Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

RItA: The Italian severe/uncontrolled asthma registry.

BACKGROUND: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. METHODS: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. RESULTS: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1 % pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. CONCLUSIONS: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services.

Severe asthma in adolescents and adults: a national, multicenter registry in real life.

Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Clinical relevance is associated with allergen-specific wheal size in skin prick testing.

BACKGROUND: Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. OBJECTIVE: To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. METHODS: The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. RESULTS: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. CONCLUSION: These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use.

Design of pharmaceutical products to meet future patient needs requires modification of current development paradigms and business models.

Drugs represent the most common intervention strategy for managing acute and chronic medical conditions. In light of demographic change and the increasing age of patients, the classic model of drug research and development by the pharmaceutical industry and drug prescription by physicians is reaching its limits. Different stakeholders, e.g. industry, regulatory authorities, health insurance systems, physicians etc., have at least partially differing interests regarding the process of healthcare provision. The primary responsibility for the correct handling of medication and adherence to treatment schedules lies with the recipient of a drug-based therapy, i.e. the patient. It is thus necessary to interactively involve elderly patients, as well as the other stakeholders, in the development of medication and medication application devices, and in clinical trials. This approach will provide the basis for developing a strategy that better meets patients' needs, thus resulting in improved adherence to treatment schedules and better therapeutic outcomes.

Safety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment.

BACKGROUND: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. METHODS: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed. RESULTS: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment. CONCLUSIONS: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD.

[Prevalence of contact dermatitis as occupational diseases in a group of construction workers followed up by the 'Territorial Joint Committee of Bergamo' between 2003-2011]. / Prevalenza delle dermatiti da contatto occupazionali in una coorte di lavoratori edili seguiti presso il Comitato Paritetico Territoriale di Bergamo nel periodo 2003-2011.

UNLABELLED: Occupational contact dermatitis is the most represented skin disease within the broad spectrum of occupational dermatoses, that also include skin cancers, skin infections and "scleroderma like disease." The scientific literature has long noted an increase in dermatological disease in the construction industry. MATERIALS AND METHODS: retrospective evaluation (2003-2011), in a group of construction workers followed by the 'Territorial Joint Committee of Bergamo', of the prevalence of allergic and irritant contact dermatitis. DISCUSSION AND CONCLUSIONS: The following report confirms the literature data and reaffirms the need for a careful medical surveillance, as a result of a strict cooperation between the different professionals involved (company physicians, dermatologists/allergists, family physicians).

[The skin cancer in the construction industry]. / La neoplasia cutanea nel settore edile.

UNLABELLED: The risk factors for the development of cutaneous neoplasms are well-known (skin type, ultraviolet rays, familiar occurrence, etc.) and the exposure to ultraviolet light is probably the most important one. Construction workers, due to the characteristics of the work performed (outdoor work), are exposed to UV rays for most of their workday, often in association with the exposure to chemicals (PAHs, solvents) with a role in promoting skin carcinogenesis. The construction industry is therefore a true "test" for the prevention of skin cancer. MATERIALS AND METHODS: description of skin cancer in the construction workers subject to medical surveillance at the "Territorial Joint Committee of Bergamo" (8 basal cell cancers, 1 squamous cell carcinomas and 4 melanomas). PURPOSE: review of the medical literature data, evaluation of the exposure to multiple risk factors, prevention proposals in a professional field where the "culture of tanning" is still widespread.

[Role of ECG screening and cardiologic examinations in occupational health prevention program for construction workers; results of study in the Province of Bergamo]. / Utilità dell'elettrocardiogramma e degli approfondimenti cardiologici nella sorveglianza sanitaria di una popolazione di operatori edili della Provincia di Bergamo.

Aim of this study was to estimate prevalence of resting electrocardiogram (ECG) abnormalities in men with high physical work demand, like construction workers and the prevalence of secondary related cardiovascular examinations. Several guidelines for cardiovascular risk management recommend an ECG in patients with cardiovascular risk but there are no clear indications about the frequency of resting ECG during evaluation for fitness for work. The results of our study confirm the presence of age-related ECG abnormalities with a similar stratified prevalence distribution in all age-classes. Our fundings intend to contribute to further discussion in occupational health policies and periodical medical evaluations.

[Occupational injuries and lifestyle in construction working population workers: which interaction?]. / Fenomeno infortunistico e stili di vita di una popolazione di lavoratori edili: quale correlazione?

Many factors of organizational, technical, social and human are involved in determining occupational injury. The purpose of this study was to evaluate how the characteristics of the human factor can influence the accident phenomenon. From records of the construction firms involved in the project "Protection of health on construction sites" promoted by CPT Bergamo and Occupational Medicine of Bergamo Hospital were extracted data on lifestyle of workers involved in occupational injuries in the period 2007-2011. The indicators of lifestyles used were the smoking status, alcohol consumption and drugs, body mass index (BMI), physical activity.

