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(Chest. 1999;115:68-74.)
© 1999 American College of Chest Physicians

Lung Volumes in 4,774 Patients With Obstructive Lung Disease*

Brian J. Dykstra, MD; Paul D. Scanlon, MD, FCCP; Monica M. Kester, MS; Ken C. Beck, PhD and Paul L. Enright, MD

* From the Rehoboth McKinley Clinic (Dr. Dykstra), Gallup, NM; the Mayo Clinic (Drs. Scanlon and Beck), Rochester, NY; and the University of Arizona (Ms. Kester and Dr. Enright), Tuscon, AZ.


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To determine the correlates of static lung volumes in patients with airways obstruction, and to determine if static lung volumes differ between asthma and COPD.

Patients and methods: We examined the data from all of the adult patients (mean age of 69) who were referred to a pulmonary function laboratory from January 1990 through July 1994 with an FEV1/FVC ratio of < 0.70 and tested using a body plethysmograph. Correlates were determined using regression analysis.

Measurements and results: Of the 4,774 patients observed with evidence of airways obstruction, 61% were men. Self-reported diagnoses included asthma, 19%; emphysema or COPD, 23%; chronic bronchitis, 1.5%; and {alpha}1-antiprotease deficiency, 0.6%. Fifty-six percent of the patients did not report a respiratory disease. The degree of hyperinflation, as determined by the residual volume (RV)/total lung capacity (TLC) ratio, or the RV % predicted (but not the TLC % predicted), was strongly associated with the degree of airways obstruction (the FEV1 % predicted). Patients with moderate to severe airways obstruction and high RV and TLC levels were more likely to have COPD than asthma. Of the 1,872 patients with a reduced vital capacity determined by spirometry testing, 87% had hyperinflation as defined by the RV/TLC, and 9.5% had a low TLC (with less severe airways obstruction).

Conclusion: In patients found to have airways obstruction by spirometry, the additional measurement of static lung volumes added little to the clinical interpretation.

Key Words: asthma • COPD • hyperinflation • lung volumes


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Static lung volume tests are often routinely ordered along with spirometry for patients with various chronic obstructive airway diseases. Two common reasons for ordering the lung volumes are (1) to determine the presence or degree of lung hyperinflation, and (2) to look for a superimposed restrictive lung disorder. Static lung volumes include the total lung capacity (TLC), the residual volume (RV), and the functional residual capacity (FRC). The definition of airways obstruction has been standardized as an abnormally low FEV1/FVC ratio and a low FEV1 % predicted.1 However, the definition of the term "lung hyperinflation" is currently imprecise and is variously based on posteroanterior and lateral chest radiograph patterns, the FRC % predicted, the RV/TLC ratio, the RV % predicted, or the TLC % predicted.

Thousands of static lung volume tests are performed in pulmonary function laboratories each year in the United States, with estimated costs in the range of $75 to $200 per test. The American Thoracic Society (ATS), the National Heart, Lung, and Blood Institute, and the European Respiratory Society formed a working group in 1992 to recommend standards for the measurement and interpretation of static lung volumes for pediatric and adult patients.2 The working group noted that there was a paucity of reported data regarding the correlates of static lung volumes in patients with obstructive lung diseases, and that the diagnostic or predictive value of static lung volumes in these common disorders was poorly described.

The goal of this study was to determine the spirometric, anthropometric, and diagnostic correlates of static lung volumes in adult patients with airways obstruction noted during spirometry testing. Our working hypothesis was that the association of hyperinflation with airway obstruction would differ between asthma, chronic bronchitis, and emphysema.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The study population was comprised of adult outpatients of > 30 years old who were referred to the Mayo Clinic outpatient pulmonary function (PF) laboratory in Rochester, MN between January 1990 and July 1994, and who had completed measurements of spirometry and static lung volumes. All of the patients with a prebronchodilator FEV1/FVC of > 0.70 were excluded from the study. The FEV1, the FVC, and the slow vital capacity (VC) were measured according to ATS recommendations3 using a model 1070 spirometer (Medical Graphics; St. Paul, MN) that utilizes a heated Fleisch #3 pneumotachometer. The static lung volumes were measured using a model 1085 pressure-type body plethysmograph (Medical Graphics) according to standardized methods,4 using slow (1 to 1.5 Hz) panting maneuvers following the closure of the mouth shutter. The TLC was determined by measuring the thoracic gas volume (TGV) and adding the inspiratory capacity performed immediately following the TGV determination. The RV was calculated by subtracting from the TLC the largest VC value obtained during any one of the baseline (prebronchodilator) tests. The FRC (the box TGV) is not reported here because it is less reproducible than other static lung volumes, and varies with body position, noseclips, mouthpiece, anxiety, and other factors. Accuracy checks for body plethysmograph mouth flow, mouth pressure, and box pressure were performed daily. Spirometry and static lung volume predicted values were taken from the study of Miller and coworkers,5 ,6 with the fifth percentile used to define the lower limit of the normal range for the VC and the TLC.

With the patients in their stocking feet, height and weight measurements were taken. A short respiratory questionnaire included the question, "Has your doctor ever said you have a lung disease, or any condition that affects your ability to breathe? If YES, please name the disease(s)." This questionnaire was administered by the technician prior to PF tests. Up to three respiratory-related diagnoses were reported by each patient; the responses were coded and entered into a data file. The numeric results of all the tests, and the flow-volume graphs, were stored in an archival database after a quality review.

We also wanted to compare the static lung volumes found in nonsmoking patients with asthma to the volumes found in former and current smokers with COPD. Therefore, from the 4,774 patients, we derived two subsets: "asthma only" and "COPD only." We first eliminated patients who had reported a pulmonary diagnosis other than asthma, COPD, emphysema, chronic bronchitis, or bronchitis. We also eliminated patients who had reported any type of lung surgery, lung biopsy, or lung resection. The "asthma only" group had to report asthma as a diagnosis (but could also have reported bronchitis), and current smokers or former smokers were excluded from the asthma group. The COPD only group had to have reported either COPD, emphysema, or chronic bronchitis as a diagnosis (but could have additionally listed bronchitis) and must have reported a > 30-pack-year smoking history.

Data transformations, descriptive statistics, linear regression models, and graphs were performed using SPSS for Windows, version 5, with the RV/TLC x 100%, the RV % predicted, or the TLC % predicted as continuous dependent variables.7 We used the FEV1 % predicted as an index of the severity of airways obstruction as recommended by the ATS.1 We determined the ranges of the significant differences in the linear regression lines of the associations of hyperinflation with the degree of airways obstruction between the asthma and COPD groups by using the methods of Zerbe and coworkers.8


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
There were 4,774 adult patients who met the entry criteria of an FEV1/FVC of < 0.70; 61% were men, and the mean age was 69 (see Fig 1 for the age distribution). At the time of testing, 908 patients (19%) reported a diagnosis of asthma, 1,099 patients (23%) reported a diagnosis of emphysema or COPD, 70 patients (1.5%) reported chronic bronchitis, 31 patients (0.6%) reported an {alpha}1-antiprotease (AAP) deficiency, and 56% did not report having a respiratory disease. More than one respiratory diagnosis was reported by 11.2% of the patients, and 78% of the patients reported being current or former smokers (see Table 1 for the mean PF values).



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  		Figure 1. The age distribution of the 4,774 adult patients with airways obstruction.

 

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  		Table 1. Mean Spirometry and Static Lung Volume Results From 4,774 Adult Patients With Airways Obstruction

 
Hyperinflation
In the overall group of 4,774 patients, the degree of hyperinflation was significantly associated with the degree of airways obstruction, as indicated by the FEV1 % predicted: the bivariate correlation coefficients for the RV/TLC %, the RV % predicted, and the TLC % predicted with the FEV1 % predicted were all highly significant, respectively: 0.76, 0.66, and 0.33 (p < 0.0001). All three indices of hyperinflation were also significantly associated with a self-reported diagnoses of asthma and emphysema, and with age, gender, height, weight, and smoking status (patients who never smoked vs former or current smokers).

All of the variables mentioned above were then offered as predictor variables to each of the three separate linear regression models, with dependent variables of the RV/TLC %, the RV % predicted, and the TLC % predicted. Entry was stepwise, with a p< 0.01 (in) and a p> 0.05 (out). Most of the variability of the RV/TLC was explained by the degree of airways obstruction (the FEV1 % predicted), height, age, and gender (see Table 2 ). Chronic bronchitis, emphysema, and smoking status were not independent predictors of the degree of hyperinflation as measured by the RV/TLC %, and the mean RV/TLC % was only 0.6% higher for those reporting asthma when compared to the other patients.


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  		Table 2. Independent Correlates of RV/TLC % From a Linear Regression Model

 
Similar to the RV/TLC %, the independent correlates of hyperinflation as measured by the RV % predicted also included the degree of airways obstruction, and the patient's height, age, and gender (see Table 3 ). However, the reported type of obstructive lung disease also made a difference: after correcting for the above variables, the mean RV % predicted was 35% higher for patients with an AAP deficiency, 13% higher for those reporting emphysema, and 8% higher for those reporting asthma when compared to patients not reporting these diagnoses. Current smokers also had a mean RV % predicted that was 5% higher than what was found in patients who had never smoked or had quit smoking.


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  		Table 3. Independent Correlates of Residual Volume (% predicted RV) From a Linear Regression Model

 
Ninety percent of the TLC variability resulted from factors not measured by this study. The independent correlates of the TLC % predicted included gender, age, and height, but not the degree of airways obstruction (see Table 4 ). The effects of asthma, emphysema, and the AAP deficiency on the TLC were less than their effect on the RV. Current smoking was also independently associated with a higher TLC. Obesity was independently associated with both a lower RV and a lower TLC. Patients whose body weight was 20 kg (44 lb) heavier than average had a 6% lower RV and a 4% lower TLC.


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  		Table 4. Independent Correlates of Total Lung Capacity (% predicted TLC) From a Linear Regression Model

 
Asthma vs COPD
Table 5 shows the mean anthropometric and PF values for the two patient subgroups of (1) never-smokers who reported asthma only (n = 268), and (2) smokers who reported COPD only (n = 668). The mean age, height, and weights were similar, but there were more men with COPD only. The COPD patients had more severe airways obstruction and more hyperinflation when compared to those reporting asthma only.


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  		Table 5. Anthropometric and Spirometric Measurements of Patients With Asthma Only and COPD Only

 
The strong association of the degree of RV/TLC hyperinflation with the degree of airways obstruction was virtually identical in both asthma and COPD patients (see Fig 2 ). On the other hand, for patients with moderate to severe airways obstruction (an FEV1 of < 53% of predicted), the mean RV was higher in patients with COPD only (an RV of usually > 200% of predicted and up to 350% of predicted) when compared to patients with asthma only (see Fig 3 ).



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  		Figure 2. The association of RV/TLC ratio (RV/TLC %) with the severity of airways obstruction (FEV1 % predicted) in patients with asthma only (open circles) and COPD only (solid squares).

 
Hyperinflation of the TLC was not associated with the degree of airways obstruction in the entire group of 4,774 patients or in the subgroup with asthma only (see Fig 4 ). However, patients with moderate to severe airways obstruction resulting from COPD were more likely than patients with mild airways obstruction to have a high TLC (from 120 to 180% of predicted).



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  		Figure 4. The association of the % of predicted total lung capacity (TLC % predicted) with the severity of airways obstruction (FEV1 % predicted) in patients with asthma only (open circles) and COPD only (solid squares). The two regression lines are significantly different below the 59% of predicted FEV1.

 
Superimposed Restriction
Of the total of 4,774 patients, 1,872 patients (39.2%) had a reduced VC. Of these patients, 1,634 patients (87.3%) had a high RV/TLC (above the normal range), and only 177 patients (9.5%) had a low TLC (below the lower limit of the normal range). The mean FEV1/FVC was significantly higher for patients with a low TLC when compared to the other patients, respectively: 62 vs 51% (p < 0.001). Patients with a low TLC were also less likely than the other patients to have a severe airways obstruction (an FEV1 of < 40% of predicted), respectively: 36 vs 52% (p < 0.001).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this large retrospective study of patients referred to a single PF laboratory, we have confirmed that hyperinflation of lung volumes is associated with the degree of airway obstruction. However, the strength of this association, as well as other clinical correlates, vary considerably according to whether "hyperinflation" is defined as a high RV/TLC, a high RV, or a high TLC. The RV or the RV/TLC are much more sensitive than the TLC to the degree of airways obstruction (see Figs 2 ,3 ,4 ). As airways obstruction moves from borderline (90% of predicted FEV1) to moderate (50% of predicted FEV1), the mean RV increases from 100 to 140% of predicted (see Fig 3 ) while the TLC remains relatively constant (see Fig 4 ).



