Sputum Inflammatory Patterns Are Associated With Distinct Clinical Characteristics in Patients with Occupational Asthma Independently of the Causal Agent

Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize interactions between induced sputum inflammatory patterns, asthma-related outcomes, and the high- or low-molecular-weight category of causal agents in a large cohort of patients with OA. Methods: We conducted a multicenter, retrospective, cross-sectional study of 296 patients with OA confirmed by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (OR [95%CI], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting ß2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild, 2.48 [1.21-5.08]; moderate/severe, 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male sex (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), use of short-acting ß2-agonists once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the previous 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the specific inhalation challenge (4.45 [1.85-11.59]). Conclusion: The findings indicate that sputum inflammatory patterns in patients with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with findings reported in nonoccupational asthma and are not related to the type of causal agent. (AU)

Antecedentes: La heterogeneidad clínica en el asma ocupacional (AO) inducida por agentes sensibilizantes y su relación con los perfiles inflamatorios de las vías respiratorias siguen siendo muy poco conocidas. Objetivos: Profundizar en la caracterización de las interrelaciones entre los patrones inflamatorios en esputo inducido, diversas variables relacionadas con el asma y la categoría de agentes causales de alto o bajo peso molecular, en una gran cohorte de sujetos con AO Métodos: Este estudio multicéntrico, retrospectivo y transversal se llevó a cabo en 296 sujetos con OA confirmada mediante una provocación bronquial específica (SIC) positiva, en los que se obtuvieron muestras de esputo inducido antes y 24 horas después de la SIC. Resultados: El análisis de regresión logística multivariable reveló que la presencia de eosinofilia en esputo ≥3 % se asoció significativamente con una dosis alta de corticosteroides inhalados (odds ratio [intervalo de confianza del 95 %], 1,31 [1,11-1,55] por cada incremento de 250 µg en la dosis diaria), el uso de agonistas ß2 de acción corta menos de una vez al día (3,54 [1,82-7,00]), y un nivel de hiperreactividad bronquial inespecífica inicial (leve: 2,48 [1,21-5,08]); moderado/grave: 3,40 [1,44-8,29]). La neutrofilia en esputo ≥76%, se asoció con la edad (1,06 [1,01-1,11]), el sexo masculino (3,34 [1,29-9,99]), la ausencia de uso de corticosteroides (5,47 [2,09-15,16]), el uso de agonistas ß2 de acción corta una vez o más al día (4,09 [1,71-10,01]), la presencia de ≥ 2 exacerbaciones graves en los últimos 12 meses en el trabajo (4,22 [1,14-14,99]) y reacciones inmediatas aisladas durante la SIC (4,45 [1,85-11,59])... (AU)

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

Predicting occupational allergy in culinary and hairdressing apprentices.

BACKGROUND: Apprentices are usually exposed to the same workplace agents as qualified professionals. There is therefore a risk of the development of occupational allergy in apprentices exposed to high (HMW-A) and low molecular inhalant allergens (LMW-A). AIMS: To evaluate and compare the occurrence of work-related allergy-like symptoms in apprentices exposed to HMW-A and LMW-A in a culinary and hairdressing school during the first and second year of vocational training. METHODS: We asked culinary and hairdressing apprentices in their first and second year of vocational training to complete a questionnaire about work-related allergy-like symptoms. In first-year apprentices, we undertook spirometry, skin prick tests for occupational allergens and blood tests for allergen-specific Immunoglobulin E (IgE) antibodies. RESULTS: Hypersensitivity to occupational allergens was more frequent in first-year apprentices exposed to HMW-A compared to LMW-A (P < 0.05). Apprentices exposed to LMW-A reported increasing occurrence of skin disorders and upper respiratory tract symptoms between the first and second years of training. First-year apprentices exposed to HMW-A more frequently reported rhino-conjunctivitis and dyspnoea (approximately P < 0.001 and P < 0.05) and those exposed to LMW-A more often reported skin symptoms (P < 0.05). CONCLUSIONS: Periodic skin and respiratory health surveillance for apprentices exposed to LMW-A or HMW-A might help with early identification and management of occupational allergy.

Subclinical chronic left ventricular systolic dysfunction resulting from phosphine poisoning.

We present a case of a 32-year-old male crew member of a cargo ship, accidentally exposed to phosphine, a fumigating substance. He and other crew members developed increasing fatigue and digestive disorders 24 h later; two died from acute pulmonary oedema. The patient was admitted to hospital, where bilateral pneumonia, acute nephritis, hepatopathy, electrolyte imbalance and leucopenia were diagnosed. He was discharged from hospital 3 weeks later. He was examined 4 months later for possible chronic consequences of acute phosphine poisoning, which included echocardiography showing normal heart size and cardiac function. However, on advanced quantitative analysis, using two-dimensional speckle tracking echocardiography, depressed global longitudinal strain was found. Our report extends previously published findings of phosphine-induced left ventricular (LV) dysfunction by demonstrating that subclinical myocardial dysfunction resulting from acute phosphine exposure may persist several months after the exposure in an otherwise asymptomatic patient, and potentially may not be entirely reversible. The persistence of subclinical abnormalities of LV longitudinal function can be diagnosed using the advanced quantitative echocardiographic analysis we describe.

