Long-term effects of air pollutants on respiratory and cardiovascular mortality in a port city along the Adriatic sea.

BACKGROUND: Shipping and port-related air pollution has a significant health impact on a global scale. The present study aimed to assess the mortality burden attributable to long-term exposure to ambient particulate matter (PM2.5, PM10) and nitrogen dioxide (NO2) in the city of Ancona (Italy), with one of the leading national commercial harbours. METHODS: Exposure to air pollutants was derived by dispersion models. The relationship between the long-term exposure of air pollution exposure and cause-specific mortality was evaluated by Poisson regression models, after adjustment for gender, age and socioeconomic status. Results are expressed as percent change of risk (and relative 95% confidence intervals) per 5 unit increases in the exposures. The health impact on the annual number of premature cause-specific deaths was also assessed. RESULTS: PM2.5 and NO2 annual concentrations were higher in the area close to the harbour than in the rest of the city. Positive associations between each pollutant and most of the mortality outcomes were observed, with estimates of up to 7.6% (95%CI 0.1, 15.6%) for 10 µg/m3 increase in NO2 and cardiovascular mortality and 15.3% (95%CI-1.1, 37.2%) for 10 µg/m3 increase PM2.5 and lung cancer. In the subpopulation living close to the harbour, there were excess risks of up to 13.5%, 24.1% and 37.9% for natural, cardiovascular and respiratory mortality. The number of annual premature deaths due to the excess of PM2.5 and NO2 exposure (having as a reference the 2021 World Health Organization Air Quality Guidelines) was 82 and 25, respectively. CONCLUSIONS: Our study confirms the long-term health effects of PM and NO2 on mortality and reveals a higher mortality burden in areas close to shipping and port-related emissions. Estimating the source-specific health burdens is key to achieve a deeper understanding of the role of different emission sources, as well as to support effective and targeted mitigation strategies.

Predictors of Worse Prognosis in Young and Middle-Aged Adults Hospitalized with COVID-19 Pneumonia: A Multi-Center Italian Study (COVID-UNDER50).

Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in the overall COVID-19 population, but limited information is available on their roles in young and middle-aged adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics and role of selected prognostic predictors in a large cohort of young and middle-aged hospitalized patients. Nine pulmonology units, across north and center of Italy, were involved in this retrospective study. Comorbidities were classified according to their known or potential association with COVID-19. A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 27.7%, and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only independent, significant predictors for MV. Comorbidities, such as hypertension, diabetes, asthma, and increased D-dimer levels were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Obesity in young and middle-aged adults is a strong predictor of a more complicated COVID-19, without, however, evidence of a significant effect on in-hospital mortality. Selected comorbidities, including hypertension, diabetes and asthma, significantly impact survival even in a younger population, suggesting the need for prompt recognition of these conditions.

Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. METHODS: In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. RESULTS: 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. INTERPRETATION: It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

Honeybee venom immunotherapy: certainties and pitfalls.

The honeybee is an interesting insect because of the fundamental agricultural role it plays, together with the composition of its venom, which presents new diagnostic and immunotherapeutic challenges. This article examines various aspects of honeybee venom allergy from epidemiology to diagnosis and treatment, with special emphasis on venom immunotherapy (VIT). Honeybee venom allergy represents a risk factor for severe systemic reaction in challenged allergic patients, for the diminished effectiveness of VIT, for more frequent side effects during VIT and relapse after cessation of treatment. Some strategies are available for reducing the risk of honeybee VIT-induced side effects; however, there is considerable room for further improvement in these all-important areas. At the same time, sensitized and allergic beekeepers represent unique populations for epidemiological, venom allergy immunopathogenesis and VIT mechanism studies.

The ImmunoCAP ISAC molecular allergology approach in adult multi-sensitized Italian patients with respiratory symptoms.

