Non-responders to hepatitis B vaccination: a review.

Hepatitis B virus (HBV) infection is a major public health issue throughout the world and vaccination of those at risk is the main method of containment. Of healthy vaccinees, 5-10% fail to mount an adequate antibody response. The antibody levels of an unknown further fraction of vaccinees fall considerably over time rendering them at a potential risk of infection. The scope of this article is to review the factors that might influence the immune response to HBV vaccination, to review the methods used to overcome the problem of poor response and to discuss what possible guidelines are available or needed in treating these vaccinees.

Interpretation of occupational peak flow records: level of agreement between expert clinicians and Oasys-2.

BACKGROUND: Oasys-2 is a validated diagnostic aid for occupational asthma that interprets peak expiratory flow (PEF) records as well as generating summary plots. The system removes inconsistency in interpretation, which is important if there is limited agreement between experts. A study was undertaken to assess the level of agreement between expert clinicians interpreting serial PEF measurements in relation to work exposure and to compare the responses given by Oasys-2. METHOD: 35 PEF records from workers under investigation for suspected occupational asthma were available for review. Records included details of nature of work, intercurrent illness, drug therapy, predicted PEF, rest periods, and holidays. Simple plots of PEF and the Oasys-2 generated plots were available. Experts were advised that approximately 1 hour was available to review the records. They were asked to score each work-rest-work (WRW) period and each rest-work-rest (RWR) period for evidence of occupational effect. At the end of each record scores of 0-100% were given for evidence of "asthma" and "occupational effect" for the whole record. Kappa values were calculated for each scored period and for the opinions on the whole record. The scores were converted into four groups (0-25%, 26-50%, 51-75%, 76-100%) and two groups (0-50% and 51-100%) for analysis. This is relevant to scores produced by Oasys-2. Agreement between Oasys-2 scores and each expert was calculated. RESULTS: 24 of 35 records were analysed by seven experts in the allotted time. For whole record occupational effect, median kappa values were 0.83 (range 0.56-0.94) for two groups and 0.62 (0.11-0.83) for four groups. For asthma, median kappa values were 0.58 (0-0.67) and 0.42 (0.15-0.70) for two and four groups respectively. For all WRW and RWR periods kappa values were 0.84 (0.42-0.94) and 0.70 (0.46-0.87) respectively. Agreement between Oasys-2 and individual experts showed a median kappa value of 0.75 (0.50-0.92) for two groups and 0.50 (0.39-0.70) for four groups. Kappa values for the median expert score v Oasys-2 were 0.75 for two groups and 0.67 for four groups. Agreement was poor for records with intermediate probability, as defined by Oasys-2. CONCLUSION: Considerable variation in agreement was seen in expert interpretation of occupational PEF records which may lead to inconsistencies in diagnosis of occupational asthma. There is a need for an objective scoring system which removes human variability, such as that provided by Oasys-2.

Extrinsic allergic alveolitis and asthma in a sawmill worker: case report and review of the literature.

A 34 year old sawmill maintenance engineer developed a dry cough that was associated with widespread wheezes and crackles in his lungs. His symptoms worsened, with work related lethargy, fever, and breathlessness, and the loss of a stone in weight. At that time, while still at work, he had a neutrophil leucocytosis and increased concentration of gamma globulins. When seen subsequently some two months after stopping work, his chest radiograph and lung function tests were normal, but the cells recovered at bronchoalveolar lavage showed an increase in lymphocytes and mast cells, a pattern consistent with extrinsic allergic alveolitis. Serum precipitins were identified to extracts of sawdust, wood chips, and bark from the sawmill, and to eight species of mould grown from these samples. Specific IgG binding inhibition studies suggested that a common epitope present on Trichoderma koningii might be responsible for the cross reactivity of the patient's serum with the wood and fungal extracts. A diagnosis of wood associated extrinsic allergic alveolitis was made and since changing his job the patient has remained well. Wood associated allergic alveolitis has not previously been described in British sawmill workers, but has been reported in Sweden, with a prevalence of 5%-10% in exposed workers. A review of published data suggests extrinsic allergic alveolitis in wood workers is primarily caused by inhalation of the spores of contaminating fungi, but inhaled wood dust may exert a synergistic effect.