Anaphylactic reaction in a hairdresser due to sensitization to persulphates.

Severe occupational systemic reactions to persulphates have rarely been described and if so mainly after skin contact with bleaching products. We report the first case of a hairdresser with an allergy to persulphates obtained during professional work, who developed anaphylaxis caused by persulphates present in dental cement during dental treatment. This case documents that sensitization to occupational allergens can induce severe systemic reactions outside the workplace. Additionally, it also recommends the need for greater awareness of medical professionals, including dentists, of the possibility of anaphylaxis in patients with occupational allergy.

Sensitization to xylanolytic enzymes: an underestimated health hazard among bakers.

BACKGROUND: The most important occupational allergens in baking include flour and enzymes, especially α-amylase. Although xylanolytic enzymes have previously been described as sensitizers, they may be overlooked during assessment of bakery workers with work-related symptoms. AIMS: To report a case of a baker who suffered from work-related respiratory, ocular and skin symptoms as a consequence of sensitization to xylanolytic enzymes. METHODS: Physical examination, chest X-ray, routine laboratory tests, skin prick tests (SPTs) with common and occupational allergens (wheat, pearl, rye, corn and oat flours, α-amylase, bakery adjuvants) and spirometric measurements, as well as assessments by a laryngologist, dermatologist and ophthalmologist were performed. Specific IgE (sIgE) to occupational agents were evaluated for flours, α-amylase, xylanase, cellulose and glucoamylase. Specific inhalation challenges (SICs) with flours and bakery adjuvants were carried out. RESULTS: Hypersensitivity to Aspergillus moulds, flours and α-amylase was confirmed in SPTs; however, SIC with those agents gave a negative result. Further investigation revealed the presence of sIgE to xylanolytic enzymes. During SIC with bakery adjuvants, allergic skin, ocular and respiratory symptoms occurred and were confirmed by objective assessment. CONCLUSIONS: In the assessment of work-related allergic symptoms in bakers, sensitization to xylanolytic enzymes should be considered. Completion of diagnostic procedures having excluded asthma and rhino-conjunctivitis related to flour hypersensitivity might result in a false-negative assessment.

How to diagnose mould allergy? Comparison of skin prick tests with specific IgE results.

BACKGROUND: Diagnosis of mould allergy is complicated due to the heterogeneity of the test material and the decrease in the number of commercial mould skin test solutions that are currently available. OBJECTIVES: The aim of this study was to compare skin prick tests (SPT) from different manufacturers to one another and concurrently with sIgE tests for Aspergillus fumigatus (Asp f), Cladosporium herbarum (Cla h), Penicillium chrysogenum (Pen ch), Alternaria alternata (Alt a) and Aspergillus versicolor (Asp v) to ascertain a feasible diagnostic procedure for mould sensitization. METHODS: In this multi-centre study, 168 patients with mould exposure and/or mould-induced respiratory symptoms were included. Mould SPT solutions were analysed biochemically and tested in duplicate on patients' arms. Specific IgE (sIgE) concentrations to corresponding mould species and mould mix (mx1) were measured by ImmunoCAP. SPTs in accordance with one another and with sIgE were further considered. The test efficiency was calculated using receiver-operating characteristic (ROC) analysis. RESULTS: Mould sensitization was more frequently detected by the SPT (90 of 168) than by the sIgE tests (56 of 168). Concordances of double SPT positives were only sufficient (≥ 80%) for environmental allergens, two Asp f and three Alt a SPT solutions, whereas all other mould solutions revealed concordances < 80%. The antigen content of SPT solutions was positively associated with concordant SPT double values as well as with sIgE. Taking sIgE as the 'positive standard', all mould SPT solutions revealed test efficiencies > 80%, but varied up to 20% in sensitivity and positive predictive value with the exception of Alt a. CONCLUSIONS: SPT solutions are sensitive and essential diagnostic tools for the detection of mould sensitization. Our recommendation for diagnosis would be to test at least Alt a, Asp f and Pen ch using SPT and additional sIgE test to mx1.

Cough-variant asthma: a diagnostic dilemma in the occupational setting.

