Rebecca Bascom

Environmental factors and respiratory hyper sensitivity: the Americas

Diverse environmental exposure profiles exist in the Americas because of widely different climates, ambient pollutants, and bioaerosols in these continents. This paper reviews selected studies from the Americas that support the broad hypothesis that environmental factors contribute to respiratory hypersensitivity. Processes influenced by environmental factors include primary immunologic sensitization, the development and exacerbation of specific immunologic diseases and the activation of nonspecific mechanisms with tissue inflammation, injury and remodeling. Endpoints resulting from these processes include respiratory symptoms, diseases such as asthma, with measures of disease severity including medication use and hospitalization rates, and death due to cardiorespiratory disease. Studies associate sensitization rates to specific allergens with environmental factors such as humidity and indices of allergen exposure. Regional variation occurs with exposure to outdoor source pollutants such as ozone, but varies by household to bioaerosols such as dust mite, cat or cockroach allergen. Indoor allergens are associated with asthma while outdoor allergens are associated with allergic rhinitis. In a national survey, the atopic sensitization rate in the USA increased with urban residence (defined as towns of population > 2500) and varied by region. Controlled human challenge studies show that ozone increases the response of allergic subjects to allergen. Increased ambient photochemical pollution concentrations, of which ozone is an important component, are associated with increased emergency room visits for asthma in cities such as Toronto, New York, Atlanta, and Mexico City. In Sao Paolo, Brazil, mortality due to childhood respiratory disease was influenced by the ambient levels of NO2. Epidemiologic studies including the recent meta-analysis of a large, longitudinal study population associate ambient concentrations of particulate matter < 10 microns and respiratory symptoms, disease severity and increased cardiorespiratory deaths. Toxicology studies show that individual variation in responsiveness is important in nonspecific inflammatory responses to irritant pollutants such as ozone and environmental tobacco smoke. These studies indicate that environmental factors influence primary allergen sensitization, secondary allergic responses, the activation of nonspecific inflammatory responses, and the severity of respiratory diseases, including asthma.

Tobacco Smoke Upper Respiratory Response Relationships in Healthy Nonsmokers

This study determined exposure-response relationships to side-stream tobacco smoke (2 hrs; 0, 1, 5, and 15 ppm CO) in 29 healthy nonsmoking young adults. Sixteen subjects had no history of environmental tobacco smoke rhinitis (ETS-NS) while 13 subjects had a history of ETS rhinitis (ETS-S). Eye irritation and odor perception showed a statistically significant exposure response in both groups; headache was significant in ETS-S and nose irritation was significant in ETS-NS subjects. Significant postexposure (P1) symptoms were first reported at 1 ppm CO among both groups, but in 3/9 symptoms were significantly greater at this exposure level in ETS-S subjects. Nasal congestion, rhinorrhea, and cough increased significantly at 15 ppm CO only. In ETS-S subjects, nasal volume decreased and nasal resistance increased in an exposure-response fashion. ETS-NS subjects had a qualitatively different shape to the exposure-response curve; significant dimensional reductions in mid- and posterior nasal volume occurred with exposure at 1 ppm CO but not at 5 ppm CO and reductions in posterior nasal volume occurred at 15 ppm CO exposure. These studies indicate subjective and objective response relationships with exposure to sidestream tobacco smoke at concentrations from 1 to 15 ppm CO. Some differences are noted among the two subject groups in the magnitude of some symptoms at the lowest exposure level and in the qualitative shape of the acoustic rhinometry and nasal resistance exposure-response curves.

Multiple Chemical Sensitivity: A Respiratory Disorder?

Features of multiple chemical sensitivity point to the respiratory mucosa as both a possible target and an effector organ. Exposures associated with the onset of the condition are frequently airborne, as are exposures that subsequently trigger symptoms. Multiple chemicals are, therefore, likely to have encountered the respiratory mucosa. In this discussion, the term exposures refers to a patients perceived contact with a chemical, without an implied quantitative exposure level (e.g .. the one-tenth of the threshold limit value used by industrial hygienists). A patients perception of exposure may occur either with the detection of an odor or with a sensation of respiratory mucosal irritation. Exposures that trigger symptoms involve diverse chemical structures, making a specific immune response an unlikely mechanism for augmented responsiveness. However, most of these chemicals can probably stimulate the c-fiber neurons, a non-specific response pathway (Nielsen, 1991).

