FEV1 Response to Bronchodilation in an Adult Urban Population

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Orig inaI Research PULMONARY FUNCTIONTESTING

FEV, Response to Bronchodilation in an Adult Urban Population* Annette Kainu, MD; Ari Lindqvist, PhD; Seppo Sarna, PhD; Bo Lunrlhack, PhD; and Anssi Sovijarvi, PhD

Background: Most studies evaluating bronchodilation in flow-volume spirometry have been conducted in patients with obstructive airways diseases, but less is known about bronchodilation responses in the general population or in healthy subjects. Methods: We evaluated an urban population sample of 628 adults (260 men, 368 women) aged 25 to 74 years with flow-volume spirometry using inhalation of 0.4 mg of a salbutamol aerosol with a spacer device for bronchodilation. On the basis of a structured interview, a subgroup of 219 healthy, asymptomatic nonsmokers was selected. Results: In the population sample, the average increase in FEV, from baseline after salbutamol inhalation was 77.2 mL (SD, 109.7 mL) or 2.5% (SD, 3.9%).In healthy asymptomatic nonsmokers, the mean change in FEV, was 62.0 mL (SD, 89.7 mL) or 1.8% (SD, 2.6%). In the whole population, the 95th percentile limit of the increase in FEV, was 8.5%, while it was 5.9%among healthy asymptomatic nonsmokers. The absolute change in FEV, correlated significantly with baseline FVC (p < 0.01).The FEV,/FVC ratio at baseline was the strongest influencing factor for the bronchodilation response. Conclusions: The results indicate that a significant increase in FEV, from baseline in a bronchodilation test is around 9% in an urban population. The level of the significant absolute increase in FEV, seems to depend on FVC. Low baseline FEV,/FVC ratio, reflecting aidlow limitation, is the strongest determinant for FEV, response to bronchodilation. (CHEST 2008; 134:387-393) Key words: bronchodilation; FEV,; flow-volume spirometry; lung function Abbreviations: ATS = American Thoracic Society; BMI = body mass index; ERS = European Respiratory Society; PEF = peak expiratory flow

low-volume spirometry is a reproducible and reliable method for assessing lung function. The bronchodilation test is used to detect reversible airways obstruction, which is considered to be important for diagnosing asthma.l.2 In clinical use, the spirometric bronchoddation response has previously been related to either baseline or reference values.3-5 In 2005, the joint American Thoracic Society (ATS) and European Respiratory Society (ERS) Task Force on the Standardization of Lung Function Testing recommended2 that the limit for a significant bronchodilation response in adults be an increase in FVC or FEV, of 12% and 200 mL from baseline.2 When assessing the response in terms of FVC, the updated recommendation2 included a requirement for the standardization of expiratory times.

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Numerous studies on bronchodilation responses have been published on patients with obstructive airways diseasesfi-12 or in selected populations.' 3 ~ A few studies15 l6 have been based on unselected population samples. Bronchodilating medication and its mode of delivery, and the type of spirometer used have varied. FEV, has been shown to be the best variable in terms of statistical power17 and reproducibility,18but it is dependent on baseline FEV, at the population level.16 Most reports have documented smaller bronchodilation responses in older peoplel.5.16 and an effect of gender,"f but the concurrent changes in baseline lung function, age, arid gender have not been reported to date in nonselected population samples. Further, the prevalence of obstructive airways diseases has increased, but very little is known about eventual long-term changes in CHEST J 134 I 2 I AUGUST, 2008

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bronchodilation responses in the general population. Updating reference values regularly is recommended to take into account changes in population structure (eg, improvements in the general level of health and nutrition, and in the prevalence of diseases).4,1Y The aim of this study was to determine the distribution and range of the bronchodilation response in terms of changes in FEV, in a general adult urban population and in a subgroup of healthy, asymptomatic, nonsmoking subjects to identify the normal response, and its anthropometric and spirometric determinants.

MATERIALSAND METHODS Subjects and Study Design In 1995, a total of 8,000 adults aged 20 to 69 years were randomly sampled from the population of Helsinki, Finland, as a part of an epidemiologic multicenter questionnaire study on respiratory health in Finland, Estonia, and Sweden (or FinEsS study).2"-22 The population sample was obtained from the Population Register Center, and was randomized by 10-year age cohorts and by gender. No exclusion criteria were applied. In the year 2000, a randomized sample of 1,200 subjects was selected from the original postal survey responders (n = 6,062; 2,600 men and 3,462 women) to the subsequent clinical phase of the study; 1,139 responders were traced and 643 responders participated in the study. Participants did not differ significantly from nonresponders regarding respiratory symptoms, diseases, or smoking habits when evaluated with the x2 test. Of these 643 subjects, 633 completed flow-volume spirometry and a structured interview by a physician using a questionnaire developed in Obstructive Lung Disease in North Sweden (or OLIN) studies,2" containing questions about asthma, chronic bronchitis, various respiratory symptoms, and smoking habits. Five individuals did not participate in the subsequent bronchodi"From the Division of Pulmonary Medicine (Dr. Kainu), and Research Unit of Pulmonary Diseases (Dr. Lindqvist), the Department of Medicine, and the Division of Clinical Physiology and Nuclear Medicine (Dr. Sovijarvi), Laboratory De artment, Helsinki University Central Hospital, Helsinki, Finyand; the De artment of Public Health (Dr. Sarna), University of Helsinki, HeEinki, Finland; the Department of Medicine/Respiratory Medicine and Allergology (Dr. Lundback), University of Gothenburg, Gothenburg, Sweden; and the Division of Clinical Physiology and Nuclear Medicine (Dr. Sovi'iimi), Laboratory Department, Helsinki University Central Hospitaf, Helsinki, Finland. This research was supported by a special governmental subsidy for health sciences research (Helsinki University Central Hospital project rant numbers TYH 1235, TYH 2303, and TYH 4251). The augors have reported to the ACCP that no significant conflicts of interest exist with any com anies/organizations whose products or services may be discusseBin this article. Manuscript received August 31, 2007; revision accepted March 12, 2008. Reproduction of this article is rohibited without written permission from the American College ofchest Physicians (w.chestjournal. orglmisdre rints shtml). Correspon&nm to: Annette Kainu, MD, Division of Pulnwnay

Medicine, Department of Medicine, Helsinki University Central Hospital, PO Box 340, FIN-OOO29HUS, Helsinki, Finland D01: 10.1378/chest.07-2207

388

lation test. Thus, the final sample consists of spirometry results for 628 subjects (260 men and 368 women). The anthropometric parameters used for the analysis were gender, age, height, weight, and body mass index (BMI). Based on the responses to the questionnaire, individuals were considered to be healthy and asymptomatic if they gave no positive answers to > 50 questions dealing with symptoms, diagnosed respiratory diseases, and the use of pulmonary medications. The respiratory symptoms that were evaluated included wheezing, attacks of shortness of breath, sputum production, dyspnea, and dyspnea on exertion. The criterion for nonsmokers was never-smokers or former smokers who had smoked a maximum of 5 pack-years and had discontinued smoking at least 5 years prior to entering the study. Accordingly, 43.3% of men and 61.8% of women were classified as nonsmokers in this population sample. The descriptive statistics of anthropometric and spirometric variables of the study population are summarized in Table 1. The study was conducted according to the Helsinki Declaration and was approved by the Ethics Committee of the Department of Medicine of Helsinki University Central Hospital. All participants gave informed consent.

Flow-Volume Spiromety and Brnnchodilation Te,yt Subjects were advised to refrain from smoking for at least 4 h; from consuming coffee or tea, and engaging in heavy eating for 2 h; and from alcohol consumption for at least 1.5 days prior to the study visit. The regular use of medications, if any, could be continued. Spirometry was completed with a flow-volume device (VMax 20c; SensorMedics: Yorba Linda, CA) with the subject seated using ATS 1994 criteria for performing the m a n e ~ v e rbut , ~ the repeatability criteria were determined according to the 1993 ERS standard.5 Thus, the reproducibility criteria of the curves used were as follows: the two largest FEV, and FVC values were required to be within 5% of the respective volume or within 100 mL, whichever was greater; and the two largest peak expiratory flow (PEF) values were required to be within 10% of each other. In addition, each of the curves used for analysis should fulfill the quality criteria concerning the extrapolated volume.4 The adherence to these predefined quality criteria was documented in the patient file. Nose clips and disposable bacterial filters were used. At least three technically acceptable measurements were recorded with a maximum of eight efforts. Inspiratory spirograms were recorded in conjunction with the expiratory spirograms whenever possible. Two trained nurses performed the measurements. The calibration of the spirometer was checked with a 3-L calibration syringe (SensorMedics) once a day and whenever the spirometer software requested calibration. For bronchodilation, the subjects inhaled 0.4 mg of salbutamol aerosol (Ventoline: GlaxoSmithKline; London, UK) through a spacer device (Volumatic: GlaxoSmithKline) in two separate doses. This was the same dose recommended by the ATSIERS Task Force.*Ig Subjects then remained seated for 15 min, without smoking or consuming beverages other than water, after which a repeated spirometry was performed in an identical fashion to determine the bronchodilation response. Baseline spirometry findings were evaluated using current Finnish reference values,24and the postbronchodilator spirometry findings were assessed by calculating the absolute and relative changes in FEV, and PEF from baseline values. The PEF values were analyzed to evaluate the effort of forced expiration. Examining other spirometric variables was beyond the scope of this study. Original Research

Table l-Descriptive Statistics of Anthropometric and Spirometric Variables Strati$ed by Gender Population Sample I

Men (n = 260)

Healthy Asymptomatic Nonsmokers

Women (n = 368)

' '

Men (n = 76)

Women (n = 143)

Variables

'Mean (SD)

Range

'

'Mean (SD)

Range

'

'Mean (SD)

Range

'

'Mean (SD)

Range

Age, F Height, m Weight, kg BMI, kdm2 FVC L % predicted* FEV, L % predicted* FEV,/FVC ratio

48.6 (12.7) 1.78 (0.07) 83.9 (14.1) 26.5(4.3)

262-74.2 1.62-1.98 86.6139.0 17.144.9

49.5 (13.2) 1.64 (0.06) 68.8 (13.7) 25.7(5.1)

25.7-74.4 1.4e1.83 44.0-133.0 16.953.3

46.8 (12.9) 1.79 (0.06) 80.3 (11.2) 25.1 (3.1)

26.3-72.0 1.62-1.94 57.0-118.0 17.8-33.7

48.2 (12.8) 1.65 (0.06) 66.1 (9.7) 24.3(3.5)

25.7-73.6 1.51-1.79 44.0-98.0 18.334.0

'

5.075 (0.912) 98.1 (12.3)

2.182-8.033 50.8-131.2

3.549 (0.660) 99.5 (12.5)

2.013-5.388 71.9-144.6

5.369 (0.861) 102.1(12.4)

3.513-7.413 70.7-131.2

3.686 (0.605) 100.6 (11.5)

2.091-5.199 71.9-144.6

3.897 (0.832) 92.9 (14.9)

1.0163.895 29.2-128.7

2.784 (0.591) 94.7 (13.1)

0.9924.495 40.6132.8

4.241 (0.706) 99.5 (12.4)

2.6765376 72.4-128.7

2.953 (0.499) 97.9 (10.6)

1.5664.081 74.5-129.4

34.8-96.3 42.6-121.2

78.3 (7.0) 95.3 (8.0)

44.7-92.9 55.1-114.9

79.1 (5.3) 97.6 (6.4)

68.7-93.5 85.5-112.7

80.2 (5.4) 97.6 (5.9)

64.5-92.9 79.5-114.9

% %

'

predicted*

76.5 (7.8) 94.5 (9.6)

*Predicted values from the study by Viljanen et al.24

Statistical Analysi P Statistical analyses were performed using a statistical software package (SPSS for Windows, version 15.01; SPSS; Chicago, IL), with the exception of the 95% confidence intervals (CIS) for the 95th percentile values (CIA, version 2.1.2; Trevor Bryant; University of Southampton; Southampton, UK). The distribution of parameters was assessed using scatter graphs, and normality was assessed using the Kolmogorov-Smirnov test. The Pearson correlation coefficient ( r value) was used to assess the association of anthropometric and spirometric variables with changes in FEV, after bronchodilation. The effect of gender on bronchodilation was assessed with an analysis of covariance model using height and baseline FEV,/FVC ratio as the covariates. Linear regression modeling was used to evaluate the role of different determinants on the bronchodilation response in the population. A p value of < 0.05 was considered to be significant for all analyses other than correlations, for which a p < 0.01 was regarded as significant.

RESULTS Population Sample The absolute and relative changes in FEV, after inhaling salbutamol with respect to the baseline spirometry values are shown in Figure 1. Both absolute and relative changes in FEV, showed normal or a near-normal distribution within the population. For the population, the mean change in FEV, was + 77.2 mL (95% CI, 68.6 to 85.8 mL) or 2.5% (95% CI, 2.2 to 2.8%); for men, the mean change in FEV, was 107.4 mL (95% CI, 91.4 to 123.3 mL) or 3.0% (95% CI, 2.5 to 3.5%);and for women, the mean change in FEV, was + 55.9 mL (95% CI, 47.1 to 64.8 mL) or 2.2% (95% CI, 1.8 to 2.6%). In 2.7% of participants of both genders, FEV, decreased by > 100 mL, and in 19.6% of participants the decrease was < 100 mL. The PEF increased on average 1.8% (95% CI, 1.2 to 2.4%).

