New Mexico Female Miners Have Lower Odds for COPD than Their Male Counterparts

Abstract

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity among miners. There is an increasing number of women in the mining industry and the differences in their risk for COPD compared to men miners are not understood. Our objective is to compare the odds for COPD between male and female miners. Using cross-sectional data from the Mining Dust in the United States (MiDUS) Cohort, that included New Mexico miners between 1989 and 2018, we compared the odds for airflow obstruction or chronic bronchitis between women and men. There were 299 women in this diverse cohort of 7,464 miners. Compared to men, female miners reported lower cumulative smoking but higher prevalence of current smoking. Multivariable analysis showed that women miners had significantly lower odds for having airflow obstruction (OR 0.40; 95% CI (0.26, 0.6)) and chronic bronchitis (OR 0.31, 95% CI (0.19, 0.53)) than men. Future studies need to determine whether this sex difference is explained by residual confounders or true biological difference.

Keywords:

• Sex differences
• COPD
• chronic bronchitis
• airflow obstruction

Introduction

Chronic obstructive pulmonary disease (COPD) with its different phenotypes (including but not limited to emphysema and chronic bronchitis) is an important cause of occupational morbidity and mortality in miners [1]. COPD from occupational dust exposure in miners is associated with functional impairment [1], even without chest radiographic evidence of pneumoconiosis [1]. The development of emphysema, independent of smoking history, is often underappreciated amongst miners [2]. Cumulative occupational exposure to dust is a significant risk factor for COPD, best described among coal miners [1]. Prior studies, like the one by Santo Thomas have shown that the duration of coal mine dust exposure is directly proportional to the risk of death due to COPD [3]. In newly employed coal miners, symptoms of bronchitis are associated with a “rapid” reduction of forced expiratory volume in one second (FEV₁) within two years [4]. Previous studies have also revealed that mining dust exposure correlates with greater morbidity and mortality from pulmonary and other associated conditions [4]. Another study detailing effects of respirable quartz showed an increase in the risk of COPD with continuous exposure over the years [5].

In the United States, New Mexico (NM) mines had one of the highest outputs of uranium [6], and are still a major producer of potassium salts, copper and coal [7]. Most of the coal extraction is in Northern NM in the Raton and San Juan basins. Working conditions in these mines are usually extremely dusty. In the early 1960s, the first major pulmonary consequences started revealing themselves in Northern NM – pulmonary fibrosis, silicosis, lung cancer, pneumoconiosis and tuberculosis. As detailed in the mining section of the New Mexico Museum of Art website, these ailments were nicknamed “red lungs” by the Navajo miners for the red phlegm they coughed up [8].

Although there have been studies in the past measuring sex differences in the “general population” with regards to the incidence, prevalence and natural history of COPD [9], we are unaware of any study on sex differences in the prevalence of airflow obstruction/emphysema and chronic bronchitis phenotypes of COPD amongst miners. Sex differences in pulmonary physiology and anatomy are present in infancy and carry on through adulthood [9]. Lung diseases are also affected by communal, ethnic, territorial and behavioral factors [9]. Our objective was to examine the odds for airflow obstruction/emphysema and chronic bronchitis phenotypes of COPD amongst male and female miners in NM. We hypothesized that NM female miners have a lower odds for COPD than their male counterparts.

Methods

Study design

In this cross-sectional study, we used data obtained from the NM-based Mining Dust in the United States (MiDUS) cohort from 1989 to 2018. The MiDUS cohort recruits current or former workers employed in the NM mining industry who voluntarily undergo medical surveillance.

These surveillance activities are performed using a mobile outreach clinic, organized by rotation in 20 rural NM communities with high concentration of miners. This surveillance program is jointly run by Miners’ Colfax Medical Center (MCMC) at Raton, NM and the University of New Mexico (UNM) School of Medicine at Albuquerque, NM.

Inclusion criteria

The study included all those employed in the mining industry for at least one year who also participated in the aforementioned clinical surveillance initiative. Miners included in the analyses had valid age and spirometry results.

