The fifty percent male excess of infant respiratory mortality.

AIM: To test whether infant mortality from clearly respiratory causes has a consistent male excess that is different from the male excess in most cardiac conditions. METHODS: Analysis of male excess in infant mortality data from the United States and from north European countries. Data are analyzed for the period 1979-2002 in autopsied and unautopsied cohorts. RESULTS: Several modes of respiratory death in infancy are characterized by an approximate 50% male excess. This common excess is demonstrated in vital statistics for infant respiratory distress syndrome, sudden infant death syndrome, inhalation of food and other objects causing obstruction of respiratory tract or suffocation, congenital pneumonia, viral pneumonia, bronchiolitis and bronchitis, and accidental drowning. Results are presented for these and other respiratory causes of mortality in all United States infant deaths from 1979-1998 and for sudden infant death syndrome from the United Kingdom and Scandinavia. In sudden infant death syndrome, the common male excess appears to exist only for the autopsied post-neonatal cases. Comparisons are made to the male excess mortality from congenital cardiac anomalies showing a similarly large male excess for those conditions resulting in severe hypoxic and ischemic hypoxia. CONCLUSION: Because these respiratory disease conditions are quite different, it is proposed that their common approximately 50% male excess implies a common terminal hypoxic condition and mechanism of death reached via the different pathways. We hypothesize that an unknown X-linkage may be responsible for this consistent male excess in infant mortality.

Sudden unexpected infant deaths in Dundee, 1882-1891: overlying or SIDS?

Using a cohort study of all deaths in infants under 12 months in Dundee born between 1882-91 we set out to compare the aetiology of sudden unexpected infant deaths in Dundee at the end of the 19th Century with the aetiology of present day Sudden Infant Death Syndrome (SIDS). During 1882-1891, 361 infants died suddenly and unexpectedly and without obvious cause while in bed with their parents. The sex ratio of deaths was even (0.51 male) whereas the typical male fraction of SIDS today is 0.61. The mean age at death was almost two and one-half weeks younger in the Dundee cohort than for SIDS in modern Scotland. The infants in the Dundee cohort were discovered more frequently early in the morning than is typical. Their social class distribution was different in that no overlying cases were found in the higher classes whereas SIDS affects all classes. The overlying rate for illegitimate infants was lower than that reported for SIDS today. The epidemiological characteristics of the Dundee cohort and of those dying from present day SIDS differ considerably. The Dundee cohort apparently died from overlying rather than from SIDS as it is classified today. Present day advice that co-sleeping is safe should be given more cautiously until the safety of co-sleeping is resolved. It might be prudent to inform parents that co-sleeping is a risk factor for SIDS and that it should therefore be avoided.

Carbon monoxide as a tracer for assessing exposures to particulate matter in wood and gas cookstove households of highland Guatemala.

Kitchen-area 22-h gravimetric PM2.5 and passive diffusion stain-tube carbon monoxide (CO) concentrations were measured in homes with open fire and improved wood cookstoves in two studies. In the first study (Guat-2), which also studied homes with gas cookstoves, three samples were collected per stove condition from each of three test houses. In the second study (Guat-3), one sample was collected per house from 15 open fire and 25 improved-stove houses. CO personal samples were also taken for mother and child in both studies. Spearman correlation coefficients (R) between kitchen-area CO and PM2.5 levels in homes using open fires or impoved wood cookstoves were high ranging from 0.92 (Guat-2) to 0.94 (Guat-3), as were those between the personal samples for mother and child ranging from 0.85 (Guat-3) to 0.96 (Guat-2). In general, the correlations were lower for less-polluted conditions. The study found that CO is a good proxy for PM2.5 in homes using open fires or planchas (improved wood cookstove with chimney) but not under gas stove use conditions. It also determined that mother personal CO is a good proxy for child's (under 2 years of age) personal CO and that area CO measurements are not strongly representative of personal CO measurements. These results generally support the use of Draeger CO passive diffusion tubes as a proxy for PM2.5 in such cases where a single type of emission source is the predominant source for CO and PM2.5.

A procedure for use in estimating human exposure to particulate matter of ambient origin.

