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.

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 microg OVA or OVA 323-339 absorbed on 300 microg Alum, or saline; on days 21-23, all groups were challenged intranasally with either 20 microl 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-gamma 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.

Airway inflammation and bronchial remodelling in toluene diisocyanate-exposed BALB/c mouse model.

UNLABELLED: 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 microg OVA or pep absorbed on 300 microg alum, 300 microg alum or saline on days 0, 7 and 14. For the TDI group, mice were sensitized subcutaneously with 20 microl neat TDI on day 0; 20 microl of TDI in olive oil (1:10) on days 7 and 14; on days 21-23. Then each group was challenged intranasally with 20 microl 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-gamma 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.

Effects of a standard hyperbaric oxygen treatment protocol on pulmonary function.

The prescription of hyperbaric oxygen (HBO) therapy for disorders not related to diving is increasing. Pulmonary oxygen toxicity is well known, but the effect of the cumulative oxygen exposure corresponding to a standard HBO treatment protocol has not been quantified before. Twenty patients (10 male) had 21 HBO treatments at a partial pressure of oxygen of 240 kPa for 90 min daily. None had any previous lung disease and all had normal chest radiography and lung function at the start of the study. Dynamic lung volumes, forced expiratory flows and the transfer factor of the lung for carbon monoxide (TL,CO) were measured before the HBO treatment, on days 7, 14 and 21 during treatment and then 3-4 weeks after treatment. Four patients (one male) reported nonproductive coughing during the last week of treatment. There was a progressive reduction in forced expiratory volume in one second (FEV1) (p<0.001), mean forced mid-expiratory flow rate (FEF25-75%) (p<0.001) and forced expiratory flows at 50 and 75% of forced vital capacity (FVC) expired during HBO treatment. The reduction in FEV1 on day 21 was 4.4+/-1.7% and in FEF25-75% 10.3+/-6.1%. Four weeks after treatment there was a partial normalization. There were no changes in FVC or peak expiratory flow (PEF). TL,CO was slightly reduced on day 21 of treatment only (p<0.01) and fully normalized 1 month later. A reduction in small airways conductance is consistent with other studies where total oxygen exposures have been below the limit causing toxic pulmonary effects traditionally measured as a reduction in vital capacity. This effect is not considered to be of any clinical significance for patients treated with hyperbaric oxygen unless repeated treatment series are to be given.

[Assessment of causal relationship in work-related pulmonary diseases. An epidemiological approach]. / Vurdering av årsaksforhold ved yrkesrelaterte lungesykdommer. En epidemiologisk tilnaerming.

A competent assessment of causal relationships in the case of work-related lung disorders depends on correct diagnosis, a detailed occupational history and updated epidemiological knowledge about causal relationships, obtained from the literature. Assessments for purposes of compensation demand, in addition, an explicit choice of methods for calculating causes, before a meaningful attempt can be made to weight the various factors in and outside the working environment. If adequate epidemiological knowledge is available, the causal probability, based on the etiological fraction among the exposed persons (attributable risk) may be a useful tool for apportioning the different causal factors.

[Principles for assessment and diagnosis of work-related pulmonary and pleural diseases]. / Prinsipper for utredning og diagnostikk ved yrkesrelaterte lunge- og pleurasykdommer.

Proposals for diagnostic methods and clinical evaluation of occupational lung and pleural diseases have been worked out by a Working Group appointed by the Norwegian Thoracic Society and the Norwegian Society of Occupational Medicine. The management of this group of diseases demands both an evaluation of occupational exposure and a specific pulmonary diagnosis. Recommendations were made especially for obstructive, interstitial, and malignant diseases.

[Expert statement and assessment of medical impairment in work-related pulmonary disease]. / Spesialisterklaeringen og fastsettelse av medisinsk invaliditet ved yrkesrelaterte lungesykdommer.

The Norwegian Societies of Thoracic Medicine and Occupational Medicine established a working group to standardise diagnostic procedures and evaluation of work-related respiratory disorders. In cases of suspected work-related diseases the physician may be asked by the National Insurance Administration or an insurance company to make a statement which will be one of the documents used to decide the patient's right to compensation benefit. We discuss the role of the physician as an independent expert. This is different from his role as clinician. The statement should include a balanced presentation of information from different sources, including health and occupational history, and the employer's information about the work environment (quantitative and qualitative exposure data). The statement must also include the results of a clinical examination and an assessment of functional status based on objective tests. The paper contains recommendations for evaluation of permanent impairment in light of the present Norwegian laws and regulations.

Lucigenin-dependent chemiluminescence in mononuclear phagocytes. Role of superoxide anion.

A method for the measurement of reactive oxygen species generated by activated mononuclear phagocytes by use of lucigenin-dependent chemiluminescence was developed. Opsonized zymosan was used as a stimulant to evaluate the chemiluminescence response of monocytes. A cell-free system in which superoxide anion and hydrogen peroxide were produced by the xanthine-xanthine oxidase reaction was used to examine the role of these radical species in the excitation of lucigenin, and to standardize the chemiluminescence method. It was found that the light emission in lucigenin-dependent chemiluminescence was evoked by the superoxide anion, but other radicals may also be active.

Fine needle aspiration biopsy of mediastinal and peripheral pulmonary masses guided by real-time sonography.

The value of fine needle aspiration biopsy guided by real-time ultrasonography was assessed in 45 patients referred with an intrathoracic mass adjacent to the chest wall. The mass, as determined by chest x-ray examination, was visualized sonographically and subsequently biopsied in 42 patients. Puncture specimen was diagnostic in 34 patients (81 percent), including nine of 12 patients (75 percent) with previous failure of biopsy under fluoroscopic guidance. The success rate was similar in pulmonary and mediastinal masses, 18 of 23 and 16 of 19 patients, respectively. A diagnostic biopsy was obtained in 26 of 31 patients with a malignant mass. No complications were observed except for a minimal pneumothorax in one patient. Thus, real-time sonographic guidance is a safe, easy, and reliable method in biopsy of pulmonary and mediastinal masses adjacent to the chest wall and may also succeed in patients where fluoroscopically guided biopsy has failed.

In vitro locomotion of blood monocytes in millipore filters--evaluation of the leading front method.

Monocyte migration in millipore filters was measured by the leading front method. The precision, sensitivity and specificity of the method was assessed. The migrational response of monocytes to N-formylmethionylleucyl-phenylalanine (FMLP) was equal in concentrations ranging from 5 X 10(-9) to 5 X 10(-7) M. No dose-response relationship was demonstrated. The random analytical variation of the method was considerable, the mean coefficient of variation of duplicate experiments being 9.05%. The inter-subject variation was also large. A sample size of 30 to 40 individuals would be necessary to demonstrate a 1 SD difference between individuals at a significance level of 0.05 and power of 0.80. It is concluded that the method is able to detect agents which stimulate monocytes at least equally well as FMLP, but may be impracticable for demonstrating changes in monocyte migration, or differences in the migratory response among different populations of monocytes.