Bronchial Challenge tests
Data are available from studies that conducted bronchial challenge tests with gaseous formaldehyde on workers with asthmatic symptoms, to determine whether the observed asthma was attributable to this chemical. Single and/or double blind bronchial challenge tests conducted in 13 workers exposed to formaldehyde for up to 9 years (Frigas et al., 1984), and a single worker who had not been exposed to formaldehyde for 3 years (Grammer et al., 1993), were negative. In the Frigas et al. (1984) study, no reaction to bronchial challenge with formaldehyde was seen in a worker who had hyperresponsive airways (i.e. positive bronchial challenge to methacholine).
Positive bronchial challenges to formaldehyde have been observed in workers with asthmatic symptoms. Over a 6-year period, 12 of 230 patients referred to a clinic and had reportedly been exposed to formaldehyde gave positive bronchial challenge tests to formaldehyde (Nordman et al., 1985). Only one of these 12 tests was conducted in a blind manner. Furthermore, 9 of the 12 responders had hyperresponsive airways as shown by positive bronchial challenge tests to histamine or methacholine.
A positive bronchial challenge to formaldehyde was observed in a recent study in a single worker who had hyperresponsive airways (positive bronchial challenge to methacholine) and was exposed to several chemical agents whose exact components were unknown but did include formaldehyde (Kim et al., 2001). Similarly, though 7 of 15 workers (47%) gave positive responses to formaldehyde in open bronchial challenge tests (Burge et al., 1985), bronchial hyperresponsiveness was observed in 2 responders and 1 non-responsive subject. Additionally, co-exposure to other chemicals including isocyanates and hardwood dust had occurred in 12 workers, of which 3 had given a positive challenge to formaldehyde.
A study was conducted with three nurses, a technician and a visitor to a dialysis unit who were all regularly exposed to formaldehyde and had developed asthmatic symptoms (Hendrick & Lane, 1975, 1977). Positive bronchial challenges to formaldehyde were seen in 2 of the nurses, one of whom had pre- existing asthma. In a follow up study on these two nurses 2 years later, a positive bronchial challenge to formaldehyde was only observed in the nurse with pre- existing asthma (Henderick et al., 1982).
Open bronchial challenge tests to formaldehyde were conducted in 7 staff from an endoscopy unit and x-ray department who had asthmatic symptoms associated with glutaraldehyde exposure (Gannon et al., 1995). Positive responses were seen in 3 workers, which included the only 2 individuals with co-exposure to formaldehyde. This result suggests possible cross-reactivity between formaldehyde and glutaraldehyde.
Data are also available for healthy workers and volunteers. Negative bronchial challenge tests were observed in 15 healthy workers exposed to formaldehyde for between 1 to 21 years (Schachter et al., 1985). Bronchial challenges with formaldehyde in healthy volunteers were also negative (Sauder et al., 1986).
Additionally, negative bronchial challenges were seen in 9 people who complained of adverse health effects from the urea formaldehyde foam insulation used in their homes (Day et al., 1984), and in asthmatic subjects with hyperresponsive airways (Sheppard, 1984; Harving et al., 1990) and those without hyperresponsive airways (Witek et al., 1987).
Studies focusing on the clinical diagnosis of asthma in patients, where no bronchial challenge test was performed to identify the agent responsible, are also available.
In studies determining the effect on lung function following workplace exposure to gaseous formaldehyde, no change in lung function was seen in a pathologist who suffered chest tightness (Kwong et al., 1983). Comparison of formaldehyde- exposed workers (with or without symptoms) with those not exposed revealed no changes in lung function in one study (Nunn et al., 1990), and a slight decrease over shift in another (Alexandersson et al., 1982). Decreased lung function was seen in a further study in (mostly) symptomatic workers compared to unexposed controls, though no changes in parameters were seen over a working day, week or weekend (Schoenberg & Mitchell, 1975).
Epidemiology studies
In a Swedish population-based case-control study of 20 000 subjects, 15 813 (aged 21 - 51 years) responded to a mailed questionnaire on occupational exposure, asthma, respiratory symptoms, smoking and atopy (Toren et al., 1999). A total of 362 subjects with physician diagnosed asthma or self-reported asthma- like symptoms were compared against a total of 2044 controls. Occupational exposure to gaseous formaldehyde (information on exposure levels not obtained) was not associated with an increased risk of asthma.
An Australian case-control study investigated the increased risk of asthma in children from exposure to gaseous formaldehyde in 80 households (Garrett et al., 1999). A total of 148 children aged 7 - 14 were investigated, of which 53 (36%) were diagnosed as asthmatic by a doctor. Information was obtained from parental interviews on parental allergy, parental asthma and presence of pets. Household formaldehyde levels were determined by passive sampling; mean of 12.6 ppb
(15.1 g/m3), with a maximum of 111 ppb (133 g/m3). After adjustment for
confounding factors, such as parental asthma, no association was seen between asthma and formaldehyde exposure. However, there was a weak, but not statistically significant, trend to more children with respiratory symptoms in higher formaldehyde exposure groups. In a further Australian case-control study (Rumchev et al., 2002), household formaldehyde levels were determined by passive sampling in the homes of 88 children aged 6 months to 3 years who were diagnosed at hospital with asthma, and compared with 104 community controls. Cases had a statistically significant higher mean formaldehyde exposure compared to controls, 32 ppb (38 g/m3) and 20 ppb (24 g/m3), respectively.
After adjustment for confounding factors, such as indoor air pollutants, relative humidity, indoor temperature, atopy, family history of asthma, age, sex socio- economic status, pets and environmental tobacco smoke, it was reported that children exposed to formaldehyde levels of 60 g/m3 have a 39% increase in odds of having asthma compared to children exposed to < 10 g/m3 (OR estimated to be approximately 1.4 95% CI 1.1-1.7 from data presented in a graph). However, considering the marginally increased risk observed, together with the number of potential sources of bias, such as selection bias and validity of diagnosis in the young, this study is not considered to provide sufficiently robust evidence of an association between formaldehyde exposure and increased risk of asthma in children.
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