Study methods

Upcoming mobile clinics are advertised in the target rural mining residential communities through print, media and radio, as well as by working with community/church leaders and mine safety officers. Patients can also self-refer for screening evaluations. Participants are not charged out-of-pocket expenses for their screening clinic visit, which takes approximately one hour to complete. At each mobile screening clinic, miners are assessed for respiratory, hearing and musculoskeletal disorders associated with mining-related exposures. Assessment also includes common health conditions such as obesity and exposures such as tobacco use.

The mobile screening clinic is held in a specially outfitted trailer which is 53 feet long with a diesel generator to supply power. The clinic consists of five separate areas, including a patient reception area, a digital chest X-ray unit, sound-proof audiometry booth, spirometry room and an examination room. The staffing model in the mobile screening clinic consists of a mid-level provider, a radiology/audiometry technician and a medical assistant/nursing technician who is certified by the National Institute of Occupational Safety and Health (NIOSH) for performing spirometry. Race and ethnicity specific predicted values were used for non-Hispanic whites and Hispanics. Crapo American Indian reference standards were used for American Indians [10,11].

Before the screening examination, patients completed a comprehensive occupational and clinical history intake form, based on the adult American Thoracic Society Diffuse Lung Disease 1978 (ATS DLD-78) Questionnaire [12]. The questionnaire responses are reviewed and confirmed by the mid-level clinical provider. The screening visit includes a vital sign assessment, including a blood pressure assessment at rest and measurement of standing height and weight without shoes, pre-bronchodilator spirometry using ATS guidelines, audiometry and a standard postero-anterior chest radiograph. A complete history and physical examination is performed by the midlevel provider who develops a treatment and care plan for the patient depending on the primary diagnosis. The records are reviewed for quality by a UNM based preventive medicine and pulmonary medicine specialist.

Exposure and definitions

The exposure variable was defined by self-reported sex of those who were ever employed with the mining industry (collectively termed miners in this study).

Outcomes

Primary study outcomes included spirometrically determined airflow obstruction and the chronic bronchitis phenotype of COPD. Chronic bronchitis was defined as self-reported productive cough for at least three months annually for at least two consecutive years. Airflow obstruction was defined by pre-bronchodilator spirometry demonstrating a forced expiratory volume in one second to forced vital capacity (FEV₁/FVC) ratio below the fifth percentile or lower limit of normal (LLN) of the NHANES III reference equations [13]. Secondary study outcomes included modified Medical Research Council dyspnea score, self-reported asthma and the presence of Preserved Ratio Impaired Spirometry or PRISm pattern, commonly known as restrictive spirometric pattern. PRISm was defined as the presence of a normal FEV₁/FVC ratio, defined by at least the fifth percentile or LLN plus low FVC defined by a value < LLN. Ever asthma was defined by answering “yes’” to the question: “Have you ever had asthma?” Current asthma was defined as answering “yes” to the question: “Do you still have asthma?”

Covariates

Selection of covariates was based upon known biological and/or mechanistic plausibility of each as a potential confounder in evaluating the risk for COPD. Standard covariates included ethnicity/race, age, body mass index (BMI), cigarette smoking status, pack-years of smoking and mining exposure duration. Mining duration was compiled from miner histories, but records were inadequate for valid determinations in 17% of miners. Since it is possible that miners may be contemporaneously exposed to more than one type of mine (e.g. coal and uranium mines) and more than one mine location (e.g. surface and underground), we took the maximum exposure time among the various types of mines as the underestimation of exposure time, and then we summed the exposure time of different types of mines together as the total mining duration. This number is likely an underestimation, but will generate less bias than the sum of all the mining duration times for each miner.