+

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Correlation coefficients between the change in FEV, and the main anthropometric and baseline spirometric measures are shown in Table 2. Baseline FEV,/FVC ratio was the strongest influencing factor in the population sample. The relationships between the change in FEV, and baseline FVC, FEV,, and FEV,/FVC ratio are demonstrated graphically in Figure 2. The relationship of the change in FEV, to the main anthropometric variables in the population sample are demonstrated graphically in Figure 3. No significant gender difference was present in either absolute FEV, response (p = 0.642) or relative change (p = 0.918) when adjusted for height and baseline FEVJFVC ratio. The absolute change in FEV, slightly but significantly increased with increasing baseline FVC (p < 0.01), but the relative change did not (Table 2, Fig 3). The 95th percentile of change in FEV, was 260 mL (95% CI, 247 to 311 mL) and 8.5% (95% CI, 7.7 to 10.7%) in the whole population. A linear regression model characterizing the influence of anthropometric and spirometric variables on the change in FEV, is shown in Table 3. The model shows the combined effect of different determinants on the change in FEV,. Age, gender, and baseline lung volumes were significant for absolute change, and age, gender, and baseline airflow limitation were significant in the relative change model.

Healthy Asymptomatic Nonsmokers Among healthy asylnptomatic nonsmokers (n = 219), the mean absolute change in FEV, was + 62.0 mL (95% CI, 50.1 to 74.0 mL) or + 1.8% (95% CI, 1.4 to 2.1%); among men, the change was + 97.6 mL (95% CI, 73.1 to 122.1 mL) or 2.3% (95% CI, 1.7 to CHEST / 134 / 2 /AUGUST, 2008

389

* I

30i

n=628

-10

L*jen

women

1

?D

dFEVl [I]

FIGURE1. Absolute and relative change of FEV, (dFEV,) from baseline in bronchodilation test with salbutamol aerosol (0.4 mg) in the population sample.

2.9%); and among women, the change was + 43.1 mL (95% CI, 31.2 to 55.1 mL) or 1.5% (95% CI, 1.1 to 1.9%). Reductions in FEV, of > 100 mL after bronchodilation were seen in 2.6% and 2.1%, respectively, of healthy asymptomatic nonsmoking men and women. Both the absolute and relative changes in FEV, showed normal or near-normal distribution. Overall, the 95th percentile of change in FEV, was 240 mL (95% CI, 224 to 254 mL) and 5.9% (95% CI, 5.6 to 7.7%). Height, baseline FVC, and age had the strongest independent effects on the absolute change in FEV,, and FEV,/FVC ratio and age had the strongest independent effects on the relative change in FEV, in healthy asymptomatic nonsmokers. The effect of gender on the height and baseline FEV,/FVC ratio-adjusted absolute FEV, response (p = 0.380) or relative FEV, response (p = 0.618) was not significant.

DISCUSSION We have shown with flow-volume spirometry that baseline spirometry variables reflecting preexisting airflow limitation, age, and height are the most important determinants of bronchodilation response in an unselected random urban population. Also, in healthy asymptomatic nonsmokers preexisting airflow limitation was the strongest determinant. We found FEV, to improve on average by 77.2 mL (or 2.5%) in the population sample and by 62.0 mL (or 1.8%)in healthy asymptomatic nonsmokers. A slight gender difference was present both in the absolute change and relative change in FEV,, but it was accounted for by the concurrent variations in airflow limitation and height. Age had a weak negative correlation and height a positive correlation with the change in FEV,; however, anthropometric factors explained only a small portion of the total variance observed. Previously, in an unselected rural population sample of 2,609 individuals aged 7 to 75 years,16 the average FEV, bronchodilation response to the inhalation of 500 pg of terbutaline aerosol was 68 mL (or 2.1%), which is close to the response of 2.5% found here. Healthy never-smokers in that study had an average FEV, response of 57 mL (or 1.8%),with a 95th percentile of 10% from baseline values.16 In another population sample of 1,063 individuals who were > 8 years of age, a bronchodilation test was performed in individuals without any cardiac disease, hypertension, diabetes mellitus, or regular use of bronchodilating medication, finding an upper limit of normal response in FEV, of 7.7% from ba~e1ine.I~ Probably due to a variety of methodological differ-