EVALUATION OF ACOUSTIC RHINOMETRY AND POSTERIOR RHINOMANOMETRY AS TOOLS FOR INHALATION CHALLENGE STUDIES

Objective measures of upper respiratory function are needed to understand the effects of inhaled toxicants on the nasal passages. Acoustic rhinometry (AR) is a simple new technique that determines nasal volume by measuring the cross-sectional area of the upper airway as a function of the distance along the nasal passage. This study compares acoustic rhinometry with the more traditional posterior rhinomanometry (NAR) and correlates these objective measures with the symptom of nasal congestion. Healthy young adults (n = 29) were studied on 4 days, each separated by at least 1 wk, in a climate-controlled environmental chamber for 6 h, with exposure to clean air or sidestream tobacco smoke (SS) (2 h, 1, 5, and 15 ppm CO). The coefficient of variation for single measurements was 8-15% (AR) and 4% (NAR); for across-day measurements it was 15-25% (AR) and 13-15% (NAR); and for between days it was 19-27% AR and 17-21% (NAR). These coefficients were similar in subjects with a history of environmental tobacco smoke sensitivity (ETS-S) and those with no history of ETS sensitivity (ETS-NS). At baseline, the perception of unilateral nasal congestion was significantly correlated with unilateral nasal dimensions or nasal resistance; the symptom of baseline bilateral nasal congestion (estimated for both nasal passages simultaneously) correlated less well with objective measures of nasal patency. Under challenge conditions (SS at 1-15 ppm CO), there were typically significant correlations between changes in unilateral congestion and both unilateral rhinomanometry and acoustic rhinometry, but correlations of bilateral congestion and measurable dimensions were much lower. ETS-S and ETS-NS subjects differed in correlations between bilateral subjective and objective measures: ETS-S subjects showed significant correlation between baseline congestion and NAR; in contrast, ETS-NS subjects showed significant correlation between baseline congestion and acoustic rhinometry. These results indicate that NAR and AR are complementary tests for use in inhalation challenge studies and have different correlations with nasal congestion under baseline and challenge conditions.

Acute pulmonary response in healthy, nonsmoking adults to inhalation of formaldehyde and carbon.

Formaldehyde (HCHO) is a common chemical found in occupational and residential environments and has been suggested as a cause of asthmalike symptoms in some individuals. Clinical and animal studies suggest that HCHO adsorbed on respirable particles may elicit a greater pulmonary physiologic and inflammatory effect than gaseous HCHO alone. The purpose of this study was to determine if respirable carbon particles have a synergistic effect on the acute symptomatic and pulmonary physiologic response to HCHO inhalation. We randomly exposed 24 normal, nonsmoking, methacholine-nonreactive subjects to 2 h each of clean air, 3 ppm formaldehyde, 0.5 mg/m3 respirable activated carbon aerosol, and the combination of 3 ppm formaldehyde plus activated carbon aerosol. The subjects engaged in intermittent heavy bicycle exercise (VE = 57 l/min) for 15 min each half hour. Measures of response included symptom questionnaires, spirometry, body plethysmography, and postexposure serial peak flows. Formaldehyde exposure was associated with significant increases in reported eye irritation, nasal irritation, throat irritation, headache, chest discomfort, and odor. We observed synergistic increases in cough, but not in other irritant respiratory tract symptoms, with inhalation of formaldehyde and carbon. Small (less than 5%) synergistic decreases in FVC and FEV3 were also seen. We observed no HCHO effect on FEV1; however, we did observe small (less than 10%) significant decreases in FEF25-75% and SGaw which may be indicative of increased airway tone. Overall, our results demonstrated synergism, but the effect is small and its clinical significance is uncertain.

