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COPD Clinic, National Institute of Respiratory Diseases of Mexico, Mexico City, Mexico
ABSTRACT
Rationale: Women exposed chronically to biomass develop airflow limitation, as tobacco smokers do, but their clinical profile and survival have not been described in detail.
Objective: To determine the clinical profile, survival, and prognostic factors of chronic obstructive pulmonary disease associated with biomass exposure and tobacco smoking.
Methods: During a 7-yr period (1996–2003), a consecutive series of 520 patients were recruited and followed up at the COPD Clinic of the National Institute of Respiratory Diseases. Prognostic factors of survival were evaluated taking into account the interaction between sex and exposure.
Measurements: Spirometry, arterial blood gases and oxygen saturation, body mass index, exercise capacity, and health-related quality of life were performed at baseline. The main outcome was survival.
Main Results: A total of 481 patients were followed up. The patients in the biomass group, mainly women (84%), were older and shorter and had a greater body mass index than those in the tobacco group (p < 0.0001). Airflow obstruction was more severe in smokers (p < 0.001). Quality of life and distance walked showed similar abnormalities in both groups. In the multivariable Cox regression analysis including an interaction term exposure-sex, we found that age (relative risk [RR], 1.02; 95% confidence interval [CI], 1.02–1.07), FEV1 as percentage of predicted (RR, 0.96; 95% CI, 0.96–0.99), body mass index (RR, 0.95; 95% CI, 0.90–1.01), and oxygen saturation (RR, 0.96; 95% CI, 0.92–0.99) were predictors of mortality but not exposure or sex.
Conclusions: Women exposed domestically to biomass develop chronic obstructive pulmonary disease with clinical characteristics, quality of life, and increased mortality similar in degree to that of tobacco smokers.
Key Words: chronic obstructive pulmonary disease exposure mortality sex women
Cigarette smoking is by far the most important risk factor for chronic obstructive pulmonary disease (COPD) in developed countries (1, 2) and consequently most of the information on COPD comes from smokers (3, 4). Tobacco smoking clearly increases respiratory symptoms, lung function abnormalities, and mortality (5–7), but knowledge about COPD can advance observing the course of the disease provoked by agents other than tobacco. Indoor air pollution from biomass burning has been implicated as a risk factor for the development of chronic bronchitis and COPD, especially in developing countries (8–12). This exposure is important in regions where biomass is used as a fuel for cooking and heating in poorly ventilated dwellings, leading to high levels of particulate matter in indoor air (9). The clinical profile of COPD associated with biomass smoke (BS) and its prognostic factors have not been well described thus far, although it has been reported that mainly women are affected (13). Therefore, the aim of this study was to describe the clinical, functional, and health-related quality of life (HRQL) and survival characteristics of a cohort of patients with COPD exposed to BS. These patients live at moderate altitudes, have never been smokers, and have lifelong exposure to biomass smoke. Data were compared with those coming from patients with COPD associated with tobacco smoking. In addition, prognostic factors for mortality were assessed in both groups. Some of the results of this study have been previously reported in the form of an abstract (14).
METHODS
The study was performed in Mexico City at the COPD Clinic of the National Institute of Respiratory Diseases, a referral hospital that mainly provides a service to the economically deprived population of Mexico. Mexico City's mean altitude is 2,240 m above sea level; mean PaO2 and PaCO2 values in young subjects are about 66 to 72 and 28 to 32 mm Hg, respectively (15).
