Anthony Newman Taylor

Allergen and dust exposure as determinants of work-related symptoms and sensitization in a cohort of flour-exposed workers; a case–control analysis

OBJECTIVES To estimate the incidence of specific IgE sensitization and allergic respiratory symptoms among UK bakery and flour mill workers; and to examine the roles of flour aeroallergen and total dust exposures in determining these outcomes. METHODS A cohort of 300 new employees, without previous occupational exposure to flour, were followed prospectively for a median (range) of 40 (1-91) months. Cases-defined as those developing work-related symptoms or a positive skin prick test to flour or alpha-amylase during follow up--were compared with controls, matched for duration of employment. Exposures to flour aeroallergen and total inhalable dust were estimated using a questionnaire and personal sampling techniques. RESULTS Incidence rates for work-related eye/nose and chest symptoms were 11.8 and 4.1 cases per 100 person years (py), respectively. Fewer employees developed positive skin prick tests to flour (2.2 cases per 100 py) or alpha-amylase (2.5 cases per 100 py). Positive skin tests to occupational allergens were more common among those with new work-related symptoms. There were clear relationships between the risks of developing work-related symptoms or a positive skin prick test and three categories of estimated exposure to total dust or flour aeroallergen. Atopic employees were more likely to develop a positive skin prick test-but not work-related symptoms. These findings were unaffected by age, sex or cigarette smoking. CONCLUSIONS In this population, many work-related symptoms which develop after first employment in modern UK bakeries or flour mills were not accompanied by evidence of IgE sensitization to flour or alpha-amylase. Although average dust exposures were within current occupational standards, the risks of development of upper and lower respiratory symptoms and of specific sensitization were clearly related to total dust and/or flour aeroallergen exposure. The incidence of work-related chest symptoms in the presence of a positive skin test to flour or alpha-amylase in this setting was approximately 1 case per 100 py.

Coal mining and chronic obstructive pulmonary disease: a review of the evidence

The potential of coal mine dust to cause disabling pneumoconiosis has long been recognised, but research now suggests that pneumoconiosis is not the only respiratory hazard of coal mining. Over the last 30 years evidence has accumulated that miners also experience an excess of chronic obstructive pulmonary disease (COPD), and this has led the British Government to classify chronic bronchitis and emphysema in coal miners as an occupational disease for which industrial injuries benefit can be paid. In Germany, too, COPD in miners is now compensated as an occupational disease. However, some scientists have expressed doubts as to whether coal mine dust can cause clinically important loss of lung function in the absence of complicated pneumoconiosis.1 In view of this continuing controversy, it is helpful to review the evidence as it now stands. The epidemiological investigations that bear on the relation between coal mining and COPD are of four main types: (1) studies comparing lung function in miners and non-miners; (2) studies of the patterns of symptoms and lung function in miners according to their exposure to coal mine dust; (3) analyses of mortality from COPD in relation to coal mining; and (4) analyses of the relation between emphysema in coal miners at necropsy and their previous exposure to dust. In addition, investigations in the laboratory provide information about the toxicological mechanisms whereby coal mine dust might cause obstructive lung disease. A series of early studies by the MRC Pneumoconiosis Research Unit in South Wales found significantly lower mean levels of indirect maximum breathing capacity (IMBC) in miners and ex-miners than in non-miners of the same age.2 However, there was no clear relation between IMBC and duration of underground or face work. Moreover, in a sample of men who were examined at two surveys five years apart, the …

Outcome of occupational asthma after cessation of exposure: a systematic review

Background: Patients with occupational asthma, and their medical advisers, need valid information about the prognosis of their disease. Methods: A systematic review of the published literature on the symptomatic and functional outcomes of occupational asthma was carried out after avoidance of exposure to the causative agent. Through a full search of electronic and bibliographic sources, original studies documenting complete recovery from asthma (n = 39,1681 patients) or improvement in non-specific bronchial hyper-responsiveness (NSBHR; n = 28,695 patients) were identified. The median duration of follow-up was 31 (range 6–240) months for studies of symptomatic recovery and 37 (6–240) months for studies of NSBHR. Most studies were of patients recruited from special clinics. Results: Reported rates of symptomatic recovery varied from 0% to 100%, with a pooled estimate of 32% (95% CI 26% to 38%). These rates were lower with increasing age (p = 0.019) and among clinic based populations (p = 0.053). Patients with the shortest durations of exposure (⩽76 months) had the highest rate of recovery (36%; 95% CI 25% to 50%), but the effect was not linear. The pooled prevalence of persistent NSBHR at follow-up was 73% (95% CI 66% to 79%). This figure was higher among patients whose disease was due to high-molecular-weight agents (p = 0.006) and, less clearly, those from clinic-based populations (p = 0.561). In between-study comparisons, no clear patterns of improvement relating to total duration of exposure or follow-up were found. From within-study comparisons there was some evidence that a shorter duration of symptoms was associated with a higher rate of symptomatic recovery. Conclusion: The available data on the prognosis of occupational asthma are insufficiently consistent to allow confident advice to be given to patients with the disease. Clinicians and epidemiologists with an interest in this disease should consider a collaborative and carefully standardised study of the prognosis of occupational asthma.