Statistical analysis and IRB approval

Nonparametric Wilcoxon tests and parametric chi-square tests were utilized for univariate analysis of continuous and categorical outcomes, respectively. To minimize the selection bias from missing data, a nearest-neighbor matching using the propensity score method was conducted with replacement for female miners. Because we have 7,165 males and 299 females, the matching ratio between females and males was 1:4, i.e. four males were theoretically matched for each female observation. The propensity score is the probability of group assignment conditional on observed baseline characteristics. Nearest-neighbor matching uses the propensity scores as the criteria to pair a given point with another “closest” point [14]. When the matching is run with replacement, each member of the target set can be a match for more than one data point. The matched samples are applied in the conditional logistic regression as the multivariable analyses (SAS proc logistic and STATA clogit). Data were analyzed using Statistical Analysis Software (SAS) 9.4 version (Cary, NC) and Stata/SE version 15, with two-sided p values <0.05 considered significant.

This study was approved by the UNM Human Research Protection Office Institutional Review Board (HRPO 14-058) under a HIPPA waiver of consent from participants. This work was partially supported by the National Institute of Health-funded Clinical Translational Science Center grant UL1TR001449 and Health Resources and Services Administration grant H37RH0057.

Results

The study included 7,165 male and 299 female miners, mostly Hispanic and American Indian. As shown in Table 1, female miners were more likely to be younger and have higher total years of education than male miners. The race/ethnicity distribution was similar between the two groups. Although women were more likely to currently smoke, they had less pack years of cumulative smoking than men. The percentage of women who reported underground mining is significantly lower than the percentage of men (Table 1). Overall, women had fewer years of mining tenure, both with respect to underground as well as above ground mining.

Table 1. Characteristics of female and male New Mexico miners.

Baseline characteristics	Female miners, N = 299, % or mean ± SD	Male Miners, N = 7165, % or mean ± SD
Age (years)*
<40	17.4	15.0
40–59	48.5	42.2
60–74	30.8	33.7
≥75	3.3	8.8
Unknown	0	0.2
Mean age for all	52.4 ± 13.2	55.7 ± 14.3
Race/ethnicity
Non-Hispanic White	29.4	28.8
Hispanic	31.4	36.8
Black	0.7	0.5
Native American	35.8	31.8
Other/unknown	2.7	2.1
BMI category (kg/m^2)*
Underweight (<18.5)	3.0	1.8
Healthy weight (18.5 to <25)	1.0	0.5
Overweight (25 to <30)	18.7	20.5
Obese (≥30)	32.4	43.5
Unknown	44.8	33.7
Total years of education*	8.5 ± 6.2	7.5 ± 5.7
Pack years of smoking among ever smokers	6.4 ± 13.0	10.5 ± 23.1
Current smoking*	23.1	17.6
Smoking status undetermined	1.7	1.6
Total mining exposure (years) (median (IQR))*	5.0 (3.0, 10.0)	12.0 (6.0, 22.0)
Total mining years undetermined*	34.7%	24.1%
Above ground mining (years)*	5.5 ± 7.9	8.0 ± 9.8
Under-ground mining (years)*	4.2 ± 4.8	10.8 ± 10.7
Percentage with below ground mining*	15.1%	50.8%
Self-reported ever asthma diagnosis*	17.1	9.0
Self-reported current asthma diagnosis	13.0	5.7

Abbreviations: SD: standard deviation; BMI: body mass index; IQR: interquartile range; kg: kilogram; m²: meter squared.

* p value < 0.05.

As shown in Table 2, female miners had lower odds for airflow obstruction than their male counterparts after adjusting for covariates (adjusted OR 0.40, 95% CI 0.26–0.60). The odds for chronic bronchitis were similarly lower in female miners than male miners (adjusted OR 0.31, 95% CI 0.19–0.53). There was no significant difference in the prevalence of PRISm pattern between the two groups. Although fewer female miners reported significant exertional dyspnea (mMRC score of ≥ 2) than men, this sex difference was not significantly different after adjusting for covariates (Table 2). Although female miners had higher likelihood of self-reporting ever asthma than men (adjusted OR 1.72, 95% CI 1.18–2.49), there was no sex difference with respect to self-reported current asthma after adjusting for covariates. Since pack years of smoking may be correlated with age, exclusion of pack-years as a covariate did not change the results.

Table 2. Association between sex (women vs. men referent) and COPD-related outcomes with adjustment for covariates.