We included all patients with diagnosis of COPD on the basis of the American Thoracic Society/European Respiratory Society (ATS/ERS) standards for the diagnosis and treatment of patients with COPD (16), referred to the clinic for evaluation from 1996 to 2003. Risk factors for COPD were considered to be exposure to either BS or tobacco smoke (TS) as determined by the clinical interview and a standardized Spanish version of the ATS questionnaire with the addition of some questions referring to cooking fuels (17). BS exposure was considered a significant and possible risk factor for COPD when patients cooked with a biomass stove for a period of at least 6 mo. Cumulative exposure was expressed as hour-years (h-yr), the product of the number of years cooking with wood stoves multiplied by the average number of hours spent daily in the kitchen. The risk of airflow obstruction increases briskly above 200 h-yr (13). Cumulative smoking was expressed as pack-years. At baseline, all patients underwent physical examination, routine laboratory studies, including chest X-ray, ECG, spirometry, arterial blood gases, a 6-min walk test (6MWT), and HRQL using the Chronic Respiratory Questionnaire (CRQ). Evaluation was made when patients had been free of exacerbations for at least 1 mo. Post-bronchodilator spirometry was done with a dry rolling seal volume spirometer (Sensormedics, Yorbalinda, CA) following the procedures recommended by ATS (18) and using Mexican standard reference equations (19), which are similar to the third National Health and Nutrition Examination Survey values for Mexican Americans (20). A translated version of the CRQ (21) previously validated in the Mexican population (22) was administered at baseline. The 6MWT was performed following a validated protocol (23, 24) using distance walked during the second test for the analysis. To compare severity of symptoms in both groups, data from the St. George's Respiratory Questionnaire applied to the last 110 patients were included. The resources of health services during 1 yr were evaluated by reviewing the clinical charts of 66 randomized patients. The study was approved by the local ethics committee.
Statistics
Patients were compared according to exposure using a t test for independent groups for normally distributed variables or a Mann-Whitney test. Zero time was considered the hospital admission day for the initial evaluation. In December 2004, we obtained the vital status of each patient by reviewing clinical charts and using telephone calls or telegrams in all patients who had been lost in the follow-up. Data from patients lost to follow-up and not located in December 2004 were analyzed to the point of their last contact. The cause of death was obtained from clinical charts, necropsy, or relatives.
Data were analyzed with STATA for Windows version 8.0 (StataCorp, College Station, TX) (25) to generate survival curves according to the Kaplan and Meier method, log-rank tests, proportional-hazards models, and median survival times.
Survival was assessed in relation to all baseline (zero time) variables and examined individually and in pertinent combinations, both maintained in dimensional form and categorized in two or three groups of an equal number of patients. Variables evaluated were as follows: age, sex, type of exposure, body mass index (BMI), FVC and FEV1 expressed as percentage of predicted, FEV1/FVC, PaO2, SaO2, PaCO2, and the 6MWT.
Survival between groups was compared by the log-rank 2 test. Because most subjects in the biomass group were women, whereas the tobacco group was formed mainly by men, and considering the potential influence of sex, we analyzed separate models in terms of survival for women and men, respectively. We also tested the interaction between sex and exposure on survival.
Univariate Cox proportional hazard analyses allowed identification of significant predictors of mortality that were further evaluated in a multivariate model.
RESULTS
Initially, 647 consecutive patients were evaluated to be monitored by our service. Of this number, 127 were excluded from our cohort due to comorbidities such as obesity and sleep apnea (32), chronic and severe asthma (49), bronchectasies (9), a BMI higher than 32 (15), uncertainty on diagnosis because of lack of risk factor such as TS and/or wood smoke (7), an obstructive lung pattern with exposure to fumes and dust (6), normal spirometry despite tobacco use (4), and the inability to keep coming to our center for follow-up and surveillance (5). The remaining 520 patients, all with COPD with varying degrees of severity, were accepted for our study and evaluated. Thirty-nine patients (7.6%) were seen only once and their final survival status was unavailable. They did not differ significantly from the rest of the cohort with respect to baseline measurements of FEV1, BMI, gas exchange, or HRQL. Table 1 shows the general characteristics of the remaining 481 patients. Most of the patients exposed to BS were women (84%), whereas most of the smokers were men (76%; p < 0.0001). Of the total number of women, 58% belonged to the BS group and 42% belonged to the TS group. Approximately 82% of the patients were currently residing in Mexico City and the remaining patients in the metropolitan area. However, most patients with biomass exposure were living in a rural area during the time of exposure. In this regard, no significant differences were observed between groups.