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)

Cryptogenic fibrosing alveolitis and lung cancer: the BTS study

Background: The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). Methods: Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. Results: 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02). Conclusions: These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

Analysis of rat urine proteins and allergens by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting

BACKGROUND In rats, urine has been identified as a major source of the allergens that cause laboratory animal allergy, an important occupational health problem. METHODS AND RESULTS Urinary proteins and allergens of Wistar rats were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Proteins excreted by male and female rats during puberty were similar and of low molecular weight. In adulthood, moderate increases in diffuse staining of 26 and 21 kd occurred in female urine. In males the 17 kd protein increased dramatically and the 23 and 21 kd proteins moderately. The urine excretion of high-molecular-weight proteins (75 to 63 kd) increased with age in males (females not studied). Immunoblot studies with six sera showed allergens in urine of male and female rats of all ages, three of which were present in all urine (75, 68, and 21 kd). Three allergens (17, 16, and 15 kd) in female urine may be allergenically similar to the 17 kd allergen in adult male urine. Adult male urine allergens were studied further with sera from 83 rat-hypersensitive subjects. Major allergens were identified at 23, 21, and 17 kd, and all sera had IgE to one or more of these proteins. Twenty-seven percent had IgE to 68 and 63 kd allergens. Minor allergens were identified at 75, 51, and 44 kd. CONCLUSIONS Rat urine is an important source of the major allergens associated with rat hypersensitivity. Age and sex markedly influence the protein and allergenic constituents of rat urine.

Distinctive patterns of static and dynamic gamma motor activity during locomotion in the decerebrate cat

1 Simultaneous recordings were made from gamma (γ) motor axons and from muscle spindle afferents of the medial gastrocnemius (MG) muscle during locomotion in decerebrate cats. The γ‐neurons were identified as static or dynamic (γs or γd) by correlating their behaviour during midbrain stimulation with changes in muscle spindle afferent responses to muscle stretch. 2 On the basis of their behaviour during locomotion, γs neurons could be divided into two groups. One group (type‐1) showed strongly and smoothly modulated discharge increasing in parallel with the active muscle shortening in ankle extension, but with phase advance. The other group (type‐2) also showed a modulated pattern, but with increased firing centred on the flexion phase. The proportions of the two were 13 type‐1 and 7 type‐2. 3 The type‐1 firing pattern accurately predicted the difference in firing frequency for secondary afferents obtained by subtracting from the recordings made during active movements the response of the same units to the movements repeated passively in the absence of fusimotor activity. 4 The type‐2 pattern also became consistent with the difference signal, when operated on by a phase lag appropriate to the effects of bag2 intrafusal fibres. These results suggest that there may be some degree of separate control of chain and bag2 intrafusal fibres. 5 The discharge of γd axons was also found to fluctuate with the locomotor cycle, with a pattern very distinct from that of the γs records. The γd firing frequency rose very suddenly from zero to a maximum at the onset of muscle shortening and continued into the beginning of lengthening. The term ‘interrupted’ discharge is suggested as a useful description. The timing of this discharge was shown to be appropriate for sensitising the primary afferents to detect the onset of stretch.

Recorded infections and antibiotics in early life: associations with allergy in UK children and their parents.

Background: It is suggested that the inverse relationship between allergic disease and family size reflects reduced exposure to early life infections, and that antibiotic treatment in childhood diminishes any protective effect of such infection. Methods: A birth cohort study was undertaken in 642 children recruited before birth and seen annually until the age of 8 years. Reported infections and prescribed antibiotics by the age of 5 years were counted from GP records and comparisons were made with a previous study of their parents. Results: At the age of 8 years, 104 children (19%) were atopic, 79 (13%) were currently wheezy and 124 (21%) had seasonal rhinitis. 577 children (97%) had at least three infections recorded by age 5, a figure much higher than that of their parents (69%). By the age of 5 only 11 children (2%) had never received a prescription for antibiotics; the corresponding figure for the parents was 24%. Higher numbers of infections were recorded for firstborn children. After adjusting for parental atopy and birth order, there was no association between infection counts and atopy (OR 1.01 (95% CI 0.99 to 1.03) per infection). Significant positive associations were found for wheeze and seasonal rhinitis. An increased risk of current wheeze was found for each antibiotic prescription (adjusted OR 1.07 (95% CI 1.03 to 1.10)) but not for atopy. This was primarily explained by prescriptions for respiratory infections. Similar patterns were observed for seasonal rhinitis. Conclusions: Despite very high rates of recorded early life infections and antibiotic prescriptions, no plausibly causative relationships were found with subsequent respiratory allergies.