Respiratory symptoms, immunological responses, and aeroallergen concentrations at a sawmill.

After identification of a case of extrinsic allergic alveolitis due to exposure to wood dust at a sawmill, all employees at the sawmill where he worked were studied with an occupational, environmental, and symptom questionnaire, spirometry, skin prick tests, and serum specific IgG measurements. Ninety five of current and 14 of 17 ex-sawmill workers were studied. As a basis for comparison, a group of 58 workers from a nearby light engineering factory were also studied. Few women (6) were employed and they were excluded from the analysis. Workers at the sawmill were stratified into high and low exposure groups depending on their place of work. This division was supported both by their subjective assessment of the dustiness of their environment and the results of personal dust samples. There were no significant differences between the three groups in age, height, smoking habits, exposure to other causes of extrinsic allergic alveolitis, forced expiratory volume in one second, forced vital capacity, atopic state, or cutaneous reactivity to moulds. In the high exposure group the prevalence of work related cough and nasal and eye symptoms was higher than in the low exposure and comparison groups. The prevalence of work related wheeze was similar in both the high exposure and comparison groups, but was lower in the low exposure group. The prevalences of chronic bronchitis and symptomatic bronchial hyper-reactivity were similar in the high and low exposure groups but were lower in the comparison group. Serum concentrations of specific IgG against extracts of sawdust and Trichoderma koningii were significantly higher in the high exposure group than in the other two groups. The prevalence of symptoms suggestive of extrinsic allergic alveolitis was 4.4% in the high exposure group, greater than in the low exposure group (0%), and the comparison group (1.9%). In conclusion extrinsic allergic alveolitis probably occurs in British sawmills, and among the exposed population its prevalence may be as high as that reported in Sweden. The allergen responsible is likely to be from mould growing on the wood and may be from Trichoderma koningii.

Bronchial responsiveness and the reproducibility of forced expiratory volume in one second.

Although poorly reproducible spirometric tests, "test failures," are associated with respiratory morbidity, it is not clear what causes them. Bronchial responsiveness was examined in relation to test failure for forced expiratory volume in 1 s (FEV1.0) (1979 definition of the American Thoracic Society) in 249 bakers, 165 chemical industry workers, and 204 office workers. The first two groups were studied by the same methods and were combined. Test failure was observed in 4%, and for 38% the provocative dose of inhaled methacholine causing a 20% fall in FEV1.0 relative to FEV1.0 after the inhalation of normal saline (PD20) was < or = 120 mumol (7% with a PD20 of < or = 8 mumol). Test failure was not related to the level of PD20. Of the office workers, 3% had test failure, 11% a PD20 of < or = 8 mumol of histamine, and no significant relation was observed. The study does not exclude the possibility that bronchial responsiveness might be related to test failure in patients with airway disease or that a clearer relation might be demonstrable in a larger study, but it does suggest that it is not a major determinant of test failure.

Respiratory symptoms questionnaire for asthma epidemiology: validity and reproducibility.

BACKGROUND: There is a need for a new respiratory symptoms questionnaire for use in epidemiological research in asthma. METHOD: A questionnaire was designed following a pilot study in 78 subjects. It contains nine questions on symptoms such as wheeze and difficulty with breathing in defined circumstances such as exercise and sleep. It was completed by 211 adults and validated by comparison with a self reported history of asthma and with bronchial hyperresponsiveness to histamine. Its short term reproducibility was measured by three repeat administrations over two weeks. RESULTS: Subjects with asthma (n = 33), particularly those having had an asthma attack in the last year (n = 23), were more likely to report any symptom and to report a greater number of symptoms than those without asthma. The same relationship was found for bronchial hyperresponsiveness and symptoms. Either two or more, or three or more, symptoms appeared to be good indices of self reported asthma and bronchial hyperresponsiveness, or both, with a high sensitivity (65-91%) and specificity (85-96%). Reproducibility was good, with few subjects changing the number of symptoms reported by more than one symptom and none by more than four symptoms. The results compared favourably with those from questions on phlegm production from the MRC questionnaire and were better than those reported for the MRC wheeze questions. CONCLUSIONS: The questionnaire will be useful for epidemiological research on asthma and could form part of a new standardised questionnaire with wide applications.