Differential Responsiveness to Irritant Mixtures: Possible Mechanisms

All people encounter low-level irritant mixtures in their daily lives.’ These mixtures include combustion products, gasoline fumes, perfumes or colognes, cleaning materials, environmental tobacco smoke, paints, and new furnishings. People’s responses to these encounters differ greatly, however. For some, these exposures pass unnoticed. For many, the exposures are recognized, but cause no symptoms. For some, the exposures are unpleasant (but only mildly), alter their health (but only temporarily), and may be avoided if it is convenient to do so. For still others, encounters with the mixtures become major life events.’ The exposures are uncomfortable, alter perceived health markedly, and must be avoided to maintain a sense of good health. This latter group provokes sharp debate among physicians, in part because traditional measures of disease may or may not readily demonstrate objective evidence of pathology for some or all of the symptom^.^ Exposure to irritants may result in chronic respiratory health effects, and differential susceptibility exists to illnesses resulting from chronic exposure to irritant mixtures. The best known example is tobacco smoke, in which a minority of exposed individuals (smokers) develop lung cancer or chronic obstructive airways Exposure, at lower levels, to environmental tobacco smoke is also associated with a range of health hazards6 including increased respiratory symptoms, respiratory illness and decreased lung function in ~ h i l d r e n , ~ . ~ and increased airflow limitation in a d u l t ~ . ~ There is a need to understand the fundamental process of irritation, so that the health risks of irritation may be weighed. There is also a need to understand differential responsiveness to low-level irritant mixtures. Finally, there is a need to understand the relationship between acute responsiveness to an irritant and the risk of chronic disease. The debates among physicians, patients, disability claims examiners, employers, advocacy groups, attorneys, manufacturers, and public health officials underscore these needs. It is interesting to note that countries and organizations differ in how they use the symptom of irritation in setting occupational or environmental standards. Swedish investigators Berglund and Lindvall recommend that “priority should be given to the protection of the sensitive part of the occupant population” in a building, and that “sensory irritants should never exceed the 10th percentile for detection.”I0 They point out that the American Conference of Governmental and Industrial Hygienists,

A Portable Air Cleaner Partially Reduces the Upper Respiratory Response to Sidestream Tobacco Smoke

Abstract Environmental tobacco smoke (ETS) is a common indoor pollutant which often causes acute upper respiratory tract symptoms and measurable nasal congestion. This study evaluated the effect of a room air cleaner on the response to sidestream tobacco smoke (SS) in 12 healthy, nonsmoking adults with previously documented subjective and objective upper respiratory congestive responses to SS. Each subject served as his or her own control and was exposed in a climate-controlled chamber on 2 days, each separated by at least 2 weeks, to SS (15 ppm carbon monoxide, 2 hours, at rest) in the presence of a functioning (AC) or sham room air cleaner. Subjects recorded symptoms and underwent posterior rhinomanometry and acoustic rhinometry. The AC significantly reduced the concentration of particles, total organic vapors, and nicotine, but not carbon monoxide. The AC reduced symptoms of headache [1.4 ± 0.3 sham (net postexposure) versus 0.5 ± 0.2 AC, p < 0.001, analysis of variance] and rhinorrhea (1.8 ± 0.4 sham ...

Differential susceptibility to inhaled pollutants: effects of demographics and diseases.

Inhaled pollutants and respiratory disease deserve particular attention at a conference focused on susceptibility and environmental risk. Inhaled air contains diverse biological, physical and chemical stressors which may cause upper and lower respiratory inflammation and exacerbate complex polygenic disorders such as asthma and sinusitis. This paper focuses on intrinsic susceptibility factors of demographics and diseases as well as genetic background. The National Health Information Survey shows that acute and chronic respiratory conditions are common at all ages, but their incidence and prevalence vary between age groups. Susceptibility is therefore not a fixed characteristic, but the aggregate effect of changing intrinsic factors such as age and disease. While ethnicity is often cited as a risk factor for disease prevalence or severity, recent research shows that measurable factors such as nasal ellipticity determine exposure-dose relationships, while the imperfect surrogate of ethnicity does not. Studies also show that exposure-dose relationships can be modified by recent exposures, and additional information is clearly needed in this area. We propose that evidence for the genetic contribution to pollutant susceptibility be sought in inter-individual variation in responses of homogenous, well characterized individuals to short term controlled pollutant exposure. Future improvements in risk assessment models will be based on a precise identification of factors that determine exposure-dose relationships, and a mechanistic understanding of the reasons that a demographic factor or disease appears to confer altered susceptibility.