[Work-related diseases and the fitness to work in construction industry]. / Malattie lavoro-correlate e giudizio di idoneità lavorativa in edilizia.

The construction industry is characterized by a high number of fatal and nonfatal injuries and even higher prevalence of work-related diseases. The aim of this work is to analyze the results of a research project that has among its objectives the study of the prevalence of work-related diseases and the fitness to work in construction industry. In the period 2003-2011 were evaluated 2069 construction workers, from 218 companies (average age 37.9 years, mean seniority 21.1 years, 17.1 in the construction industry). The prevalence of work-related diseases was 14.06%, in the first place the noise-induced hearing loss, followed by musculoskeletal disorders and entrapment neuropathies. The 24.7% of fitness to work was influenced by the presence of limitations, the 0.6% of the population was not suitable for the specific task. The prevalence of work-related diseases in construction industry is high, with a peak among the elderly, but also significant occurrence among young people. It is important the percentage of the population with health problems that limit the fitness to work.

[Energy expenditure in construction industry]. / Il dispendio energetico in edilizia.

The aim of this study is to show the results obtained from measuring energy expenditure (EE) during work, through portable devices, in a group of male construction workers. After defining cardio-respiratory parameters in laboratory, authors applied to all subjects an heart rate monitor for measuring the heart rate (HR) and, at the same time, a calorimeter for measuring energy expenditure (EE). To analyse data obtained, authors calculate the Relative Aerobic Strain (RAS), both for the measurements of EE and for HR detected. Results confirm that in many of the typical activities of construction industry, in particular in those characterised by an higher component of manual engagement compared to foreman, workloads are exceeding limits of the probable threshold fatigue (33% of RAS), both for energy expenditure than for HR measured.

[Survey on alcohol and construction workers]. / Indagine conoscitiva su alcool e lavoro in edilizia.

On the basis of the data drawn by national and international literature and the introduction of legislation concerning "alcohol and alcohol-related problems" authors studied alcohol consumption in a group of 512 building workers during the periodic health surveillance examination (years 2011-2012). Another group of 209 construction workers were examined for alcohol concentration in expired air and during work on building sites. In the first group, 62.1% of workers refers to drink alcoholic beverages; we found GGT and CTD alterations in about 1/3 of workers who reported high alcohol consumption. Alcohol tests in building sites demonstrated that alcohol consumption during pauses in work is still common.

[Plastering: assessment of risk for upper limb biomechanical overload and of energy expenditure]. / L'attività di intonacatura manuale: valutazione del sovraccarico biomeccanico degli arti superiori e del dispendio energetico.

This work analyzes the activities carried out by a plaster construction worker, describing the data obtained from the assessment of risk for upper limb biomechanical overload, through the application of checklist and the OCRA method, and the operator's energy expenditure, measured using portable calorimeter. By analyzing the pattern of energy expenditure in relation to the actions performed we observe a direct correlation between posture, force employed, and metabolic rate. The activity of plastering involves biomechanical overload of upper extremity and high energy expenditure.

Nerve growth factor localization in the nasal mucosa of patients with persistent allergic rhinitis.

BACKGROUND AND OBJECTIVES: Nerve growth factor (NGF) and NGF receptors have been shown to be expressed by structural and infiltrating inflammatory cells in the human allergic bronchial mucosa and conjunctiva. In the nose, a positive immunostaining for NGF was recently reported in biopsies of subjects undergoing surgery for refractory nasal obstruction. This study was aimed at studying by immunohistochemistry NGF expression and localization in the nasal mucosa from subjects with moderate/severe persistent allergic rhinitis and natural allergen exposure. METHODS: Immunostaining for NGF, tryptase and eosinophil cationic protein was performed in human nasal turbinate sections of 25 patients affected by persistent allergic rhinitis and sensitization to Dermatophagoides pteronyssinus. RESULTS: NGF was consistently expressed in the epithelium and in the submucosa of allergic rhinitic subjects, preferentially localized in eosinophils and mast cells. A strong NGF immunostaining was found in mucous cells of the epithelial lining and in the submucosal glands. CONCLUSIONS: As previously shown for allergic asthma and allergic conjunctivitis, NGF is also detectable in the nasal mucosa of patients with persistent allergic rhinitis. The preferential NGF localization in mucous cells of the epithelial lining and in the submucosal glands suggests a possible role for NGF in modulating secretion in allergic rhinitis and possibly other allergic diseases.

GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe.

BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe. AIMS: The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel. METHODS: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres. RESULTS: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe. CONCLUSION: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe.

BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis. RESULTS: While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated. CONCLUSION: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.

GA2LEN skin test study III: minimum battery of test inhalent allergens needed in epidemiological studies in patients.

BACKGROUND: The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies. OBJECTIVE: To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA(2)LEN skin prick test study. METHOD: In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection. RESULT: Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects. CONCLUSION: Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.