Modern epidemiology has shown that fluctuations of mortality data are statistically significantly correlated with fluctuations of ambient particulate matter (PM) concentration data. This relation cannot be confounded by exposure to PM of indoor origin because the concentrations of ambient PM are not correlated with concentrations of PM of indoor origin. It has been suggested, given the above understanding, that modern PM exposure measurements and analysis should create separate estimates of exposure to all PM of ambient origin and exposure to all PM of nonambient origin (primarily of indoor origin), and not exposure to total PM. This paper reviews the developments of the form of the general microenvironmental mass balance equation that can be utilized for estimating human exposure to PM of ambient origin and for estimating the portion of total PM exposure that is attributable to nonambient origin PM. The equation is perfectly general and can be applied to conditions of time-varying factors that influence exposure, such as rapidly changing air-exchange rates in a home as doors and windows are opened and closed, and turning on and off air cleaners in a home. It is suggested that this procedure be applied in exposure assessment studies and validated using independent techniques of estimating exposure to PM of ambient origin available in the literature.

Estimating separately personal exposure to ambient and nonambient particulate matter for epidemiology and risk assessment: why and how.

This paper discusses the legal and scientific reasons for separating personal exposure to PM into ambient and nonambient components. It then demonstrates by several examples how well-established models and data typically obtained in exposure field studies can be used to estimate both individual and community average exposure to ambient-generated PM (ambient PM outdoors plus ambient PM that has infiltrated indoors), indoor-generated PM, and personal activity PM. Ambient concentrations are not highly correlated with personal exposure to nonambient PM or total PM but are highly correlated with personal exposure to ambient-generated PM. Therefore, ambient concentrations may be used in epidemiology as an appropriate surrogate for personal exposure to ambient-generated PM. Suggestions are offered as to how exposure to ambient-generated PM may be obtained and used in epidemiology and risk assessment.

A model for predicting the frequency of high pesticide exposure events in the Agricultural Health Study.

The frequency of self-reported high pesticide exposure events (HPEE) has been recorded in the NCI/EPA/NIEHS Agricultural Health Study (AHS). Fourteen percent (14%) of the enrolled applicators responding reported "an incident or experience while using any pesticide which caused an unusually high exposure." These data show, as expected, that the probability of a report of an HPEE increases with the cumulative number of days of pesticide application reported by the applicator. We have developed a three-parameter model that predicts the risk odds ratio (OR) of an HPEE as a function of the number of days that pesticides are applied. These events are costly in terms of resulting health-care visits, lost time from work, and potential risk for cancer and other chronic diseases. We propose that failure to carefully follow all the pesticide manufacturer's label requirements, inexperience, and random events (i.e., breaking hose) are the three factors responsible for the events observed. Special precautions for new or infrequent users of pesticides are indicated.

Characteristics of pesticide use in a pesticide applicator cohort: the Agricultural Health Study.

Data on recent and historic pesticide use, pesticide application methods, and farm characteristics were collected from 35,879 restricted-use pesticide applicators in the first 2 years of the Agricultural Health Study, a prospective study of a large cohort of private and commercial licensed pesticide applicators that is being conducted in Iowa and North Carolina. (In Iowa, applicators are actually "certified," while in North Carolina they are "licensed"; for ease of reference the term license will be used for both states in this paper.) Commercial applicators (studied in Iowa only) apply pesticides more days per year than private applicators in either state. When the types of pesticides being used by different groups are compared using the Spearman coefficient of determination (r2), we find that Iowa private and Iowa commercial applicators tend to use the same type of pesticides (r2=0.88). White and nonwhite private applicators tended to use the same type of pesticides (North Carolina r2=0.89), as did male and female private applicators (Iowa r2=0.85 and North Carolina r2=0.84). There was less similarity (r2=0. 50) between the types of pesticides being used by Iowa and North Carolina private applicators. A greater portion of Iowa private applicators use personal protective equipment than do North Carolina private applicators, and pesticide application methods varied by state. This heterogeneity in potential exposures to pesticides between states should be useful for subsequent epidemiologic analyses using internal comparison groups.

Characteristics of persons who self-reported a high pesticide exposure event in the Agricultural Health Study.

Characteristics of persons who report high pesticide exposure events (HPEE) were studied in a large cohort of licensed pesticide applicators from Iowa and North Carolina who enrolled in the Agricultural Health Study between December 1993 and December 1995. Fourteen percent reported having "an incident or experience while using any pesticide which caused an unusually high personal exposure. " After taking into account total number of applications made and education, females (OR=0.76), applicators from NC (OR=0.65), and privately licensed applicators (OR=0.65) were less likely to have reported an HPEE. Work practices more common among both private and commercial applicators with an HPEE included delay in changing clothing or washing after pesticide application, mixing pesticide application clothing with the family wash, washing up inside the house after application, applying pesticides within 50 yards of their well, and storing pesticides in the home. Job characteristics more common among those with an HPEE included self-repair of application equipment and first pesticide use more than 10 years in the past. These job characteristics explained much of the difference in reported HPEE between males and females, but not between IA and NC subjects or between commercial or private applicators.