Surveillance and management.

Recognising the early signs of occupational asthma can prevent the onset of this debilitating disease. Consultant occupational health physician, Dr Bernard Graneek, suggests methods of surveillance and management to control its development.

Respiratory symptoms, lung function, and sensitisation to flour in a British bakery.

A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery.

Late asthmatic reactions and changes in histamine responsiveness provoked by occupational agents.

The temporal and quantitative relationship between increases in airway responsiveness and late asthmatic reactions provoked by inhalation challenge with occupational agents was studied in nine individuals who underwent a total of thirteen active inhalation challenge tests with one of the following agents: toluene diisocyanate (TDI), maleic anhydride (MA), trimellitic anhydride (TMA), carmine, or colophony (pine wood resin). Airway responsiveness to inhaled histamine (histamine PC20) was measured before and at approximately 3 and 24 h after control and active challenge exposure, when, on all but four occasions, FEV1 was within 10% of pre-challenge values. Significant increases (p less than 0.02) in histamine responsiveness were present at 3 h following challenge exposures which subsequently provoked a definite late asthmatic reaction (FEV1 decrease greater than 15% 3-11 h post challenge). These increases in histamine responsiveness were significantly greater than those at 3 h following the challenges which provoked an isolated early (FEV1 decrease less than 6% 3-11 h post-challenge) or equivocal late asthmatic reaction (FEV1 decrease 6-15% 3-11 h post-challenge) (p less than 0.03). Although histamine responsiveness remained high at 24 h after challenges provoking late asthmatic reactions (p less than 0.05), this was less than the increase at 3 h and not significantly different from the PC20 at 24 h after challenges provoking either single early or equivocal late asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

The temporal relationship between increases in airway responsiveness to histamine and late asthmatic responses induced by occupational agents.

The temporal relationship between increases in airway responsiveness and the late asthmatic response was assessed in nine patients challenged with occupational agents toluene diisocyanate (one patient), carmine (one patient), maleic anhydride (two patients), colophony (four patients), and trimellitic anhydride (one patient). The provocation concentration of histamine causing a 20% decrease in FEV1 (PC20) was measured before challenge and at approximately 3 hours and 24 hours on control and active-challenge days. Thirteen active challenges provoked eight definite late asthmatic responses (maximum fall in FEV1 greater than 15% at 3 to 11 hours). At 3 hours after the challenges that provoked late responses, there was a significant (p less than 0.02) decrease in PC20 that was more (p less than 0.03) than that observed for the five tests provoking early (late FEV1 fall 0% to 5%) or equivocal late (FEV1 fall 6% to 15%) responses. At 24 hours, PC20 remained decreased (p less than 0.05), although it was less so than at 3 hours (p less than 0.05) and not significantly when compared with challenge tests causing single early or equivocal late responses. The 3-hour decreases in PC20 were identified when FEV1 (five of seven observations) was greater than 90% of prechallenge values. For the nine independent tests, the 3-hour decreases in PC20 correlated (r = 0.72; p less than 0.05) with the magnitude of the late falls in FEV1, whereas this was not observed at 24 hours (r = 0.35; p, not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid anhydrides and asthma.

We have studied asthma caused by inhaled acid anhydrides as a model of hapten-induced airway hyperresponsiveness. Inhalation tests with the relevant anhydride in sensitised individuals reproducibly provoked a significant increase in non-specific airway responsiveness identifiable 3 h after the test and prior to the development of the late asthmatic reaction. Seven cases of asthma caused by tetrachlorophthalic anhydride (TCPA) had specific IgE in their serum to a TCPA-human serum albumin conjugate. RAST inhibition studies showed the anhydride to be involved in the antibody-combining site. Survey of the factory population where these 7 cases worked allowed investigation of the determinants of the specific IgE response: its presence was associated with intensity of exposure and current cigarette smoking; in addition smoking interacted with atopy to increase the prevalence of specific IgE. During a 5-year period of avoidance of exposure to TCPA specific IgE declined exponentially with a half-life of one year, suggesting continuing IgE secretion. Five years after avoidance of exposure, airway hyperresponsiveness remained increased in several cases.