A retrospective study on two cohorts of immunocompetent women treated with nonavalent HPV vaccine vs. Ellagic acid complex: outcome of the evolution of persistent cervical HPV infection.

OBJECTIVE: The nonavalent HPV vaccine has demonstrated its efficacy in women and men who already suffer from HPV genital lesions, with little chances to clear the infection. The efficacy of new therapeutic or complementary alternatives as Ellagic acid plus Annona Muricata (Ellagic acid complex) has emerged recently. Our retrospective study compares the evolution of persistent cervical HPV infection in two cohorts of immunocompetent women after the administration of nonavalent vaccine or Ellagic acid complex. PATIENTS AND METHODS: At Tor Vergata University Hospital, Rome, forty women in childbearing age, suffering from persistent cervical HPV infection, were enrolled in two study's groups: nonavalent HPV vaccine (20 women) vs. Ellagic acid complex tablets (20 who refused the vaccine). Cytological features, HPV DNA genotypes and mRNA oncogenic genes E6/E7 presence and clearance were analyzed and confronted between the groups. RESULTS: Demographics and clinical features of the cohorts were comparable. Evaluation of Pap smear, HPV DNA test and mRNA genes E6/E7, were performed at baseline (T0) and after 6 months (T1) and 12 months (T2) from the last dose of vaccine/tablet. At T1 and T2, Ellagic acid complex group showed a statistical reduction of abnormalities in Pap smears (p = 0.018 and 0.006, respectively), probably due to its direct anti-inflammatory, antioxidative and antiviral activities. At T1, vaccinated group showed a higher rate of HPV clearance (p = 0.001), instead Ellagic acid complex group didn't report significative differences. At T2, respect to T0, both groups showed an increase in percentage of negative HPV DNA detection, although more marked for vaccinated group respect to Ellagic acid complex group (p = 0.039 and 0.062 respectively). Regarding mRNA E6/E7 clearance, at T1 and T2, the group of vaccinated women showed a higher negativization respect to the other group (p= 0.077 and 0.042, respectively). CONCLUSIONS: Despite the limited sample of women enrolled for the present study, the results confirmed the clinical usefulness of HPV vaccination as adjuvant agent for the immune system of women affected by persistent HPV infection. Moreover, in women who refused to be vaccinated, the administration of a biocompound like Ellagic acid plus Annona Muricata, represented an interesting clinical strategy in terms of increasing chance of HPV viral clearance.

Toxoplasma infection in individuals in central Italy: does a gender-linked risk exist?

An accurate estimate of the impact of toxoplasmosis on the population in Italy is not available. We performed a cross-sectional study on individuals living in Italy to assess: (1) differences in access to Toxo testing and in the prevalence of recent and past Toxoplasma gondii infection according to gender and age, and (2) the clinical impact of disease burden on the male patient subset. Reason for testing, condition of in- or outpatient and clinical data were analysed. Between-gender differences were observed in access to the test. Immunoglobulin M (IgM) prevalence was increased in males in the age range 5-34 years [odds ratio (OR) = 2.03, 95% confidence interval (CI) 1.18-3.49, p = 0.01), with a peak at 25-34 years. In females, it decreased in the age range 20-39 years (OR = 0.49, 95% CI 0.32-0.74, p = 0.0008). The attack rate of recent infection was twice as high for males than for females. Estimates pointed out 3.3 and 1.7 events in 1000 at-risk person-years in the male and female cohorts, respectively. Most IgM-positive subjects did not experience severe forms of toxoplasmosis, with 35% having lymphadenopathy. Chorioretinitis, systemic and neurological manifestations were also observed. Our findings suggest that the acute phase of toxoplasmosis is largely unapparent or clinically mild in this area. It is also possible that the disease burden for Toxoplasma infection in Italy is underestimated. Further study should focus on information acquisition and Toxo test access in hospital units for a better estimation of the real burden of mild and severe forms of the disease.

Occupational hypersensitivity pneumonitis: an EAACI position paper.

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.

Occupational anaphylaxis--an EAACI task force consensus statement.

