Modelling the long-term health impact of COVID-19 using Graphical Chain Models brief heading: long COVID prediction by graphical chain models.

BACKGROUND: Long-term sequelae of SARS-CoV-2 infection, namely long COVID syndrome, affect about 10% of severe COVID-19 survivors. This condition includes several physical symptoms and objective measures of organ dysfunction resulting from a complex interaction between individual predisposing factors and the acute manifestation of disease. We aimed at describing the complexity of the relationship between long COVID symptoms and their predictors in a population of survivors of hospitalization for severe COVID-19-related pneumonia using a Graphical Chain Model (GCM). METHODS: 96 patients with severe COVID-19 hospitalized in a non-intensive ward at the "Santa Maria" University Hospital, Terni, Italy, were followed up at 3-6 months. Data regarding present and previous clinical status, drug treatment, findings recorded during the in-hospital phase, presence of symptoms and signs of organ damage at follow-up were collected. Static and dynamic cardiac and respiratory parameters were evaluated by resting pulmonary function test, echocardiography, high-resolution chest tomography (HRCT) and cardiopulmonary exercise testing (CPET). RESULTS: Twelve clinically most relevant factors were identified and partitioned into four ordered blocks in the GCM: block 1 - gender, smoking, age and body mass index (BMI); block 2 - admission to the intensive care unit (ICU) and length of follow-up in days; block 3 - peak oxygen consumption (VO2), forced expiratory volume at first second (FEV1), D-dimer levels, depression score and presence of fatigue; block 4 - HRCT pathological findings. Higher BMI and smoking had a significant impact on the probability of a patient's admission to ICU. VO2 showed dependency on length of follow-up. FEV1 was related to the self-assessed indicator of fatigue, and, in turn, fatigue was significantly associated with the depression score. Notably, neither fatigue nor depression depended on variables in block 2, including length of follow-up. CONCLUSIONS: The biological plausibility of the relationships between variables demonstrated by the GCM validates the efficacy of this approach as a valuable statistical tool for elucidating structural features, such as conditional dependencies and associations. This promising method holds potential for exploring the long-term health repercussions of COVID-19 by identifying predictive factors and establishing suitable therapeutic strategies.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

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.

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.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.

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.

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.

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 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.

[Epidemiological evidence of possible musculoskeletal, cardiovascular and neoplastic effects in professional drivers]. / Le evidenze epidemiologiche sui possibili danni muscoloscheletrici, cardiovascolari e neoplastici nei lavoratori del settore dei trasporti terrestri.

The road and rail transport sector, since the several work tipology and risk factors for workers safety and health, is an area where assessing exposure effects is very difficult. Muscoskeletal cardiovascular and neoplastic diseases are the disorders more frequently associated to professional drivers. The role of professional driving is rather well-defined in low back pain occurence, correlated to whole body vibration exposure. Professional drivers are at higher risk of ischemic cardiovascular diseases, but it is not clear whether the risk is attributable just to the occupational exposures or also to their life-style risk factors. Evidence of an excess of risk for lung, genito-urinary and hemolymphopoietic cancer is clear in the scientific literature for professional drivers. Anyway the lack in the control of confounding factors, in exposure assessment force to be very cautious in results interpretation.

[Reduction of tobacco smoking among physicians of a hospital in central Italy]. / Riduzione dell'abitudine al fumo di tabacco tra i medici di un'Azienda Ospedaliera dell'Italia centrale.

This study assessed the variations in smoking habit in physicians in a General Hospital in Central Italy in 12 years. Data were collected from medical records of workers who underwent health surveillance in 1998-99 and in 2010-11. The prevalence of smokers was 26.3% (male 25.6%, female 27.6%) in 1998-99 and 19.2% (male 19.8%, female 18.5%) in 2010-11. As compared to 1998-99, the prevalence of smokers in 2010-11 was reduced in both sex and in all age classes. Despite the relevant reduction, the prevalence of smokers among physicians remains still high. Occupational physicians could play an important role against tobacco smoking, as they can provide a brief counseling to all smoking physicians during medical health surveillance at workplace and take part in worksite health promotion programmes.

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.

Sensitization to horse allergens in Italy: a multicentre study in urban atopic subjects without occupational exposure.

