Strategies in Preserving Lung Health and Preventing COPD and Associated diseases: The National Lung Health Education Program

Anthonisen NR , Connett JE , Kiley JP , et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: The Lung Health Study. JAMA 1994; 272:1497–1505. This landmark article reported the results of the Lung Health Study. This study enrolled 5,887 patients in 10 centers in North America. Twothirds were randomized to receive special care with strong emphasis on smoking cessation; ipratropium was randomly assigned to one half of special-care patients. One-third received “usual” care. At the end of 5 years, more patients receiving special care had stopped smoking compared with those having usual care. Those who stopped smoking had an initial increase in FEV, followed by a slow decline. At the end of 5 years, their FEV, was the same as at the beginning of the study. Continuing smoking was associated with an excessive loss of FEV1. Ipratropium was effective in improving FEV, above baseline throughout the study. Ipratropium did not improve baseline FEV1. The most common cause of death was lung cancer (n=57), followed by heart attack and stroke (n=37). No patient died of COPD during the study because FEV, decline had not yet reached the symptomatic range.

The health consequences of smoking: chronic obstructive pulmonary disease a report of the Surgeon General. Washington DC: Office of Smoking and Health; 1984, DHH publication No. CPHS, p 455. This is the classic collection of data showing how cigarette smoking is the basic cause of chronic obstructive pulmonary disease.

Burt VL , Whelton P , Roccella EJ , et al. Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension 1995; 25:305–13. This examination of a sample of the US population showed a striking improvement in patient awareness of hypertension and a significant improvement in treatment and control, but not a good attainment of ideal BP control.

Johnson CL , Rifkind BM , Sempos CT , et al. Declining serum total cholesterol levels among US adults: the National Health and Nutrition Examination Surveys. JAMA 1993; 269:3002–08. This important study revealed a decrease in the average cholesterol level in the United States during the past 30 years. A reduction of deaths from heart attack and stroke paralleled this reduction in cholesterol.

Expert Panel Report. Guidelines for the diagnosis and management of asthma. Bethesda MD: National Institutes of Health; 1991, NIH publication 91-3042. The detailed report of the National Asthma Education Program; 36 pages.

Barnes PJ . A new approach to the treatment of asthma. N Engl J Med 1989; 312:1517–27. A landmark article by one of the world's best known authorities on asthma mechanisms and treatment. It stressed the importance of infections as the basic factor in asthma. In addition, it emphasized the importance of treating inflammation in maintenance management and the use of bronchodilators for breakthrough attacks.

Goldstein RA , Paul WE , Metcalfe DD , et al. NIH conference: asthma. Ann Intern Med 1994; 121:698–708. A report of the NIH Conference on Asthma, during the development of the National Asthma Education Program.

Mathias CA . Management of severe exacerbations of asthma. Am J Med 1995; 99:298–308. This article describes treatment strategies in the management of asthmatic emergencies, focusing on the use of systemic corticosteroids to treat inflammation.

Global Initiative for Asthma. Global strategy for asthma management and prevention: NHLBI/WHO workshop report. Bethesda MD: National Institutes of Health, National Heart, Lung, and Blood Institute, January 1995; publication No. 95-3569. A report of the Global Initiative for Asthma, known as the GINA project. This 137-page report outlines a global strategy for asthma management and prevention, the result of a combined NHLBI/WHO Workshop.

Siafakes NM , Vermeire P , Pride NB , et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995; 8:1398–1420. This is a consensus statement of the European Respiratory Society. COPD is the third most common cause of death in Europe. Early identification in asymptomatic patients must be accomplished via spirometric testing. Treatment of all stages of disease can improve the length and quality of life.

American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152:S78–83. A summary of definitions, epidemiology, pathophysiology, and diagnosis in staging (COPD) in the complete management.

Niewoehner DE , Sobonya RE . Structure-function correlations in chronic obstructive pulmonary disease. In: Baum GL , Wolinsky E , eds. Textbook of pulmonary diseases. Boston: Little Brown, 1993; 973–93. A readable description of the mechanisms for expiratory airflow limitation.

Snider GL , Faling LJ , Rennard SI . Chronic bronchitis and emphysema. In: Murray JF , Nadel JA , eds. Textbook of respiratory medicine. Philadelphia: WB Saunders, 1994; 1331–97. A comprehensive review of chronic bronchitis and emphysema in a popular textbook.

Woolcock AJ . Asthma. In: Murray JF , Nadel JA , eds. Textbook of respiratory medicine. Philadelphia: WB Saunders, 1994; 1288–1330. A comprehensive review of asthma in a major textbook.

Cosio M , Ghezzo H , Hogg JC , et al. The relations between structural changes in small airways and pulmonary function tests. N Engl J Med 1978; 298:1277–81. A “classic” reference that showed a correlation between tests of socalled “small airways disease” and simple spirometric tests with grades of airway inflammation and fibrosis. Among the common spirometric tests, the FEV1/FVC percent related best to the lesions found in small airways.

Mitchell RS , Stanford RE , Johnson JM , et al. The morphologic features of the bronchi, bronchioles and alveoli in chronic airway obstruction: a clinicopathologic study. Am Rev Respir Dis 1976; 114:137–45. An early clinical pathologic correlative study related histologic alterations to airflow limitation.

Petty TL , Silvers GW , Stanford RE . Functional correlations with mild and moderate emphysema in excised human lungs. Am Rev Respir Dis 1981; 124:700–04. This is a study in 24 human lungs with various degrees of emphysema. The major reason for reduction of airflow proved to be a reduction in elastic recoil.

Laurell CB , Eriksson S. The electrophoretic alpha 1-globulin pattern of serum in a-1-antitrypsin deficiency. Scand J Clin Lab Invest 1963; 15:132–40. The classic description of a-1-antitrypsin deficiency state and its association with emphysema, which clusters in family and often begins at an early age.

Tager IB , Rosner B , Tishler PV , et al. Household aggregation of pulmonary function and chronic bronchitis. Am Rev Respir Dis 1976; 114:485–92. A study of 148 randomly selected households in an urban community showed a significant tendency for chronic bronchitis to aggregate within households. The reduction of FEV, was significantly correlated between siblings. Maternal household smoking correlated with FEV, in children.

Carp H , Janoff A. In-vitro suppression of serum elastase inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes. J Clin Invest 1979; 63:793–97. One of the first reports from a series of investigations demonstrating smoke-induced oxidation and inactivation of a-1-antitrypsin. There have been many subsequent studies.

