Gerald J. Beck

Mycosis fungoides: Clinicopathologic relationships, survival, and therapy in 59 patients with observations on occupation as a new prognostic factor

Clinicopathologic relationships, survival, and therapy were reviewed in 59 patients with mycosis fungoides (MF). An analysis of patient survival disclosed that stage of disease was a significant prognostic variable only if both cutaneous and visceral manifestations were considered in the staging design. The classical three‐stage format, based solely on findings of eczema (I), plaques (II), or skin tumors (III), was not a significant factor in predicting survival. However, the inclusion of lymphadenopathy (IV) and organomegaly (V) or circulating Sézary cells (VI) in an expanded model revealed a significant decline in the probability of survival with increasing stage of disease. Regarding cases where the original histopathologic material was available for review, there was no association between the histologic stage of the specimen and the morphology of skin lesions. These data militate against the use of a staging scheme based on histologic criteria. Among 30 different types of treatment employed during the course of this study, highdose electron beam was superior to all other physical and chemotherapeutic modalities. In a case‐control study considering occupational factors, patients with MF who were employed in manufacturing or construction industries were at significantly increased risk (relative risk = 4.3). Patient survival was reduced considerably for those with industrial backgrounds, suggesting that this subgroup was inclined to have severe disease. The concept that occupational factors may be implicated in the etiology of mycosis fungoides provides a new dimension to previous pathogenic hypotheses that needs further evaluation.

A Prospective Study of Chronic Lung Disease in Cotton Textile Workers

A cohort of both active and retired older cotton textile workers was examined prospectively over a 6-year period to establish the nature and extent of chronic lung disease. Respiratory symptoms and lung function were studied in these workers and in a group of similarly aged controls. The cotton textile workers had higher prevalence and attack rates of respiratory symptoms than did controls even with smoking habits taken into account. Chronic bronchitis developed in 16% of all cotton textile workers compared to 1% of controls over the follow-up period (p less than 0.001). The cotton workers suffered a larger loss of lung function over 6 years than did controls. Male workers lost 42 mL/yr of forced expiratory volume in 1 second, although male controls lost only 25 mL/yr (p = 0.001). Similar differences were seen in women, and in both men and women who were nonsmokers. Retired cotton textile workers had more symptoms and disability than active workers. We conclude that chronic lung disease is not only irreversible but may progress even after exposure to cotton dust has ended.

Airway effects of low concentrations of sulfur dioxide: Dose-response characteristics

The acute respiratory effects of exposure to low-level, short-term sulfur dioxide (SO2) were studied in ten asthmatic and ten healthy subjects. Subjects were exposed in an environmental chamber in a double-blind, random sequence to SO2) levels of 0.00, 0.25, 0.50, 0.75, and 1.00 ppm for 40 min. During the first 10 min subjects exercised on a cycloergometer at a level of 450 kpm/min. On separate days, subjects were exposed to 0 and 1.0 ppm SO2 in the absence of exercise. In exercising asthmatic subjects, breathing 1 ppm SO2 resulted in significant changes from baseline in airway resistance (Raw), forced expiratory volume in 1 sec (FEV1.0), maximal expiratory flow at 60% of the vital capacity (VC) below total lung capacity on the partial flow volume curve [MEF40% (P)] as well as reductions in flows at 50% of VC (Vmax50%). None of these parameters showed significant changes for exposures to 0.5 ppm or less, with the exception of small decreases (i.e., less than 0.2 L/sec) in Vmax50% at 0.25 and 0.5 ppm. Ten minutes after the end of exercise, there were no statistically significant differences from baseline, even though SO2 was still present in the chamber atmosphere. For asthmatic subjects, the average changes in Raw, FEV1.0, MEF40%(P), and Vmax50% increased as SO2 levels increased, suggestive of a dose-response relationship with a consistent effect first seen at 0.75 ppm. In individual exercising asthmatics, responses may occur at levels of SO2 below 0.75 ppm. No changes were seen in healthy individuals on any day, or in asthmatic subjects at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of chronic lung disease in a cotton mill community.

