High Molecular Weight Agents Research Articles

Characterizing Inflammatory Cell Asthma Associated Phenotypes in Dental Health Workers Using Cytokine Profiling.

Cytokines elicit a pro-inflammatory response by modifying the airway microenvironment in patients with acute or chronic asthma. The expression pattern of several distinct cytokines could be a useful discriminator in asthma. This study aimed to identify asthma subject groupings based on common inflammatory patterns and to determine the relationship between these identified patterns and asthma-associated clinical indices. A sub-group of 76 dental healthcare workers (HCWs) identified from a larger cross-sectional study of 454 dental HCWs in five dental institutions were evaluated further. A self-administered questionnaire elicited the health and employment history of subjects. Sera were analyzed for atopic status, latex sensitization, and 12 cytokines (IL-1β, 3, 4, 5, 6, 7, 8, 10, 12p70, eotaxin, GM-CSF, TNF-α). Pre and post-bronchodilator spirometry was performed on all HCWs. Data clustering and factor analysis were used to identify inflammatory cluster patterns of cytokines. Associations between the cytokine cluster groupings and relevant asthma-associated clinical indices were determined using multivariate logistic regression. The classification of asthma subtype based on cytokine patterns demonstrated both eosinophilic and neutrophilic inflammatory responses. Four phenotypically distinct subgroups relating to the severity of inflammation (acute or chronic) of the cell types were identified. Cytokine determinants for the neutrophilic subtype included IL-1β, 6, 8, 10, 12p70, and TNF-α whereas for the eosinophilic subtype these included IL-3, 4, 5, 7, eotaxin, and GM-CSF. The multivariate models showed a significant association between work-related chest symptoms and all four inflammatory patterns. However, stronger associations were observed for the acute neutrophilic (OR = 6.00, p < 0.05) compared to acute and chronic eosinophilic responses (OR = 4.30, p < 0.05; OR = 4.93, p < 0.05), respectively. Subjects with airway obstruction were more likely to have a mixed cellular infiltrate. The odds of work-exacerbated asthma were increased in acute or chronic eosinophilia (OR = 7.75 and 8.12; p < 0.05), respectively as well as with acute neutrophilia (OR = 6) sub-type. This study demonstrated that neutrophilic inflammatory cell asthma phenotypes coexist with eosinophilic inflammatory phenotypes suggesting a possible dual pathway for asthma in dental health workers, probably due to mixed exposures to high molecular weight (e.g., latex) and low molecular weight (e.g., acrylates) agents.

Phénotypage de l’asthme professionnel par la réalisation d’expectoration induite après test d’exposition spécifique

RationaleAlthough the non-invasive assessment of airway inflammation through the induced sputum (IS) technique identified distinct asthma phenotypes, there is few information on the determinants of airway inflammatory pattern in sensitizer-induced occupational asthma (OA). AimTo investigate whether the pattern of airway inflammation in IS is associated with distinct clinical phenotypes of OA. MethodsThis retrospective multicentric study was conducted among 372 patients with OA confirmed by a positive specific inhalation challenge (SIC) who were recruited in the European network for the Phenotyping of OCupational Asthma cohort (2006–2018). Each patient underwent an analysis of IS before and 24 hours after the SIC. Sputum eosinophilia and neutrophilia were defined by the presence of≥3% eosinophils and≥76% neutrophils in sputum samples collected after the SIC. ResultsIn total, 268 (72%) and 42 patients (11%) exhibited sputum eosinophilia and neutrophilia, respectively. Multivariate logistic regression analysis revealed that eosinophilia was associated with exposure to a high molecular weight agent (odds ratio [OR], 1.89; 95% CI, 1.18–3.04), moderate asthma (OR, 3.17; 95% CI, 1,43–7.0) and severe asthma (OR, 2.39; 95% CI, 1.06–5.43). Sputum neutrophilia was associated with age (OR for each additional year, 1.04; 95% CI, 1.01–1.08), male gender (OR, 2.74; 95% CI, 1,21–6.8), mild asthma (OR, 3.26; 95% CI, 1.24–8.88), and dysphonia (OR, 2.83; 95% CI, 1.14–6.87). ConclusionsSputum eosinophilia post-SIC was predominant in OA patients. Sputum eosinophilia and neutrophilia were associated with distinct clinical phenotypes of OA, especially in terms of causal agents and asthma severity.