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  		Figure 3. The association of increase in the log RV % predicted with airways obstruction (FEV1 % predicted) in patients with asthma only (open circles) and COPD only (solid squares). The two regression lines are significantly different below the 53% of predicted FEV1.

 
As previously reported in healthy individuals,5 ,9 the RV was larger in men, taller patients, and younger patients with airways obstruction. In addition, patients who weighed more had a lower RV. After correcting for gender, height, and age, the RV was strongly correlated with the FEV1 % predicted. On average, the RV was 14% higher for each 10% decrease in the FEV1. Patients (n = 31) reporting an AAP deficiency had much higher RV levels (+ 35%) than the other patients. Patients reporting emphysema had somewhat higher RVs (+ 13%) when compared to patients reporting asthma (+ 8%), after correcting for the degree of airways obstruction. Chronic bronchitis was not independently associated with static lung volumes (RV/TLC, RV, or TLC).

Our results confirm a review10 of the indications for the measurement of static lung volumes stating that "in patients with COPD, RV and FRC are elevated in proportion to the degree of airflow obstruction; TLC, on the other hand, may be affected variably by the different obstructive diseases: elevated in emphysema but often normal in chronic bronchitis and asthma, for the same degree of flow obstruction."

A review11 of the differential diagnosis of emphysema, chronic bronchitis, and asthma stated that "although elevations of static lung volumes are associated almost exclusively with these obstructive lung diseases, measurement of static lung volumes have not proven useful for separating these three classic diagnostic categories." We generally agree with this statement because there is a large overlap in the degree of hyperinflation seen in these obstructive diseases in our patients; however, in patients with moderate to severe airways obstruction, patients with COPD tend to have higher levels of RV and TLC when compared to patients with asthma.

Decades ago, investigators demonstrated that static lung volumes in cigarette smokers were associated with the degree of anatomic emphysema, but they did not attempt to correct for the degree of airways obstruction. Asthma has also been associated with increases in lung volumes during acute bronchospasm and during asymptomatic periods.12 ,13 Some of the increase in TLC noted during induced bronchospasm was due to an artifact of measurement, because mouth pressure does not reflect alveolar pressure well during panting maneuvers in patients with severe airways obstruction.14 ,15 More recent measurements of the TLC using chest radiograph planimetry showed that the TLC does increase slightly during bronchospasm.16 However, our results do not support an association of TLC with the degree of airways obstruction in adult patients with asthma.

A population study of 2,680 subjects in Italy found that the RV was inversely related to weight in healthy adult women.9 Our results confirm this finding in both men and women with airways obstruction (see Table 3 ). Perhaps reference equations for RV17 should include a correction for body weight. We also found that current smokers (when compared with ex-smokers) had higher values of RV and TLC, after correcting for other factors (see Tables 3, 4), although the Italian study9 found this association only in men.

A limitation of the present study is the use of self-reporting when classifying lung disease patients. Some patients may not remember correctly the diagnosis given to them by their physician. Some patients undoubtedly had lung disease but had not been told so by their physician. Some patients were sent to the PF lab because of a history suggesting lung disease, and the results may have then prompted their physician to apply a lung disease diagnosis (which we did not obtain).

The predicted values of Miller and coworkers5 ,6 were used because both spirometry and static lung volume reference values were available from the same population sample. We did not use single- or multiple-breath helium dilution techniques (or nitrogen washout) to measure static lung volumes, because these methods are known to seriously underestimate lung volumes in patients with moderate to severe airways obstruction when compared with body plethysmography.18 Errors in the measurement of lung volumes using body plethysmography (without using an esophageal balloon to estimate alveolar pressure changes) are also known to occur in patients with severe airways obstruction14 , but these are very small when compared with measurements of the TLC from chest radiographs, especially if rapid panting during airway occlusion is avoided,15 ,18 as in our study.

