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Original Research: PULMONARY FUNCTION TESTING |

The Nonspecific Pulmonary Function Test: Longitudinal Follow-up and Outcomes FREE TO VIEW

Vivek N. Iyer, MD, MPH; Darrell R. Schroeder, MS; Kenneth O. Parker, MS; Robert E. Hyatt, MD, FCCP; Paul D. Scanlon, MD, FCCP
Author and Funding Information

From the Division of Pulmonology and Critical Care Medicine (Drs Iyer, Hyatt, and Scanlon; Mr Parker), and the Department of Biostatistics (Mr Schroeder), Mayo Clinic College of Medicine, Rochester, MN.

Correspondence to: Vivek N. Iyer MD, MPH, Mayo Clinic College of Medicine, Division of Pulmonary and Critical Care Medicine, Gonda E18, 200 First St SW, Rochester, MN 55905; e-mail: iyer.vivek@mayo.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(4):878-886. doi:10.1378/chest.10-0804
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Published online

Background:  The nonspecific (NS) pulmonary function (PF) pattern refers to a PF test with a normal total lung capacity (TLC), normal FEV1/FVC ratio, and a low FEV1, a low FVC, or both. Currently, no information is available regarding the long-term stability of the NS pattern or variables that predict changes in subjects with an initial NS PF pattern.

Methods:  From 1990 to 2005 we identified 1,284 subjects with an NS pattern on initial PF testing with one or more follow-up PF tests 6 months or more after the initial NS test result. Lung volumes, diffusing capacity, and spirometry data were analyzed. A multivariate, multinomial logistic regression model was used to study the association between different variables and the final PF pattern.

Results:  Overall, 3,674 PF tests were performed in 1,284 subjects over a median follow-up period of 3 years. At last follow-up, 818/1,284 (64%) subjects continued to show the NS pattern, whereas 208/1,284 (16%) showed a restrictive pattern, 191/1,284 (15%) an obstructive pattern, 42/1,284 (3%) a normal pattern, and 25/1,284 (2%) a mixed pattern. The multinomial logistic regression analysis showed that increasing values for specific airway resistance and the difference between TLC and alveolar volume were predictors of a change to an obstructive pattern on follow-up.

Conclusions:  The NS pattern is a distinct and stable PF test pattern with roughly two-thirds of patients continuing to show this pattern on follow-up testing. Current interpretation guidelines erroneously label the NS pattern as representing obstruction and need to be changed to reflect these data.

Figures in this Article

We have previously described a pulmonary function (PF) test pattern in which subjects have a normal total lung capacity (TLC) and a normal FEV1/FVC ratio, but either have a low FVC, a low FEV1, or low values for both FEV1 and FVC.1 These PF tests cannot be categorized as obstructive because of the normal FEV1/FVC ratio nor can they be categorized as restrictive because of the normal TLC (Table 1). We labeled these PF tests as a nonspecific (NS) PF test pattern. Data from our institution indicate that the NS test pattern is seen in roughly 10% of subjects undergoing a full PF test (spirometry and lung volume measurements).2

Table Graphic Jump Location
Table 1 —Different PF Pattern Possibilities Including the NS Pattern (N = 3,674)

BOO = borderline obstruction; N = normal; NS = nonspecific; PF = pulmonary function; REDU = reduced; TLC = total lung capacity.

There is currently no long-term follow-up available in these subjects to determine outcomes of this PF pattern. Some authors have deemed this PF pattern to actually represent occult small airways because of the concomitantly increased residual volumes.3 The current American Thoracic Society (ATS)/European Respiratory Society consensus statement on pulmonary function test interpretation considers this pattern to represent incomplete inhalation and/or exhalation.4 The diagnostic algorithm in that paper goes on to classify a PF test with the NS pattern as being obstructive.

Hyatt et al2 provided some data that demonstrated that a small subset (17/40, 42%) of subjects in their study continued to show the NS pattern on follow-up PF tests without transforming to either an obstructive- or restrictive-type pattern. These findings led us to carefully study the NS test pattern in order to provide long-term outcomes in a large cohort of subjects.

The study was carried out at the Mayo Clinic in Rochester, Minnesota. The study was approved by the local institutional review board and only included subjects who had provided research authorization. There were no commercial interests involved with the study. A computerized database of all PF tests performed from the years 1990 to 2005 at the three Mayo Clinic facilities in the United States (Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona) served as the reference database.