Occupational Respiratory Allergy: Risk Factors, Diagnosis, and Management.

Occupational allergies are among the most common recorded occupational diseases. The skin and the upper and lower respiratory tract are the classical manifestation organs. More than 400 occupational agents are currently documented as being potential "respiratory sensitizers" and new reported causative agents are reported each year. These agents may induce occupational rhinitis (OR) or occupational asthma (OA) and can be divided into high-molecular weight (HMW) and low-molecular weight (LMW) agents. The most common occupational HMW agents are (glycol)proteins found in flour and grains, enzymes, laboratory animals, fish and seafood, molds, and Hevea brasiliensis latex. Typical LMW substances are isocyanates, metals, quaternary ammonium persulfate, acid anhydrides, and cleaning products/disinfectants. Diagnosis of occupational respiratory allergy is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard. Accurate diagnosis of asthma is the first step to managing OA as shown above. Removal from the causative agent is of central importance for the management of OA. The best strategy to avoid OA is primary prevention, ideally by avoiding the use of and exposure to the sensitizer or substituting safer substances for these agents.

Novel approaches in occupational asthma diagnosis and management.

To describe the recent findings of the last 2 years on the epidemiology and phenotypes of occupational asthma, as well as new developments in its diagnosis and management. Data from nine longitudinal studies showed a population attributable fraction for the occupational contribution to incident asthma of 16%. The main phenotypes of occupational asthma are: occupational asthma caused by high-molecular-weight (HMW) or low-molecular-weight (LMW) agents, irritant-induced asthma and occupational asthma-chronic obstructive pulmonary disease overlap. Among the variety of causative agents of occupational asthma, food-derived components are increasingly being reported, accounting for up to 25% cases of occupational asthma and/or occupational rhinitis. Recently, a specific inhalation challenge (SIC)-independent model has been developed to calculate the probability of occupational asthma diagnosis in workers exposed to HMW agents. In this model, work-specific sensitization, bronchial hyperresponsiveness, inhaled corticosteroid use, rhinoconjunctivitis and age 40 years or less were the most relevant predictive factors. Specific IgE measurements showed a pooled sensitivity of 0.74 and a specificity of 0.71 in the diagnosis of occupational asthma for HMW agents, while a lower sensitivity (0.28) and a higher specificity (0.89) was shown for LMW agents. Cessation of exposure to workplace sensitizers is the cornerstone of management of work-related conditions. An early and precise diagnosis of occupational asthma is crucial, allowing appropriate management and implementation of preventive strategies.

Occupational Exposure to Metals and Solvents: Allergy and Airway Diseases.

Occupational allergic diseases (OAD) such as occupational contact dermatitis (OCD), occupational asthma (OA), and occupational rhinitis (OR) are the most prevalent occupational diseases in industrialized countries. The purpose of this review is to provide an update about the main occupational metal and solvent exposures related to allergy and airway diseases and to discuss newly defined causative agents and industries in this field. Currently for over 400 causative agents for OA and OCD, several hundreds of agents for OR have been identified. Although many studies have reported an overall decline in OAD related to known agents after implementation of efficient and effective workplace preventive measures, the constant development of new products continuously introduces to the market potential unknown respiratory hazards. Workplace allergens are often high molecular weight (HMW) agents that are > 10kDa molecular weight and capable of eliciting IgE sensitization. Sensitizing low molecular weight (LMW) agents are often reactive chemicals. Metals and solvents are two large causative agent groups related to OADs that mainly behave as LMW (< 10kDa) sensitizers and/or irritants. Avoidance of causative exposures through control strategies is the primary prevention approach for OADs. These strategies must be applied and covered for all known and newly defined causative agents. This review aims to summarize current status of known occupational metal and solvent exposures related to allergy and airway diseases and to discuss newly defined causative agents and industries in this field.

Are high- and low-molecular-weight sensitizing agents associated with different clinical phenotypes of occupational asthma?

