Prevention of COPD 15 HyoungKyu Yoon Introduction Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases . Chronic airway inflammation, which is a pathogenic mechanism of COPD, is caused by gene–environment interactions. Although the genetic factors contributing to gene–environment interactions cannot be controlled, COPD can be prevented if the environmental risk factors are eliminated. COPD prevention is more important than treatment because it is almost impossible to lung function normalization after airflow limitation occurs in COPD. Rates of COPD have continuously increased worldwide, as people become increasingly exposed to COPD environmental risk factors, especially in developing countries. Until now, the majority of research and therapeutic interventions have focused on treating COPD after it develops. There has been limited focus on COPD prevention. Efforts to prevent COPD are lacking, HK. Yoon Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea e-mail: email@example.com particularly because they have not focused on primary prevention. Strategies used to prevent any chronic disease can be divided into three stages: (1) primary prevention to suppress the occurrence of disease, (2) secondary prevention to diagnose and treat a disease in its early stages, and (3) tertiary prevention to treat a patient with a disease in progress so that he or she can resume a normal life. In the case of COPD, primary prevention involves preventing healthy people from becoming exposed to COPD risk factors to prevent the development of COPD. Primary prevention is the most crucial aspect of COPD management. To make an effective COPD prevention strategy, it is necessary to clarify what a COPD risk factor is. Among several risk factors, smoking is the most important for COPD. Smoking prevention and smoking cessation are central aspects of epidemiological measurements to counteract COPD epidemics . However, at least one-fourth of patients with COPD are nonsmokers, and the burden of COPD in nonsmokers is higher than previously believed . Risk factors for COPD in nonsmokers include genetics, long-standing asthma, outdoor air pollution (from traffic and other sources), environmental smoke exposure, indoor air pollution such as biomass smoke, diet, recurrent respiratory infection in early childhood, tuberculosis, and exposure to toxic gas or dust in the workplace. Indoor pollution, which is caused by using biomass for heating and cooking in developing © Springer-Verlag Berlin Heidelberg 2017 S.-D. Lee (ed.), COPD, DOI 10.1007/978-3-662-47178-4_15 211 212 countries, is a significant problem. Additional causes of COPD include old age, low socioeconomic status, chronic bronchitis, airway hypersensitivity, and infection. Preventive strategies are also important in patients with established COPD. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk of repeated exacerbations, eventually leading to end-stage disease. Without major prevention efforts, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with increased suffering and costs. Therefore, secondary prevention, which involves diagnosing COPD in its early stages and preventing constant exposure to risk factors, is also very important. Indeed, preliminary research has shown that early intervention based on minimizing these risk factors might be a cost-effective way to prevent COPD. The main point of tertiary prevention is to prevent death by COPD by controlling the rapid decrease of lung function through proper treatment and by preventing acute exacerbation. This chapter primarily discusses the primary prevention of COPD and the use of spirometry related to early diagnosis during secondary prevention. Tertiary prevention is about controlling the progression of COPD and treatment related to the prevention of acute exacerbation. rimary Prevention: COPD Risk P Factors and Their Prevention Interventions based on reducing exposure to COPD risk factors are critical to strategies aimed at preventing COPD. The most important way to prevent COPD is to avoid smoking and reduce exposure to toxic gases or dust in many ways, such as via occupational exposure. Smoking The major risk factor for the development of COPD is cigarette smoking, and 90% of deaths HK. Yoon due to COPD are directly attributable to smoking. It is well known that cigarette smoking accounts for 80% of the total COPD burden. Therefore, smoking cessation is the most effective means of halting or slowing the progress of this disease. Although previous studies suggested that 10–15% of smokers develop COPD, more recent studies indicate that some degree of airflow limitation is present in up to 50% of smokers, with clinically significant COPD being present in approximately 25% of smokers . Smoking cessation is the most effective means of stopping the progression of COPD as well as increasing survival and reducing morbidity. This is why smoking cessation should be the top priority in the treatment of COPD . Presently, quitting smoking and home oxygen therapy are the only ways to lower mortality rates among COPD patients. Smoking cessation can lead to primary, secondary, and tertiary prevention, so it is the most important part of any COPD prevention strategy. Encouraging people to quit smoking in order to prevent further lung damage is the most important and valuable task and should be the most important goal of all doctors who treat COPD. Of course, this is true for all smokers, whether they are COPD patients or not. However, many COPD patients are unable to quit smoking. Smoking is very common among COPD patients; 54–77% of mild COPD patients and 38–51% of severe COPD patients smoke . In order to achieve a reasonable quit rate, it is necessary to administer behavioral support (e.g., counseling) in combination with pharmacological drugs . Preventing or limiting lung damage through smoking cessation should be the foremost goal of all physicians managing COPD. Of course, all smokers should be encouraged to stop smoking, whether they have COPD or not. Smoking cessation reduces the rate of FEV1 decline and improves respiratory symptoms and health- related quality of life. Even brief counseling can be effective. All doctors must ask their patients whether they smoke and determine if they want to quit smoking, and smokers should be encouraged to quit. 15 Prevention of COPD Of the various behavioral interventions available that can increase the likelihood of smoking cessation, one of the simplest and most effective strategies that physicians can use is to simply advise their patients to quit, particularly if this advice is combined with information about the patient’s “lung age” . However, doctors should consider drug treatment to induce more effective smoking cessation results. First-line pharmacological drugs used for smoking cessation include nicotine-replacement therapy (patches, gum, inhalers, nasal sprays, lozenge/tablets, and oral sprays), varenicline, and bupropion SR. These drugs have scientific, well- documented efficacy when used for 2–3 months [6, 8, 9]. All pharmacologic therapies must be combined with support and counseling for maximum efficacy . Verified quit rates at 12 months of follow-up were 13.6 and 6.4% in the intervention and control groups, respectively. Thus, telling smokers their lung age based on spirometry results may increase the likelihood that they will quit smoking . Exposure to Biomass Smoke It is increasingly recognized that a significant proportion of patients with COPD are nonsmokers. This proportion is generally higher in developing countries, where exposure to biomass smoke for heating and cooking is common (e.g., up to nearly 70% of people in India with COPD are nonsmokers) , but it is also significant in the developed world, with just under 40% of people with COPD in a recent New Zealand study being people who smoked and overall international figures ranging from 25 to 45% . According to the World Health Organization, approximately 50% of all households and 90% of rural households utilize biomass or coal fuels for cooking and heating in the world. About three billion people worldwide are exposed to smoke produced from biomass or coal fuel burning . According to the World Health Organization, approximately 50% of all families and 90% of 213 families in rural areas use biomass or coal for cooking and heating in developing countries. About three billion people are affected by smoke from biomass or coal combustion. There are several ways to reduce indoor air pollution exposure, such as by changing fuel type or using an improved vented coal stove. Most of all, recognition of indoor air pollution as a cause of COPD is a key element of prevention. Outdoor Air Pollution According to longitudinal cohort studies, outdoor air pollution is related to a decrease in lung function in children and adolescents [13, 14]. Therefore, the risk of COPD can be increased upon exposure to air pollution. This harmful effect of air pollution may be caused by lung development impairment during childhood. Several studies have indicated that particulate pollution and nitrogen dioxide (NO2) are significantly associated with impaired lung development. The two air pollutants that most commonly exceed standards are ozone and particulate matter. Ozone and particulate matter can harm anyone if levels are sufficiently elevated, but health risks from air pollution are greatest among vulnerable populations. Both ozone and particulate matter can cause pulmonary inflammation, decreased lung function, and exacerbation of asthma. Particulate matter is also strongly associated with increased cardiovascular morbidity and mortality. Children, older adults, and other vulnerable persons may be sensitive to lower levels of air pollution. For persons who are aware of local air pollution levels, the seriousness of air pollution (provided by a government agency) can be checked on the Internet in real time. For avoiding exposure to outdoor pollution, simple measures can be taken; these include limiting the exertion and time spent outdoors when air pollution levels are highest and reducing the infiltration of outdoor air pollutants into indoor spaces . In adults, higher levels of particulate matter (<10 mm [PM10]) are negatively associated with FVC, FEV1, and FEV1/FVC. Higher PM10 levels are also correlated with an increased risk of COPD. HK. Yoon 214 COPD acute exacerbation and symptoms become worse when outdoor air pollution is high. COPD patients should limit their outdoor activity, and younger people also needed to avoid exposure to outside when air pollution levels are high. The most effective solution is to reduce air pollution, which will require more effort across the country as well as international cooperation, as pollution is not limited to the country; it is produced in and also influences nearby countries. vitamin E, have good lung function, but the reasons for this are not clear. Many studies report COPD “outbreaks” in obese patients although many other studies have opposite findings . The relationship between nutrition and COPD prevention is not clear, but proper nutrition and maintaining a normal weight lead to a better prognosis in COPD patients. Bronchial Asthma Occupational Exposure There is consistent evidence from population studies that a median of 10–15% of the total burden of COPD is associated with exposure to inhaled vapors, gases, dust, and fumes (VGDF) in the workplace . The evidence supporting these risks varies. For example, the role of coal, cadmium, silica, and biomass in COPD is relatively well established, and the role of more generic exposure to potentially harmful inhaled substances in the workplace is supported by evidence from a number of studies. The causes of inorganic dust exposure are welding, coal, coke, asphalt, silica, cement, tunnel work, cadmium, glass, bangle, and bleach. The causes of organic dust are cotton, flax, jute, farming, grain, and wood. Control measures to prevent or reduce exposure to VGDF in the workplace are the most effective methods of reducing occupational COPD. However, it is also important to diagnose COPD at the early stage and in patients with rapidly decreasing lung function. These individuals can be identified at work by accurate annual assessments of lung function . Lung function programs and health surveillance systems are needed for this purpose. Workers in high-COPD- risk workplaces should undergo regular examinations of lung function and surveys of pulmonary symptoms. Nutrition Many studies have reported that people who eat a diet high in antioxidants, such as vitamin C and Asthma is associated with accelerated lung function decline. This decline is greater in smoking asthmatics. Low baseline lung function (FEV1% predicted), less reversibility to β2-agonists, more severe bronchial hyperresponsiveness, mucus production, male sex, and frequent exacerbations are associated with an excess decline in FEV1 among persons with asthma. Most studies indicated that irreversible obstruction occurs in older patients with a longer duration of asthma; duration of asthma appears to be more important than chronological age. Whether interventions designed to control tissue remodeling in asthma can prevent the development of COPD is a question that needs to be addressed. Several studies have shown that childhood asthma may be associated with abnormal lung function in adults. Optimal control of bronchial asthma, especially during childhood and adolescence, is important to prevent permanent impairment of lung function. Risk Factors of Early Origin There is growing evidence that COPD may begin very early in life. It may be associated with lung damage to the developing lung during the intrauterine period and the first few years of postnatal life, when lung growth and development are rapid. Early-life risk factors may include fetal and early infant growth patterns; preterm birth; maternal obesity, diet, and smoking; the child’s diet; allergen exposure; respiratory tract infections; and genetic susceptibility . The most 15 Prevention of COPD important risk factor for chronic obstructive lung diseases in childhood is maternal tobacco smoking . Recently, information about early-life risk factors has become more accessible, but people do not know how big this influence is, and there is no effective prevention. However, it will be very important to identify those individuals who are exposed to these risk factors early in life in order to begin proper observation and treatment. Furthermore, physicians need to recognize that lung disease is potentially associated with early- life insults and provide better education regarding diet, exercise, and the avoidance of smoking to preserve the precious reserves of lung function in susceptible adults . Secondary Prevention Early Detection: Spirometry According to the Lung Health Study (LHS), lack of awareness and knowledge about COPD among healthcare providers is an important factor in misdiagnosis and/or delays in diagnosis. Major overhauls in both cultural and primary care settings are needed to achieve the goal of early COPD diagnosis. Extensive innovation and changes are needed in primary treatment to diagnose COPD in its early stages. Spirometry is a method commonly used to