Development and validation of the Cholinergic Urticaria Quality-of-Life Questionnaire (CholU-QoL).

BACKGROUND: Cholinergic urticaria (CholU), a common form of chronic inducible urticaria, is characterized by itchy weals that occur in response to physical exercise or passive warming. CholU patients frequently exhibit a high burden of disease. As of yet, no specific instrument is available to assess their disease-related quality-of-life (QoL) impairment. OBJECTIVE: The aim of this study was to develop and validate the first disease-specific QoL instrument for CholU patients, the Cholinergic Urticaria Quality-of-Life Questionnaire (CholU-QoL). METHODS: Using a combined approach of the literature search, semistructured patient interviews and expert opinion, we developed 96 potential CholU-QoL items. Subsequent item selection was performed by means of impact analysis complemented by an expert review for face validity. The resulting final CholU-QoL was then tested for levels of validity, reliability and influence factors in 88 CholU patients. In parallel, an US American-Canadian English version of the CholU-QoL was developed. RESULTS: The final 28-item CholU-QoL was found to have a 5-domain structure ("symptoms," "functional life," "social interaction," "therapy," "emotions") with excellent internal consistency. The CholU-QoL also showed a valid total score, and good levels of convergent validity, known-groups validity, as well as test-retest reliability. Multiple regression analysis found no significant drivers of the CholU-QoL total score. CONCLUSIONS AND CLINICAL RELEVANCE: The CholU-QoL is the first disease-specific QoL instrument for CholU and also the first specific QoL measure in the field of chronic inducible urticarias. It may serve as a valuable tool for clinical trials and improve routine patient management.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma.

BACKGROUND: Recent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy. METHODS: Data from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils <300/µL [low] vs ≥300/µL [high]) and baseline markers of asthma severity (emergency asthma treatment in prior year, asthma hospitalization in prior year, forced expiratory volume in 1 second [FEV1 ; FEV1 <65% vs ≥65% predicted], inhaled beclomethasone dipropionate dose [<600 vs ≥600 µg/day], and long-acting beta-agonist [LABA] use [yes/no]). RESULTS: Adults/adolescents (N = 1071) were randomized to receive either omalizumab (n = 542) or placebo (n = 529). In the 16-week ICS dose-stable phase, rates of exacerbations requiring ≥3 days of systemic corticosteroid treatment were 0.066 and 0.147 with omalizumab and placebo, respectively, representing a relative rate reduction in omalizumab-treated patients of 55% (95% CI, 32%-70%; P = .002). For patients with eosinophils ≥300/µL or with more severe asthma, this rate reduction was significantly more pronounced. CONCLUSION: In patients with allergic asthma, baseline blood eosinophil levels and/or clinical markers of asthma severity predict response to omalizumab.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision

BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

[Evaluation of liver function between indoor and outdoor workers: preliminary results].

INTRODUCTION: The aim of our study is to compare liver damage in "outdoor" environment technicians, a category occupationally exposed, and in "indoor" workers. MATERIALS AND METHODS: We studied 142 male technicians of the environment exposed to urban pollution and 142 male "indoor" workers not exposed. We compared mean and standard deviation of the following liver parameters: glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl-traspeptidasi (γGT) and alkaline phosphatase (PHA), total bilirubin (TB) and direct (DB). We made the two groups comparable for age, length of service, BMI, alcohol consumption and smoking habits, and excluded the workers who presented confounding factors. RESULTS: We found statistically significant differences about the levels of γGT, PHA, GPT and albumin between the "outdoor" workers exposed and the "indoor" control group. In the outdoor group we observed statistically significant values, GPT (51.8 ± 30.6 I.U./l vs. 30 ± 22.3 I.U./l; p = 0.000), γ-GT (42.2 ± 29.4 I.U./l vs. 22.4 ± 20.7 I.U./l; p = 0.000) and PHA (75.7 ± 20.6 I.U./l vs. 59.1 ± 19.6 I.U./l; p= 0.000) compared to the unexposed group. No statistically significant difference emerged between the averages for the values of GOT (25.3 ± 20.7 I.U./l vs. 26 ± 17.7 I.U./l; p = 0.736) in two groups. CONCLUSIONS: It clearly emerges that the contaminants may alter the values of liver tests after prolonged exposure.

Work-related stress in healthcare workers.

BACKGROUND: In the assessment of work-related stress it is crucial to find the factors that generate and increase it in order to identify categories of individuals at risk, to plan interventions for prevention, elimination or reduction of risk. The aim of the study is to assess the subjective stress in 68 workers of a large Italian company dealing with human health, through the use of a questionnaire-indicating tool, elaborated by the Italian National Institute for insurance against accidents at work (INAIL) and developed by the Health and Safety Executive (HSE). METHODS: We studied a final sample of 68 individuals (34 drivers/rescuers and 34 video display unit (VDU) operators). The questionnaire consists of 35 items (divided into six areas) with five possible answers each, that cover working conditions considered potential causes of stress. RESULTS: The drivers/rescuers had a better performance than the VDU operators, especially in the areas "demand", "relationships" and "role". We compared men and women in the two groups, finding that, in VDU operators, women had a better performance than men in all areas, except "role" and "changes", in which the overall scores were the same in men and women. In the drivers/rescuers women showed more critical scores in the items "relationships" and "change". CONCLUSION: The results show that: the questionnaire-indicating tool is useful, with a demonstrated effectiveness for the occupational physician during the visits and proven validity; additional future efforts should focus on understanding the psycho-social, organizational and individual problems related to stress and the consequent implementation of preventive measures.

