Formaldehyde and asthma: a plausibility?

Formaldehyde (FA) is a ubiquitous indoor air pollutant emitted from construction, consumer, and combustion-related products, and ozone-initiated reactions with reactive organic volatiles. The derivation of an indoor air quality guideline for FA by World Health Organization in 2010 did not find convincing evidence for bronchoconstriction-related reactions as detrimental lung function. Causal relationship between FA and asthma has since been advocated in meta-analyses of selected observational studies. In this review, findings from controlled human and animal exposure studies of the airways, data of FA retention in the respiratory tract, and observational studies of reported asthma applied in meta-analyses are analyzed together for coherence of direct association between FA and asthma. New information from both human and animal exposure studies are evaluated together with existing literature and assessed across findings from observational studies and associated meta-analyses thereof. Retention of FA in the upper airways is > 90% in agreement with mice exposure studies that only extreme FA concentrations can surpass trachea, travel to the lower airways, and cause mild bronchoconstriction. However, taken together, detrimental lung function effects in controlled human exposure studies have not been observed, even at FA concentrations up 4 ppm (5 mg/m), and in agreement with controlled mice exposure studies. Typical indoor FA concentrations in public buildings and homes are far below a threshold for sensory irritation in the upper airways, based on controlled human exposure studies, to induce sensory-irritative sensitization nor inflammatory epithelial damage in the airways. Analysis of the observational heterogeneous studies applied in the meta-analyses suffers from several concomitant multifactorial co-exposures, which invalidates a direct association with asthma, thus the outcome of meta-analyses. The evidence of a direct causal relationship between FA and asthma is insufficient from an experimental viewpoint that includes retention data in the upper airways and controlled animal and human exposure studies. Taken together, a coherence of controlled experimental findings with individual observational studies and associated meta-analyses, which suffer from caveats, is absent. Further, lack of identified evidence of FA-IgE sensitization in both experimental studies and observational studies agrees with indoor FA concentrations far below threshold for sensory irritation. The assessment of experimental data with uncontrolled observational studies in meta-analyses is incompatible with a direct causal relationship between FA and asthma or exacerbation thereof due to lack of coherence and plausibility.