diagnose early-stage COPD. Medical personnel should be educated to perform spirometry when smokers older than 40 years show respiratory symptoms . The LHS showed that spirometry can be successfully used to assess smoking cessation as a means to prevent COPD progression . According to recent research, spirometry can effectively encourage patients to quit smoking, especially those whose spirometry results show respiratory obstruction . However, in other studies, public spirometry not with high-risk groups did not effectively encourage people to quit smoking. However, there are limitations to these findings, as many young people were included as a target group in this research. There is no definite evidence showing that public 215 spirometry in smokers older than 40 years increases the possibility that a person will quit smoking or identifies early-stage COPD patients. Smoking Cessation in COPD Patients The LHS, a 5-year early intervention study combining behavioral therapy and nicotine gum versus standard care in 3926 smokers with mild-to-moderate airflow limitation due to COPD, demonstrated that participants who quit smoking and remained abstinent had improved FEV1 in the year after quitting smoking and demonstrated a subsequent age-related decline in FEV1 that was half the rate of continuing smokers . This benefit of sustained smoking cessation in slowing the rate of progressive lung function loss to a level comparable to that of never- smokers persisted for at least an additional 6 years among the quitters who remained abstinent . Brief advice and spirometry are effective to support smoking cessation in COPD patients. In one study, subjects were made to underwent spirometry and were given smoking cessation advice by a nurse and a letter from a physician reinforcing the results of their spirometry annually for 3 years. After various exclusions, of those remaining in the study after 3 years, 25% of smokers with COPD at baseline had been smoke- free for 1 year compared to 7% of those smokers with normal lung function who received the same level of intervention . In a separate analysis of data from the LHS, a reduction in the number of cigarettes smoked per day in the absence of complete cessation did not influence the rate of decline in lung function unless the percentage reduction was very marked (>85%), a degree that was achieved by only a small minority of subjects . When COPD patients quit smoking, infection causing acute exacerbation and a decrease in lung function occurs at lower rates. Additionally, COPD patients who quit smoking consistently show reasonable decreases in allcause mortality, cardiovascular disease, lung cancer, coronary heart disease, and death due to other factors . HK. Yoon 216 Tertiary Prevention tions could be more effective in early disease than in late disease . Prevention of Disease Progression COPD is a heterogeneous disease. As shown in the ECLIPSE study, the speed of decrease in lung function varies among patients, such that one patient can show almost no decrease in lung function while another patient shows a rapid decrease. Tertiary prevention of COPD involves controlling this decrease of lung function by finding the causes of the rapid decrease in lung function and providing active treatment that is designed for end-stage COPD. It is very important to discover biomarkers to help identify this rapid-decliner group early. To discover this biomarker, it is necessary to use diverse methods, such as spirometry and chest computed tomography scan and to assess airway hyperreactivity, health status, physical activity, and comorbidity. The proper treatment of COPD phenotypes has not been identified, but phenotypic-specific treatment will be a crucial aspect of COPD tertiary prevention in the future. Smoking cessation is the most crucial and effective method to control the speed of lung function decline in COPD patients. Therefore, all COPD patients must not smoke, regardless of the severity of COPD. Several large randomized controlled studies [22, 28, 29], suggest that disease progression can be slowed in established COPD. In the TORCH study, spirometry also showed significantly reduced progression with fluticasone propionate (13 mL/year), salmeterol (13 mL/year), and the combination (16 mL/year) compared with placebo although these differences are less than the generally accepted clinical target of 20 mL/year. The UPLIFT study reported no significant difference in lung function decline between patients given tiotropium and those given placebo. However, among individuals with moderate disease, the rate of FEV1 loss among those given tiotropium was 6 mL less than that of controls. Although not tested for primary or secondary prevention, these findings suggest that, as with smoking cessation, pharmacological interven- Prevention of Acute Exacerbation Acute exacerbation represents the biggest portion of the socioeconomic cost of COPD treatment. Additionally, acute exacerbations reduce quality of life and lung function and can even cause death. 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