High-molecular-weight (HMW) proteins and low-molecular-weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles. Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n=544) and LMW (n=635) agents. Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work-related rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]), atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52 [1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07-2.91]), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide. This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.

Inflammatory proteins in nasal lavage of workers exposed to occupational agents.

Low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have been recognized as causes of occupational rhinitis (OR). Immunological mechanisms underlying OR differ according to the type of exposure. While HMW agents act mainly through IgE-mediated mechanisms, LMW agents appear to act through both immunological and non-immunological mechanisms. The objective of this study was to identify potential differences in the upper airways inflammatory response after exposure to LMW and HMW agents by specific inhalation challenge test (SIC). Nasal lavage (NL) samples from 20 subjects who were exposed to HMW (n = 10, Group I) and LMW (n = 10, Group II) at their workplaces were collected after SIC with control and specific occupational agents. These samples were analysed for 47 inflammatory markers using multiplex bead technology. After exposure to specific agent, Group I exhibited higher concentrations of the following proteins compared to Group II: fibrinogen (median (interquartile range) Group I: 0.09 (0.00) μg/mL, Group II: 0.04 (0.05) μg/mL, P = .05); haptoglobin (Group I: 0.86 (0.01) μg/mL, Group II: 0.14 (0.20) μg/mL, P = .02); vascular cell adhesion molecule-1 (VCAM-1) (Group I: 0.34 (0.67) ng/mL, Group II: 0.11 (0.11) ng/mL, P = .01); vascular endothelial growth factor (VEGF) (Group I: 157.0 (154.0) pg/mL, Group II: 98.0 (20.25) pg/mL, P = .01); and vitamin D (VDBP) (Group I: 0.06 (0.13) μg/mL, Group II: 0.03 (0.03) μg/mL, P = .04). No statistically significant differences in proteins profiles were observed between the groups after exposure to control agent. Also, subjects exposed to HMW agents showed a significant increase in NL levels of C-reactive protein compared to control-day exposure. Exposure to HMW and LMW agents by SIC induced a differential nasal airway response including acute-phase reactants proteins (fibrinogen, haptoglobin and CRP), cell adhesion molecules (VCAM-1), endothelial growth factors (VEGF) and VDBP.

Fractional Exhaled Nitric Oxide (FeNO) in the Screening and Diagnosis Work-Up of Occupational Asthma

FeNO is a simple non-invasive tool used as a surrogate marker of airway inflammation in the management of asthma. FeNO has been assessed in several populations of workers exposed to high- and low-molecular weight agents. However, there are many confounding factors to consider in the interpretation of FeNO. As such, its use in the investigation of occupational asthma (OA) has yielded inconsistent results. In screening studies of OA to high molecular weight (HMW) agents, an increase of FeNO over time has been associated with the development of bronchial hyperresponsiveness (BHR). When used in the investigation of OA, increases in FeNO show high positive predictive values for a positive specific inhalation challenge (SIC) to HMW agents. Subjects with high specific IgE to their workplace allergens seem to present higher increases in FeNO than subjects without specific IgE to causal agent. Changes in FeNO have less frequently been observed in studies of OA to low molecular weight (LMW) agents than OA to HMW agents, except for isocyanate-induced OA. Cluster analyses of patients exposed to various HMW and LMW agents have documented significant increases of FeNO in clusters of patients with OA to HMW agents, but not LMW. Recent studies have provided useful information for improving our understanding of the pathophysiology of exhaled NO in OA despite the previously reported conflicting results. Future studies are still required to clarify its role in the screening, investigation, and management of OA.

New Eliciting Agents of Occupational Asthma

Occupational asthma is a type of asthma that arises from exposures in the workplace. There are more than 400 known causes of occupational asthma and the list is growing. New causes of allergic occupational asthma involving high and low molecular weight agents are continuously being reported. Their knowledge is important for physicians and occupational health and safety professionals to maintain a high level of suspicion in exposed workers to these substances. The majority of new causes of allergic occupational asthma between 2011 and mid-2016 were seen with high-molecular-weight agents. Most new cases are observed in food and agro-alimentary industry, but also in the cosmetic industry, and frequently are associated with other IgE-mediated manifestations, especially allergic rhinoconjunctivitis and contact urticaria. Among the low-molecular weight agents, new acrylate and aldehyde compounds have been identified as eliciting agents of occupational asthma, as well as drugs, biocides, and other chemicals recently introduced in industry.