Anaphylaxis is a systemic allergic reaction, potentially life-threatening that can be due to nonoccupational or, less commonly, to occupational triggers. Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of triggers and conditions attributable to a particular work environment. Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn. Other triggers include food, medications, insect/mammal/snake bites, and chemicals. The underlying mechanisms of anaphylactic reactions due to occupational exposure are usually IgE-mediated and less frequently non-IgE-mediated allergy or nonallergic. Some aspects of work-related allergen exposure, such as route and frequency of exposure, type of allergens, and cofactors may explain the variability of symptoms in contrast to the nonoccupational setting. When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction and identification of the trigger are required. Prevention of further episodes is important and is based on removal from further exposure. Workers with a history of OcAn should immediately be provided with a written emergency management plan and an adrenaline auto-injector and educated to its use. Immunotherapy is recommended only for OcAn due to Hymenoptera stings.

Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution.

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.

EAACI position paper: irritant-induced asthma.

The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

OCCUPATION study (OCCUPationl asthma: a naTIONal based study): a survey on occupational asthma awareness among Italian allergists.

Occupational asthma (OA) is the most common work-related respiratory disease. Case identification still remains underperformed. The present survey aimed at investigating the awareness about OA among Italian allergists. 538 Italian Allergists completed a web anonymous questionnaire concerning: patient profile, occupational history, disease features, diagnostic work-up, causal agents, management after diagnosis. 80 cases were registered by 14 members (2.4%). Patients were mostly between 30 and 62 years old; noteworthy, 19% were between 18 and 30. All the patients had a concomitant rhinitis, usually preceding asthma onset. Bakers, hairdressers and healthcare workers were more frequently involved. Diagnostic process included: skin prick test (85%), stop/resume test (57%), specific IgE dosage for occupational allergens (52.5%), peak expiratory flow monitoring (32.5%). Noteworthy, only 27,5% of patients underwent specific challenge. After the diagnosis 50% of patients did not change job. One third of the subjects were not referred to the national Workers Compensation Authority. Our data show that OA is quite neglected by Italian allergists, despite they have a pivotal role both in early identification and in primary prevention of OA. Thus, it is worth increasing awareness concerning OA and creating an easy-access network involving allergists and referral centers for Occupational respiratory diseases.

EAACI Position Paper on assessment of cough in the workplace.

Cough is a nonspecific and relatively common symptom that can present difficulties in diagnosis and management, particularly when it is reported to be associated with the workplace. The present consensus document, prepared by a taskforce of the Interest Group on Occupational Allergy of the European Academy of Allergy and Clinical Immunology by means of a nonsystematic review of the current literature, is intended to provide a definition and classification of work-related chronic cough (WRCC) to assist the daily practice of physicians facing with this symptom. The review demonstrates that several upper and lower airway work-related diseases may present with chronic cough; hence, the possible link with the workplace should always be considered. Due to the broad spectrum of underlying diseases, a multidisciplinary approach is necessary to achieve a definite diagnosis. Nevertheless, more epidemiological studies are necessary to estimate the real prevalence and risk factors for WRCC, the role of exposure to environmental and occupational sensitizers and irritants in its pathogenesis and the interaction with both upper and lower airways. Finally, the best management option should be evaluated in order to achieve the best outcome without adverse social and financial consequences for the worker.

Asthma and exposure to cleaning products - a European Academy of Allergy and Clinical Immunology task force consensus statement.

Professional and domestic cleaning is associated with work-related asthma (WRA). This position paper reviews the literature linking exposure to cleaning products and the risk of asthma and focuses on prevention. Increased risk of asthma has been shown in many epidemiological and surveillance studies, and several case reports describe the relationship between exposure to one or more cleaning agents and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and specific job tasks have been identified as specific causes and/or triggers of asthma. Because research conclusions and policy suggestions have remained unheeded by manufactures, vendors, and commercial cleaning companies, it is time for a multifaceted intervention. Possible preventive measures encompass the following: substitution of cleaning sprays, bleach, and ammonia; minimizing the use of disinfectants; avoidance of mixing products; use of respiratory protective devices; and worker education. Moreover, we suggest the education of unions, consumer, and public interest groups to encourage safer products. In addition, information activities for the general population with the purpose of improving the knowledge of professional and domestic cleaners regarding risks and available preventive measures and to promote strict collaboration between scientific communities and safety and health agencies are urgently needed.

