhinolaryngologists (ORLs), and allergologists (ALRGs) for nasal complaints is unknown but important in estimating the number of subjects with nasal symptoms bothersome enough to warrant physician consultations and assessing nasal pathological conditions' burden on a national health care system. OBJECTIVE: The Symptoms of Nasal Inconvenience Fact Finding (SNIFF) survey was developed to (1) assess incidence of physician visits attributable to nasal complaints; (2) characterize patients' nasal conditions; and (3) outline differences across physician categories. METHODS: The SNIFF survey was completed over 20 days by Bulgarian GPs, ORLs, and ALRGs whom patients consulted for nasal symptoms. Survey forms differentiated type and severity of patients' conditions according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and ranked bothersome symptoms. Smell impairment, comorbidities, and prescription practices were documented. RESULTS: Sixty-nine physicians (30 GPs, 8 ORLs, 31 ALRGs) completed 1,685 surveys. The proportion of patients with nasal symptoms over the total patients seen was 15.7%: ALRGs, 18.0%; GPs, 14.6%; ORLs, 13.1%. Patients were classified as having intermittent (38.8%) or persistent (61.2%) rhinitis, with most having moderate/severe symptoms (94.4%). Congestion was the leading symptom in 59.1%. Smell was impaired in 69.8% of patients, asthma was present in 21.4%, and cough in 62.9%. ALRGs were more likely to diagnose and manage patients per ARIA guidelines than were ORLs or GPs. CONCLUSION: The SNIFF survey results demonstrate congestion's role as a leading symptom motivating patients to seek medical advice. SNIFF also uncovered differences in practices among different categories of health care providers.

Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles.

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Food allergy in adults in Europe: what can we learn from geographical differences?

PURPOSE OF REVIEW: The aim of this article is to characterize the present state-of-the-art on the topic of food allergies across Europe. RECENT FINDINGS: A systematic review and metaanalysis on the epidemiology of food allergy in Europe have been performed by the Food Allergy and Anaphylaxis Guidelines Group of the European Academy of Allergology and Clinical Immunology. The authors had made an extensive search of four different electronic databases which retrieved thousands of hits. A critical appraisal of the documents reduced their number to just over 100 articles covering the period 2000-2012, revealing striking methodological inhomogeneity and blank areas on the map of the continent, particularly for the adult population. A major new development intending to fill in the gaps in the field of food allergy is the launch and implementation of the European Union-funded project 'Prevalence, Cost and Basis of Food Allergy Across Europe,' acronym 'EuroPrevall.' Among the deliverable of the project are several seminal articles on food allergy in adults which are presented in this review. SUMMARY: The EuroPrevall project confirmed much more reliably and in more detail the existing inhomogeneity in the prevalence of food allergy, which reflects environmental and climate differences between the separate countries, but possibly also the level of public awareness.

Evaluation of a simple, potentially individual device for exhaled breath temperature measurement.

RATIONALE: Inflammation is a universal pathological reaction and is characterized among other things by increased heat production. The question stays whether the contribution of the inflamed lung tissues to the overall exhaled breath temperature (EBT) can be reliably detected and used in everyday clinical practice. METHODS: We have designed a simple device for assessment of EBT and explored its performance under standard indoor conditions. We made our measurements in the morning hours, documenting the ambient conditions (room temperature, humidity, atmospheric pressure), and physiological characteristics of the tested subjects (heart rate, blood pressure, otic and axillary temperature). We assessed its day-to-day reproducibility in 17 healthy volunteers and its ability to discriminate between the same subjects without respiratory disease and uncontrolled asthmatics (n=14). We also compared the EBT of the 14 asthmatics before and after anti-inflammatory treatment. RESULTS: No association was found between EBT and any of the ambient conditions: room temperature, atmospheric pressure and humidity. While otic and axillary temperatures, which were measured in parallel, maintained high correlation between each other (Spearman's rho=0.71, p<0.01), EBT did not show meaningful association with any of them. The EBT (degrees C) of asthmatics (median 35.45, range 34.12-36.09) was higher than that of controls (34.84, 32.29-35.84), (p=0.009, Mann-Whitney U test). Anti-inflammatory treatment brought down the EBT of the asthmatics (34.78, 33.23-36.06), (p=0.001, Wilcoxon Signed Ranks test), while significantly improving their spirometry too. CONCLUSIONS: Measurements of EBT with the device we constructed are not significantly influenced by changes within the accepted range of a standard indoor environment. EBT represents a different characteristic of the human organism than otic and axillary temperatures. EBT is increased in uncontrolled asthmatics and decreases under anti-inflammatory treatment.

The added value of exhaled breath temperature in respiratory medicine.