Specific inhalation challenge: the relationship between response, clinical variables and lung function

IntroductionThe specific inhalation challenge (SIC) is considered the gold standard for the diagnosis of occupational asthma (OA). However, its use is not standardised, and the intensity of exposure is regulated...

Diagnostic accuracy of specific IgE antibodies measurements in occupational airway allergy to high molecular weight agents

The performance of specific inhalation challenge test (SICT) - reference method in diagnostics of occupational allergy - has some limitations due to health status of a particular patient. Therefore, it is extremely important to identify usefulness of other tests, and the evaluation of diagnostic accuracy of commercially available serum specific immunoglobulin E (sIgE) kits to the most common high molecular weight agents has been launched. The study group comprised 141 subjects - 110 bakers and 31 farmers - with suspicion of occupational airway allergy. All patients underwent evaluation of serum sIgE to occupational allergens with the use of Phadia and Allergopharma kits: in bakers to flour mix and α-amylase, in farmers to epithelium of cow, pig and feathers. Specific inhalation challenge test with workplace allergens performed in all subjects was a reference method for further analysis. Serum specific IgE to flour mix had the highest sensitivity (Phadia - 95.6%, Allergopharma - 88.3%), while its specificity was relatively low (Phadia - 47.8%, Allergopharma - 25%). There were numerous discrepancies between the results of sIgE estimation for particular single allergens (k87, e4, e83), as well as for their mixtures (fx901, fx20, ex71), performed with the kits of both companies (Phadia vs. Allergopharma). Evaluation of serum specific IgE is characterized by inadequate sensitivity, specificity and predictive value to take the place of specific inhalation challenge test in diagnostics of occupational respiratory allergy. Med Pr 2017;68(1):31-43.

Impact of occupational exposures on exacerbation of asthma: a population-based asthma cohort study.

BackgroundAsthma is a prevalent chronic disease and occupation contributes to approximately 15 % of cases among adults. However, there are still few studies on risk factors for work-exacerbated asthma. The current study investigated the association between asthma exacerbations and occupational exposures.MethodsThe study comprised all currently working adults (n = 1356) who reported ever asthma in prior population-based cohorts. All subjects completed a questionnaire about exposures, occupations and exacerbations of asthma. Exposure to high and low molecular weight agents, irritating agents and asthmagens were classified using the asthma-specific job exposure matrix for northern Europe (N-JEM). Severe exacerbation of asthma was defined as sought emergency care at a hospital, admitted to a hospital overnight, or made an urgent visit to a primary care physician or district medical office due to breathing problems during the last 12 months. Moderate exacerbation was defined as both being not severe exacerbation and an additional visit to a primary care physician or district medical office, or had extra treatments with corticosteroid tablets. Mild exacerbation was defined as being neither severe nor moderate exacerbation, and increasing usage of inhaled corticosteroids.Multiple logistic regression was applied to investigate the association between exacerbation of asthma and occupational exposures while adjusting for potential confounders.ResultsApproximately 26 % of the working asthmatics reported exacerbation, and more than two-thirds of them had moderate or severe exacerbation. From 23 to 49 % of the asthmatics reported occupational exposure to a variety of different types of agents. Exposure to any gas, smoke or dust (OR 1.7[95 % CI 1.2–2.6]) was associated with severe exacerbation of asthma, as were organic dust (OR 1.7[1.2–2.5]), dampness and mold (OR 1.8[1.2–2.7]), cold conditions (OR 1.7[1.1–2.7]), and a physically strenuous job (OR 1.6[1.03–2.3]). Asthmagens and low molecular weight agents classified by the N-JEM were associated with mild exacerbation, with OR 1.6[1.1–2.5] and OR 2.2[1.1–4.4], respectively.ConclusionsSelf-reported exposure to any gas, smoke or dust, organic dust, dampness and mold, cold conditions and physically strenuous work, and jobs handling low molecular weight agents were associated with exacerbation of asthma. Reduction of these occupational exposures may help to reduce exacerbation of asthma.

