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Biomedical subjects

C A Newill

Publications and source records attributed to C A Newill.

13 recordsLinked to original sources
PubMed1995

Prospective study of occupational asthma to laboratory animal allergens: stability of airway responsiveness to methacholine challenge for one year.

The stability of airway hyperresponsiveness was studied in a group of 178 young adults working with laboratory animals. At the time of their entry into the study, 132 of 178 subjects (74%) had less than 20% response to the inhalation of 25 mg/ml methacholine, whereas 26 (15%) had a methacholine dose causing a 20% fall in forced expiratory volume in 1 second after fewer than 80 breath units. The distribution of methacholine responsiveness did not differ at 6 months and 1 year; 155 of 178 volunteers (90.4%) responded during the repeated challenges to doses within one dilution of their results at entry. One hundred forty-one subjects were consistently unreactive during the year, and 17 were consistently reactive. Approximately equal numbers gained and lost reactivity. Those with consistently positive responses to methacholine were more likely to have skin test reactivity and chest symptoms. The presence of consistent chest symptoms was loosely associated with consistent methacholine responsiveness; 55% of those with consistent hyperresponsive airways had symptoms, and 24% of those who consistently had symptoms had hyperresponsive airways. We concluded that the methacholine response is relatively stable during the course of a year in laboratory animal workers who remain at their jobs and that the presence of a positive skin test response to laboratory animals or of chest symptoms does not change the pattern of stable responsiveness.

Adult↗
PubMed1992

Risk factors for increased airway responsiveness to methacholine challenge among laboratory animal workers.

As a first step in a prospective study of the incidence of asthma to laboratory animals, a group of 364 adults 18 to 48 yr of age who were beginning employment with laboratory animals were evaluated in terms of their past history, health status, allergy, and airway responsiveness to methacholine. At entry to the study, 269 had previous occupational contact with animals, 109 had chest symptoms in the previous year, 168 had a history of allergic symptoms to laboratory animals (any with asthmatic responses were systematically excluded), and 118 had positive immediate skin tests (29 had positive skin tests to laboratory animals). When defined as a PD20FEV1 of 80 breath units or less, 18.4% of these young adults had methacholine hyperresponsiveness (HRA). Significant risk factors for HRA were found to be younger age, female sex, lower educational level, a history of allergic symptoms to laboratory animals, and a history of chest symptoms. Positive skin tests to laboratory animals were present in 8% of workers; this was not a significant risk factor for HRA although positive skin tests to pollen and household allergens were. Previous work experience was a risk factor, especially among those with allergic symptoms, and a trend toward self-selection was suggested in that the rate of HRA was lowest in workers with more than 2 yr of experience or with two or more previous jobs with laboratory animals.

Adolescent↗
PubMed1989

Task-related variation in airborne concentrations of laboratory animal allergens: studies with Rat n I.

To define airborne allergen exposure during various tasks with rats in a laboratory, concentrations of allergen Rat n I were measured by radioimmunoassay in extracts from filters in personal air sampling devices that were worn by laboratory workers while they were performing these tasks. The tasks included feeding, cage cleaning, handling, injection, surgery, and sacrifice. Median concentrations encountered during feeding or cleaning (21 ng/m3) and injection or handling (13 ng/m3) were higher than those associated with surgery or sacrifice (3.1 ng/m3; p less than 0.01). Area samples in animal-holding rooms contained 3.4 ng/m3 during animal handling and 2.3 ng/m3 at other times. Very low concentrations were found in air outside the handling room, in unused laboratories, or outside air. We concluded that certain tasks incur a higher risk of allergen exposure but that exposure may occur anywhere within an animal laboratory environment.

Air Pollutants, Occupational↗
PubMed1987

Inbreeding and prereproductive mortality in the Old Order Amish. II. Genealogic epidemiology of prereproductive mortality.

The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.

Adult↗
PubMed1986

Genetic-environmental interactions in chronic airways obstruction.

To examine patterns of interaction between cigarette smoking and genetic factors in relation to airways obstruction, cross sectional data were analysed on 1787 white non-patient adult participants in a genetic-epidemiological study of airways obstruction (AO), defined as one-second forced expiratory volume FEV1 less than 68% of forced vital capacity FVC. Interaction was examined between smoking and each of four factors previously found to be related to AO: alpha-1 antitrypsin (PiZ allele), ABO blood groups (A antigen), ABH non-secretor status, and first degree relationship to a COPD or lung cancer patient. Multiple linear regression was used to test for interaction and adjust mean FEV1 (as a per cent of FVC) and prevalence of AO for age, sex, socioeconomic status, coffee and alcohol intake. Statistical interaction was observed between smoking (measured in pack-years) and two genetic factors (presence of blood A antigen and the family history). At higher pack-year levels, those individuals with the A antigen or the family history, but especially those with both factors had a much lower mean FEV1/FVC % and a much higher prevalence of AO than expected based on a simple additive model. On the other hand, there was no interaction between smoking and PiZ allele, or smoking and ABH secretor status. The findings suggest a possible biological interaction between cigarette smoke and the airways of individuals with blood group A antigen and familial lung disease. The findings also emphasize the role of genetic-environmental interactions in chronic diseases of multifactorial aetiology.

ABO Blood-Group System↗
PubMed1986

Epidemiological approach to the evaluation of genetic screening in the workplace.

Using several examples of genetic marker and disease associations in the workplace, the authors have applied formulas to estimate the sensitivity, specificity, and positive predictive value (PPV) of screening for these markers. Sensitivity, specificity, and PPV are affected independently by characteristics of the population being screened, ie, the genetic marker frequency, the disease frequency, and the magnitude of the relative risk (R). For a given disease frequency, when the genetic marker is less frequent than the disease, PPV increases with relative risk, although sensitivity remains low. When the genetic marker is more frequent than the disease, PPV remains low while sensitivity increases with R. When marker and disease frequencies are equal, PPV and sensitivity are equal and increase with R. However, when the disease frequency is very low, R must approach 100 before PPV or sensitivity approaches 50%. These relationships may be used effectively in the decision whether to implement a screening program in the workplace.

Disease Susceptibility↗
PubMed1986

Preemployment screening for allergy to laboratory animals: epidemiologic evaluation of its potential usefulness.

Employers at laboratory animal facilities have begun to use selection criteria which proscribe employment of persons thought to be at increased risk of developing allergy to laboratory animals. Some of these criteria are: a personal history of allergy, chronic rhinitis, or asthma, positive direct skin tests, elevated serum immunoglobulin E, abnormal forced expiratory volume in 1 second, and a family history of allergy. The usefulness of these criteria were examined in preemployment screening when applied to job applicants who will be handling laboratory animals, by calculating the sensitivity, specificity, and positive predictive value (PPV) of each criterion. Results illustrated that the primary goal of the screening program must be determined before an evaluation can be made of the usefulness of potential screening criteria in meeting the goal, ie, to identify persons who are themselves at high risk (high PPV), to identify a large proportion of low-risk job applicants (specificity), or to screen out a large proportion of occupational disease (high sensitivity), because it is not possible to maximize these parameters simultaneously. Results indicate that, currently, the use of these screening criteria as determinants for hiring persons to work with laboratory animals is unwarranted.

Animals↗
PubMed1985

Effects of pulmonary function on mortality.

Survivorship data from a 24 year longitudinal study of 874 male volunteers in the Baltimore Longitudinal Study of Aging were used to assess the role of pulmonary function on total mortality. Even when age and smoking were considered, the ratio of forced expiratory volume in 1 sec to its predicted value was significantly associated with mortality from all causes. Individuals with poorer pulmonary function showed greater mortality during the follow-up period of this study. This relationship was also seen among never smokers in this sample, further supporting the hypothesis that impaired pulmonary function is itself a predictor of total mortality and may contribute to a number of disease processes.

Adolescent↗
PubMed1985

Epidemiologic evaluation of screening for risk factors: application to genetic screening.

To assess the usefulness of screening for risk factors, we derived arithmetic relationships between screening parameters (sensitivity, specificity, and positive predictive value PPV) and risk factor frequency, disease frequency and relative risk. We evaluated these relationships in the special case of genetic markers and disease susceptibility. It can be shown that even in the face of very large relative risks, sensitivity and positive predictive value are affected by the relative magnitude of disease and genetic marker frequencies. When the genetic marker is less frequent than the disease, PPV increases with increasing relative risk but sensitivity remains low. When the genetic marker is more frequent than the disease, sensitivity increases with increasing relative risk but PPV remains low. When marker and disease frequencies are equal, both PPV and sensitivity increase with increasing relative risks, but very high relative risks (greater than 100) have to be obtained for rare diseases. Depending on the goals of the screening program, these relationships can be used to predict the relative magnitudes of false positives (low PPV) and false negatives (low sensitivity). This approach can be generalized to evaluate nongenetic risk factors in screening programs as well.

Epidemiologic Methods↗
PubMed1984

Risk factors associated with longitudinal change in pulmonary function.

In a longitudinal study of pulmonary function, we investigated the relationship between loss of forced expiration over time and a series of potential risk factors, as well as 4 other measures of pulmonary function at initial visit. Data on 1,912 adults tested twice, with an average of 4.7 yr between visits, were used. Of the potential risk factors examined, only age and smoking were consistently associated with increased loss of forced expiratory function in both men and women. Statistically significant differences among ABO blood types and among Pi types were also seen in women, although the direction of these differences was unexpected in that non-Z Pi variant phenotypes showed less decline in pulmonary function than did the most common Pi M phenotypes. Similar patterns of differences were seen in men, although these were not statistically significant. Of 4 initial-visit pulmonary function measures examined, only closing capacity at initial visit was consistently associated with subsequent loss of forced expiratory volume in one second (delta FEV1) in both men and women. The final predictive model for delta FEV1 accounted for a modest proportion of the total variation seen in this sample, however, limiting its potential use for predicting decline in pulmonary function over a 5-yr span in individual subjects.

ABO Blood-Group System↗
PubMed1984

Risk factors, pulmonary function, and mortality.

In a genetic-epidemiologic study of obstructive airway disease (OAD), cross sectional and longitudinal data (4.7 year follow-up) were collected to investigate relationships among risk factors, pulmonary function, and mortality. In the cross sectional evaluation of 2539 non-patient adults, 11 potential risk factors were found to be significantly associated with airways obstruction. Most important among these were age and smoking. Others included: demographic variables (gender, SES, education); the intake of coffee and diet soda; genetic markers (protease inhibitor "Pi" type, ABO type, ABH secretor status); and familial pulmonary disease. Examination of combinations of risk factors in cross sectional data indicated that some of these factors were important risk factors in cigarette smokers but less evident in never smokers. For example, ABO type, familial component, coffee drinking and diet soda intake were related to marked differences in lung function in cigarette smokers, but had little impact in never smokers. Thus, interactions of factors must be considered when assessing risk of pulmonary dysfunction. In the longitudinal evaluation, 11 factors found to be significant on cross sectional study plus 4 tests of lung function (closing capacity, diffusing capacity, slope of Phase III, and flow volume curves) were examined for correlations with loss of forced expiratory volume. Consistently greater declines of lung function were noted in males, older subjects, smokers, whites, and individuals carrying the type A blood group allele. Increased initial visit closing capacity was also associated with increased deterioration. Together, however, these factors accounted for only a modest amount of observed variation in decline in lung function (17% in females and 12% in males). Initial visit characteristics were not only associated with deterioration of lung function in survivors, as described above, but with survivorship per se. Age, sex, race and cigarette smoking were associated with differences in mortality. In addition to these, pulmonary dysfunction itself at initial visit was an independent risk factor for increased mortality. For example, the mortality of unobstructed males in the 5th decade of life was 16 per thousand compared to 25 per thousand in obstructed males. For females, the mortality in the 5th decade of life was 7 per thousand if unobstructed and 12 per thousand if obstructed. We conclude: 1) In cross sectional evaluation, multiple factors are associated with airways obstruction. Of these, smoking appears to interact strongly with other factors.(ABSTRACT TRUNCATED AT 400 WORDS)

ABO Blood-Group System↗
PubMed1982

Impaired pulmonary function as a risk factor for mortality.

Prospective follow-up information obtained between 1976 and 1981 on mortality among 2539 individuals showed that pulmonary function impairment is a risk factor for short-term mortality, even when risk factors such as age, sex, and smoking are considered. Predicted risk curves for impaired individuals (those with forced expiratory volume in one second less than 68% of forced vital capacity) are consistently higher among all race-sex categories over all ages. Survival analysis using the proportional hazards model shows a steeper decline in estimated survival among individuals with poor pulmonary function compared to those with good pulmonary function, adjusted for age, race, and smoking effects. These observations are consistent with the concept that impairment of pulmonary function is a risk factor for morbidity and mortality from several nonrespiratory as well as respiratory diseases and that it acts by contributing to various pathogenic mechanisms in different organ systems.

Adult↗