BACKGROUND: Cough-variant asthma (Corrao's syndrome) is defined as the presence of chronic non-productive cough in patients with bronchial hyperresponsiveness (BHR) and response to bronchodilator therapy. This variant of asthma may present a diagnostic problem in occupational medicine. AIMS: To describe additional evaluation of cough-variant asthma in a cyanoacrylate-exposed worker in whom standard diagnostic testing was negative. METHODS: A female beautician was evaluated for suspected occupational allergic rhinitis and asthma. A specific inhalation challenge test (SICT) was performed with cyanoacrylate glues used for applying artificial eyelashes and nails. Spirometry and peak expiratory flow (PEF) measurements were recorded hourly for 24h; methacholine challenge testing was performed and nasal lavage (NL) samples were analysed for eosinophilia. RESULTS: After SICT, the patient developed sneezing, nasal airflow obstruction and cough. Declines in forced expiratory volume in 1 s and PEF were not observed. Eosinophil proportions in NL fluid increased markedly at 4 and 24h after SICT. A significant increase in BHR also occurred 24h after SICT. CONCLUSIONS: Clinical symptoms, post-challenge BHR and increased NL eosinophil counts confirmed a positive response to SICT and validated the diagnosis of cough-variant occupational asthma. SICT may be useful in cases where history and clinical data suggest cough-variant asthma and spirometric indices are negative.

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.

Occupational allergy to squid (Loligo vulgaris).

Occupational allergy from exposure to squid has been rarely described, mainly as contact dermatitis or urticaria. Our report presents the first case of occupational asthma, rhinitis, conjunctivitis and contact urticaria to squid in a 33-year-old seafood production worker, with documented increased eosinophilia in the nasal and tear fluids after specific inhalation challenge test (SICT) with squid. IgE-mediated sensitization to squid was confirmed by positive skin prick test and opened skin test with squid extract. SICT demonstrated a direct and significant link between the exposure to squid and the allergic response from the respiratory system and conjunctiva.

What is the significance of leukoaraiosis in patients with acute ischemic stroke?

BACKGROUND: Leukoaraiosis (LA) may have specific clinical correlates in patients with stroke, but this is not well investigated, so that the significance of LA in patients with stroke remains unclear. METHODS: In a study of 2289 patients with a first-ever acute ischemic stroke, LA was noted in 149 by the use of baseline computed tomography of the brain. These patients were compared with the non-LA group. Statistical tests, including Fisher exact test or a chi(2) test, were used to compare variables, and a multivariate approach using stepwise logistic regression was performed. RESULTS: Patients with LA were significantly older (73.7 vs 62.7 years; P<. 001), and had a higher incidence of hypertension (72.5% vs 47.1%; P<. 001) and subcortical or lacunar infarction (40.3% vs 25.4% and 21.5% vs 8.0%, respectively; P<.001) on neuroimaging studies, compared with the non-LA group. The most common cause of stroke in the LA group was presumed to be small-artery disease associated with hypertension (46% vs 13.5% in the non-LA group). Age and hypertension were very strongly associated with LA (respective odds ratios [95% confidence intervals], 1.06 [1.04-1.08] and 2.33 [1.60-3. 39]). In addition to these risk factors, a close relationship was found between LA and nonsevere stenosis (<50%) of the internal carotid artery (odds ratio, 2.23 [95% confidence interval, 1.32-3. 76]), although the significance of this association remains speculative. The outcome at 1 month after stroke was similar in both groups. CONCLUSION: Our results provide further evidence that LA is related primarily to small-vessel disease.

[Transient patency loss of the internal carotid artery in a young patient]. / Przejsciowa niedroznosc tetnicy szyjnej wewnetrznej u mlodej osoby.

Ischaemic stroke has been observed more rarely among young people in comparison to old adults. The causes of ischaemic stroke among young adults are numerous. One of them is occlusion of internal carotid artery (ICA). The aetiology of the occlusion is different from arteriosclerotic disorders. Within the last few years the authors have paid much attention to the fact that spontaneous dissection is not such a rare cause of ICA occlusion. In many cases (60-70%) of dissection recanalization and benign outcome occur. Angiography has been considered as a gold standard in establishing the diagnosis. We described a young, 16-year-old patient with ischaemic stroke. The cause occlusion of ICA, probably was dissection. The diagnosis was made by angiography MR. In our patient follow-up angiography MR demonstrated recanalisation. The outcome of the stroke was benign and hemiplegia reversed.

Ischemic strokes are more severe in Poland than in the United States.

Case fatality rates for stroke were ascertained prospectively in two regional catchment hospitals in Poland and 36 teaching hospitals in the US University Hospital Consortium. Case fatality rates in Poland (23.9%) were higher than in the United States (7.5%). Angina, atrial fibrillation, and congestive heart failure were more frequent in Polish stroke patients (40%, 26%, and 25%, respectively) than in US patients (17%, 12%, and 10%). Stroke severity as indicated by higher frequencies of hemiplegia, disordered consciousness, dysphagia, and aphasia was greater in Poland (19%, 39%, 28%, and 42%, respectively) than the United States (11%, 13%, 14%, and 26%).