Occupational Respiratory Allergic Diseases in Healthcare Workers.

Healthcare workers (HCWs) are exposed to a range of high and low molecular weight agents that are allergic sensitizers or irritants including cleaners and disinfectants, natural rubber latex, and various medications. Studies have shown that exposed HCWs are at risk for work-related rhinitis and asthma (WRA). Work-related rhinitis may precede development of WRA and should be considered as an early marker of WRA. Avoidance of causative exposures through control strategies such as elimination, substitution, engineering controls, and process modification is the preferred primary prevention strategy for preventing development of work-related allergic diseases. There is limited evidence for the effectiveness of respirators in preventing occupational asthma. If sensitizer-induced WRA is diagnosed, it is important to avoid further exposure to the causative agent, preferably by more rigorous application of exposure control strategies to the workplace. This review focuses on allergic occupational respiratory diseases in HCWs.

Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

IntroductionThe aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests.MethodsSeventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed.ResultsOA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024).ConclusionsOA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents.

P35 Are testicular mixed germ cell tumours associated with hepatitis C(HCV) in HIV infected men who have sex with men?

<h3>OBJECTIVES</h3> To develop a method suitable for estimating exposure risks in population studies of asthma from job titles and international codes, by combining a new job exposure matrix (JEM) with the expert judgement approach. The method was applied in the French epidemiological study of the genetics and environment in asthma (EGEA). <h3>METHODS</h3> The JEM contains 22 exposure groups including 18 high risk groups based on known risk factors for occupational asthma, divided into high molecular weight agents, low molecular weight agents, and mixed environments. After applying the JEM to job codes, exposure estimates for each subject were re-evaluated by examining job title texts. Three high risk exposure estimates for asthma were compared: firstly, applying the JEM to original codes (from different coders in each study centre); secondly, applying the JEM to revised codes (from one experienced coder); and thirdly, after reviewing JEM exposure estimates in the light of job title texts. <h3>RESULTS</h3> The study comprised 173 cases with asthma and 285 controls (age 18–65). Odds ratios (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI) 0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3), applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM and subsequently re-evaluating exposure estimates from job title texts. Asthma ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI 1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for mixed environments. <h3>CONCLUSIONS</h3> This asthma JEM, when enhanced by expert re-evaluation of exposure estimates from job title texts, may be a useful tool in general population studies of asthma. In this study, a 1.7-fold increase in prevalence odds of high risk exposures was found among asthmatic workers compared with controls, with risk magnitude varying for different classes of exposure.

Occupational irritants and asthma: an Estonian cross-sectional study of 34,000 adults.

Occupational exposures make important contributions to asthma morbidity. The role of low/moderate level irritant exposures remains unclear. We aimed to determine which occupational exposures are associated with asthma in an eastern European country with low asthma prevalence. The Estonian Genome Center of University of Tartu collected data from 50 077 adults in 2002-2011. Asthma was assessed through a questionnaire regarding diagnosed diseases, current health status and medication. Exposures to 22 agents during the current and longest held jobs were estimated using an asthma-specific job-exposure matrix. Analyses included 34 015 subjects (aged 18-65 years, 67.0% females), of which 1209 (3.6%) reported asthma (608 with physician-confirmed diagnosis). After adjusting for age, sex and smoking habits, lifetime occupational exposure to known asthmagens (20.4%) was significantly associated with physician-diagnosed asthma (OR 1.28, 95% CI 1.03-1.59), especially high molecular weight agents (flour: OR 2.36, 95% CI 1.31-4.27; animals: OR 1.62, 95% CI 1.00-2.60). Exposure to low/moderate levels of irritants (17.4%) was associated with physician-diagnosed asthma (OR 1.88, 95% CI 1.48-2.37). More pronounced associations were observed in subjects reporting current treated asthma. Beyond confirming the effect of known asthmagens (which are well-known, mostly from observations in western countries), the results provide evidence for a role of low/moderate exposure to irritants. This finding, observed in a country with a low prevalence of asthma and atopy, provides new insight into the understanding of asthma heterogeneity.