In summary, the measurement of static lung volumes in adult patients with airways obstruction did not distinguish well the two major types of airways obstruction (asthma and COPD). In patients with airways obstruction and a low VC on spirometry testing, only 9.5% were found to have a superimposed restrictive process (a low TLC).


   Footnotes
 
Correspondence to: Paul Enright, MD, Respiratory Sciences Center, 1501 N Campbell Blvd, Tucson, AZ 85724; e-mail: lungguy@aol.com

Abbreviations: AAP = {alpha}1-antiprotease; ATS = American Thoracic Society; FRC = functional residual capacity; PF = pulmonary function; RV = residual volume; TGV = thoracic gas volume; TLC = total lung capacity; VC = vital capacity

Received for publication February 24, 1998. Accepted for publication June 9, 1998.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. . American Thoracic Society. (1991) Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 144,1202-1218[ISI][Medline]
  2. Clausen, JL, Coates, AL, Quanjer, PH (1997) Measurement of lung volumes in humans: review and recommendations from an ATS/ERS workshop. Eur Respir J 10,1205-1206[CrossRef][ISI][Medline]
  3. . American Thoracic Society. (1987) Standardization of spirometry: 1987 update. Am Rev Respir Dis 136,1285-1298[ISI][Medline]
  4. Coates, AL, Peslin, R, Rodenstein, D, et al (1997) Measurement of lung volumes by plethysmography. Eur Respir J 10,1415-1427[CrossRef][ISI][Medline]
  5. Miller, A, Thornton, J, Warshaw, R, et al (1983) Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Am Rev Respir Dis 127,270-277[ISI][Medline]
  6. Miller, A, Thornton, JC, Warshaw, R, et al (1986) Mean and instantaneous expiratory flows, FVC and FEV1: prediction equations from a probability sample of Michigan, a large industrial state. Bull Eur Physiopathol Respir 22,589-597[ISI][Medline]
  7. Norusis MJ. SPSS for Windows, Base System User's Guide, Release 6.0. Chicago, IL: SPSS, 1993
  8. Zerbe, GO, Archer, PG, Banchero, N, et al (1982) On comparing regression lines with unequal slopes. Am J Physiol 242,R178-R180[Medline]
  9. Paoletti, P, Viegi, G, Carrozzi, L, et al (1992) Residual volume in a general population: effects of body size, age, cigarette smoking, and respiratory symptoms. Chest 102,1209-1215[Abstract/Free Full Text]
  10. Ries, AL (1989) Measurement of lung volumes. Clin Chest Med 10,177-186[ISI][Medline]
  11. Clausen, JL (1990) The diagnosis of emphysema, chronic bronchitis, and asthma. Clin Chest Med 11,405-416[Medline]
  12. Woolcock, AJ, Read, J (1966) Lung volumes in exacerbations of asthma. Am J Med 41,259-273[CrossRef][ISI][Medline]
  13. Greenough, A, Everett, L, Pool, J, et al (1991) A 2-year longitudinal study of lung hyperinflation in young asthmatics. Respir Med 85,379-382[Medline]
  14. Rodenstein, DO, Stanescu, DC, Francis, C (1982) Demonstration of failure of body plethysmography in airway obstruction. J Appl Physiol 52,949-954[Abstract/Free Full Text]
  15. Shore, SA, Huk, O, Mannix, S, et al (1983) Effect of panting frequency on the plethysmographic determination of thoracic gas volume in chronic obstructive pulmonary disease. Am Rev Respir Dis 128,54-59[ISI][Medline]
  16. Blackie, SP, al-Majed, S, Staples, CA, et al (1990) Changes in total lung capacity during acute spontaneous asthma. Am Rev Respir Dis 142,79-83[ISI][Medline]
  17. Stocks, J, Quanjer, PH (1995) Reference values for residual volume, functional residual capacity, and total lung capacity: ATS workshop on lung volume measurements—official statement of the European Respiratory Society. Eur Resp J 8,492-506[CrossRef][ISI][Medline]
  18. Andersson, LG, Ringqvist, I, Walker, A (1988) Total lung capacity measured by body plethysmography and by the helium dilution method: a comparative study in different patient groups. Clin Physiol 8,113-119[Medline]



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