The EPA health risk assessment of methylcyclopentadienyl manganese tricarbonyl (MMT).

This paper describes the U.S. Environmental Protection Agency's assessment of potential health risks associated with the possible widespread use of a manganese (Mn)-based fuel additive, methylcyclopentadienyl manganese tricarbonyl (MMT). This assessment was significant in several respects and may be instructive in identifying certain methodological issues of general relevance to risk assessment. A major feature of the inhalation health risk assessment was the derivation of Mn inhalation reference concentration (RfC) estimates using various statistical approaches, including benchmark dose and Bayesian analyses. The exposure assessment component used data from the Particle Total Exposure Assessment Methodology (PTEAM) study and other sources to estimate personal exposure levels of particulate Mn attributable to the permitted use of MMT in leaded gasoline in Riverside, CA, at the time of the PTEAM study; on this basis it was then possible to predict a distribution of possible future exposure levels associated with the use of MMT in all unleaded gasoline. Qualitative as well as quantitative aspects of the risk characterization are summarized, along with inherent uncertainties due to data limitations.

Combination of direct and indirect approaches for exposure assessment.

We combine two major approaches currently used in human air pollution exposure assessment, the direct approach and the indirect approach. The direct approach measures exposures directly using personal monitoring. Despite its simplicity, this approach is costly and is also vulnerable to sample selection bias because it usually imposes a substantial burden on the respondents, making it difficult to recruit a representative sample of respondents. The indirect approach predicts exposures using the activity pattern model to combine activity pattern data with microenvironmental concentrations data. This approach is lower in cost and imposes less respondent burden, thus is less vulnerable to sample selection bias. However, it is vulnerable to systematic measurement error in the predicted exposures because the microenvironmental concentration data might need to be "grafted" from other data sources. The combined approach combines the two approaches to remedy the problems in each. A dual sample provides both the direct measurements of exposures based on personal monitoring and the indirect estimates based on the activity pattern model. An indirect-only sample provides additional indirect estimates. The dual sample is used to calibrate the indirect estimates to correct the systematic measurement error. If both the dual sample and the indirect-only sample are representative, the indirect estimates from the indirect-only sample is used to improve the precision for the overall estimates. If the dual sample is vulnerable to sample selection bias, the indirect-only sample is used to correct the sample selection bias. We discuss the allocation of the resources between the two subsamples and provide algorithms which can be used to determine the optimal sample allocation. The theory is illustrated with applications to the empirical data obtained from the Washington, DC, Carbon Monoxide (CO) Study.

A genetic basis for the sudden infant death syndrome sex ratio.

Sudden infant death syndrome, in 36 global data sets comprising 67378 postneonatal autopsied cases, has a male fraction of 0.612 which is significantly greater than the male birth fraction of 0.5122. Each of the sex ratios in the 36 data sets cannot be rejected as a random sample from a P = 0.612 binomial distribution. We hypothesize that an X-linked two-allele (a,A) single gene may be responsible for this consistent behavior. The Hardy-Weinberg principle predicts, given a 5% excess male birth rate, that a recessive allele (a) associated with sudden infant death syndrome, having a frequency of q = 2/3, could be responsible for the male fraction of 0.612. The absence of the A allele would be a necessary precondition for sudden infant death syndrome. We hypothesize that the syndrome occurs only with additional rare environmental conditions and rare physiological factors leading to extreme hypoxic stress, which reduces the sudden infant death syndrome rate to the order of 1 per 1000 live births.

A genetic hypothesis for cause of death during the 1952 London Fog.

Analysis of autopsied cause of death during the London Fog of 1952 indicates that mortality from all respiratory causes, sudden and delayed, had a consistent male fraction of 0.622. Sudden death from heart failure had a similar male fraction of 0.612. However, heart failures after the first day of illness had a male fraction of 0.48. This significant difference in male fraction between sudden (0.61) and delayed (0.48) heart failure suggests different terminal events. Coronary sudden death may be attributable to right-sided heart failure, and the delayed form may be attributable to left-sided failure leading to pulmonary congestion. The male fraction in sudden respiratory and sudden cardiac deaths (0.612) is exactly the same as the male fraction in sudden infant death syndrome-0.612 - which has been posited as being X-linked. It is hypothesized that the same X-linked gene responsible for the 0.612 male fraction in sudden infant death syndrome may be a factor in the respiratory and sudden cardiac mortalities during the London Fog.