Robbins RA , Thompson AB , Koyama S , et al. Cigarette smoking and neutrophil migration. J Immunol Res 1990; 2:178–88. A review of the multiple mechanisms by which smoke can induce a neutrophilic inflammatory response.

Nakamura Y , Romberger DJ , Tate L , et al. Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis. Am J Respir Crit Care Med 1995; 151:1497–1503. A recent paper suggesting that cigarette smoke can directly inhibit lung repair responses.

Marine WM , Gurr D , Jacobsen M. Clinically important respiratory effects of dust exposure and smoking in British coal miners. Am Rev Respir Dis 1988; 137:106–12. This is a unique study of 3,380 British coal miners. Its good was to access the independent contribution of smoking and responsible coal dust to clinically significant measures of respiratory dysfunction. Both smoking and coal dust were found to make separate contributions to COPD and were addictive. Preventive strategies should aim to reduce both pollutants.

Buist AS , Vollmer WM . Smoking and other risk factors. In: Murray JF , Nadel JA , eds. Textbook of respiratory medicine. 2nd ed. Philadelphia: WB Saunders, 1994; 1259–87. This chapter summarizes the known and possible risk factors associated with COPD.

Zejda JE , McDuffie HH , Dosman JA . Respiratory effects of exposure to grain dust. Semin Respir Med 1993; 14:20–30. This is a comprehensive review of the mechanisms involved in the chronic bronchitis of grain workers.

Bates DV . The fate of the chronic bronchitic: a report on the 10-year follow up in the Canadian Department of Veterans Affairs coordinated study of chronic bronchitis: the J. Burns Amberson Lecture of the American Thoracic Society. Am Rev Respir Dis 1973; 108:1043–65. This study compared the rates of decline of airflow in smoking men in four Canadian cities. A total of 218 men in Halifax, Montreal, Toronto, and Winnipeg were observed prospectively for 14 years. The rate of decline in airflow was less in Winnipeg with little air pollution, compared with the other cities with significant air pollution. Progressive airflow obstruction occurred in 10% of this population and was termed “malignant bronchitis.” The author strongly suggested early identification and smoking cessation in patients with progressively deteriorating airflow. Spirometry was recommended rather than more elaborate testing.

Rokaw SN , Detels R , Coulson AH , et al. The UCLA population studies of chronic obstructive respiratory disease: III. Comparison of pulmonary function in three communities exposed to photochemical oxidants, multiple primary pollutants, or minimal pollutants. Chest 1980; 78:252–62. This cross-sectioned study found more airflow abnormalities in California cities with either chemical or sulfur dioxide pollution compared with a low pollution city in both smokers and nonsmokers.

Behera D , Jindal SK . Respiratory symptoms in Indian women using domestic cooking fuels. Chest 1991; 100:385–88. This study from Northern India related respiratory symptoms to home cooking fuels. Most were nonsmokers. The smoking women experienced respiratory symptoms more often than nonsmokers (33.3% vs 13%).

Dennis RJ , Maldonado D , Norman S , et al. Wood smoke exposure and risk for obstructive airways disease among women. Chest 1996; 109(suppl):55S–56S. This case-controlled study in Bogota, Colombia, found that wood smoke associated with cooking was associated with a high risk of obstructive airways disease. Most of the women were elderly or from a low socioeconomic group.

Tager IB , Segal MR , Munoz A , et al. The effect of maternal cigarette smoking on the pulmonary function of children and adolescents: analyses of data from two populations. Am Rev Respir Dis 1987; 136:1366–70. This study demonstrated maternal smoking on the FEV, of young people living in the same household. This study used a common analytic method in two populations and found results that were similar.

Higgins MW , Keller JB , Metzner HL . Smoking, socioeconomic status, and chronic respiratory disease. Am Rev Respir Dis 1977; 116:403–10. In a large study from Tecumseh, Michigan, most of the differences in chronic bronchitis and decline in FEV, were due to differences in smoking habits of both men and women across different occupational, educational, and income classes in comparison with smoking, poor occupational, educational, and economic circumstances that had only a weak adverse effect.

Burrows B , Knudson RJ , Lebowitz MD . The relationship of childhood respiratory illness to adult obstructive airway disease. Am Rev Respir Dis 1977; 115:751–60. This study of a general population of non-Hispanics in Arizona demonstrated a close relationship between histories of childhood respiratory tract infections and the prevalence of ventilatory impairment in 2,026 adults. The decline over time in FEV, was greatest in smokers compared with nonsmokers.

Shaheen SO , Barker DJ , Holgate ST . Do lower respiratory tract infections in early childhood cause chronic obstructive pulmonary disease? Am J Respir Crit Care Med 1995; 151:1649–51. This study in two English counties related childhood medical records of respiratory infections to reductions in FEV, 60 to 70 years later. These findings were independent of smoking and social class.

Lebowitz MD . Respiratory symptoms and disease related to alcohol consumption. Am Rev Respir Dis 1991; 123:16–19. Male heavy drinkers who were also heavy smokers had more airflow abnormalities when corrected for age, smoking habits, and other risk factors. Smoking was a far greater determinant of airflow obstruction than was alcohol consumption.

Higgins MW , Keller JB , Becker M , et al. An index of risk for obstructive airways disease. Am Rev Respir Dis 1982; 125:144–51. The excess risk of airflow obstruction in men and women was calculated by age group for continuing to smoke vs stopping smoking. These projections could be used in advising smokers at risk to stop.

Bolton-Smith C , Casey CE , Gey KF . Antioxidant vitamin intakes using a food frequency intakes questionnaire: correlation with biochemical status in smokers and non-smokers. Br J Nutr 1991; 65:337–46. This study used a detailed questionnaire to quantify the food intake of antioxidant vitamins. Results of this questionnaire correlated with serum levels of these antioxidant vitamins.

Dow L , Tracey M , Villar A , et al. Does dietary intake of vitamin C and E influence lung function in older people? Am J Respir Crit Care Med 1996; 154:1401–04. For every extra milligram in vitamin E in the daily diet, FEV, increased by an estimated 42 mL and FVC an estimated 54 mL.. These results suggested that dietary intake of vitamin E may influence lung function in the elderly.

Fletcher C , Peto R , Tinker C , et al. The natural history of chronic bronchitis and emphysema. New York: Oxford University Press, 1976; 272. The classic “definitive” monograph on natural history of COPD. This review article goes into great detail about the natural history of COPD and includes Fletcher's horse race hypothesis.

Sorlie PD , Kannel WB , O'Connor G. Mortality associated with respiratory function and symptoms in advanced age: the Framingham Study. Am Rev Respir Dis 1989; 140:379–84.

Law M , Tang JL . An analysis of the effectiveness of interventions intended to help people stop smoking. Arch Intern Med 1995; 155:1933–41. A review of the relative effectiveness of various means to help smokers quit. Spirometry can be helpful as a cessation aid.

Singh GK , Matthews TJ , Clarke SC , et al. Annual summary of births, marriages, divorces, and deaths: United States, 1994: monthly vital statistics report (vol 43, No. 13). Hyattsville, Md: National Center for Health Statistics, 1994. Provisional mortality and other vital statistics for the US population. Includes crude numbers and rates for 72 causes of death, including COPD and asthma.

Morbidity and Mortality Chartbook on Cardiovascular, Lung, and Blood Diseases. Bethesda, Md: National Heart, Lung and Blood Institute, May 1994. Annotated tables and figures providing national and limited international data on levels and trends in mortality, hospitalizations, and prevalence of cardiovascular lung and blood diseases and risk factors.

American College of Chest Physicians and American Thoracic Society. Pulmonary terms and symbols: a report of the ACCP-ATS Joint Committee on Pulmonary Nomenclature. Chest 1975; 67:583–93. An extensive review of terminology for pulmonary diseases.

Benson V , Marano MA . Current estimates from the National Health Interview Survey, 1993. Washington, DC: National Center for Health Statistics, Vital and Health Statistics 10(190), 1994; DHHS publication No. (PHS) 95-1518. Self-reported data including prevalence of COPD in its various manifestations, with information on socioeconomic conditions.

Wilder C. Prevalence of selected chronic respiratory conditions: United States, 1970. Washington, DC: National Center for Health Statistics, Vital and Health Statistics 10(84), 1973; DHEW publication No. (HRA) 74-1511. Older COPD prevalence data for comparison with current trends.

Collins JC . Prevalence of selected chronic conditions: United States, 1986-1988. Washington, DC: National Center for Health Statistics, Vital and Health Statistics 10(182), 1993; DHHS publication No. (PHS) 93-1510 415 and 6. Estimates of prevalence in the noninstitutionalized population of chronic conditions, including chronic bronchitis, emphysema, and asthma. Numbers and rates are based on responses to a standard set of questions asked in a household health interview.

Rogot E , Sorlie PD , Johnson NJ , et al. A mortality study of 1.3 million persons by demographic, social, and economic factors: 1979- 1985 follow up: US National Longitudinal Mortality Study. Bethesda, Md: National Institutes of Health, July 1992; NIH publication No. 92-3297. A data book presenting standardized mortality ratios for socioeconomic, demographic, and occupational characteristics for leading causes of death, including COPD plus asthma (ICD codes 490-496). Individual records from Census Bureau samples for over 1 million people were matched to the National Death Index for the years 1979 to 1985. Standardized mortality ratios are presented by age, sex, and race.

National Center for Health Statistics. Health, United States, 1993. Hyattsville, Md: Public Health Service, 1995; DHHS publication No. (PHS) 95-1232. This 19th report on the health status of the nation presents trends in public health statistics; charts and text provide an overview of data contained in detailed tables on health status and determinants, utilization of health resources, health care resources, and health care expenditures.

Connett J , Bailey W , Wu M. Design of the Lung Health Study: a randomized clinical trial of early intervention for chronic obstructive pulmonary disease. Control Clin Trials 1993; 14:3S–19S. This is the definitive description of the research design of the Lung Health Study showing, among other things, the importance and unique value of the FEV, as an outcome measure when examining airflow obstruction.

Dockery DW , Speizer FE , Farris BG , et al. Cumulative and reversible effects of lifetime smoking on simple tests of lung function in adults. Am Rev Respir Dis 1988; 137:266–92. This is a model that estimates how much lung function is irreversibly lost by smoking. This model also estimates how much could be regained with smoking cessation. It predicts the future loss of lung function in both scenarios.

Sluiter HJ , Keoter GH , deMonchy JG , et al. The Dutch hypothesis (chronic nonspecific lung disease) revisited. Eur Respir J 1991; 4:479–89. Here the Dutch hypothesis is explained in detail with a large amount of additional material added since it was first proposed. In brief, the Dutch hypothesis relates allergic factors and bronchial hyperreactivity to the development of COPD in smokers.

O'Connor GT , Sparrow D , Weiss ST . The role of allergy and nonspecific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease. Am Rev Respir Dis 1989; 140:225–52. A complete review of the literature on bronchial hyperreactivity as it relates to the pathogenesis of COPD.

US Department of Health and Human Services. The health benefits of smoking cessation. Washington, DC: US Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 1990; DHHS publication No. (CDC) 90-8416. A remarkably detailed summary of the health benefits of smoking cessation.

Dompeling E , van Schayck CP , van Grunsven PM , et al. Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids: a 4-year prospective study. Ann Intern Med 1993; 118:770–78. A large study from the Netherlands that examined the effect of beclomethasone on the long-term course of asthma and COPD. The effect was clearly favorable in asthma, but not definitive in COPD.

Connett JE , Bjornson-Benson WM , Daniels K. Recruitment of participants in the Lung Health Study II: assessment of recruiting strategies. Control Clin Trials 1993; 14(suppl):38S–51S. This is an ongoing study with 1,110 participants recruited from the participant population of Lung Health Study I, who were either currently smoking or had smoked within the previous 2 years. Subjects were randomized to receive inhaled triamcinolone acetonide or placebo. The outcome will be rate of decline of FEV, and respiratory morbidity and mortality. This study will conclude in 1999.

Wedzicha JA . Inhaled corticosteroids in COPD: awaiting controlled trials [editorial]. Thorax 1993; 48:305–07. This editorial describes the controlled clinical trial of inhaled corticosteroids in multiple centers in Europe, known as the Euroscope Study.

Rennard SI , Serby CW . Extended therapy with ipratropium is associated with improved lung function in patients with COPD: a retrospective analysis of data from seven clinical trials. Chest 1996; 110:62–70. This is a detailed analysis of the data from seven randomized controlled trials that compared the spirometric responses of ipratropium with a B-agonist over a 90-day period. This included all of the available data from 1,445 evaluated patients. This study indicated that extended administration of ipratropium bromide was associated with improved results of baseline spirometric tests. In contrast, B-agonists appeared to have little effect on results of baseline spirometric tests.

Rahman I , MacNee W. Oxidant/antioxidant imbalance in smokers and chronic obstructive pulmonary disease. Thorax 1996; 51:348–50. This is a concise review with 50 references of the evidence of oxidant excess and antioxidant deficiency as central to the pathogenesis of COPD in smokers. This imbalance may help explain the susceptibility of 10 to 30% of smokers to the development of COPD.

Tockman M , Comstock G. Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland. Am Rev Respir Dis 1989; 140:S56–63. A classic study documenting the utility of airflow obstruction as a predictor of deaths from all causes, including mortality from arteriosclerotic heart disease. All-cause mortality was also related to smoking.

Kuller LH , Ockene J , Meilahn E , et al. Relation of forced expiratory volume in 1 second (FEV1) to lung cancer mortality in the multiple risk factor intervention trial (MRFIT). Am J Epidemiol 1990; 132:265–74. This large study showed that impaired pulmonary function is an independent risk factor for the development of lung cancer.

Wannamethee SG , Shaper AG , Whincup PH , et al. Smoking cessation and the risk of stroke in middle-aged men. JAMA 1995; 274:155–60. This is part of the British Regional Heart Study of 7,735 men aged 40 to 59 years at baseline (1978 to 1980) selected from general practices in 24 towns in England, Scotland, and Wales. In this study, smoking cessation was associated with a considerable and rapid benefit, and a decreasing in the risk of stroke.

Clausen JL . The diagnosis of emphysema, chronic bronchitis, and asthma. Clin Chest Med 1990; 11:405–16. A review of the differential diagnosis of disease characterized by airflow obstruction.

Christopher KL , Wood RP , Eckert RC , et al. Vocal cord dysfunction presenting as asthma. N Engl J Med 1983; 308:1566–70. A classic article describing a series of patients, mostly women, with episodic vocal cord dysfunction viewed directly during an attack of dyspnea, believed at first to be asthma. The classic blunting of the inspiratory flow loop is presented in this article. The basic nature appears to be a somatization disorder. Speech therapy, but not bronchodilators or corticosteroids, is helpful in management.

Irwin RS , Curley FJ , French CL . Chronic cough: the spectrum and frequency of causes, key components of diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 1990; 141:640–47. This is a study of 102 consecutive patients with chronic cough with normal immunocompetence. Cough was the sole presenting symptom in patients with asthma and gastroesophageal reflux. Other causes of cough were postnasal drip, chronic bronchitis, bronchiectasis, and miscellaneous conditions.

Brenden J , Mullen M , Wright JL , et al. Reassessment of inflammation of airways in chronic bronchitis. BMJ 1985; 291:1235–39. This study examined the cartilaginous airways in 20 patients with a clinical diagnosis of chronic bronchitis based on symptoms of chronic cough exacerbations. Surgical specimens were compared with those of 25 patients who did not have the diagnosis of chronic bronchitis. Inflammation was found in the patients with chronic bronchitis. The groups had equivalent proportions of mucous glands and no differences in the Reid Index or pulmonary function. Inflammation of the conducting airways was believed responsible for the symptoms of chronic bronchitis.

Burrows B , Knudson RJ , Cline MG , et al. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977; 115:195–205. A study in a general population that related smoking to a decline in FEV. Other factors in low airflow were childhood respiratory infections and allergy skin test reactivity.

DeGowin EL , DeGowin RL . Bedside diagnostic examination. 2nd ed. London: Macmillan, 1970; 286–301. A description of the bedside examination of the pulmonary patient.

Fischl MA , Pitchenrik L , Gardner L. An index predicting relapse and need for hospitalization in patients with acute bronchial asthma. N Engl J Med 1981; 305:783–89. This study offered objective measurements that aimed to predict the need for hospitalization in severe attacks of asthma in patients evaluated in the emergency department.

Mueller RE , Petty TL , Filley GF . Ventilation and arterial blood gas changes induced by pursed lips breathing. J Appl Physiol 1970; 28:784–89. This is a detailed physiologic study that demonstrated that pursed lip breathing resulted in slower, deeper breathing. This method augmented oxygen transfer across the lungs.

American Thoracic Society. Standardization of spirometry. Am Rev Respir Dis 1979; 119:831–38. This was the first statement by the ATS providing guidelines for standardizing spirometry, including equipment requirements, maintenance, and calibration suggestions and performance recommendations.

American Thoracic Society. Standardization of spirometry: 1987 update. Am Rev Respir Dis 1987; 136:1286–96. This is a detailed update of the ATS Spirometry Standards. The earlier standards were published following the Snowbird Workshop on Spirometry (Am Rev Respir Dis 1979;119:831-38)

American Thoracic Society. Standardization of spirometry: 1994 update. Am J Respir Crit Care Med 1995; 152:1107–36. Both this and the above reference provide updates to the original ATS recommendations on the standardization of pulmonary function testing. These updates take into account changes in clinical emphasis, knowledge gained from experience using the tests, and new developments in technology.

American Thoracic Society. Lung function testing: selection of reference values and interpretive strategies. Am Rev Respir Dis 1991; 144:1202–18. Many published, accepted “normal” reference values exist to which patient data may be compared. This ATS statement provides an overview of the scientific basis for reference values and guidelines for selecting reference values for a particular population and for interpreting data in relation to the reference values.

Bergin CJ , Muller NL , Miller RR . CT in the qualitative assessment of emphysema. J Thorac Imaging 1986; 1:94–103. This is an early article that demonstrated the ability of the CT scan to identify emphysema or loss of alveolar walls and also the emphysema type, ie, centrilobular, panlobular, and paraseptal emphysema.

Feigin DS , Abraham JL . 'Increased pulmonary markings'-a radiologic-pathologic correlation study [abstract]. Invest Radiol 1980; 15:425. Lungs from consecutive autopsies were compared with recent chest radiographs if pulmonary infiltrates suggesting pneumonia or cancer were not present. So-called increased pulmonary markings were due histologically to edema, infiltration, and possibly fibrosis. Correlation with emphysema was poor.

Fraser RG , Fraser RS , Renner JW , et al. The roentgenologic diagnosis of chronic bronchitis: a reassessment with emphasis on perihilar bronchi seen end-on. Radiology 1976; 120:1–9. The thickness of bronchial walls as judged by radiographic shadows was compared for normal men and men with a clinical diagnosis of COPD. Airway wall thickening was best visualized when bronchi were seen “end on.” So-called tramlines were described and illustrated in this article. It was concluded that chronic bronchitis is not a radiographic diagnosis.

Laws JW , Heard BE . Emphysema and the chest film: a retrospective radiological and pathological study. Br J Radiol 1962; 35:750–61. This is an early attempt at radiographic and pathologic correlations in emphysema, using whole lung sections. Marked degrees of emphysema could accurately be diagnosed by chest radiograph, but not mild or moderate degrees of destruction. Large-volume lungs correlated with emphysema in only a minority of cases.

Milne ENC , Bass H. The roentgenological and functional analysis of combined left heart failure and chronic obstructive pulmonary disease. Invest Radiol 1969; 4:129–47. A study that shows a reduction in lung hyperinflation and reduction of vascular flow to upper lung regions in the presence of pulmonary congestion from left heart failure. These changes tend to minimize the radiographic evidence of emphysema, which is hyperinflation and reduced lung vascular shadows.

Sanders C , Nath PH , Bailey WC . Detection of emphysema with computed tomography: correlation with pulmonary function tests and chest radiology. Invest Radiol 1988; 23:262–66. CT proved to be more sensitive than the standard chest radiograph and as sensitive as pulmonary function tests (spirometry and diffusion) in identifying emphysema. Some evidence of emphysema was found in 69% of patients with normal results of pulmonary function tests. CT may be useful as a noninvasive test in the diagnosis of early emphysema and before pulmonary function abnormalities occur.

Simon G. Chronic bronchitis and emphysema: a symposium: III. Pathological findings and radiological changes in chronic bronchitis and emphysema: (b) Radiological changes in chronic bronchitis. Br J Radiol 1959; 32:292–94. This is an early report from one of the leaders of modern chest radiology. The chest radiograph in chronic bronchitis was often judged normal. Thickened airway walls were found in only about one half of chronic bronchitis patients. In contrast, bronchography revealed a high percentage of irregular mucosal changes. Distention of bronchi and abrupt cutoffs of the contrast material, probably due to mucus plugs, were observed in some patients with chronic bronchitis.

A Communications Strategy for Public Education. The national cholesterol education program. Bethesda MD: National Institutes of Health, 1994; NIH/NHLBI publication No. 94-3292. A communication discussing the scientific evidence for the objectives and strategies presented for lowering cholesterol levels in highrisk and general populations. Various approaches are recommended.

Lilienfeld A. 'Chronic diseases. In: Last JM , ed. Public health and preventive medicine. New York: Appleton Century Crofts, 1980; 1142–43. The broadest and most comprehensive overview of public health and preventive medicine education currently in its 12th edition.

Owens G. Public screening for lung disease: experience with the NIH Lung Health Study. Am J Med 1991; 91:37S–40S. This study revealed that COPD is more prevalent than previously recognized, that it is widespread in women as well as men, and that it is far more common in young individuals than was thought.

Rylander R. Organic dusts from knowledge to prevention. Scand J Work Environ Health 1994; 20:116–22. A review of the clinical and subjective symptoms and pathology related to organic dust exposure is presented with a discussion of the inflammatory processes they induce. Preventive approaches include dust control, information, and medical surveillance.

Kentner M , Valentine H. Identification and prevention of work-related diseases and premature incapacity. Zentralbl Hyg Umweltmed 1993; 193:495–512. While in many cases preventive actions have led to a decrease in occupational diseases, more complex studies taking into account multifactorial designs are needed to delineate the needs in obstructive lung diseases.

Bascomb R (Chairman), Committee of the Environmental and Occupational Assembly of the American Thoracic Society. State of the art: health effects of outdoor air pollution, part I-II. Am J Respir Crit Care Med 1996; 153:3–50, 477–98. A detailed and comprehensive review of the effects of outdoor pollutants on respiratory health, morbidity, mortality, genotoxicity and carcinogenicity, clinical toxicology, atopy, and sensitivity.

Lynch BS , Bonnie RJ . Growing up tobacco free. Washington, DC: Institute of Medicine, National Academy Press, 1994. A comprehensive review of the relationship between tobacco-related scientific knowledge and social policy regarding public health objectives to reduce the onset of tobacco use and addiction among children and youths.

Lee PR . Healthy People 2000-progress report for tobacco. Washington, DC: Public Health Service, Aug 18, 1994. A fact sheet published by the Public Health Service to update the public on smoking prevalence, and incidence rates as well as cessation efforts in youths.

Children and tobacco: the facts. Washington, DC: FDA Press Office, Aug 10, 1995. A fact sheet released by the Food and Drug Administration listing the latest figures in teen smoking and associated pediatric diseases leading to premature deaths.

Pierce JP , Gilpin E. How long will today's new adolescent smoker be addicted to cigarettes? Am J Public Health 1996; 86:253–56. A study estimating expected smoking duration for cohorts of young smokers by age and gender using modeling techniques and based on the National Health Interview Surveys.

American Thoracic Society. ATS statement: cigarette smoking and health. Am J Respir Crit Care Med 1996; 153:861–65. A comprehensive statement covering prevalence of smoking, costs, health effects, passive smoking, the role of addiction, cessation efforts, and benefits of quitting.

Opening Session. ALA/ATS Annual International Conference, New Orleans, May 1996.

Jubran A , Gross N , Ramsdell J , et al. Comparative cost-effectiveness analysis of theophylline and ipratropium bromide in COPD: a three-center study. Chest 1993; 103:678–84. This comparative study of 311 COPD patients receiving theophylline and 289 receiving ipratropium in three different health care settings found that treatment of COPD with ipratropium was more cost-effective.

Carrat F , Valleron AJ . Influenza mortality among the elderly in France, 1980-90: how many deaths may have been avoided through vaccination? J Epidemiol Community Health 1995; 49:419–25. This study calculated the mortality rate due to influenza in the elderly in France between 1980 and 1990, and how many deaths could have been avoided through vaccination.

Rothbarth PH , Kempen BZM , Sprenger MJ . Sense and nonsense of influenza vaccination in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 151:1682–86. A review of the efficacy of influenza vaccination in the prevention of further morbidity and mortality in patients with asthma and COPD.

McBean AM , Babish JD , Warren JL . The impact and cost of influenza in the elderly. Arch Intern Med 1993; 153:2105–11. A study comparing Medicare costs for “an epidemic influenza season,” a “nonepidemic season,” with an “interim period without influenza virus circulation.” Results show that the costs of influenza virus infection are significant even in nonepidemic years.

Phillips CJ , Prowle MJ . Economics of a reduction in smoking case study from Heartbeat Wales. J Epidemiol Community Health 1993; 47:215–23. This 4-year study (1985 to 1989) identified costs of a smoking intervention program and estimated reduced morbidity and displaced mortality from coronary heart disease, lung cancer, and chronic bronchitis.

Haggerty MC , Stockdale-Woolley R , Nair S. Resp-Care: an innovative home care program for the patient with chronic obstructive pulmonary disease. Chest 1991; 100:607–12. A before and after evaluation of 48 months of hospital-based home care program, the results of which show a decrease in both emergency care and hospitalization and thus a cost savings during the program.

Kaplan PM , Atkins CT . Behavioral interventions for patients with COPD. In: McSweeny AJ , Grant I , eds. Chronic obstructive pulmonary disease: a behavioral perspective; lung biology in health disease. New York: Marcel Dekker, 1988; 123–62. A data-based overview and critical evaluation of the impact of various behavioral interventions in the rehabilitation of patients with COPD.

Parker SR . Behavioral science aspects of COPD: current status and future directions. In: McSweeny AJ , Grant I , eds. Chronic obstructive pulmonary disease: a behavioral perspective; lung biology in health disease. New York: Marcel Dekker, 1988; 279–303. A careful review of cognitive and behavioral factors contributing to and resulting from COPD, including management and rehabilitation approaches.

Fishman AP . Pulmonary rehabilitation research. Am J Respir Crit Care Med 1994; 149:825–33. An overview bridging the roles of the pulmonary specialist in the treatment of the patient with COPD with discussion of functional assessment and outcomes research.

Haggerty MC . Outpatient management of common problems in patients with chronic obstructive pulmonary disease. Nurse Pract Forum 1993; 4:16–22. Assessment, management, and education for three main problems (dyspnea, ineffective secretion clearance, and potential for exacerbation) improve functional capacity and quality of life in patients with COPD.

Smith K , Cook D , Guyatt GH , et al. Respiratory muscle training in chronic airflow limitation: a meta-analysis. Am Rev Respir Dis 1992; 145:533–39. This is a summary of 17 relevant articles that were randomized trials, selected from a total of 73 articles. Overall, there was little evidence of clinical benefit from respiratory muscle training in COPD. Resistance training may be useful if adequate generation of mouth pressures can be achieved.

Folgering H , Rooyakkers J , Herwaarden C. Education and cost/benefit ratios in pulmonary patients. Monaldi Arch Chest Dis 1994; 49:166–68. The need for patient education stems from poor symptom perception, problems using inhalers and assessment instruments, a lack of understanding of the disease process, and thus the need for medication.

Molken MP , Van Doorslaer EK , Rutten FF . Economic appraisal of asthma and COPD care: a literature review 1980-1991. Soc Sci Med 1992; 35:161–75. An overview summarizing the 20 studies that have been published over an 11-year period on economic factors relating to both treatment and rehabilitation approaches for asthma and COPD.

Strijbos JH , Postma DS , Van Altena R , et al. A comparison between an outpatient hospital-based rehabilitation program and a home care rehabilitation program in patients with COPD: a follow up of 18 months. Chest 1996; 109:366–72. This randomized, stratified study compared the outcome of a 12-week hospital-based pulmonary rehabilitation program with a 12-week home-based pulmonary rehabilitation program. Walking tests and well-being were assessed in 45 patients with moderately advanced COPD. A control group received no rehabilitation. Beneficial effects in feelings of well-being were achieved by both programs over 18 months. Improvements in walking tolerance and dyspnea scores were significantly better maintained in the home-based compared with the hospital-based program.

Ries AL , Kaplan RM , Limberg TM , et al. Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary disease. Ann Intern Med 1995; 122:823–32. This is a large controlled clinical trial of exercise training plus education vs education alone in pulmonary rehabilitation. Patients who received the exercise component by random assignment experienced less dyspnea, increased exercise tolerance, and improved feeling of well-being, which was partly sustained for 1 year.

Ferguson GT , Cherniack RM . Management of chronic obstructive pulmonary disease. N Engl J Med 1993; 328:1017–22. A state-of-the-art review of the current concepts in the management of COPD patients, including a suggested treatment algorithm for bronchodilators. This differs slightly from the ATS standards (reference 111).

Edelman NH , Kaplan RM , Buist AS , et al. Chronic obstructive pulmonary disease (Task Force on Research and Education for the Prevention and Control of Respiratory Diseases). Chest 1992; 102:243S–56S. A summary on the current status of COPD from the ACCP Task Force on Research and Education for the Prevention and Control of Respiratory Diseases. This succinct summary covers both treatment and research needs. It emphasizes the importance of early identification and intervention in COPD.

Kottke TE , Battista RN , DeFriese GH , et al. Attributes of successful smoking cessation interventions in medical practice: a meta-analysis of 39 controlled trials. JAMA 1988; 259:2883–89. A comparison was made of 108 controlled smoking cessation trials. The number of intervention modalities used predicted success. A team of physicians and nonphysicians using multiple intervention modalities was related to the type of intervention session (group or individual). Combined interventions were more successful than group or individual sessions alone.

Clinical practice guidelines, No. 18-smoking cessation. Rockville, Md: USPHS Agency for Health Policy and Research, April 1996. This 125-page monograph presents strategies and recommendations designed to help clinicians, smoking cessation specialists, health care administrators, and third-party payers in supporting and delivering effective smoking cessation interventions. It is peer reviewed by 67 contributors.

Tonnesen P , Fryd V , Hansen M , et al. Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. N Engl J Med 1988; 318:15–18. A controlled clinical trial that demonstrates the added effect of nicotine polacrilex to group counseling for smoking cessation.

Sachs DP . Effectiveness of the 4 mg dose of nicotine polacrilex for the initial treatment of high-dependent smokers. Arch Intern Med 1995; 155:1973–80. This controlled clinical trial showed an improved smoking cessation rate with 4-mg gum compared with 2-mg gum. A strategy for dealing with the most addicted smokers is presented.

Fiore MC , Smith SS , Jorenby PE , et al. The effectiveness of the nicotine patch for smoking cessation. JAMA 1994; 271:1940–47. This meta-analysis revealed a twofold improvement in smoking cessation compared with various behavioral modification strategies without use of the patch. The patch was effective across all behavioral modification strategies.

Tonnesen P , Mikkelsen K , Norregaard J , et al. Recycling of hard core smokers with nicotine spray. Eur Respir J 1996; 9:1619–23. This is a controlled clinical trial of nicotine nasal spray. It proved to be effective in a substantial number of patients who had failed previous smoking cessation attempts with the use of other forms of nicotine replacement.

Hurt RD , Sachs DPL , Glover ED , et al. A comparison of sustainedrelease bupropion and placebo for smoking cessation. N Engl J Med 1997; 337:1195–1202.

Fiebach N , Beckett W. Prevention of respiratory infections in adults: influenza and pneumococcal vaccines. Arch Intern Med 1994; 154:2545–57. This is a review article that summarizes the effectiveness of both influenza virus vaccine and pneumococcal vaccine. Efforts to expand the use of these protective measures to populations at risk, such as in COPD, are emphasized.

Recommendations of the Immunization Practices Advisory Committee, Center for Disease Control. Ann Intern Med 1987; 107:521–25. This statement gives recommendations for both the use of influenza virus vaccines and amantadine in influenza prophylaxis.

Fine MJ , Smith MA , Carson CP , et al. Efficacy of pneumococcal vaccine in adults: a meta-analysis of randomized controlled trials. Arch Intern Med 1994; 154:2666–77. This summarizes the scientific basis for the use of pneumococcal vaccine. It helps to reduce the severity of disease, including bacteremic complications.

Shapiro ED , Berg AT , Austrian R , et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:1453–60. This is a controlled clinical trial in 15 cooperating hospitals that showed that pneumococcal vaccine, either 14 valent or 23 valent, provided protection against these strains, but as expected, not against strains not represented by antigens in the vaccines.

Mostow SR , Cate TR , Ruben FL . Prevention of influenza and pneumonia. Am Rev Respir Dis 1990; 142:487–88. An official statement of the ATS. This statement laments the underutilization of effective vaccines for influenza and pneumococcal pneumonia. At the time of this report, only 20 to 30% of high-risk individuals received influenza virus vaccine and <10% received pneumococcal vaccine. The report concludes that both vaccines reduced morbidity and mortality.

Easton PA , Jadue C , Dhingra S , et al. A comparison of the bronchodilating effect of a B-2-adrenergic agent (albuterol) and an anticholinergic agent (ipratropium bromide) given by aerosol alone or in sequence. N Engl J Med 1986; 315:735–39. A study suggesting equal efficacy of albuterol and ipratropium using standard doses with no additive effects when the two agents are combined in the treatment of patients with stable COPD.

Skorodin MS . Pharmacotherapy for asthma and chronic obstructive pulmonary disease. Arch Intern Med 1993; 153:814–28. A concise overview of medicine pharmacology and relevant studies associated with drugs used in the management of COPD patients.

Ziment I. Pharmacologic therapy of obstructive airway disease. Clin Chest Med 1990; 11:461–86. An overview of medicine pharmacology and relevant studies associated with drugs used in the management of COPD patients.

Martin RJ , Pak J. Overnight theophylline concentrations and effects on sleep and lung function in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 145:540–44. A study documenting the efficacy of evening dosing of long-acting theophyllines in the treatment of COPD patients, improving morning symptoms and airflows.

Matthay RA . Favorable cardiovascular effects of theophylline in COPD. Chest 1987; 92(suppl 1):22S–26S. This study offers evidence of improved both left and right heart systolic function in response to theophylline administration. A reduction in ventricular afterload and a positive inotropic effect of theophylline was the mechanism of improved hemodynamics in patients with COPD.

Combivent Inhalation Aerosol Study Group (Petty TL, Chairman). In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone: an 85-day multicenter trial. Chest 1994; 105:1411–19. A large multicenter trial suggesting an additive effect to the combination of albuterol plus ipratropium when compared to using each agent alone (using conventional doses) in the treatment of patients with stable COPD.

Callahan CM , Dittus RJ , Katz BP . Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease: a metaanalysis. Ann Intern Med 1991; 114:216–23. This analysis of all available controlled clinical trials of corticosteroids in chronic stable COPD showed only about a 20% objective improvement in FEV, in 20% of patients.

Kenstjens HAM , Brand PLB , Hughes MP . A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. N Engl J Med 1992; 327:1413–19. The addition of an inhaled corticosteroid to maintenance treatment substantially reduced morbidity and airway hyperresponsiveness and airway obstruction in a spectrum of patients with airways obstructive disease.

Postma DS , Peters I , Steenhuis EJ , et al. Moderately severe chronic airflow obstruction: can corticosteroids slow down obstruction? Eur Respir J 1988; 1:22–26. A retrospective study suggesting that low-dose corticosteroids may slow the rate of decline of FEV, in COPD patients.

Hirsch SR , Viernes PF , Kory RC . The expectorant effect of glycerol guaiacolate in patients with chronic bronchitis. Chest 1973; 63:9–14. Glycerol guaiacolate (guaifenesin) was no more effective than placebo in lowering the consistency (viscosity) of 27 sputum specimens for 11 patients with chronic bronchitis. In a 20-day period, results with glycerol guaiacolate were no different than with a placebo in improving the ease of expectoration.

Petty TL . The National Mucolytic Study: results of a randomized, double-blind, placebo-controlled study of iodinated glycerol in chronic obstructive bronchitis. Chest 1990; 97:75–83. This multicenter randomized controlled clinical trial documented a reduction in cough, chest tightness, chest discomfort, and ability to clear mucus in patients assigned to iodinated glycerol compared with placebo.

Bowman G , Backer U , Larsson S , et al. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983; 64:405–15. This is a multicenter placebo-controlled study of 285 patients. Exacerbations were statistically less common in the active treatment vs the placebo groups. Forty percent of the treatment group and 19% of the placebo group had no exacerbations.

Radford R , Barett J , Billingsly JC , et al. A rational basis for percussionaugmented mucociliary clearance. Respir Care 1982; 27:556–63. This is a study of the effect of percussion energy on mucus transport in experimental animals and man. It demonstrated a positive effect of percussion and gravity in mucus flow.

Gross D , Zidulka A , O'Brien C , et al. Peripheral mucociliary clearance with high-frequency chest wall compression. J Appl Physiol 1985; 58:1157–63. This study in anesthetized and spontaneously breathing dogs demonstrated an increase in mucus clearance rate as indicated by radioisotopes in response to high-frequency chest wall compression with moderate pressures applied.

van der Schans CP , Piers DA , Beekhuis H , et al. Effect of forced expirations on mucus clearance in patients with chronic airflow obstruction: effect of lung recoil pressure. Thorax 1990; 45:623–27. Eight patients with chronic airflow obstruction and low elastic recoil due to emphysema and seven patients with similar chronic airflow obstruction but normal elastic recoil were studied. Mucus clearance from the peripheral lung regions improved during forced exhalation and coughing when normal elastic recoil was present, but not with reduced elastic recoil. Thus, physical therapy procedures designed to enhance mucus clearance will be successful only when normal elastic recoil is present.

Hasani P , Pavia D , Agnew JE , et al. Regional mucus transport following unproductive cough and the forced expiration technique in patients with airways obstruction. Chest 1994; 105:1420–25. In 14 patients with chronic airflow obstruction, this study demonstrated that even if cough is unproductive, it can still result in movement of secretions proximally from all regions of the lung.

Konstan MW , Stern RC , Doershuk CF . Efficacy of the flutter device for airway mucus clearance in patients with cystic fibrosis. J Pediatr 1994; 124:689–93. This controlled clinical trial demonstrated improvement in mucus clearance when intra-airway vibrations are produced by inhaling and exhaling from a flutter valve.

Anthonisen NR , Manfreda J , Warren CPW . Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106:196–204. A controlled clinical trial that showed clinical effectiveness of antibiotics compared with placebo in some but not all patients with exacerbations of chronic bronchitis.

Murphy TF , Sethi S. State of the art: bacterial infection in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 146:1067–83. This is a comprehensive review of the various prevention and treatment strategies for bacterial pulmonary infections of all types that affect patients with COPD. This is extensively referenced (n = 197).

Lewczuk J , Sobkowicz-Wozniak B , Piszko P , et al. Long-term prazosin therapy for COPD pulmonary hypertension. Chest 1992; 102:635–36. This is a case report of a 51-year-old patient with severe COPD, obesity, and pulmonary hypertension-18 months of administration of 3 mg prazosin resulted in a significant improvement in pulmonary hypertension and pulmonary vascular resistance.

Matthay RA , Berger HJ , Davies R , et al. Improvement in cardiac performance by oral long-acting theophylline in chronic obstructive pulmonary disease. Am Heart J 1982; 104:1022–26. This study offers data on the influence of theophylline on cardiac performance in COPD in Table 3.

Mathur PN , Powles ACP , Pugsley SO , et al. Effect of digoxin on right ventricular function in severe chronic airflow obstruction. Ann Intern Med 1981; 95:283–88. This study in 15 patients showed that pulmonary heart disease, defined as a reduced right ventricular ejection fraction, was improved only if combined left ventricular ejection fraction abnormality was also present (n=4) and improved during digoxin therapy.

Brochard L , Mancebo J , Wysocki M , et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333:817–22. This is a prospective randomized study comparing noninvasive pressure support ventilation with a face mask compared with standard treatment of controlled oxygen, antimicrobials, bronchodilators, and corticosteroids. The use of noninvasive ventilation significantly reduced the need for intratracheal intubation. The in-hospital mortality was significantly reduced by noninvasive ventilation as was the length of hospital stay.

Light RW , Muro JR , Sato RI , et al. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1989; 139:126–33. This study demonstrated that an increased maximum workload tolerance and reduced dyspnea resulted from the use of oral morphine, presumably due to a blunting of excessive respiratory drives. Patients exercised at a higher Pco, with lower ventilatory requirements for a given workload and also a reduced perception of breathlessness.

Janoff A. Elastases and emphysema: current assessment of the protease-anti-protease hypothesis. Am Rev Respir Dis 1985; 132:417–33. This is a state-of-the-art review covering studies of the previous 10 years that dealt with the role of elastases in the pathogenesis of emphysema. It emphasizes the role of antielastases in protecting the lower airway. The discovery of new low molecular weight secretory elastases was reviewed. New evidence on the structure and function of the a-1-proteinase (elastase) inhibitor is reviewed. The potential of designing new elastase inhibitors was suggested by this pioneer in the pathogenesis of emphysema.

Wewers MD , Casalaro MA , Sellers SE , et al. Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema. N Engl J Med 1987; 316:1055–61. The feasibility and safety of a-1-antitrypsin replacement therapy was evaluated in 21 patients. Weekly infusions of a-1-antitrypsin could reverse the biochemical abnormalities in serum and lung fluid. This was the first extensive study to suggest the logic of regular lifetime replacement therapy.

Hubbard RC , Sellers S , Czerski D , et al. Biochemical efficacy and safety of monthly augmentation therapy for a-1-antitrypsin deficiency. JAMA 1988; 260:1259–64. This study reports the results of monthly administration of two times the weekly dose of a-1-antitrypsin exceeded the purported protective threshold for 25 days. These results suggested the feasibility and efficacy of monthly rather than weekly replacement therapy.

Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; 1:681–86. This major randomized controlled clinical trial demonstrated a survival benefit from oxygen given 15 hours/day compared with no oxygen in patients with chronic stable hypoxemia with COPD.

Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease. Ann Intern Med 1980; 93:391–98. This study demonstrated a survival benefit of continuous ambulatory oxygen averaging 17.8 hours/day compared with nocturnal oxygen from a stationary source given 11.8 hours/day in patients with COPD.

Tarpy SP , Celli BR . Long-term oxygen therapy. N Engl J Med 1995; 333:710–14. This is a brief state-of-the-art review on the pathophysiology of hypoxemia and the improvements produced by long term oxygen therapy. The most commonly used oxygen delivery systems are described and outcomes of controlled clinical trials are cited.

Bye PT , Esau SA , Levy RD , et al. Ventilatory muscle function during exercise in air and oxygen in patients with chronic airflow limitation. Am Rev Respir Dis 1985; 132:236–44. This study documented increased exercise tolerance and evidence of decreased respiratory muscle fatigue during maximal exercise with oxygen compared with exercise with air.

Barker AF . Oxygen conserving devices for adults. Chest 1994; 105:248–52. This describes the relative performance characteristics of oxygen reservoir devices, demand oxygen delivery devices, and transtracheal oxygen delivery. The economics of long-term oxygen therapy are considered.

Corsello PR , Make BJ . Which oxygen conserving device is best for your patient? J Respir Dis 1992; 13:27. This brief article compares the options available among the oxygenconserving devices, including mechanical, battery powered, and the use of transtracheal oxygen delivery.

Christopher KL , Spofford BT , Petrun MD , et al. A program for transtracheal oxygen delivery assessment of safety and efficacy. Ann Intern Med 1987; 107:802–08. This study describes the technique of transtracheal oxygen delivery, indications for its use, and preliminary results of switching from double nasal cannulas (pump) to the transtracheal method of oxygen delivery.

Petty TL , Weinmann GG . Building a national strategy for the prevention, management, and research in chronic obstructive pulmonary disease. JAMA 1997; 277:246–53. This is a consensus report of a workshop held in Bethesda, Md, August 29-31, 1995. It forms the foundation for the NLHEP.

Petty TL . A new national strategy for COPD. J Respir Dis 1997; 18:365–69. This is a brief version of the Bethesda, Md, 1995 workshop that highlights the new national strategy for COPD that constitutes the NLHEP.