PF Test Details

All tests were performed on the 1085 MEDGRAPHICS system (Medical Graphics Corporation; St. Paul, Minnesota) using whole-body plethysmography for lung volume estimation. From 1990 to February 2001, all three sites (Rochester, Jacksonville, and Scottsdale) used the same MEDGRAPHICS system. After February 2001, only data from Jacksonville and Scottsdale were included in the database, as the Rochester site had switched to a different system. Uncorrected diffusing capacity for carbon monoxide (Dlcou), lung volumes (plethysmography), and spirometry measurements were available for all study subjects. The slow vital capacity (SVC) was determined to be the best vital capacity from any maneuver. The difference between SVC and the FVC was calculated (SVC − FVC). Specific airway resistance (Sraw) was also determined. TLC and alveolar volume (Va) were also determined on all patients and the difference between TLC and Va (TLC − Va) was calculated. Data on smoking status were available for each PF test via a standard intake form. Published reference equations were used to determine the lower limit of normal for the various spirometric measurements.5,6 Standard corrections for race were made from the reference values for whites as follows: 0.88 for FEV1 and FVC for blacks and Asians.

PF Test Quality Control Procedures

Our laboratory follows ATS specifications for quality assurance with daily calibration of all equipment and regular biologic quality assurance checks. Full details of these procedures have been published.7 ATS criteria for acceptability and repeatability were achieved in > 90% of patients in our laboratory.8

Definition of the NS PF Test and Selection of Subjects

We first identified all subjects who had undergone a complete PF test, which was defined as any test that included spirometry, lung volumes, and diffusing capacity for carbon monoxide (Dlco) measurements. We defined the NS pattern as a PF test with a normal TLC and a normal FEV1/FVC ratio, but with an abnormal FEV1, abnormal FVC, or both. Subjects with both normal and abnormal Dlco values were included in the study. We then identified all subjects with an NS PF test and at least one follow-up PF test 6 months or more after the initial NS test to be included in the final study cohort (N = 1,284). The 6-month follow-up period was chosen so we had a reasonable follow-up period in order to detect longitudinal changes in the PF pattern.

Our definition differs slightly from the one used by Hyatt et al9 in their original article in which they restricted the definition of the NS pattern to those tests with a low FVC and a low FEV1 and with a normal Dlco. This definition continued to exclude certain categories of tests that would have otherwise been called NS (Table 1).

Statistical Analysis

The data were analyzed using SAS, version 9.1 (SAS Institute Inc; Cary, North Carolina). Data are summarized as mean ± SD or median (25th, 75th percentile) for continuous variables and frequency percentages for categorical variables. The primary outcome of interest was the pattern on the final follow-up PF test (NS, restrictive, obstructive, normal, or mixed). Secondary outcomes of interest were the annual rate of change in FEV1, FVC, and Dlco. For these outcomes, linear regression was used for each individual to estimate the annual rate of change in the PF parameters of interest. Characteristics assessed as potentially related to the outcomes of interest included age, sex, BMI, smoking status, bronchodilator (BD) response, Sraw,10 and SVC − FVC. Smoking history was categorized into three groups according to self-reported smoking status at the last follow-up visit (nonsmokers, former smokers, or current smokers). For statistical analysis, subjects were divided into four groups for age (≤ 49, 50-59, 60-69, and ≥ 70 years); BMI (≤ 24.9, 25-29.9, 30-34.9, and ≥ 35 kg/m2); Sraw (≤ 5.56, 5.57-7.33, 7.34-9.91, and ≥ 9.92), SVC − FVC (≤ 0.1, 0.1-0.21, 0.22-0.35, and ≥ 0.36 L), and TLC − Va (≤ 0.13, 0.14-0.41, 0.42-0.78, and ≥ 0.79 L). The annual rate of change in PF parameters was compared across groups using the Kruskal-Wallis test and the final PF pattern was compared across groups using the χ2 test. To assess multivariable associations with the final PF pattern, a multinomial logistic regression model was used and included all variables assessed in the univariate model. The multinomial model was performed with both the inclusion and exclusion of Sraw because Sraw values were available in only 662 subjects and thus limited the size of the final multinomial regression model. The final multinomial model included Sraw and all other variables (n = 573).

From 1990 to 2005, we identified 1,284 subjects who had an NS pattern and at least one follow-up PF test 6 months or more after the initial NS test. Baseline PF, demographic, and smoking data are described (Tables 2, 3). A cohort of 33,132 normal PF tests from the same time period was used for purposes of comparison (Table 2). Subjects were also divided into four groups each for age, BMI, SVC − FVC (mL), and Sraw as described in the “Materials and Methods” section.