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.

BACKGROUND: New treatment options are required for patients with asthma not sufficiently controlled with inhaled therapies. In a Phase 2a trial, CYT003, a Toll-like receptor-9 agonist immunomodulator, improved asthma control during inhaled glucocorticosteroid reduction in patients with allergic asthma. This double-blind Phase 2b study assessed the efficacy and safety of CYT003 in patients with persistent moderate-to-severe allergic asthma not sufficiently controlled on standard inhaled glucocorticosteroid therapy with/without long-acting beta-agonists (LABAs). METHODS: Overall, 365 patients received seven doses of subcutaneous CYT003 (0.3, 1, or 2 mg) or placebo as add-on therapy to conventional controller medication. Change from baseline in Asthma Control Questionnaire (ACQ) score was the primary outcome; secondary outcomes included change in forced expiratory volume, Mini Asthma Quality of Life Questionnaire, and safety. RESULTS: All groups, including placebo, showed a clinically important improvement in ACQ score; however, there was no significant difference between the CYT003 and placebo groups at week 12 (least-squares mean difference 0.3 mg: -0.027 [95% confidence interval -0.259 to 0.204]; 1 mg: 0.097 [-0.131 to 0.325]; 2 mg: 0.081 [-0.148 to 0.315]). No significant differences were seen in secondary outcomes. CYT003 was well tolerated; the most common treatment-emergent adverse events were injection site reactions. Due to lack of efficacy, the study was prematurely terminated at the end of the treatment phase with no further follow-up. CONCLUSIONS: Toll-like receptor-9 agonism with CYT003 showed no additional benefit in patients with insufficiently controlled moderate-to-severe allergic asthma receiving standard inhaled glucocorticosteroid therapy with or without LABAs.

Early diagnosis of hearing loss: otoacoustic emissions evoked by distortion products and pure-tone audiometry: Preliminary findings.

OBJECTIVE: Literary studies underline the effectiveness of distortion product otoacoustic emissions (DPOAEs), which are not affected by the collaboration of the subject examined, in the early diagnosis of hearing loss. Aim of the study is to compare the objective technique of DPOAEs with respect to the pure-tone audiometry in early diagnosis of hearing loss. MATERIALS AND METHODS: The clinical research was carried out on 852 workers. All subjects underwent pure-tone audiometry, tympanometry and distortion products. RESULTS: The results show: a) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries in the studied samples; and, after division by gender: b) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries only in men; c) a prevalence of impaired DPOAEs and of impaired audiometries in men higher than in women. CONCLUSIONS: The results suggest the higher effectiveness of DPOAEs compared to pure-tone audiometry in making an early diagnosis of hearing loss.

[Prolonged exposure to urban pollutants and arterial blood pressure: a whole evaluation of our researches]. / Esposizione protratta ad inquinanti urbani e pressione arteriosa: una valutazione d'insieme delle nostre ricerche

AIM: A significant relationship between exposure to cadmium and PAHs from urban air pollution and blood pressure has already been found. The aim of the study is to evaluate if other urban pollutants maintain a similar relationship in outdoor workers. MATERIALS AND METHODS: 349 subjects of both sexes were enrolled in the study; we evaluated values of environmental and biological monitoring of respirable dust, arsenic, lead, benzene, toluene, xylene and we measured blood pressure (BP) in upright and in supine position; to analyze data we used multiple linear regression. Also we valued our results in the light of those we have obtained in previous research. RESULTS: Multiple linear regression showed no significant results that demonstrate a relationship between BP and these pollutants. CONCLUSIONS: The results of our study lead to assume that exposure to urban pollutants studied has not connection with blood pressure, and to retain valid the relationship previously observed for cadmium and PAHs, which seem to be the only pollutants that can affect blood pressure.

[Stress and work-related injuries]. / Stress e infortuni sul lavoro.