Management of unruptured brain aneurysms: retrospective analysis of a single centre experience.

Embolization is very effective in preventing bleeding of unruptured aneurysms with lower rates of mortality and morbidity than surgical treatment. Neurosurgery remains, however, a good alternative. This retrospective analysis examined data stored the digital database of Bellaria Hospital Radiology Department, evaluating patients, treatments and devices used as well as outcomes and complications. Therapy should be tailored to each individual case to offer each patient the best treatment. Out of 265 unruptured intracranial aneurysms detected, 182 were treated by embolization. 16 cases presented complications (12 only radiologically found); severe clinical consequences occurred in 3%: one ischaemia and five haemorrhages. Conservative treatment was adopted in 21 patients. Long-term follow-up is mandatory as aneurysms could increase their size and develop an irregular morphology in ten years' time. Endovascular embolization is a very effective treatment with positive outcomes in the majority of cases and a percentage of retreatments of 8%. In order to increase the number of successful cases, a multidisciplinary cooperation with neurosurgeons is strongly recommended.

Evaluation of commercial skin prick test solutions for selected occupational allergens.

BACKGROUND: Skin prick testing (SPT) is an important step in the diagnosis of IgE-mediated occupational allergic diseases. The outcome of SPT is related to the quality of allergen extracts. Thus, the aim of the study was to assess different commercially available SPT solutions for selected occupational allergens. METHODS: SPT was performed in 116 bakers, 47 farmers and 33 subjects exposed to natural rubber latex (NRL), all with work-related allergic symptoms. The SPT solutions from different manufacturers (n = 3-5) for wheat flour, rye flour, soy, cow hair/dander, storage mites (Tyrophagus putrescentiae, Lepidoglyphus destructor, Acarus siro) and NRL were analysed with respect to their protein and antigen contents. SPT was carried out in 16 allergy centres in six European countries using standardized procedures. Specific IgE values were used as the gold standard to calculate the sensitivity and specificity of SPT solutions. The optimal cut-point for each SPT solution was determined by Youden Index. RESULTS: Protein and antigen contents and patterns of the SPT solutions varied remarkably depending on the manufacturer. While SPT solutions for wheat flour and soy reached overall low sensitivities, sensitivities of other tested SPT solutions depended on the manufacturer. As a rule, solutions with higher protein and antigen content showed higher sensitivities and test efficiencies. CONCLUSIONS: There is a wide variability of SPT solutions for occupational allergens, and the sensitivity of several solutions is low. Thus, improvement and standardization of SPT solutions for occupational allergens is essential.

EAACI position paper: skin prick testing in the diagnosis of occupational type I allergies.

Skin prick testing (SPT) in combination with the clinical history of the patient is one important step in the diagnosis of IgE-mediated occupational allergies. However, skin test performance is related to the quality of allergen extracts. The present consensus document was prepared by an EAACI Task Force consisting of an expert panel of allergologists and occupational physicians from Germany, Italy, Spain, France, Austria, and Poland. All members of the panel were also involved in the data collection within the European multicentre study STADOCA (Standard diagnosis for occupational allergy). The aim of this Task Force was the assessment of the quality of commercially available SPT solutions for selected occupational allergens under standardized procedure conditions in different European centres and institutes of Occupational Medicine. The data evaluation shows a wide variability among SPT solutions and also indicates that the sensitivity of several SPT solutions is low. Therefore, improvement and standardization of SPT solutions for occupational allergens is highly recommended. Clinical practitioners should also not presume that their SPT solutions are fully reliable. The main objective of the document is to issue consensus suggestions for the use of SPT with occupational allergens based on the European multicentre study STADOCA, on existing scientific evidence and the expertise of a panel of allergologists.

EAACI consensus statement for investigation of work-related asthma in non-specialized centres.