Patients in the BS group were older and shorter and had a greater BMI than those in the TS group. The mean cumulative exposure was 214 ± 146 h-yr for the biomass group and 56 ± 43 pack-years for smokers. The use of long-term oxygen in 47% of the patients and the use of other medications did not differ significantly in both smokers and nonsmokers. No differences in severity of cough, phlegm, sputum, and wheezing were found between the exposure groups (Table 1).
Regarding resources of health, there were no statistically significant differences between the TS and BS groups in the number of emergency room admissions (0.91 ± 2.45 vs. 1.10 ± 1.84), hospital admissions (0.98 ± 2.48 vs. 1.19 ± 1.72), and exacerbations (0.98 ± 2.80 vs. 1.29 ± 1.85), respectively.
According to the ATS/ERS classification, a significant proportion of patients (28%) from the TS group had stage IV disease. In contrast, only 7% of patients in the BS group were in this category (p < 0.0001). Both groups had airflow limitation and hypoxemia, but no differences were found in terms of FVC%predicted or PaO2. However, FEV1 as a percentage of predicted and FEV1/FVC ratio were significantly lower (p < 0.0001) in tobacco smokers than in BS patients. On the other hand, %SaO2 was lower and PaCO2 was higher in the BS group compared with the TS group (p < 0.01; Table 1). Quality of life and distance walked showed similar abnormalities in both groups.
Patients had a median follow-up of 83 mo with 124 (26%) deaths occurring in the period: 25 patients (20%) were from the BS group and 99 (80%) were from the TS group. Death occurred at home in 51 patients, at the hospital in 33, and at other hospitals in 40. The main cause of death in the TS group was due to respiratory failure (60%), ischemic heart disease (12%), and lung cancer (3%). In 15% of the cases, the cause of death was not established. In the BS group, 48% died due to respiratory failure and in 52% (13 patients) the cause of death was not recognized because the majority of this group died at home.
Compared with survivors, nonsurvivors were older and thinner and had a reduced FEV1, FEV1/FVC ratio, PaO2, and SaO2. Similarly, the score domains of emotion, mastery, and total score of the CRQ at first evaluation were worse in nonsurvivors than in survivors.
Women exposed to tobacco or biomass showed a better crude survival than men exposed to tobacco (log-rank test, p = 0.002; Figure 1). In univariate Cox regression analysis, age, sex, type of exposure, FEV1 as percentage of predicted, FEV1/FVC, BMI, SaO2, PaO2, distance at 6MWT (in meters), and CRQ score were significantly associated with mortality (Table 2).
In the multivariate Cox regression analysis, including the variables with a statistically significant association with mortality in the univariate analysis and an interaction term exposure-sex, we found that age, FEV1 as percentage of predicted, BMI, and SaO2 were predictors of mortality but not exposure or sex (Table 3 and Figure 2).
DISCUSSION
In the present study, the most relevant findings were that patients exposed to BS are women and have less airflow obstruction, whereas smokers are mainly men and have more severe obstruction. Mortality was similar in smokers and in women exposed to BS once FEV1, SaO2, BMI, and age were taken into account. Finally, both groups had similar bronchial symptoms, exercise capacity, quality of life, use of health services, and supplementary oxygen.
BS is composed of a relatively equal mixture of coarse (2.5– 3.5 μm) and ultrafine/fine (0.02–2.5 μm) particles and can penetrate deeply into the lung, producing a variety of morphologic and biochemical changes (26, 27). Several reports document that smoke from biomass combustion can produce airflow limitation, respiratory failure, cor pulmonale (9, 10, 28, 29), and pathologic changes of COPD similar to those observed in cigarette smokers (30–32). The majority of the investigations related to biomass exposure have certain limitations because of their cross-sectional designs. To our knowledge, this is the first longitudinal study describing the clinical, functional, HRQL, and survival characteristics of subjects exposed to chronic inhalation to BS in comparison with smokers. Our study includes a large sample of patients studied, monitored, and treated similarly.