Table Graphic Jump Location
Table 2 —Demographics

Values are presented as mean ± SD or No. (%). PFT = pulmonary function test. See Table 1 legend for expansion of other abbreviation.

Table Graphic Jump Location
Table 3 —Baseline PFT Values

Values are presented as mean ± SD or No. (%). BD = bronchodilator; Dlcou = uncorrected diffusing capacity for carbon monoxide; RV = residual volume; Sraw = specific airway resistance; SVC = slow vital capacity; Va = alveolar volume. See Table 1 and 2 legends for expansion of other abbreviations.

The rate of change of FEV1, FVC, and Dlco was calculated for all subjects in the cohort (N = 1,284) and was reported as median and interquartile range (IQR). For the entire cohort (N = 1,284), the median yearly decline in FEV1 was 46 mL (IQR, −104 to 4 mL), in FVC was 44 mL (IQR, −116 to 20 mL), and in Dlco was −0.46 mL/s/mm Hg (IQR, −1.37 to 0.17).

In all, 3,674 PF tests were performed in the 1,284 study subjects, including the initial NS test. Each subject underwent an average of 2.9 (± 1.8) tests, including the initial NS test. The mean follow-up period was 3.6 (± 2.5) years, and the median follow-up period was 3 years (IQR, 1.5-5.1). Of these 3,674 tests, 2,730 tests were NS, 415 tests were obstructive, 400 tests were restrictive, 87 tests were normal, and 42 had a mixed pattern.

We also evaluated baseline PF tests using post-BD data (Table 4) and found that the vast majority of subjects (83%) continued to be classified as NS, with about 10% of subjects converting to a normal PF test profile. Following are the details for the final PF test pattern and for the rates of decline in FEV1, FVC, and Dlco among the various groups analyzed in univariate and multivariate models.

Table Graphic Jump Location
Table 4 —Post-BD Patterns of the Initial PFT

Values are presented as No. (%). See Table 1, 2, and 3 legends for expansion of abbreviations.

Final PF Pattern and Stability Over Time

On the final PF test, 64% of subjects continued to show the NS pattern (Fig 1, Table 5). Sixteen percent of subjects converted to a restrictive pattern and 15% of subjects converted to an obstructive pattern. Three percent converted to a normal PF pattern and 2% converted to a mixed (restrictive plus obstructive) pattern. We also analyzed the final PF pattern based on follow-up time from the initial NS PF test (0.5-1, 1-3, 3-5, > 5 years) and found that the NS pattern was still the predominant pattern (61%) even after ≥ 5 years. There were no significant differences in the final PF patterns across the four groups based on length of follow-up (P = .13).

Figure Jump LinkFigure 1. Pulmonary function pattern at last follow-up (N = 1,284).Grahic Jump Location
Table Graphic Jump Location
Table 5 —Length of Follow-up and Final PF Pattern

Values are presented as No. (%). See Table 1 legend for expansion of abbreviations.

a 

For overall comparison using χ2 test for categorical variables.

Univariate Analysis

We analyzed several variables individually to test their association with the final PF pattern as well as rate of change in FEV1, FVC, and Dlco. The details are listed next.

Smoking Status:

Smokers were divided into three categories: never smokers (n = 585), former smokers (n = 568), and current smokers (n = 131), based on information provided by the subjects at the time of the final PF test (Table 6). The final PF pattern was significantly different between the three groups (P = .004, χ2 test). The NS pattern continued to be present on the final PF test in 64% of never smokers, 62% of former smokers, and 69% of current smokers. The restrictive pattern was seen more frequently in never smokers (19%) as compared with current smokers (9%). The obstructive pattern was more commonly seen in current smokers (20%) as compared with never smokers (11%).

Table Graphic Jump Location
Table 6 —Annual Rate of Change and PFT Pattern at Last Follow-up According to Smoking Status

Values are presented as median (25th, 75th percentile) or No. (%). See Table 13 legends for expansion of abbreviations.

a 

For overall comparison across smoking status groups using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for never vs former smokers and never vs current smokers.

The median yearly decline in FEV1 for never smokers (37 mL) was lower than those observed in former smokers (50 mL) and current smokers (55 mL) (P = .03). No significant differences between the three groups were seen in rates of decline for FVC (P = .24) or for Dlco (P = .99).

Gender:

No significant differences were seen in final PF pattern or rates of decline for spirometric parameters for men (n = 684) vs women (n = 600). The NS pattern continued to be seen in 64% of men and in 63% of women on their final follow-up PF test. The restrictive and obstructive PF patterns were seen in 16% and 15% of men and in 17% and 15% of women, respectively.

BD Response:

A positive BD response (2 puffs of albuterol) by standard ATS criteria (12% and 200 mL improvement in FEV1 or FVC post-BD testing) was observed on initial testing in 11% of study subjects (n = 147). A significant difference was noted in the final PF patterns based on initial BD response (Table 7) (P = .03). The NS pattern continued to be seen in 55% with a positive BD response as compared with 63% in those with a negative BD response. Subjects with a positive BD response were more likely to show an obstructive pattern on their final follow-up PF testing (24% vs 15%) and less likely to show a restrictive pattern (14% vs 17%). Interestingly, the rate of decline in FEV1 was significantly lower in those with a positive BD response (−26 mL vs −47 mL, P = .02) as was the rate of decline in the FVC (−18 mL vs −45 mL, P = .01). Both these differences were significant even after correcting for percent predicted decline. The rate of decline in Dlco was not significantly different in the two groups after adjusting for percentage predicated differences.

Table Graphic Jump Location
Table 7 —Annual Rate of Change and PFT Pattern at Last Follow-up According to BD Response

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison between BD groups using the Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found based on BD response.

Age:

The final PF pattern was significantly different among the four age groups (P = .01). The NS pattern continued to be present in 65% of subjects in group 1 (≤ 49 years) vs 59% in the oldest age group (≥ 70 years). The restrictive pattern was seen in 20% in group 1 vs 15% in group 4. The obstructive pattern was more frequently seen in group 4 (19% vs 9% in group 1). The rate of decline in Dlco was significantly different between the four groups with a progressive increase in the rate of decline with increasing age. (P = .0002) The rates of decline in FEV1 and FVC were not different between the four groups.

BMI:

There were no significant differences in final PF pattern (P = .88) or rates of decline in FEV1 (P = 0.89), FVC (P = .98), or Dlco (P = .88) between the four BMI groups. The NS pattern continued to be seen on the final PF test in 65% of subjects with a BMI ≤ 24.9 and in 65% of subjects with a BMI ≥ 35. The restrictive and obstructive patterns were each seen in about 15% of subjects in all four BMI groups.

Specific Airway Resistance:

Data on normal values for Sraw have been previously published.10 Data on Sraw were available on 662 individuals and they were divided into four groups. The final PF pattern was significantly different between the four groups (P < .0001) (Table 8). The NS PF pattern was seen on the final PF test in 64% of those in group 1(lowest Sraw) vs 54% in group 4 (highest Sraw). The restrictive pattern was seen more commonly in group 1 (29%) as compared with group 4 (8%). On the other hand, the obstructive pattern was seen in only 3% of subjects in group 1 vs 34% in group 4.

Table Graphic Jump Location
Table 8 —Annual Rate of Change and PFT Pattern at Last Follow-up According to Sraw Strata

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison across Sraw strata using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for the four groups based on Sraw strata.

SVC − FVC:

The FVC was subtracted from the SVC and the values obtained (liters) were divided into four groups. We hypothesized that those individuals with larger values for SVC − FVC (questionable occult airway obstruction) might have more obstruction on the final PF tests. However, we found no differences in the final PF pattern between the four groups (P = .24). The NS pattern was seen in 65% of those in group 1 (lowest SVC − FVC) and in 65% of those in group 4 (highest SVC − FVC). The restrictive pattern was seen in 18% in group 1 and in 12% in group 4. The obstructive pattern was seen in 12% in group 1 and in 18% in group 4. The rate of decline in FEV1 and FVC progressively decreased from group 1 to 4 and was statistically significant (P ≤ .001 for both). There were no significant differences in the rate of decline in Dlco between the groups (P = .63).

Total Lung Capacity − Va:

The Va obtained during the diffusion capacity maneuver was subtracted from the TLC (obtained by body plethysmography) and divided into four groups. We hypothesized that higher values for TLC − Va reflected increasing air trapping and that these subjects were likely to show an obstructive pattern on follow-up PF tests. There was a significant difference in the final PF patterns between the four groups (P < .0001) (Table 9). The NS pattern was seen in 62% of subjects in group 4 vs 69% of subjects in group 1. Obstruction was seen in 24% of subjects in group 4 vs 8% of subjects in group 1. The restrictive pattern was seen in 9% of subjects in group 4 vs 17% of subjects in group 1.

Table Graphic Jump Location
Table 9 —Annual Rate of Change and PFT Pattern at Last Follow-up According to TLC–Va Strata

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison across TLC–Va strata using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for the four groups based on TLC–Va strata.

Multinomial Logistic Regression Analysis

All the previous variables were incorporated into a multinomial logistic regression model with the NS pattern being used as the reference pattern (Table 10). In addition, the first group of each variable was also taken as the reference group for that particular variable. The model was run both with (n = 573) and without Sraw (n = 1,095) because of the high proportion of missing data with Sraw. The final model included all variables (n = 573) and confirmed that higher values for Sraw and TLC − Va were strongly predictive of a shift to an obstructive pattern on the final PFT test. Increasing Sraw also predicted a shift away from restriction. When we ran the model after excluding Sraw (n = 1,095), we found that a positive BD response, a history of smoking, and higher TLC − Va values were all predictors of a shift to obstruction. Age, sex, BMI, and SVC − FVC were not predictive of converting to an obstructive or restrictive pattern in either model.

Table Graphic Jump Location
Table 10 —Multinomial Logistic Regression Results (n = 573)

Multivariable associations with the final PF pattern were assessed using a multinomial logistic regression model. For this analysis, only subjects whose final PF pattern was NS, restrictive, or obstructive were included with logits modeled using the NS pattern as the reference. See Table 1 and 3 legends for expansion of abbreviations.

This article provides, for the first time, to our knowledge, longitudinal follow-up and outcomes for the NS PF pattern. Our data clearly show that the NS pattern remains stable in a majority of subjects over a median follow-up period of 3 years with about two-thirds of our study subjects continuing to show the NS pattern at the end of the follow-up period (Fig 1). The NS pattern remains the dominant pattern (61%) even in those patients followed for > 5 years after their initial NS PF test (Table 5).

The NS PF pattern has not been well recognized in the literature, although it clearly is a distinct pattern observed in the pulmonary function laboratory (Table 1). Over the years, there have been several explanations for this pattern.3,11,12 The assertion that this pattern represents occult obstruction3 is not borne out by our data, which show this pattern to be stable in more than two-thirds of subjects, with the other one-third showing obstruction and restriction in roughly equal numbers. The multivariate model showed that the only variables that predicted a shift away from the NS pattern and toward obstruction were increasing values for TLC − Va and Sraw. However, even in subjects in the highest quartiles for Sraw and TLC − Va, > 50% of the subjects remained NS on follow-up. Subjects with large values for SVC − FVC are often believed to have occult obstruction. One might then argue that individuals with large values for SVC − FVC would ultimately end up with an obstructive pattern on follow-up PF tests. However, our study did not show any tendency toward the obstructive pattern in these patients.

Our study serves to highlight the fact that the NS pattern is indeed a unique PF test pattern and should not be considered a transitory state on the road to obstruction, as has been previously suggested in the literature.3 Interpreting the NS pattern as impending or occult obstruction leads to falsely labeling patients as having obstructive airway disease with its attendant consequences. A case in point are the current ATS/European Respiratory Society recommendations on PFT interpretation, which fail to acknowledge the NS PF pattern and incorrectly guide the reader toward a diagnosis of obstruction in their diagnostic algorithm (see Figure 2 in that article).4

There are several interesting aspects to data we have presented. Our study looked at the effects of smoking on lung function and found that median rate of decline in the FEV1 in never smokers and current smokers (37 mL/y and 55 mL/y, respectively) was very close to the mean declines in the Lung Health Study in sustained quitters vs current smokers (31 mL/y and 62 mL/y, respectively).7 Our data also showed that the rate of decline in Dlco accelerated with advancing age. These findings are concordant with the results reported from a large population-based study in Italy by Viegi et al.13 We also found that subjects with a positive BD response had a lower rate of decline in their FEV1 and FVC. One explanation for this finding could be that subjects with a positive BD response had a treatable condition and responded to appropriate BD therapy with significant improvement in lung function. We did not have reliable patient-level medication and compliance data to test this hypothesis in our study cohort. Our study was not restricted to subjects with COPD and thus these findings cannot be compared with those from the Intermittent Positive Pressure Breathing Study14 or the Lung Health Study.15

There are several limitations to the present study, which include the fact that this is a single institutional (although multicenter) experience in a tertiary referral practice setting. Subjects in our study were predominantly white (> 90%) and thus the results of this study may not be generalized to other ethnic groups. The retrospective nature of our study limits control over individual subjects who differed in their follow-up periods and time intervals between PF tests.

There are a number of strengths to our study. All PF studies were performed in a high-volume PF laboratory with a strict quality assurance program. In addition, all lung volumes were measured using whole-body plethysmography. Although helium dilution, nitrogen washout, and whole-body plethysmography have shown comparable results in healthy subjects, it is well known that helium dilution and nitrogen washout can underestimate the lung volumes in subjects with obstructive airway diseases.16 The large number of subjects in our cohort also allowed us to provide robust data and perform both univariate and multivariate analysis in order to predict long-term PF test outcomes.

In conclusion, we present the first longitudinal study on a large cohort of subjects with the NS pulmonary function test pattern. Our data suggest that the NS pattern is indeed a distinct entity that warrants inclusion in standard diagnostic and interpretation algorithms for PF tests.

Author contributions:Dr Iyer: contributed to study design, planning, and writing the article.

Mr Schroeder: contributed to statistical analysis.

Mr Parker: contributed to data retrieval and technical support.

Dr Hyatt: contributed to study design, planning, and writing the article.

Dr Scanlon: contributed to study design, planning, and writing the article.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

ATS

American Thoracic Society

BD

bronchodilator

Dlco

diffusing capacity for carbon monoxide

Dlcou

uncorrected diffusing capacity for carbon monoxide

IQR

interquartile range

NS

nonspecific

PF

pulmonary function

Sraw

specific airway resistance

SVC

slow vital capacity

TLC

total lung capacity

Va

alveolar volume

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Figures

Figure Jump LinkFigure 1. Pulmonary function pattern at last follow-up (N = 1,284).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Different PF Pattern Possibilities Including the NS Pattern (N = 3,674)

BOO = borderline obstruction; N = normal; NS = nonspecific; PF = pulmonary function; REDU = reduced; TLC = total lung capacity.

Table Graphic Jump Location
Table 2 —Demographics

Values are presented as mean ± SD or No. (%). PFT = pulmonary function test. See Table 1 legend for expansion of other abbreviation.

Table Graphic Jump Location
Table 3 —Baseline PFT Values

Values are presented as mean ± SD or No. (%). BD = bronchodilator; Dlcou = uncorrected diffusing capacity for carbon monoxide; RV = residual volume; Sraw = specific airway resistance; SVC = slow vital capacity; Va = alveolar volume. See Table 1 and 2 legends for expansion of other abbreviations.

Table Graphic Jump Location
Table 4 —Post-BD Patterns of the Initial PFT

Values are presented as No. (%). See Table 1, 2, and 3 legends for expansion of abbreviations.

Table Graphic Jump Location
Table 5 —Length of Follow-up and Final PF Pattern

Values are presented as No. (%). See Table 1 legend for expansion of abbreviations.

a 

For overall comparison using χ2 test for categorical variables.

Table Graphic Jump Location
Table 6 —Annual Rate of Change and PFT Pattern at Last Follow-up According to Smoking Status

Values are presented as median (25th, 75th percentile) or No. (%). See Table 13 legends for expansion of abbreviations.

a 

For overall comparison across smoking status groups using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for never vs former smokers and never vs current smokers.

Table Graphic Jump Location
Table 7 —Annual Rate of Change and PFT Pattern at Last Follow-up According to BD Response

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison between BD groups using the Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found based on BD response.

Table Graphic Jump Location
Table 8 —Annual Rate of Change and PFT Pattern at Last Follow-up According to Sraw Strata

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison across Sraw strata using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for the four groups based on Sraw strata.

Table Graphic Jump Location
Table 9 —Annual Rate of Change and PFT Pattern at Last Follow-up According to TLC–Va Strata

Values are presented as median (25th, 75th percentile) or No. (%). See Table 1-3 legends for expansion of abbreviations.

a 

For overall comparison across TLC–Va strata using Kruskal-Wallis test for continuous variables, χ2 test for categorical variables.

b 

From supplemental pairwise group comparisons significant differences were found for the four groups based on TLC–Va strata.

Table Graphic Jump Location
Table 10 —Multinomial Logistic Regression Results (n = 573)

Multivariable associations with the final PF pattern were assessed using a multinomial logistic regression model. For this analysis, only subjects whose final PF pattern was NS, restrictive, or obstructive were included with logits modeled using the NS pattern as the reference. See Table 1 and 3 legends for expansion of abbreviations.

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