Work-related asthma (WRA) is a relevant problem in several countries, is cause of disability and socioeconomic consequences for both the patient and the society and is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. This consensus document was prepared by a EAACI Task Force consisting of an expert panel of allergologists, pneumologists and occupational physicians from different European countries. This document is not intended to address in detail the full diagnostic work-up of WRA, nor to be a formal evidence-based guideline. It is written to provide an operative protocol to allergologists and physicians dealing with asthma useful for identifying the subjects suspected of having WRA to address them to in-depth investigations in a specialized centre. No evidence-based system could be used because of the low grade of evidence of published studies in this area, and instead, 'key messages' or 'suggestions' are provided based on consensus of the expert panel members.

EAACI position paper: prevention of work-related respiratory allergies among pre-apprentices or apprentices and young workers.

Apprenticeship is a period of increased risk of developing work-related respiratory allergic diseases. There is a need for documents to provide appropriate professional advice to young adults aiming to reduce unsuitable job choices and prevent impairment from their careers. The present document is the result of a consensus reached by a panel of experts from European and non-European countries addressed to allergologists, pneumologists, occupational physicians, primary care physicians, and other specialists interested in this field, which aims to reduce work-related respiratory allergies (rhinoconjunctivitis and asthma) among allergic or nonallergic apprentices and other young adults entering the workforce. The main objective of the document is to issue consensus suggestions for good clinical practice based on existing scientific evidence and the expertise of a panel of physicians.

[Professional eosinophilic bronchitis: considerations and new diagnostic methods in a clinical case]. / La bronchite eosinofila professionale: considerazioni e nuovi strumenti diagnostici a margine di un caso clinico.

Nonasthmatic eosinophilic bronchitis (NAEB) is a condition characterized by corticosteroid-responsive chronic cough, sputum eosinophilia and absence of symptoms or objective evidence of variable airflow obstruction and airway hyper-responsiveness. Like asthma, NAEB can be associated with exposure to occupational sensitizers and can be considered as being a variant of occupational asthma when it develops as a consequence of work exposure. Few case reports of NAEB caused by workplace exposure have been reported. Bakers are at high risk of developing occupational respiratory disorders and three cases of occupational NAEB have been described. We describe the first case of occupational NAEB due to storage mites in a baker in which the offending agent was identified by means of the basophil activation test (BAT), a new tool which has never been proposed in diagnostic procedures of occupational respiratory allergy. BAT's results allowed the recognition of the offending agent, that is mandatory for diagnosis.

Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis.

BACKGROUND: The relationships between asthma and rhinitis are still a crucial point in respiratory allergy and have scarcely been analysed in occupational setting. We aimed to compare the clinical and inflammatory features of subjects with occupational asthma only (OA) to subjects with OA associated to occupational rhinitis (OAR) caused by persulphate salts. METHODS: The clinical charts of 26 subjects diagnosed in our Unit as respiratory allergy caused by ammonium persulphate (AP), confirmed by specific inhalation challenge (SIC), were reviewed. Twenty-two out of twenty-six patients underwent pre-SIC-induced sputum challenge test (IS) and 24/26 underwent nasal secretion collection and processing. RESULTS: Twelve out of twenty-six patients received a diagnosis of OA-only and 14/26 of OAR. Duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV(1), airway reactivity to methacholine and asthma severity did not differ in the two groups. Eosinophilic inflammation of upper and lower airways characterized both groups. Eosinophil percentage in IS tended to be higher in OAR [11.9 (5.575-13.925)%] than in OA-only [2.95 (0.225-12.5)%] (P = 0.31). Eosinophilia in nasal secretions was present both in subjects with OAR [55 (46-71)%] and in subjects with OA-only [38 (15-73.5)%], without any significant difference. DISCUSSION: Our results indicate that OA because of ammonium persulphate coexists with occupational rhinitis in half of the patients. Unexpectedly, rhinitis did not seem to have an impact on the natural history of asthma. The finding of nasal inflammation in subjects with OA-only without clinical manifestations of rhinitis supports the united airway disease concept in occupational respiratory allergy as a result of persulphates.

Noninvasive methods for assessment of airway inflammation in occupational settings.

The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of 'united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued.