Air pollution and human health: a review and reanalysis.

Since 1970, Lave and Seskin have published a series of articles dealing with the question, "Does air pollution shorten lives?" Their recent book reports revised and extended analyses of their previous studies emphasizing policy implications. We have undertaken a review of Lave and Seskin's book to evaluate the methodology used and hence gain some insight into the strength of the conclusions reached. This review concentrates on methodology and its application to establishing and quantifying the association between air quality and health. Beyond simply reviewing the analyses reported in Lave and Seskin's book, we have duplicated and expanded two of the reported analyses. Our detailed reanalysis is presented both to verify reported results, and to illustrate the difficulties encountered in such an analysis. Our overall conclusion is that Lave and Seskin have done a thorouth job of reporting and interpreting the various analyses that they performed. Lave and Seskin have made a pioneering effort in showing an association between mortality rates and air pollution. We do not disagree with the conclusion of the existence of an association but have some reservations about their methods of estimating its magnitude. We were particularly concerned that Lave and Seskin did not fully investigate how well their models fit these data. Our reanalysis results in estimated effects which differ considerably from the values reported by Lave and Seskin. Thus, we conclude that the regression coefficients are quite unstable and so must be used with care. Assessing the relative costs and benefits of reducing air pollution without extensive sensitivity analysis could, therefore, be misleading.

Respiratory disease rates and pulmonary function in children associated with NO2 exposure.

As part of a long-range, prospective study of the health effects of air pollution, approximately 8,000 children from 6 yrs to 10 yrs of age from 6 communities had questionnaires completed by their parents and had simple spirometry performed in school. Comparisons were made between children living in homes with gas stoves and those living in homes with electric stoves. Children from households with gas stoves had a greater history of respiratory illness before age 2 (average difference, 32.5/1,000 children) and small but significantly lower levels of FEV1 and FVC corrected for height (average difference, 16 ml and 18 ml, respectively). These findings were not explained by differences in social class or by parental smoking habits. Measurements taken in the homes for 24-h periods showed that NO2 levels were 4 to 7 times higher in homes with gas stoves than in homes with electric stoves. However, these 24-h measurements were generally well below the current federal 24-h outdoor standard of 100 micrograms/m3. Short-term peak exposures, which were in excess of 1,100 micrograms/m3, regularly occurred in kitchens. Further work will be required to determine the importance of these short-term peaks in explaining the effects noted.

Effects of sulfur oxides and respirable particles on human health. Methodology and demography of populations in study.

As part of a study of health effects of sulfur dioxide and particulate matter, we have established a cohort of adults 25 to 74 yr of age in 6 communities who will be followed prospectively. At the conclusion of our first cycle of measuring the health of adults in 6 sites we found that, although we used different sampling frames, our samples were close to the distribution shown in the U.S. Census for age, sex, and occupation, with the possible exception of one city. Analysis of the cross-sectional data indicated that for both age- and height-adjusted values for forced expiratory volume in 1 s and for selected rates of various respiratory symptoms standardized for age, differences among smoking groups were apparent. Differences in these parameters between sites suggest trends that were associated with levels of pollution. Further analyses of the prospective data currently being collected will be required before definitive statements can be made about the effect of specific levels of exposure.

A contribution to the electron microscopic morphometric analysis of peripheral nerve.

Several aspects of data collection and analyses of peripheral nerve experiments employing light and electron microscopic morphometric techniques have not been adequately discussed in the literature. From statistical tests performed on nerve data, it was found that light compared with electron microscopic morphometry underestimates the number of small fibers. An optimum sampling strategy must take into account a potential bias toward small fibers introduced by measuring fibers from electronmicrographs. It must also take into account a potential bias introduced by the non-random distribution of nerve fibers of different sizes in nerves. These biases are offset by sampling a large enough number of fibers from large enough area electron micrographs. A method is presented for analysing periopheral nerve data using the nested analysis of variance. This requires first dividing the usual bimodal nerve fiber distribution into component normally distributed parts. The number of fibers in the two portions of a bimodal distribution must be considered in data analysis. Knowledge of the variances of parameters to be studied in any particular nerve is necessary for optimum sampling strategies.

Statistical methods for hazards and health.

The objective of this article is to document the need for further development of statistical methodology, training of more statisticians and improved communication between statisticians and the many other disciplines engaged in environmental research. Discussion of adequacy of the current statistical methodology requires the use of examples, which will hopefully not be offensive to the authors. Reference is made to recent developments and areas of unsolved problems delineated in three broad areas: enumeration data and adjusted rates; time series; and multiple regression. A brief outline of the ideas behind current methods of analyzing discrete data is followed by a demonstration of their utility using an example of the effects of exposure, sex, and education on bronchitis rates. Examples are listed of the ubiquity of the time component when relating pollution effects to each other and to health effects. An artificial example is used to emphasize the effects of time-dependent autocorrelations, trends, and cycles. References are given to a variety of new developments in time-dependent autocorrelations, trends, and cycles. References are given to a variety of new developments in time-series analysis. Discussion of the pitfalls in multiple regression analysis, and possible alternative approaches is largely based on two recent reviews and includes references to recent developments of robust techniques.

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone.

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.

Prophylaxis of varicella in children with neoplastic disease: comparative results with zoster immune plasma and gamma globulin.

The incidence and severity of varicella following a close family contact were evaluated in children with neoplastic diseases who received prophylaxis either with commerical gamma globulin or with zoster immune plasma, as compared to patients who did not receive any prophylaxis. In the untreated group, all 14 patients developed varicella, complicated by 1 case of encephalitis and 2 cases of fatal pneumonia. In the group of 17 patients who received 0.6-1.2 ml/kg body weight of gamma globulin, 16 developed varicella, complicated by pneumonia in 2 cases, with 1 death. In the third group of 27 patients who received 10 ml/kg body weight of zoster immune plasma (ZIP), obtained from healthy adults convalescing from herpes zoster, there were only 8 cases of varicella, all very mild. Thus, prophylaxis with ZIP significantly reduced the incidence of clinical varicella (p less than 0.01) and attenuated the severity of its course.

Adverse effects of intrathecal methotrexate in children with acute leukemia in remission.

A toxic syndrome characterized by fever, headache, and vomiting, lasting 2-5 days, occurred in 61% of 39 children with acute leukemia in complete remission, receiving central nervous system prophylaxis with intrathecal methotrexate, and in 14% of 34 children receiving the same plus cranial radiation. The syndrome was accompanied by pleocytosis with lymphocytes, monocytoid cells, and neutrophils. There was evidence of cumulative Mtx toxicity, since the toxic syndrome occurred mostly after the third and fourth dose and did not recur with longer intervals between doses. The incidence of the syndrome was significantly reduced by the use of Elliott's B solution as Mtx diluent, rather than water or normal saline. The occurrence of pleocytosis and toxic clinical syndrome was also significantly reduced in patients receiving concomitant cranial radiation, probably due to the lympholytic action of radiotherapy and the depressed cellular response of irradiated tissues. The use of Elliott's B solution as diluent for IT Mtx and an appropriate interval between Mtx doses are suggested for prevention of this toxic syndrome.