We recorded respiratory symptoms and maximum expiratory flow-volume curves in 645 white male and female cotton textile workers, aged 45 years and older, with an average of 35 years employment in carding, spinning, yarn preparing, weaving and other jobs in cotton textile mills. We included retired as well as active workers, to avoid the biases inherent in studies of active workers only. We compared the data on the textile workers with those of 662 female and 498 male white residents of three communities without cotton textile mills (controls), considering sex, age and smoking habits. Textile workers of both sexes, irrespective of age, had significant excesses of chronic cough, wheezing, dyspnea and other symptoms, in comparison with the controls. Work in textile mills was the prime variable affecting symptom prevalence, with smoking as an additional significant variable for all symptoms except dyspnea. The lungfunction data confirmed that textile workers were at much greater risk of chronic lung disease, with loss of function, than the controls, in all smoking categories. There was evidence that chronic lung disease often led to premature retirement among the male textile workers. The excess risk of lung-function loss occurred among workers in yarn preparing and weaving, as well as in carding and spinning, but not among workers employed in clothrooms and in other dust-free jobs. At least 35,000 men and women in the U.S. may suffer from disabling lung-function loss, owing to chronic lung disease, as a result of their work in cotton textile mills. Adequate programs of prevention and control of chronic lung disease, a late stage of byssinosis, as well as of the earlier acute manifestations of byssinosis, are urgently needed.

Latent Variable Models for Clustered Dichotomous Data with Multiple Subclusters

SUMMARY Regression models for clustered binary data are derived from nonlinear mixed models in terms of latent normal variables. The marginal response probabilities are functions of covariates through generalized linear models. Within a cluster, the pairwise tetrachoric correlations are all equal and are not restricted by marginal probabilities. This approach accommodates hierarchically nested binary data. An algorithm for estimation using generalized estimating equations is proposed. An example illustrates the application of this approach.

A study of respiratory effects from exposure to 2 ppm formaldehyde in healthy subjects.

Formaldehyde (FA) is a common indoor air pollutant with irritative properties. It has been suggested that FA may produce physiologic alterations of the respiratory system. To study such responses, 15 nonsmoking, healthy subjects were exposed in a double blind, random manner to 0 and 2 ppm FA for 40 min in an environmental chamber. In addition, the same exposures were repeated on a separate day with the subjects performing moderate exercise (450 kpm/min) for 10 min. Exposures were carried out under controlled environmental conditions (temperature = 23 degrees C, relative humidity = 50%). Pulmonary function was measured before, during, and after exposures using partial and maximal flow-volume curves and airway resistance. Symptom diaries were given to the subjects; upper and lower airway symptoms were recorded for up to 24 hr following exposures. No significant bronchoconstriction was noted in this group. In 3 subjects, sequential measurements of peak flow over a 24-hr period following FA exposure failed to reveal any delayed airway response. On a separate day, 6 healthy subjects failed to demonstrate changes from their baseline responsiveness to methacholine after exposure to 2 ppm FA. Respiratory symptoms were, in general, confined to the upper airways and were mild to moderate in severity. We conclude that short exposures to 2 ppm FA do not result in acute or subacute changes in lung function among healthy individuals either at rest or with exercise. Subjective complaints following such exposures are confined to irritative phenomena of the upper airways.

A study of respiratory effects from exposure to 2.0 ppm formaldehyde in occupationally exposed workers.

