What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study.

BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF, MUC5B rs35705950, is unknown. METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs35705950 was investigated using a genetic dominant model. RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs35705950. CONCLUSION: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of MUC5B rs35705950. TRIAL REGISTRATION NUMBER: NCT03211507.

Chronic Obstructive Pulmonary Disease and Breathlessness in Older Workers Predict Economic Inactivity. A Prospective Cohort Study.

Rationale: There is an aspiration to retain increasing numbers of older workers in employment, and strategies to achieve this need to make provision for the increasing prevalence of chronic diseases with age. There is a consistent body of cross-sectional evidence that suggests that patients with chronic obstructive pulmonary disease are more likely to have adverse employment outcomes.Objectives: We report the findings of the first longitudinal study of this issue.Methods: We recruited full-time employed men and women in their 50s and followed them for a period of 18 months; we examined, after adjustment for potential confounders, the associations between breathlessness and airway obstruction at baseline and loss of employment in the intervening period.Measurements and Main Results: Among participants responding to the follow-up questionnaire (1,656 of 1,773 [93%]), the majority (78.5%) continued in full-time employment, but 10.6% were in part-time employment and 10.9% were no longer in paid employment. The adjusted risk of loss of employment was significantly increased for those with moderate or severe chronic obstructive pulmonary disease (risk ratio, 2.89; 95% confidence interval, 1.80-4.65) or breathlessness (risk ratio, 3.07; 95% confidence interval, 2.16-4.37) at baseline. There was no evident modification by sex or by manual/nonmanual work.Conclusions: Airway obstruction and breathlessness are independently associated with premature loss from the workforce in older workers; these observations provide strong support to the available cross-sectional evidence and suggest that interventions to help those with chronic obstructive pulmonary disease who wish to remain in work need to be tested.

Obliterative bronchiolitis in fibreglass workers: a new occupational disease?

RATIONALE AND OBJECTIVES: Obliterative bronchiolitis (OB) is a rare disease with a small number of established occupational aetiologies. We describe a case series of severe OB in workers making glass-reinforced plastics. METHODS: Workplace exposures were the likely cause after the independent diagnosis of OB in two workers laying up the fibreglass hulls of yachts; the second worker took over the job of the first after he left following a lung transplant. Presentation of these two cases at international meetings led to others identifying similar workers. MAIN RESULTS: We identified six workers with good evidence of OB. All were involved in preparing fibreglass with styrene resins, five as boat builders laying up fibreglass hulls and one during cooling-tower fabrication. The disease came on rapidly without unusual acute exposures. Two patients had lung transplants, while another died while waiting for one. Histology confirmed OB in the four with biopsies/post-mortem examinations or explanted lungs. CONCLUSIONS: A rare, potentially fatal disease occurring in six workers laying up fibreglass with styrene resins from five different worksites suggests that work exposures were the cause of their OB. The precise agent responsible awaits identification.

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 (< or =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.

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.

Early-life allergen exposure and atopy, asthma, and wheeze up to 6 years of age.

RATIONALE: Although it is widely assumed that the incidence of childhood respiratory allergies to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups. OBJECTIVES: To assess, in a prospective manner and in a general population, the role of early life exposures to Der p1 and Fel d1 on the inception of sensitization and asthma. METHODS: Pregnant women and their children were recruited for the Asthma Multicentre Infant Cohort Study. Overall, 1,611 newborns were initially enrolled in three cohorts in the United Kingdom and Spain. Der p1 and Fel d1 allergens were measured in household dust samples at 3 months of age for 1,474 (91.5%) participants, and skin prick tests were performed at 6 years of age on 1,182 (80.2%) participants. Wheeze and diagnosed asthma were reported in yearly questionnaires. MEASUREMENTS AND MAIN RESULTS: Exposure to Der p1 early in life was not related to a positive specific prick test or to asthma or persistent wheeze at 6 years of age. Fel d1 showed an association with all these outcomes (third vs. first tertile; odds ratio, 4.43 for positive specific prick test and 2.6 for diagnosed asthma). CONCLUSIONS: Dose-response relationships between allergen exposure and sensitization or asthma may be allergen specific and nonlinear; a minimum threshold level is needed to induce sensitization, but no dose-response relationship exists above this level. The effect of a particular allergen seems to be similar on atopy and asthma inception.

Asbestos-induced and smoking-related disease: apportioning pulmonary function deficit by using thin-section CT.

PURPOSE: To retrospectively correlate the extent of individual diseases seen at thin-section computed tomography (CT) with pulmonary function in an initial group of patients with asbestos-related parenchymal disease (asbestosis) and to test these findings in a subsequent group of patients whose CT scans were retrospectively identified. MATERIALS AND METHODS: This retrospective study had Institutional Review Board approval; informed consent was not required. The study included 133 individuals who had been exposed to asbestos. In the initial study group (81 patients; 79 men, two women; median age, 67 years), two observers used a CT scoring system to quantify the extent of pulmonary fibrosis, diffuse pleural thickening, small-airways disease, and emphysema. Multivariate equations were formulated by using independent CT variables to predict changes in total lung capacity (TLC) and carbon monoxide diffusing capacity (Dlco). The validity of these equations was then tested in a subsequent group of patients (52 patients; all men; median age, 60 years). RESULTS: At thin-section CT, the extent of asbestos-induced pleuropulmonary disease and emphysema correlated significantly with physiologic impairment (P<.001). Combined CT variables predicted 58% and 57% of the variability in TLC and Dlco, respectively, despite considerable variation in the proportion of coexisting pathologic conditions. When predictive equations with CT variables derived from the initial study group were applied to the subsequent study group, predicted TLC (rho=0.75, P<.001) and Dlco (rho=0.64, P<.001) correlated strongly with measured values. CONCLUSION: The proposed CT system provides a semiquantitative method for assessing the relative contribution of asbestos-induced pleuropulmonary disease and smoking-related emphysema to functional impairment.

Asthma: environmental and occupational factors.

Asthma is in several ways a difficult disease to study. Generally arising in childhood, its pattern is often one of remission and relapse; at any point there are difficulties in translating its characteristic, clinical features into an operational definition. Geographical and temporal patterns in its distribution - whereby the disease appears to have increased in frequency in more 'westernised' countries -suggest strong environmental determinants in its causation although there are, too, undoubted and important genetic influences on both its incidence and presentation. Recent aetiological research has concentrated on the function of allergen exposure or on the role of early-life microbial contact that may regulate the development of a range of childhood allergies, including asthma. To date the 'hygiene hypothesis' offers the most efficient explanation for the distribution of the disease in time and place although convincing evidence for it remains elusive.