Recognition of the huge economic burden chronic respiratory diseases pose for society motivated fundamental and clinical research leading to insight into the role of airway inflammation in various disease entities and their phenotypes. However, no easy, cheap and patient-friendly methods to assess it have found a place in routine clinical practice. Measurement of exhaled breath temperature (EBT) has been suggested as a non-invasive method to detect inflammatory processes in the airways as a result of increased blood flow within the airway walls. As EBT values are within a narrow range, the thermometers designed for the purpose of assessing it need to be precise and very sensitive. EBT increases linearly over the pediatric age range and seems to be influenced by gender, but not by height and body weight. In non-smoking individuals with no history of respiratory disease EBT has a natural circadian peak about noon and increases with food intake and physical exercise. When interpreting EBT in subjects with alleged airway pathology, the possibilities of tissue destruction (chronic obstructive pulmonary disease, cystic fibrosis) or excessive bronchial obstruction and air trapping (severe asthma) need to be considered, as these conditions drive (force) EBT down. A prominent advantage of the method is to assess EBT when patients are in a steady state of their disease and to use this 'personal best' to monitor them and guide their treatment. Individual devices outfitted with microprocessors and memory have been created, which can be used for personalized monitoring and disease management by telemedicine.

Clinical characteristics of patients seeking medical advice for nasal symptoms in Bulgaria with special focus on children.

BACKGROUND: In an attempt to circumvent low response rates and high cost of classical epidemiological trials, we carried out a real-life survey among practicing physicians consulting patients for nasal symptoms. In this fragment of our work we analyze similarities and differences between children and adults and within the different strata of pediatric age. METHODS: A survey was carried out by 69 physicians across Bulgaria (general practitioners, allergists and otorhinolaryngologists) and made possible calculation of the proportion of subjects with nasal symptoms from all other patients seen. Its structure allowed classification of rhinitis according the ARIA guidelines. RESULTS: Out of the 1685 completed survey forms, 506 pertained to the age group below 18 years. The gender predominance differed in children and adults: 57.3 % vs. 42.8 % of males respectively, P < 0.001. The prevalence of persistent rhinitis in children was 55.7 %, lower than in adults, 63.3 %, P = 0.004. In both pediatric and adult patients moderately severe and severe forms of rhinitis prevailed, 93.7 % vs. 94.6 %, with nasal obstruction as leading symptom: 59.9 % vs. 58.8 %. Cough was significantly more prevalent among children, 72.5 %, gradually decreasing until reaching adulthood, 58.7 %, P < 0.001. Prevalence of doctor diagnosed asthma was also higher among children, 25.1 %, than in adults, 19.5 %, P = 0.011. A gradient for characteristics, which were different in children, emerged across the pediatric age strata. DISCUSSION: Our study uses an unorthodox design targeting the patient population visiting physicians' offices because of nasal symptoms, achieving a much higher level of credibility of the results at minimal expense. As we base our survey on international guidelines, we believe this approach demonstrates the applicability of such consensus documents for practical purposes when in the hands of qualified physicians. CONCLUSIONS: Moderate and severe rhinitis symptoms motivate patients and their guardians to seek medical advice. While nasal congestion is a leading bothersome symptom in both adults and children, specific other features characterize the pediatric age and differ across its strata.

A real - life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough.

BACKGROUND: Different conditions make the proximal airways susceptible to tussigenic stimuli in the chronic cough (CC) syndrome. Leukotrienes can be implicated in the inflammatory mechanism at play in it. Montelukast is a selective cysteinyl-leukotriene receptor antagonist with proven effectiveness in patients with asthma. The aim of our real-life pilot study was to use montelukast to relieve cough symptoms in patients with CC allegedly due to the two frequent causes other than asthma - upper airway cough syndrome and gastroesophageal reflux (GER). METHODS: 14 consecutive patients with CC were evaluated before and after 2 weeks of treatment with montelukast 10 mg daily. Cough was assessed by validated cough questionnaire. Questionnaires regarding the presence of gastroesophageal reflux were also completed. Cough reflex sensitivity to incremental doubling concentrations of citric acid and capsaicin was measured. Lung function, airway hyperresponsiveness and exhaled breath temperature (EBT), a non-invasive marker of lower airway inflammation, were evaluated to exclude asthma as an underlying cause. Thorough upper-airway examination was also conducted. Cell counts, eosinophil cationic protein (ECP), lactoferrin, myeloperoxidase (MPO) were determined in blood to assess systemic inflammation. RESULTS: Discomfort due to cough was significantly reduced after treatment (P < 0.001). Cough threshold for capsaicin increased significantly (P = 0.001) but not for citric acid. The values of lactoferrin and ECP were significantly reduced, but those of MPO rose. EBT and pulmonary function were not significantly affected by the treatment. CONCLUSION: Patients with CC due to upper airway cough syndrome or gastroesophageal reflux (GER) but not asthma reported significant relief of their symptoms after two weeks of treatment with montelukast. ECP, lactoferrin, MPO altered significantly, highlighting their role in the pathological mechanisms in CC. Clinical trial ID at Clinicaltrials.gov is NCT01754220.