Patterns of fusimotor activity during locomotion in the decerebrate cat deduced from recordings from hindlimb muscle spindles.

Recordings have been made from multiple single muscle spindle afferents from medial gastrocnemius (MG) and tibialis anterior (TA) muscles of one hindlimb in decerebrate cats, together with ankle rotation and EMG signals, during treadmill locomotion. Whilst the other three limbs walked freely, the experimental limb was denervated except for the nerves to MG and TA and secured so that it could rotate only at the ankle joint, without any external load. Each afferent was characterised by succinylcholine testing with regard to its intrafusal fibre contacts. Active movements were recorded and then replayed through a servo mechanism to reproduce the muscle length changes passively after using a barbiturate to suppress γ‐motor firing. The difference in secondary afferent firing obtained by subtracting the discharge during passive movements from that during active movements was taken to represent the profile of static fusimotor activity. This indicated an increase before the onset of movement followed by a strongly modulated discharge in parallel with muscle shortening during locomotion. The pattern of static firing matched the pattern of unloaded muscle shortening very closely in the case of TA and with some phase advance in the case of MG. The same effects were observed in primary afferents. Primary afferents with bag1 (b1) contacts in addition showed higher firing frequencies during muscle lengthening in active than in passive movements. This indicated increased dynamic fusimotor firing during active locomotion. There was no evidence as to whether this fluctuated during the movement cycles. When the mean active minus passive difference profile of firing in bag2‐chain (b2c) type primary afferents was subtracted from that for b1b2c afferents, the difference was dominated by a peak centred on the moment of maximum lengthening velocity (v). The component of the active minus passive difference firing due to b1 fibre contacts could be modelled by f(t)=av (where a is a constant) during lengthening and by f(t)= 0.2av during shortening. The remainder of the difference signal matched the predictions of the static fusimotor signal derived from secondary afferents. The findings are discussed in relation to the concept that the modulated static fusimotor pattern may represent a ‘temporal template’ of the expected movement, though the relationship of the results to locomotion in the intact animal will require further investigation. The analysis of the data indicates that the combined action of muscle length changes and static and dynamic fusimotor activity to determine primary afferent firing can be understood in terms of the interaction between the b1 and b2c impulse initiation sites.

Static and dynamic γ-motor output to ankle flexor muscles during locomotion in the decerebrate cat

In locomotion, the flexor muscles of the leg are mainly concerned with the relatively constant task of raising the foot, whereas the extensors have the more variable task of support and propulsion at different speeds. This suggests that the way in which the fusimotor system works may differ between the two muscle groups. Observations previously made of the static and dynamic γ‐motor firing patterns in the ankle extensor medial gastrocnemius (MG) have therefore been repeated in the flexor tibialis anterior (TA). One or more single γ‐motor axons, dissected from a small filament of TA nerve, were recorded simultaneously with a number of single spindle afferents in dorsal rootlets. Cats were decerebrated and locomoted spontaneously on a treadmill. Identification of each γ‐motor axon depended on relating the changes in firing caused by midbrain stimulation to the changes in static and dynamic behaviour of the spindle afferents in response to repetitive ramp and hold stretches. Static γ axons all showed a smooth modulation in frequency, increasing in phase with muscle shortening, superimposed on a minimum frequency of about 20–30 impulses s−1. Dynamic γ axons showed interrupted firing with the frequency rising abruptly from zero at the onset of shortening, and falling again to zero shortly after the onset of lengthening. The frequency during the active periods was relatively constant, even when movement amplitudes varied. The basic similarity in the static and dynamic gamma discharge patterns for the two muscles suggests that the strategy of γ‐motor control is common to both flexors and extensors. The static γ pattern is thought to be a ‘temporal template’ of the expected movement, effectively expanding the dynamic response range of the spindles in active movements. The dynamic γ pattern sensitizes the primary afferents to detect the onset of muscle lengthening and to detect departures from the intended movement trajectory.