Outcomes	Female miners (N = 299)	Male miners (N = 7165)	p value
Airflow obstruction (FEV1/FVC < LLN)
Prevalence of event	15.4%	18.4%
Adjusted OR (95% CI)	0.40 (0.26, 0.60)	1 (ref)	<0.001
Preserved Ratio Impaired Spirometry (PRISm) ^a
Prevalence of event	8.0%	8.5%
Adjusted OR (95% CI)	1.26 (0.83, 1.92)	1 (ref)	0.27
Chronic bronchitis
Prevalence of event	12.0%	17.2%
Adjusted OR (95% CI)	0.31 (0.19, 0.53)	1 (ref)	<0.001
Modified Medical Research Council (mMRC) Dyspnea Score > 2
Prevalence of event	23.4%	28.6%
Adjusted OR (95% CI)	1.01 (0.57, 1.82)	1 (ref)	0.96
Ever asthma
Prevalence of event	17.1%	9.0%
Adjusted OR (95% CI)	1.72 (1.18, 2.49)	1 (ref)	0.005
Current asthma
Prevalence of event	13.0%	5.7%
Adjusted OR (95% CI)	1.24 (0.61, 2.53)	1 (ref)	0.56

Abbreviations: CI: confidence interval; ref: reference; OR: odds ratio; FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; LLN: lower limit of normal.

^a PRISM is defined as FVC < LLN & FEV₁/FVC ratio ≥ LLN.

The multivariable analysis was adjusted for standard covariates including self-reported age, race/ethnicity, body mass index (BMI), cigarette smoking status, pack years of smoking, and mining exposure duration. The mMRC dyspnea scale score was additionally adjusted for prevalent disease outcomes (i.e. airflow obstruction, PRISm and chronic bronchitis).

Discussion

COPD is a major cause of mortality and morbidity worldwide and in the United States [15]. Researchers estimate that by 2030, it will be third leading cause of death worldwide [16]. Initially considered a disease of older, male smokers, recent evidence suggests that globally, the mortality and prevalence has been greater in women in the last 20 years [17]. The increase in tobacco consumption by women is widely regarded as the most important cause for the rising COPD prevalence, but the relationship may be more complicated, with issues like greater exposure to household biomass fuel, hormonal differences, differences in susceptibility to tobacco, as well as behavioral and sociocultural differences in attitude to therapeutic modalities also playing a role [18]. COPD prevalence also varies geographically, partly due to the variance in the disease definition used in studies, since spirometric testing is less frequent in studies from rural areas [19]. In this study, we assessed the prevalence of airflow obstruction/emphysema and chronic bronchitis phenotypes of COPD among miners in rural NM, and concluded that female miners have lower odds for COPD phenotypes, in comparison to their male counterparts.

Sex-based differences in the incidence, prevalence and severity of emphysema and chronic bronchitis have not been well studied. The sex-related biologic differences in body mass and life expectancy affects the prevalence of chronic pulmonary conditions [20]. Bronchi and bronchioles may also be affected by sex hormones [21]. The impact of sex hormones on airway function in asthma is established, but their influence on COPD pathogenesis is less clear [22]. Sex hormones also affect the growth and development of the respiratory tree, with women having smaller airways, which may impact bronchodilator reversibility. In the National Emphysema Trial (NETT), men with COPD were more likely than women with COPD to have bronchodilator reversibility [23]. On the contrary, the Lung Health Study showed no sex difference in bronchodilator response [24].

Studies show sex differences in lung response to tobacco smoking. In one study, increased cigarette smoking resulted in a greater decline in FEV₁ in male smokers with moderate airflow obstruction, without much change in their female counterparts [25]. The increase in the quantity of cigarettes smoked was directly proportional to the development of wheezing and phlegm production in males, but not in females [26]. Conversely, the reduction in the number of cigarettes also improved symptoms in males more than females. Interestingly, the Lung Health Study noted that smoking cessation improved lung function to a greater extent in female smokers [27]. Among sustained quitters, women had an improvement in FEV₁ that was two and a half times more than in men [27]. Thus, smoking cessation may benefit women more with respect to lung function, but less in terms of symptoms. This may partly explain why women find it more difficult to give up smoking [28], and why nicotine replacement therapy is less effective in women [29]. These differences may be partly explained by sex differences in sensitivity of acetylcholine and beta receptors to cigarette smoke, resulting in differences in cigarette smoke metabolism [30]. These biologic variances could explain some of the sex-related differences in the prevalence of COPD and the severity of symptoms among miners in our study.