OBJECTIVES: To evaluate the performances of an allergen microarray in multi-sensitized allergic patients with respiratory symptoms. DESIGN AND METHODS: 321 patients and 92 controls were included in this study. Specific serum IgE were assayed using ImmunoCAP ISAC, a microarray containing 103 components derived from 47 allergens and results were compared with extract-based ImmunoCAP Allergens sIgE to 15 common airborne allergens. RESULTS: The reproducibility of ISAC was good. The Positive Percent Agreement (PPA) varied between 75% and 100% for sIgE levels above 1 kUA/l. For samples with sIgE levels below 0.1 kUA/l, the Negative Percent Agreement (NPA) ranged between 90% and 100%. Notably, 58% of respiratory allergy patients had IgE to food-specific proteins and 52% resulted sensitized to cross-reactive pan-allergens. CONCLUSION: ImmunoCAP ISAC detects allergen sensitization at component level and adds important information by defining both cross and co-sensitization to a large variety of allergen molecules.

Hymenoptera venom immunotherapy.

Subcutaneous venom immunotherapy is the only effective treatment for patients who experience severe hymenoptera sting-induced allergic reactions, and the treatment also improves health-related quality of life. This article examines advances in various areas of this treatment, which include the immunological mechanisms of early and long-term efficacy, indications and contraindications, selection of venom, treatment protocols, duration, risk factors for systemic reactions in untreated and treated patients as well as for relapse following cessation of treatment. Current and future strategies for improving safety and efficacy are also examined. However, although progress in the past few years has been fruitful, much remains to be accomplished.

Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase.

BACKGROUND: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. METHODS: In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. RESULTS: Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. CONCLUSION: Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.

Purified vs. nonpurified venom immunotherapy.

PURPOSE OF REVIEW: Although highly effective, venom immunotherapy (VIT) may be responsible for local and systemic allergic reactions. There is a good theoretical basis for believing that purified aqueous and purified aluminium hydroxide adsorbed (so-called depot) extracts, commercially available in Europe, have the potential to reduce the incidence of VIT's side effects. The aim of this article is to review the literature on safety and effectiveness of purified preparations as well as compare them with nonpurified extracts. RECENT FINDINGS: Old and new noncomparative studies reveal good tolerance of purified aqueous and purified depot extracts. In comparative trials purified extracts appear to be better tolerated than nonpurified extracts, whereas depot extracts seem to be safer than the corresponding purified aqueous preparation, especially in the prevention of severe large local reactions. The efficacy of purified aqueous and depot extracts is supported by studies using both sting challenge and in-field stings and is comparable to that of nonpurified preparations. SUMMARY: The theoretical basis of the safer profile of purified extracts is supported by a number of clinical studies, making the use of purified depot preparations preferable for conventional treatment also by specialists with less experience in managing VIT. In specialized centres purified aqueous extracts may be preferred for faster build-up protocols. However, further prospective controlled studies are needed in order to evaluate the ability of purified extracts to reduce the frequency of severe systemic reactions over the corresponding nonpurified preparation.

Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity.

BACKGROUND: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. METHODS: In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. RESULTS: Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. CONCLUSION: In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.

Epidemiology of insect-venom anaphylaxis.

PURPOSE OF REVIEW: Knowledge of the epidemiology, natural history and risk factors of insect-venom allergy is crucial for improving the clinical management of allergic patients. This review focuses on the recent research on these aspects of Hymenoptera-sting anaphylactic reactions. RECENT FINDINGS: The latest data from population-based studies of anaphylactic reactions due to Hymenoptera stings, as well as those extrapolated from studies of epidemiology of anaphylaxis due to any cause are reviewed. The topic of biphasic anaphylactic reactions due to insect stings is also examined. Although no parameter has been identified that can predict which sensitized individuals will have a future anaphylactic reaction, several factors associated with the severity of a systemic resting reaction are known and emphasized here. SUMMARY: As half of individuals with fatal sting reactions had no documented history of previous systemic reaction, we need to further improve the knowledge of the natural history and risk factors, especially in asymptomatic-sensitized individuals. Moreover, and no less important, the epidemiological studies on sting anaphylaxis conducted in the 2000s continue to reveal the poor management of allergic patients and the startling lack of awareness of the efficacy of venom immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom-allergic patients.

Distance optical sensor for quantitative endoscopy.