BACKGROUND: Horses play a significant role in people's leisure time in Italy and other countries, but few data are available on IgE-mediated sensitization to horse allergens in patients without occupational exposure. We assessed, in a multicentric survey, the prevalence of horse sensitization in atopic subjects and its clinical characteristics. METHODS: Allergists from the whole Italian territory were required to collect the results of skin prick tests from at least 100 consecutive subjects. Those patients with a positive skin test to horse dander underwent a detailed interview concerning clinical history, pet ownership and possible exposure. RESULTS: Data from 3,235 outpatients were collected and 2,097 had at least 1 skin positivity. Among them, 113 (5.38%) were sensitized to horse dander (9 monosensitized). Thirty patients reported direct horse contact (4 owners and 26 for riding or occasional contact), 23 patients were sometimes in contact with horse owners and 60 subjects denied any direct or indirect exposure. Among 9 horse monosensitized patients, 6 had intermittent and mild rhinitis and 3 persistent moderate/severe rhinitis plus asthma. Three of them were horse owners or riders and the remaining had no contact with the animal. CONCLUSIONS: Our data evidence that the rate of sensitization to horse dander is not negligible and probably underestimated. In susceptible, not occupationally exposed individuals, horse contact, but also indirect or no apparent exposure, may induce sensitization. We recommend inclusion of horse allergen in the routine panel for the diagnosis of respiratory allergy.

Respiratory diseases and allergy in farmers working with livestock: a EAACI position paper.

Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy.

Have the prevalence and incidence of occupational asthma and rhinitis because of laboratory animals declined in the last 25 years?

BACKGROUND: Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known. OBJECTIVE: To investigate the prevalence and incidence of OA and OR over time. METHODS: We chose to review studies on the prevalence and incidence of OA and OR due to laboratory animals (LA) as a marker of changing OA and OR patterns over time and analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006. RESULTS: The estimated prevalence of OA, defined as work-related chest symptoms (WRCS), declined from 8.2% in 1976 to 4.2% in 2001 (P < 0.005). When defined by WRCS and positive skin prick test (SPT) to LA, the estimated prevalence of OA was 6.7% in 1977 and 2.9% in 1999 (P < 0.02). The prevalence of OR, defined by WRNS or WRNS and SPT to LA, was not related to study date but was inversely associated with mean exposure duration. In four longitudinal studies no clear trend emerged over time. CONCLUSIONS: This review suggests a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis.

Occupational rhinitis.

The present document is the result of a consensus reached by a panel of experts from European and nonEuropean countries on Occupational Rhinitis (OR), a disease of emerging relevance, which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored to that of occupational asthma, as well as a diagnostic algorithm based on steps allowing different levels of diagnostic evidence, are proposed. The needs for future research are pointed out. Key messages are issued for each item.

[Latex allergy in hospital workers--follow-up of symptomatic subjects]. / L'allergia al lattice tra i dipendenti dell'ospedale di Terni: follow-up dei soggetti sintomatici.

Latex allergy may be manifested in a variety of clinical disturbances such as contact urticaria, angioedema, rhinoconjunctivitis, asthma, and anaphylactic reactions. The aim of this follow-up study was to determine whether a change in glove use from powdered to powder-free latex gloves at previously surveyed hospital workers reduced the work-related symptoms. 53 hospital workers with work-related symptoms where followed up 4,6 years after first investigation. On re-examination, 54.7% use both powdered and powder-free gloves, 37.7% used only latex free gloves and 7.6% stopped the glove use. At follow-up, in 68% of subjects there was the remission or the improvement of work-related symptoms. The improvement of symptoms was greater in workers using powder-free gloves than in others (p < 0.005). In conclusion our study shows that preventive measures, such as the use a powder-free latex gloves, are sufficient to induce a reduction of work-related symptoms.

[Have the prevalence and incidence of occupational asthma and rhinitis due to laboratory animals declined in the last 25 years?]. / La prevalenza e l'incidenza dell'asma e della rinite occupazionale da animali di laboratorio si sono ridotte negli ultimi 25 anni?

Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known. To investigate trends in the prevalence and incidence of OA and OR over time, we reviewed the available literature. We analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006. In workers exposed to laboratory animals (LA) the prevalence of OA ranged from 2.2% to 11.7%; the prevalence of OR ranged from 6.7% to 41.7%. When we analysed prevalence by study date using a logistic model, the estimated prevalence of OA declined from 8.7% in 1976 to 4.2% in 2001 (p < 0.003), which is -1.8% every ten years. The prevalence of OR rose slightly from 18.5% in 1976 to 19.7% in 2001 (NS). In four longitudinal studies the incidence of OA ranged from 0.4 to 3.5/100 person years, while the incidence of OR ranged from 2.0 to 10.1/100 person years. No clear trend emerged over time. This review shows a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis.