Tor Aasen

Guidelines for the management of work-related asthma

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder. A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners’ three-star system. Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.

Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma. ERS Task Force: a statement on specific inhalation challenges in the diagnosis of occupational asthma http://ow.ly/tCvFG

The management of work-related asthma guidelines: a broader perspective

The aim of the European Respiratory Society work-related asthma guidelines is to present the management and prevention options of work-related asthma and their effectiveness. Work-related asthma accounts for 5–25% of all adult asthma cases and is responsible for a significant socioeconomic burden. Several hundred occupational agents, mainly allergens but also irritants and substances with unknown pathological mechanisms, have been identified as causing work-related asthma. The essential message of these guidelines is that the management of work-related asthma can be considerably optimised based on the present knowledge of causes, risk factors, pathomechanisms, and realistic and effective interventions. To reach this goal we urgently require greatly intensified primary preventive measures and improved case management. There is now a substantial body of evidence supporting the implementation of comprehensive medical surveillance programmes for workers at risk. Those workers who fail surveillance programmes need to be referred to a clinician who can confirm or exclude an occupational cause. Once work-related asthma is confirmed, a revised risk assessment in the workplace is needed to prevent further cases. These new guidelines confirm and extend already existing statements and recommendations. We hope that these guidelines will initiate the much-needed research that is required to fill the gaps in our knowledge and to initiate substantial improvements in preventative measures.

Occupational rhinitis: diagnostic criteria, relation to lower airway symptoms and IgE sensitization in bakery workers

Conclusions. The use of different diagnostic criteria has considerable consequences for the prevalence estimates of occupational rhinitis. There is a strong relationship between occupational rhinitis and lower airway symptoms. Storage mites appear to be important occupational allergens in Norwegian bakeries. Objectives. To study the consequences of various diagnostic criteria on the prevalence of occupational rhinitis, assess the prevalence of IgE sensitization and explore the relationships between upper and lower airway symptoms and between symptoms and IgE sensitization. Material and methods. A total of 197 employees in 6 bakeries were interviewed and completed a questionnaire. A skin prick test was performed, total and specific IgE were determined and a histamine release test was performed for relevant allergens. The criteria for the diagnosis of occupational rhinitis were based on the 1994 International Consensus Report on Rhinitis. Results. The prevalence of occupational rhinitis varied between 23% and 50%, depending on the criteria used. The occurrence of nasal symptoms was found to precede the development of lower airway symptoms. Occupational rhinitis, both IgE- and non-IgE-mediated, was associated with asthma symptoms. The most frequent causes of sensitization (20%) were different species of storage mites. Storage mite sensitization was related to occupational rhinitis and work exposure.

Airway Inflammation and Bronchial Remodelling in Toluene Diisocyanate‐exposed BALB/c Mouse Model

Toluene diisocyanate (TDI), a highly reactive industrial chemical, is one of the leading causes of occupation‐related asthma in industrialized countries. The pathogenesis of TDI‐induced asthma, however, remains not fully understood, in part due to lack of appropriate animal models. Twenty five female BALB/c mice (age: 8 weeks) were randomly divided into 5 groups: Ovabumin (OVA); OVA peptide amino acid residues No. 323–339 (Pep); TDI; alum and physiological saline. Mice were intraperitoneally injected with 25 μg OVA or pep absorbed on 300 μg alum, 300 μg alum or saline on days 0, 7 and 14. For the TDI group, mice were sensitized subcutaneously with 20 μl neat TDI on day 0; 20 μl of TDI in olive oil (1:10) on days 7 and 14; on days 21–23. Then each group was challenged intranasally with 20 μl of 1% OVA, 1% Pep, 1% TDI, 10% alum and saline respectively. On day 28, mice were killed under pentothal anesthesia. The results demonstrated that neutrophil‐dominant inflammation with a few eosinophil infiltration occurred in the peri‐bronchial and peri‐vascular regions of the lungs. This was accompanied by hyperplasia/hypertrophy of cells lining the airways and mucus production as shown by HE staining. Positive immunohistochemical MBP staining in parenchyma was also shown. Th2 cytokine IL‐4 and IgE production were significant increased 5 days after last challenge while IFN‐γ level was below the detection limit. Conclusion: the clear elevation of IL‐4 and IgE could allow to conclude a possible Th2‐like dominated allergic response in TDI‐exposed BALB/c mouse model.

Comparison between Ovalbumin and Ovalbumin Peptide 323-339 Responses in Allergic Mice: Humoral and Cellular Aspects

Ovalbumin (OVA) is widely used in allergy research. OVA peptide 323‐339 has been reported to be responsible for 25–35% of isolated BALB/c mouse T‐cell response to intact OVA. An investigation of whether OVA and OVA 323‐339 molecules can induce equivalent in vivo and in vitro immune responses was conducted. Eight‐week‐old BALB/c mice were randomly divided into three groups: OVA, OVA 323‐339 and saline. On days 0, 7, 14, mice were intraperitoneally injected with 25 μg OVA or OVA 323‐339 absorbed on 300 μg Alum, or saline; on days 21–23, all groups were challenged intranasally with either 20 μl of 1% OVA, 1% OVA 323‐339 or saline. On day 28, after killing, splenocytes were isolated and cultured under the stimulus of each allergen or medium. Evaluated by hematoxylin/eosin and major basic protein immunohistochemical stainings, OVA and OVA 323‐339 induced similar lung inflammation. Interestingly, significant serum total IgE and OVA‐specific IgE were observed in OVA mice when compared to saline control. OVA 323‐339 mice showed higher serum OVA‐specific IgE, OVA 323‐339‐specific IgE, IL‐4 and lower IFN‐γ similar to OVA mice. The proliferative response to OVA was found in cultured splenocytes of both OVA and OVA 323‐339 mice, while the similar proliferative response to OVA 323‐339 was only observed in the splenocytes of OVA 323‐339‐sensitized and challenged mice. Although OVA 323‐339 induced a Th2‐like response in the mouse model as did OVA, OVA 323‐339 has clearly limited immunogenic potency to activate OVA‐sensitized and challenged mice splenocytes, unlike OVA.

