Pulmonary Function Testing in Population-Based Studies

TERI A. MANOLIO, GAIL G. WEINMANN, A. SONIA BUIST, CURT D. FURBERG, JOAN L. PINSKY, and SUZANNE H. HURD

Division of Epidemiology and Clinical Applications and Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, Oregon Health Sciences University, Portland, Oregon; and Department of Public Health Sciences, Bowman Gray School of Medicine, Winston-Salem, North Carolina

	NEED FOR WORKSHOP

The National Heart, Lung, and Blood Institute (NHLBI) has included assessments of respiratory symptoms and pulmonary function, as well as measures of cardiovascular disease and its risk factors, in many of its population-based observational studies and clinical trials. These studies have generated a wealth of data on pulmonary function in men and women of differing ages, races, and ethnicities (Table 1). More than 130,000 spirometries have been performed in more than 50,000 participants in these studies in the past 45 yr. Although data from many of the early studies were collected with equipment or methodology that is now considered outdated, many useful publications have resulted from these data. Later studies have used more standardized methods and improved equipment, both of which have reduced the variability of measurements and improved comparability among them and over time.

Recognizing the opportunities for research on pulmonary disease epidemiology represented by the available data, as well as the need to identify future research directions in this area, NHLBI convened a workshop entitled "Pulmonary Function Testing in Population-Based Studies" on June 20 and 21, 1996. The workshop was intended to promote interaction among cardiovascular and pulmonary investigators, who were asked to review current and proposed data-collection and -analytic efforts in NHLBI studies. To illustrate the opportunities presented by the available data on pulmonary function, three research questions (listed subsequently) were addressed in detail, using summary data from a variety of studies; findings of these investigations will be published separately. The purposes of this report are to: (1) publicize the availability of these data, in the hopes of encouraging interested investigators to collaborate with these studies in further defining the epidemiology of pulmonary disease and dysfunction; and (2) summarize the recommendations of the workshop participants with regard to future data collection and analytic efforts.

	AVAILABILITY OF PULMONARY FUNCTION DATA IN NHLBI STUDIES

In 1979, the Division of Lung Diseases of the NHLBI convened a task force on the Epidemiology of Respiratory Diseases, charging it to "recommend an epidemiology program that would provide information not readily obtainable through other research approaches" (1). The task force identified a variety of research needs, and recommended that large-scale investigations be conducted to examine the distributions of and risk factors for respiratory diseases.

Subsequently, pulmonary function testing and questionnaires on respiratory symptoms were included (or continued) in NHLBI's portfolio of prospective, longitudinal, population-based studies (Tables 2 and 3). Most of these studies were designed with cardiovascular disease as their primary focus, and involved predominantly cardiovascular- rather than pulmonary-disease researchers. Although a number of publications on distributions and correlates of spirometry measures have arisen from the Atherosclerosis Risk in Communities Study (ARIC) (2), Coronary Artery Disease in Young Adults (CARDIA) (6), Cardiovascular Health Study (CHS) (8), Framingham Study (15), Honolulu Heart Program (18), and Lung Health Study (32) in the past 10 yr, the full potential of these data bases has yet to be realized. Of particular value may be investigations in which data are pooled across studies to include a full range of ages, ethnicities, and geographic areas.

To examine the possibilities afforded by addressing similar questions in a variety of studies, the workshop planning group proposed three research questions to be explored at the workshop:

1. Is the observed relationship between lung-function impairment and cardiovascular morbidity and mortality independent of smoking and other potential confounding factors?
2. Does the relationship between smoking and lung-function impairment differ by gender and ethnicity or race in persons aged 25 to 85 yr?
3. Is there an association between diet/dietary components and lung-function impairment/prevalent lung disease?

The first two of these questions lent themselves to joint analyses across studies, such as have been done in examining the associations of low cholesterol and mortality (41) and cholesterol and coronary heart disease (CHD) risk in older persons and women (42). Investigators in studies with relevant data were asked to provide summary data tables. Preliminary analyses suggest affirmative answers to all three questions and raise intriguing questions for further research. Papers arising from these analyses will be prepared separately.

In response to the workshop recommendation to encourage researchers to conduct analyses of the existing data, we wish to inform the research community of the pulmonary data collected in NHLBI population-based studies as described in Tables 123. Research questions may be addressed by pooling data across studies or through examination within one or more studies. Investigators with an interest in pursuing analyses of these data may contact the Steering Committee, Coordinating Center, or NHLBI Project Officer of the study whose data are desired (see APPENDIX). Direct collaboration with the investigators who originally designed and collected the data is essential to ensuring the accuracy of analyses and interpretation. Collaborating investigators will be expected to adhere to the publications policies of the individual studies. A form for proposing collaborative manuscripts is included in the APPENDIX.

	RECOMMENDATIONS FOR ANALYSES OF EXISTING DATA

Participants in the workshop recommended that researchers with expertise in population-based pulmonary studies be encouraged to collaborate in analysis of the pulmonary data collected in NHLBI population-based studies. Although several pulmonary researchers have been and are currently involved in the design and analysis of these studies, their numbers are probably not sufficient to explore the available data fully. Workshop participants recommended that analyses be designed to examine the data in new and different ways, such as evaluating the predictive value of the shape of the spirometric curve. Investigators in different fields, such as aging or molecular biology, should be encouraged to participate in and add their perspectives to the analyses. Analysis of lifelong nonsmoking participants should be a high priority so as to avoid potential confounding with known smoking effects on the cardiovascular and respiratory systems.

A series of research priorities was identified in relationship to four primary research areas: (1) mechanisms of association between pulmonary function and atherosclerotic cardiovascular disease; (2) mechanisms of increased susceptibility to loss of lung function; (3) association of lung function with other markers of physiologic aging; and (4) factors related to recovery of lost lung function. Specific research topics within these four areas are described in Table 4. It may be possible to address some of these topics in existing data sets; others may require future data collection.

	RECOMMENDATIONS FOR FUTURE DATA COLLECTION

Although abundant data are currently available to address many of the research questions identified in the workshop, information in several specific areas is lacking. Future data-collection efforts should include the development and implementation of the following:

Improved measures of environmental tobacco-smoke exposure.

Improved measures of smoking exposure (with greater reliability than cigarettes/day or pack-years) in past and current smokers.

Improved measures of other environmental exposures, such as particulates and other air pollutants; although ecologic data are probably insufficient for assessing individual exposures and risk, identification of cohorts from environments with diverse air quality, observed over extended periods, may be of value.

Other recommended data collection efforts include:

Measures of inflammatory and infectious markers in relation to pulmonary measures, including markers more directly related to the respiratory tract, in addition to serum markers.

Addition of measures other than spirometry, including peak expiratory flow, inspiratory and expiratory pressures, oxygen desaturation with exercise, and sleep-related breathing disorders, if these are proven to be useful in the population-based studies that have already included them.

Continued inclusion of spirometry as a standard indicator of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) risk, as in the case of blood pressure or cholesterol, which must be considered and controlled for analytically before new risk factors can be identified.

Collection and archiving of entire spirometric curves for future analysis, perhaps through development and use of a standard storage format.

	SUMMARY

TOP CONCLUSION REFERENCES

A wealth of information on pulmonary function is currently available in NHLBI-sponsored, population-based studies. These data can be used to address critically important questions in pulmonary and cardiovascular disease research, but their potential cannot be realized without the active collaboration of pulmonary- and cardiovascular-disease researchers. Investigators interested in analyzing these data in collaboration with the parent study investigators are invited to contact these investigators directly (see APPENDIX). Results of analyses recommended in the workshop should be used to identify hypotheses for future efforts in collecting data on the epidemiology of pulmonary diseases and their relationship to cardiovascular disease.

Participating Institutions and Investigators

Oregon Health Sciences University: A. Sonia Buist; University of Minnesota: John E. Connett, David R. Jacobs, Jr., Eyal Shahar; University of Utah: Robert O. Crapo, Robert L. Jensen; Boston University: Ralph D'Agostino, George T. O'Connor; University of Arizona: Paul L. Enright; Wake Forest University: Gregory W. Evans, Curt D. Furberg; National Institute for Occupational Safety and Health: John L. Hankinson; University of North Carolina at Chapel Hill: Gerardo Heiss, Verna Lamar; University of Pittsburgh: Lewis H. Kuller; University of California at Berkeley: Ira Tager; Kaiser Permanente Center for Health Research: William M. Vollmer; National Heart, Lung, and Blood Institute: Millicent Higgins, Suzanne S. Hurd, Teri A. Manolio, Joan L. Pinsky, Gail G. Weinmann.

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	Footnotes

Correspondence and requests for reprints should be addressed to Teri Manolio, M.D., M.H.S., Epidemiology and Biometry Program, DECA, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8160, Bethesda, MD 20892-7934.

(Received in original form April 9, 1997).

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