OBJECTIVE: The aim of this study was to evaluate in scientific literature the more frequent work injuries among the occupational categories examined (construction workers, healthcare workers, night workers and shift work, drivers) and to identify occupational stressors that increase the risk of injury. MATERIALS AND METHODS: The research was conducted through review of the scientific literature between 1990 and 2014. Two hundred articles were found of which 42 selected in the following categories: construction workers, healthcare workers, shift workers, lorry drivers. RESULTS: The movement of machinery and working at height are due to injury for building sector and they were positively correlated with physical (r = 0,206) and mental (r = 0,254) stress. In health workers the injuries are more frequently bruises and sprains (50%). Studies showed a higher rate of injury in a group of shift workers compared to a control group on a rota basis (p <0.0001). Road accidents for drivers represent the most frequent cause of injury of which 13% comes from falling asleep, while 31% from distractions (OR = 3.16; CI = 1:22 to 8:24). CONCLUSIONS: Nurses have frequent injuries due to bruises, lumbago, punctures with needles and surgical wounds. Construction workers often suffer serious injury derived from falls at height, handling machinery. For workers on a rota basis, injuries are often related to lack of sleep. Road accidents in drivers are the most common injuries. A synergistic action finalized to promote health and safety organization, to ensure a work environment more secure, is advisable.

Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11.

Ballet and stress. A pilot study.

BACKGROUND: Work-related stress is a complex problem requiring a work environment-based assessment. Artists like dancers represent a category of atypical workers potentially at high risk for work-related stress. Aim of our pilot study is to evaluate organizational stress in a population of professional dancers, using the HSE Indicator Tool for Work Related Stress. METHODS: We administered the Italian version of the HSE Indicator Tool to 38 ballet dancers, males and females. The questionnaire evaluates 7 key organizational dimensions: demand, control, managers' support, peer support, relationships, role and change. RESULTS: The standards required-ideal conditions are achieved in none of the above-mentioned dimensions. Change is the only dimension for which results fall between the 20th and the 50th percentile, while for other dimensions results fall below the 20th percentile suggesting the need for immediate corrective action. In male dancers an acceptable situation is highlighted for the dimension "change" compared to female dancers. In both sexes there is a high frequency of subjects complaining of verbal abuse, bullying and harassment. CONCLUSIONS: Despite the small sample size, our pilot study highlights the presence of heightened levels of organizational stress. Preventive measures targeted towards improving communication between managers and dancers and aimed at team building should be implemented.

Occupational exposure to urban stressors and effects on atrial natriuretic peptide: preliminary results.

PURPOSE: The aim of this pilot study is to evaluate whether occupational exposure to low doses of pollutants present in the air of the city selected for the study could cause alterations in the concentration of atrial natriuretic peptide (ANP) in workers from the Municipal Police with outdoor tasks, compared to those with indoor tasks. METHODS: A total of 208 non-smoking male and female subjects were enrolled and divided on the basis of whether their tasks were mainly outdoors or indoors. The dosage of plasma ANP was carried out on all workers included in the study. Differences between means and frequencies were compared using student's t-test for unpaired data and chi-square test with Yates' correction, and they were considered significant when the p value was <0.05. RESULTS: Even after the subdivision of the total sample on the basis of sex, mean plasma levels of ANP were higher but not statistically significant in traffic police compared with controls. CONCLUSIONS: The preliminary results suggest that further studies should be conducted before the influence of urban pollution on ANP could be confirmed or rejected.

Work related etiology of amyotrophic lateral sclerosis (ALS): a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to evaluate the association between ALS and occupational exposure to physical (ELF-EMF) and chemicals (solvents, heavy metals and pesticides) agents. METHODS: We considered articles published from 1980 up to April 2013; in total, 750 publications were evaluated. The studies had to satisfy the following criteria: 1) cohort or case-control studies; 2) the presence of individual exposures; 3) clinical diagnosis of sporadic ALS or sporadic ALS on the death certificate. We followed the evaluation of quality in two steps. The first step classified studies according to a rating system based on a mix of criteria developed by scientific organizations, especially developed for studies of risk factors for ALS. The ratings obtained range from I (highest) to V (lowest). The data on risk factors derived from studies with Armon ratings of I, II, and III can reach levels of evidence A (established risk factor), B (likely risk factor), or C (possible risk factor). The second step evaluated the exposure and a score from 1 to 4 was assigned to each item; an exposure with a score of 3 or 4 was considered sufficient. Different analyses were performed on ALS and exposure to metals, solvents, pesticides and electromagnetic fields. In our study the heterogeneity was assessed both by χ2-based Q-tests and through the index of inconsistency I² while the measure RR/OR and CI of 95% to estimate the relationship between ALS and the various considered risk factors was employed. RESULTS: The association between exposure to pesticides and ALS as a whole is weak and not significant. With regard to the results of individual studies the following critical synthesis can be reported: 1) the selected studies showed a low level of association between ALS and electromagnetic fields; 2) as regards the solvents, the association with ALS in some studies is combined with a slightly increased risk, particularly in women, and in others a slight but significant linear association is observed; 3) for the metals, in some cases there was a stronger association in women than in men; for individual metals, there was an association especially with chromium and lead; 4) lastly, with regard to the products of agricultural pesticides in general, there was an association with ALS in men but not in women, with a dose-response relationship. CONCLUSIONS: The lack of statistically significant association between occupational exposure and ALS is mainly due to the methodological diversity of the studies and the lack of prospective studies at the workplace.