Occupational rhinitis and allergic conjunctivitis

Occupational rhinitis is an inflammatory disease of the nose, which is characterised by intermittent or persistent symptoms, arising from causes and conditions attributable to a particular work environment and not from stimuli encountered outside the workplace. Its clinical symptoms such as nasal congestion, sneezing, rhinorrhoea, itching, nasal airflow limitation are very similar to the symptoms of allergic rhinitis caused by other (classical) agents. Occupational allergic conjunctivitis is an IgE mediated disease, provoked by a substance in the air of the workplace. Its clinical signs (itching, tearing, conjunctival hyperaemia and oedema and, in some cases when the cornea is also involved, blurred vision, photosensitivity) are similar to other forms of allergic conjunctivitis. Risk factors (which in most of the cases occur in both diseases) include history of atopy, high concentration of the irritant agent and multiple irritant agents in the air of the workplace. Atopy has been associated with an increased risk of specific sensitisation to a variety of high molecular weight agents. For the diagnosis of occupational rhinitis and occupational allergic conjunctivitis objective investigations such as allergen specific provocations are necessary in addition to clinical and occupational history. Management of these occupational diseases needs environmental interventions (increasing ventilation, decreasing the time of exposure, substitution of the irritant agent). Medical treatment of occupational rhinitis is very similar to other allergic diseases: oral antihistamines, local (nasal) corticosteroids, combined (antihistamine plus membrane stabilizer) eyedrops. The most important step in medical treatment of occupational allergic conjunctivitis is the daily application of combined eyedrops (for example: olopatadine). Orv. Hetil., 2014, 155(5), 170-175.

Sputum inflammatory profile before and after specific inhalation challenge in individuals with suspected occupational asthma.

BackgroundThe aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B4 (LTB4) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular-weight (LMW) agents.Material and MethodsFifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB4 and a 10 Th1/Th2 cytokines were measured in sputum supernatant.ResultsThirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB4 level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146).ConclusionWhen conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents.

Characterization of spherulites as a lipidic carrier for low and high molecular weight agents.

To develop spherulite formulations to achieve high entrapment efficiency for both small and macromolecules as well as cell-type specific delivery. Spherulites of various compositions were prepared, and lipid-PEG was incorporated through post-insertion. Calcein and FITC-labeled albumin were employed as model drugs for small and macromolecules. The spherulites were characterized with respect to entrapment efficiency, size, structure, and release kinetics, and the morphology was examined via cryo-EM. Finally, SV119-decorated spherulites were examined for their selective uptake by cancer cells. The spherulites are 170 ~ 290 nm in size. A loading efficiency of 55 ~ 60% can be consistently achieved for both calcein and albumin under optimized conditions. Cryo-EM shows the onion-like morphology consistent with the structure of multilamellar liposomes. A t(½) of 39.3 h and 69.7 h in cargo release in serum was observed before and after PEG decoration, and incorporation of SV119 led to selective delivery of rhodamine-labeled spherulites to PC-3 tumor cells. Our optimized formulations may represent a platform with simple preparation approach, relatively small particle size, high drug loading efficiency for both low and high molecular weight agents, and slow release kinetics for selective delivery of various types of therapeutics to target cells.

Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case–control study

ObjectivesAllergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma. MethodsThe Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998–2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases and 2296 controls with complete occupational history could be included in the analysis. Associations between HMW exposures and lymphoma were evaluated using pooled unconditional logistic regression analyses. ResultsIndividuals exposed to HMW agents had a non-statistically significant decreased risk of any lymphoma (OR, 0.88: 95% CI, 0.74–1.05) and of B-cell lymphoma (OR, 0.91; 95% CI, 0.76–1.09), and a significantly decreased risk for Hodgkin lymphoma (OR, 0.62; 95% CI, 0.40–0.98). A decrease in risk for lymphoma was found for exposure to latex (OR, 0.74; 95% CI, 0.55–0.99). ConclusionsFurther epidemiologic and mechanistic research is needed to confirm that occupational exposure to HMW agents predisposing to asthma can reduce the risk of lymphoma.