The sex difference in specific areas of mine work might be another explanation of the sex difference in the odds for COPD in our study. Unfortunately, we do not have data of the specific job description to confirm this theory, however female miners in our cohort had higher mean years of education compared to males, which may indicate that female miners are more involved in administrative and supervising positions. Due to sex discrimination and anti-women attitudes at work sites, the mining industry may favor male miners, with women making up less than 15 percent of the workforce. In earlier years, underground mine work, considered more strenuous, hazardous and “dusty” was considered to be exclusively a man’s job. Underground mining occurs in harsh conditions, under severe extremes of temperature, in areas equipped with inadequate facilities, which require the usage of very heavy machinery. Female miners were thought to be incapable of tolerating such conditions. Hence, female employees in mines often worked in the administrative, financial and human resources departments, with some working in above ground laboratories. Even after implementation of the Employment Equity Act of 1999, change was slow. Hence, it is possible that women miners were not exposed to the same intensity of mine dust as male miners, which may explain their lower odds for airflow obstruction and chronic bronchitis in our study.

The use of personal protective equipment (PPE) may play a major role in the prevention and reduction of severity of lung diseases in miners [31]. Whether female miners are more compliant than male miners with PPE to an extent that would decrease their risk for COPD is unknown. Compliance with PPE among miners can be limited by the discomfort of this equipment, particularly in extreme weather conditions. A new 3-year study at the National Institute for Occupational Safety and Health (NIOSH) is evaluating how the PPEs adversely affect the miners’ performance at work, with the hope to improve the PPE quality and increase the compliance to PPE.

The strengths of our study include the large cohort sample size, community-based participation and high proportion of minority subjects, including Hispanics and American Indians. We have used the LLN method to define airflow obstruction, which introduces less sex and age bias than using an arbitrary FEV₁/FVC ratio of 0.7, as defined by the COPD GOLD guidelines [32]. Our results were however, unchanged when the latter method was used to define obstruction (data not shown). The limitations include a relatively small proportion of women in this cross-sectional study, possibility of selection bias in the setting of voluntary participation in the screening program, lack of objective measures of mining dust exposure and lack of data on the use of personal protective equipment. Since the surveillance occurred in residential rural mining communities with mobile clinics instead of fixed urban clinics and without charge to the miner, the selection bias in relation to the voluntary participation in the surveillance program is minimized. The study outcomes are compared cross-sectionally in a study population, which was enrolled over a time period of 19 years. Thus, workplace exposure may have become less dustier and use of protective equipment may have increased over time, and occurrence of disease may have decreased over time, contributing to measurement bias. This bias is however, unlikely to explain away our findings since dust-related lung diseases have increased and not decreased in the past decade [33] and the measurement bias is likely non-differential across the two groups.

Further studies are needed to evaluate sex differences in COPD in miners. It will be worthwhile to study the specific areas in mines that women and men work in, and to also measure the “intensity” of dust burden in those areas. Future studies need to focus on reasons for an increase in the use of tobacco by women; on better physiologic and biologic descriptions of the sex differences in respiratory symptoms and diseases and also on the role of sociocultural and genetic differences.

Conclusions

Compared to their male counterparts, female miners in NM have less risk factors for chronic lung diseases; and are less likely to have the chronic bronchitis and emphysema phenotypes of COPD after adjustment for covariates. Future studies need to determine whether this sex difference is explained by residual confounding or a true biological difference.

Disclosure statement

No conflicts of interest of any author.

Additional information

Funding

This study was supported by Health Resources and Services Administration grant H37RH0057. LSC receives support from the UNM Comprehensive Cancer Center Support Grant NCI P30CA118100.