According to the World Health Organization, indoor air pollution from solid fuel use is responsible for more than 1.6 million annual deaths and 2.7% of the global burden of disease (33, 34). In rural areas of developing countries, exposure to BS produces a higher burden of COPD and disease than tobacco. This occurs mainly in women cooking in inadequately ventilated houses and shacks where the concentrations of particulate matter in the room air are in the milligram per cubic meter range, well above the recommended atmospheric standards (35). Our study did not measure air pollutant concentrations at home. In this sense, the history of exposure was obtained only through interview (7), but because women are usually dedicated full time to domestic activities for many years, a good recall of the average number of hours per day spent in cooking was expected.
As in other COPD survival studies, we confirmed in our patients an increased risk of death secondary to a low BMI (36), a low FEV1 as percentage of predicted (37), and hypoxemia (38, 39). In Mexico City, hypoxemia is common, as altitude complicates the gas exchange abnormalities present in patients with COPD, and becomes a central feature of the disease in this city.
One of the main concerns about this cohort was that subjects in the tobacco group were mainly men, whereas those in the biomass group were mainly women. We tested using either one model with an interaction term exposure-sex, or separate models comparing men and women exposed to tobacco, or women exposed to biomass or tobacco. We could not find differences in mortality due to sex or exposure once we took into account FEV1 and SaO2, BMI, and age.
In our study, the degree of airflow limitation was worse in tobacco smokers than in subjects exposed to biomass. Whether biomass exposures affect lung growth and consequently function in adulthood and elderly life is unclear. However, BS exposure starts early in life because women cook using wood stoves in the same room where children sleep, play, and eat, increasing the risk of respiratory infections and a possible reduction in lung growth. Likewise, because the girls spend more time with their mothers and help them with the domestic work at a very early age, these girls as women may be more susceptible to present with pulmonary affection, because they may have a very long time of exposure to biomass, lasting at least 40 to 50 yr. Women stop the exposure when they leave the rural community and move out to live in urban areas, such as Mexico City. In a cross-sectional study, Regalado and colleagues (40) evaluated symptoms and lung function in 834 women with a mean age of 58 yr who were exposed to biomass. Although no differences in FEV1 or FVC were found, the FEV1/FVC ratio was significantly lower in women exposed to biomass in comparison with those cooking with a gas stove. These findings suggest that some structural damage could appear at early adulthood. However, more epidemiologic research is needed to determine the impact of the biomass in lung functional growth from the first stages of life up to adulthood and/or old age.
We are unaware of any particular genetic susceptibility present in women from rural areas of Mexico, who usually have a significant indigenous background.
We were able to obtain survival data on 92.5% of the patients. The effect of including or not including the patients lost during the follow-up in the overall mortality of those exposed to tobacco is minimal and in those exposed to biomass it was moderate, even if we assume that all of them died. Most patients died at home, and we could obtain a likely cause of death in 62% of the patients. The patients were, in the vast majority of the cases, considered terminal or in an advanced stage of the disease. The cause of death in all patients who died in the hospital was related to pulmonary disease. Therefore, we consider that the results of this study closely represent the survival of treated patients with COPD in tertiary care referral hospitals of Mexico. Despite being a tertiary referral center, an important number of patients are not referred by other primary centers and they present on their own. The policy of the Respiratory Institute allows the admission of any outpatient asking for medical services and explains why we had a large percentage of patients with stage II COPD.
HRQL has achieved a preponderant role in evaluating the severity of COPD (41) and has correlated strongly with mortality (42, 43). In our study, HRQL predicted mortality in univariate analysis, but not after adjusting for other variables. It is well known that women are considered to experience worse HRQL than men (44). However, when we analyzed separate models for men and women, no association between sex, mortality, and HRQL was found either in the whole cohort during follow-up (8 yr) or in a short 2-yr follow-up (45).
In summary, we demonstrated that women exposed domestically to wood smoke while cooking for many years develop COPD with clinical characteristics, quality of life, and use of health resources similar to that of tobacco smokers. Smokers have more severe airflow obstruction, but once this is taken into account, mortality is similar to that of the biomass group.
FOOTNOTES
Originally Published in Press as DOI: 10.1164/rccm.200504-568OC on December 1, 2005
Conflict of Interest Statement: None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
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