It has been suggested that exposure to formaldehyde (FA) induces asthmatic symptomatology. We have previously studied healthy and asthmatic individuals and found that lung function was unaltered by controlled exposures to 2.0 ppm FA with and without mild exercise. Our present study extends these observations to a group of hospital laboratory workers routinely exposed to FA. Fifteen laboratory workers were exposed in double-blind, random sequence to 0 and 2 ppm FA for 40 min in an environmental chamber with temperature and relative humidity held constant at 23 degrees C and 50%, respectively. These exposures were repeated on two more occasions with a 10-min exercise regimen (450 kpm/min) after being in the chamber 5 min. In addition, a symptom diary and measurements of peak expiratory flow rate (PEFR) were recorded for 24 hr after exposure. Lung function remained unaltered for all 4 exposure days; e.g., mean FEV1.0 for the group did not change by more than 3% at any testing time on any exposure day. Also, there were no delayed obstructive changes as measured by PEFR recordings. Symptoms were mild and transient with unusual odor and eye irritation the most frequent complaint. No lower airway symptoms were reported. We conclude that this group of healthy laboratory workers did not experience any acute or delayed lung function changes from exposure to 2.0 ppm FA at rest and with exercise and that irritative symptoms were few.

Priorities in prevention of chronic lung diseases

We recorded the prevalence of respiratory symptoms as well as smoking habits, occupational and other environmental exposures, and lung function (maximum expiratory flow-volume [MEFV]) curves in 7,984 community residents (age 7 + years) and in 691 cotton textile workers (age 45 + years). Apart from a slight but significant excess among urban nonsmoking adults of usual cough, usual phlegm and dyspnea, but not of chronic bronchitis, there were no significant differences in respiratory health between residents of urban Ansonia, Connecticut, rural Lebanon, Connecticut, and rural Winnsboro, South Carolina. Lung function values, including flows on MEFV curves, did not differ significantly in nonsmokers, nor in smokers, in the three communities, after sex, race, age, height, and weight were taken into account. Smoking of cigarettes but not of pipes or cigars was associated with significant loss of lung function. Cotton textile workers had a significant excess of both symptoms and lung function loss; the effects of smoking and of cotton dust exposure were additive. Among the community residents, a history of asthma was most common in the least polluted rural town, Winnsboro. From our own data and from comparisons between our data and those of others in either more polluted or less polluted areas, we have concluded that control of air pollution outdoors is unlikely to decrease the health impact of chronic lung diseases. Prevention of cigarette smoking and of occupational exposures, on the other hand, deserves high priority as a public health problem. In particular, adequate control of exposures to dust and fumes in industry could completely prevent disabling chronic lung disease among groups of workers now at high risk, such as cotton textile workers.

The Evidence for Chronic Lung Disease in Cotton Textile Workers

Abstract This article summarizes the epidemiological evidence that documents the presence of chronic lung disease in cotton textile workers due to cotton-dust exposure in the mills. Historical, cross-sectional, and longitudinal studies are discussed. In addition, the authors present results from a recent prospective study of both active and retired cotton textile workers in Columbia, South Carolina, indicating that chronic lung disease is present even in workers no longer exposed to cotton dust.

Airway responses to exercise in mild asthmatics.

Abstract Measurements of flow on maximal and partial expiratory flow-volume (MEFV and PEFV) curves offer a simple, sensitive, and safe method for studying the prevalence, clinical characteristics, and airway changes of exercise-induced bronchospasm (EIB). These methods show that asthmatic individuals with even mild disease clearly differ from nonasthmatic persons in terms of their airway response to exercise. Nineteen asthmatic and fourteen nonasthmatic volunteers underwent graded exercise testing to elicit exercise-induced bronchospasm. Pulmonary function was measured using MEFV and PEFV curves before and after exercise. Exercise-induced bronchospasm was demonstrated in 17 of 19 asthmatic subjects without inducing marked degrees of airway constriction. The most sensitive index of EIB was changes in flow rates measured at low lung volumes, particularly those measured on PEFV curves. Analysis of flow-volume curves suggested two patterns of airway response to exercise among asthmatics, involving, respectively, small and larger airways. No significant changes in pulmonary function were demonstrated in the nonasthmatic subjects. The degree of EIB measured by changes in flow rates on the PEFV curve correlated with airway reactivity to nonspecific irritants such as cold weather, tobacco smoke, and respiratory tract infections, but not with a history of specific allergies. We suggest that EIB is a general feature of asthma, reflecting the increased reactivity of asthmatics to a wide variety of airway irritants.