Respiratory health in cleaners in Northern Europe : is susceptibility established in early life?

Rationale There is some evidence that maternal smoking increases susceptibility to personal smoking’s detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning’s unhealthy effects. Methods The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated. Main Results Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3–1.6), adult-onset asthma (1.5 [1.2–1.8]) and self-reported COPD (1.7 [1.3–2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7–1.3]; 1–4 years 1.5 [1.1–2.0]; ≥4 years 1.6 [1.2–2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5–2.3] vs. 1.3 [0.96–1.8]; pinteraction 0.035). Conclusions Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

Self-reported skin and respiratory Symptoms related to Latex exposure among 5,087 hospital employees in Norway

Background: Latex allergy has become prevalent among health care workers. Objectives: To determine the prevalence of self-reported symptoms related to latex exposure among hospital personnel. Methods: Questionnaires addressing symptoms and risk factors for latex allergy were distributed to all employees (n = 5,087) at Haukeland University Hospital. Results: Symptoms associated with latex exposure were reported by 23.8% of the participants. Skin symptoms were most frequently reported – flushing/itching/hives: 21.0%, hand eczema: 11.8% – while systemic and respiratory symptoms were reported by 1.4 and 1.2%, respectively. Approximately twice as many women than men reported symptoms (odds ratio 2.55, confidence interval 2.04–3.18). Symptoms were reported by 33.7% of those with atopy and by 20.0% of those without. The occurrence of symptoms increased significantly with the frequency of use of latex gloves but was unrelated to age, years of exposure or number of surgical procedures. Conclusions: The occurrence of self-reported symptoms was associated with the frequent use of latex gloves, atopy and female gender.

Diagnostic approach in cases with suspected work-related asthma

BackgroundWork-related asthma (WRA) is a major cause of respiratory disease in modern societies. The diagnosis and consequently an opportunity for prevention are often missed in practice.MethodsBased on recent studies and systematic reviews of the literature methods for detection of WRA and identification of specific causes of allergic WRA are discussed.Results and ConclusionsAll workers should be asked whether symptoms improve on days away from work or on holidays. Positive answers should lead to further investigation. Spirometry and non-specific bronchial responsiveness should be measured, but carefully performed and validly analysed serial peak expiratory flow or forced expiratory volume in one second (FEV1) measurements are more specific and confirm occupational asthma in about 82% of those still exposed to the causative agent. Skin prick testing or specific immunoglobulin E assays are useful to document allergy to high molecular weight allergens. Specific inhalational challenge tests come closest to a gold standard test, but lack standardisation, availability and sensitivity. Supervised workplace challenges can be used when specific challenges are unavailable or the results non-diagnostic, but methodology lacks standardisation. Finally, if the diagnosis remains unclear a follow-up with serial measurements of FEV1 and non-specific bronchial hyperresponsiveness should detect those likely to develop permanent impairment from their occupational exposures.

Can air pollution affect tear film stability? a cross-sectional study in the aftermath of an explosion accident

BackgroundAfter an explosion and fire in two tanks containing contaminated oil and sulphur products in a Norwegian industrial harbour in 2007, the surrounding area was polluted. This caused an intense smell, lasting until the waste was removed two years later. The present study reports examinations of tear film break up time among the population. The examinations were carried out because many of the people in the area complained of sore eyes. The purpose of the study was to assess the relationship between living or working close to the polluted area and tear film stability one and a half years after the explosion.MethodsAll persons working or living in an area less than six kilometres from the explosion site were invited to take part in the study together with a similar number of persons matched for age and gender living more than 20 kilometres away. Three groups were established: workers in the explosion area and inhabitants near the explosion area (but not working there) were considered to have been exposed, and inhabitants far away (who did not work in the explosion area) were considered to be unexposed. A total of 734 people were examined, and the response rate was 76 percent. Tear film stability was studied by assessing non-invasive break-up time (NIBUT) using ocular microscopy. In addition Self-reported Break Up Time (SBUT) was assessed by recording the time the subject could keep his or hers eyes open without blinking when watching a fixed point on a wall. Background information was obtained using a questionnaire. Non-parametric Wilcoxon-Mann-Whitney-tests with exact p-values and multiple logistic regression analyses were performed.ResultsBoth NIBUT and SBUT were shorter among the male exposed workers than among the inhabitants both near and far away from the explosion area. This was also found for SBUT among males in a multiple logistic regression analysis, adjusting for age and smoking.ConclusionsReduced tear film stability was found among workers in an area where an explosion accident had occurred.