We present a novel optical sensor able to measure the distance between the tip of an endoscopic probe and the anatomical object under examination. In medical endoscopy, knowledge of the real distance from the endoscope to the anatomical wall provides the actual dimensions and areas of the anatomical objects. Currently, endoscopic examination is limited to a direct and qualitative observation of anatomical cavities. The major obstacle to quantitative imaging is the inability to calibrate the acquired images because of the magnification system. However, the possibility of monitoring the actual size of anatomical objects is a powerful tool both in research and in clinical investigation. To solve this problem in a satisfactory way we study and realize an absolute distance sensor based on fiber optic low-coherence interferometry (FOLCI). Until now the sensor has been tested on pig trachea, simulating the real humidity and temperature (37 degrees C) conditions. It showed high sensitivity, providing correct and repeatable distance measurements on biological samples even in case of very low reflected power (down to 2 to 3 nW), with an error lower than 0.1 mm.

Advances in hymenoptera venom immunotherapy.

PURPOSE OF REVIEW: Venom immunotherapy is highly effective treatment, capable of improving health-related quality of life. This overview examines advances in various aspects of this treatment. RECENT FINDINGS: New findings on the immunological mechanisms of the early and long-term efficacy of venom immunotherapy have been made. The decision to start and then to stop venom immunotherapy is best made on an individual case basis and should take into account medical and other factors, like the influence on patient quality of life. Venoms for use in immunotherapy should be selected according to the geographical distribution of each species and partial cross-reactivity between certain types of venom. Rapid protocols seem to be as safe as slower ones, though the major incidence of bee venom immunotherapy side-effects remains. Patients suffering from mast cell diseases seem to be at greater risk for an adverse reaction during treatment, without influencing its efficacy that much until the immunotherapy is actually ongoing. A number of new strategies for venom immunotherapy, mostly based on genetic engineering, have been described, and so far only a few have been used in humans. SUMMARY: Although there has been progress in the past few years, much remains to be accomplished.

Specific immunotherapy with standardized latex extract versus placebo in latex-allergic patients.

BACKGROUND: Allergy to natural rubber latex proteins continues to be an important medical problem among health care professionals, but also in multioperated children. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma and anaphylactic shock. METHODS: The aim of this study was to investigate the efficacy and safety of a 12-month latex-specific immunotherapy in sensitized patients, most often health care workers. Twenty-three patients with latex rhinoconjunctivitis (20 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (11 in the active group, 12 in the placebo group). Treatment efficacy was assessed by means of symptom and medication scores. Conjunctival provocation tests and quantitative skin prick tests were also performed. RESULTS: The clinical index (derived by combining changes from baseline of six efficacy variables during the treatment period) did not differ significantly between treatment groups. Change from baseline of rhinitis, conjunctivitis, skin symptoms, asthma symptoms, medication score and cutaneous reactivity were not significantly different between the two groups. A nonsignificant difference in conjunctival reactivity was observed in favor of the active group (p = 0.09). Systemic reactions were much higher in the specific immunotherapy than in the placebo group. CONCLUSIONS: The present study failed to show a significant improvement of symptoms and medication scores, probably because of the low level of symptoms at baseline and the low maintenance dose of therapy, even if allergen-specific conjunctival reactivity decreased in the active group. Moreover, the incidence of systemic reactions was very high in the active group.

Epidemiology of Hymenoptera allergy.

PURPOSE OF REVIEW: Epidemiology and especially the natural history of Hymenoptera allergy form the background that is essential to improving the clinical management of insect venom allergic patients. This review focuses on the emergence of recent data which could help provide further enlightenment in this field. RECENT FINDINGS: The latest data on the extent of the disease, the risk factors for sensitization and for local, systemic and fatal reactions after a hymenoptera sting are reviewed. The emerging problems concerning asymptomatic sensitization, the meaning of constitutively elevated tryptase serum levels and the persisting widespread poor awareness of available therapies in Hymenoptera allergic patients are particularly emphasized. SUMMARY: The assessment of the risk for systemic reaction in skin-positive subjects with a negative case history, and the suggestion of the baseline serum tryptase level as a risk factor for reaction severity after a sting, are the most important clinical implications of the latest studies. The genetic and environmental factors involved in the persistence of venom specific immunoglobulin E after a sting and the factors which orient towards a systemic or a large local reaction after apparently the same sting remain open questions.