[Knowledge of stroke problems among adults in Poland]. / Znajomosc problematyki udarowej wsród osób doroslych w Polsce.

An inquiry questionnaire was given to 180 adults without a history of stroke. The questions concerned the problem of stroke. The responders were aged from 15 to 82 years (mean 48 years). They were asked about risk factors for stroke, symptoms preceding stroke, behaviour of stroke witnesses. A correct definition of stroke was given by 86.7% of the responders. Only a small proportion of them knew risk factors for stroke (27.8% knew that one of them was hypertension, 6.1% gave smoking, 4.4% diabetes as risk factors). Although 93.9% knew that in face of stroke physician or ambulance service should be called, 6.1% thought that it would be sufficient to lie down or take paracetamol. The inquiry showed that the knowledge of risk factors for stroke is insufficient in the Polish adult population who not yet had cerebrovascular disturbances. It seems advisable to deliver an education programme in mass media on stroke prevention and its management in case of its development.

[How do general practitioners proceed on initial contact with patients after cerebrovascular ischemia?]. / Jak postepuje lekarz pierwszego kontaktu z chorymi z zaburzeniami krazenia mózgowego?

The reported analysis of an inquiry study of first-contact physicians was carried out for establishing how the manage cases of ischaemic stroke and transient ischaemic accident (TIA). The inquiry questionnaire containing questions related to the management of these patients and outpatient diagnosis of patients after stroke or TIA was sent to general practitioners in 4 regions of the country. The form was returned by 159 out of 300 physicians, mostly those working in towns (90.6%). From 53.5% to 64.8% of physicians referred patients with symptoms suggestive of stroke to hospitals, less often were referred those with vision disturbances. Antiplatelet drugs were prescribed to patients with cerebral circulation disturbances by only 12% to 20.3% of the physicians. Only 46.8% of the physicians used anticoagulants as secondary prevention after cerebral embolism from the heart. In patients treated with anticoagulants INR was checked every 2 weeks by 50.9% physicians. Only 42.8% of the physicians referred the patients for USG examination of neck arteries. The analysis showed that too few first-contact physicians referred stroke cases to hospital and too few prescribed antiplatelet drugs for TIA. Anticoagulants were used insufficiently for secondary prevention after cerebral embolism from the heart. There is much to do in stroke cases for management and prevention.

[The difference among patients with acute ischemia stroke and with reversed flow in the ophthalmic artery and the ones with a correct direction of the flow]. / Róznice miedzy pacjentami z ostrym udarem niedokrwiennym i odwróconym kierunkiem przeplywu w tetnicy ocznej, a pacjentami z prawidlowym kierunkiem przeplywu.

METHOD: Fifty-four patients with acute ischaemic stroke (AIS) and with reversed flow direction in the ophthalmic artery (OA) were compared prospectively with patients with normal flow in that artery. Age, sex, presence of atrial fibrillation (AF) and ischaemic heart disease, the course in the acute period within 30 days after stroke onset were analysed. On the first day the following examinations were performed in all patients: routine laboratory investigations, X-ray, ECG and Doppler and USG examinations of the extracranial arteries. In some cases CT of the head was obtained. The condition of the patients was assessed by Rankin scale on the first and 30-th days after stroke onset. Improvement was accepted if on the 30-th day the score was 1 point better than on the first assessment. RESULTS: The mean age in the group with reversed blood flow in OA was 60.7 years, and in the group with normal flow it was 69 years (p < 0.0001). The male/female ratio was statistically significantly different in these groups (p = 0.01): in the younger group with reversed flow males accounted for 76% and in the older group with normal flow--52.5%. AF in the younger group was present in a low proportion of cases (3.7%) but in the older group it was 21.3%, the difference was statistically significant (p = 0.005). No significant difference was found in the presence of ischaemic heart disease. In the patients scoring 4 and 5 in Rankin scale in the first assessment no worsening was noted in the group with reversed blood flow, while in the other group 24% of the patients were worse or died (statistically significant difference, p = 0.004). The course of mild and medium severe stroke within 30 days was similar in both groups. CONCLUSIONS: Patients with AJS and reversed flow in OA-differed from those with normal flow in OA, they were younger, more often were males. AF was present in isolated cases and the course of major stroke was milder.

[Temporal arteritis as a cause of a terrible headache]. / Zapalenie tetnicy skroniowej--jako przyczyna uporczywych bólów glowy.

Two patients with temporal arteritis are reported in whom terrible headache was the predominant symptom of the disease. Both of them improved after prednisone 60 mg daily in the initial dose. The diagnosis and the treatment of giant cell arteritis are discussed.