Table B-Correlation Coefficients for Comparison of Anthropometric Parametem and Change in FEV, After Znhalation of 0.4 mg of Salbutamol Aerosol* dFEV,, L I

Population Sample

dFEV,, %

Healthy Asymptomatic Nonsmokers

'' Population Sample

Healthy Asymptomatic Nonsmokers

'

' Variables

Men Women All " Men Women All ' I Men Women All ' I Men Women All (n = 260) (n = 368) (n = 628) (n = 76) ( n = 143) (n = 219) (n = 260) (n = 368) (n = 628) (n = 76) (n = 143) (n = 219)

-0.239t Age 0.151 Height 0.050 Weight -0.016 BMI Log pack-yr of 0.020 smoking 0.165t Baseline FVC Baseline FEV, -0.017 Baseline FEVJ -0.356t FVC ratio

*dFEV,

=

'

-0.135t 0.095 -0.018 -0.053 0.077

-0.186t -0.461t 0.388t 0.252t 0.124t 0.032 -0.014 -0.201 NA 0.085

-0.190 0.037 -0.037 -0.050 NA

-0.305t 0.338t 0.156 -0.071 NA

-0.052 -0.005 -0.019 -0.018 0.116

-0.004 -0.012 -0.039 -0.034 0.118

-0.028 -0.379t 0.313t 0.072 0.024 -0.019 -0.018 -0.216 0.133t NA

-0.069 -0.064 -0.069 -0.033 NA

-0.183t 0.151 0.035 -0.074 NA

0.096 -0.034 -0.3151

0.257t 0.298t 0.124t 0.179 -0.350f -0.261

0.055

0.333t 0.273t -0.209t

-0.077 -0.294t -0.575t

-0.084

-0.235 t

0.015 -0.144t -0.515t

-0.087 -0.147 -0.169

0.122 0.060 -0.225t

change in FEV,; NA

=

0.002

-0.140

-0.448t

0.176 0.049 -0.297t

not applicable.

t p < 0.01.

390

Original Research

b,

35 30

I

-& 20 1 :I5 75

. .

I

;

10

;

5

: o * 10

5

i

-10

-15

-15

0

1

2

3

4

5

6

7

.IS I

2

3

4 5 6 b a r h e wc PI

tarnnr m1 111 0 800

..

*

0 600

= -0 400

..

; ;

0 400

d

2

g 0 200 D t ow0

s ;

8

* *.

9

-0400

40

50

60

70

80

90

100

"=628

" a 8

0 600

--

=. 0600

a

2

-;

0 200

0200 0000

orno

0100

iI

J

30

FEVIIWC [%I

.. .

"-628

0 600

7

-0 200

4 -0200

-0400

0 400

FIGURE 2. Distribution of change in FEV, in relation to baseline FEV, (Zeft, u ) , FVC (center, b ) ,and FEV,/FVC ratio (right, c ) in the population sample.

ences, the variation in the upper limits of normal of the FEV, response to bronchodilation in these studies was slightly higher than that found in our study (general population, 8.5%; healthy asymptomatic nonsmokers, 5.9%). Based on a large population sample, Lehmann et a l l 4 reported a positive correlation between age and bronchodilation as well as a difference between men and women in two age groups (47 to 48 and 71 to 73 years of age). The mean change in FEV, in the middle-aged group was 70.7 mL (or 2.35%), and in the elderly it was 64.4 mL (or 3.25%).14 These values are within the CIS of our bronchodilation study. We found that preexisting airflow limitation in terms of decreased FEV,/FVC ratio and lung volume were the strongest determinants for bronchodilation responses in the general population and in healthy asymptomatic nonsmokers. The number of

20

30

50

40 .Be

b"l

60

70

80

20

25

30

pack-years of smoking did not correlate significantly with the change in FEV, in the population. Although a larger absolute bronchodilation response was found in men than in women, the phenomenon can be explained by the more frequently found airflow limitation (ie, reduced FEVJFVC ratio) and a larger FVC in men. In our sample of subjects who were 25 to 74 years of age, we showed a significant negative correlation of age more clearly with the absolute change in FEV,, but less so with the relative change in FEV,. This can be partially attributed to the aging-related reduction in FEVJFVC ratio and smaller lung volumes found in persons in older age groups. A weak negative correlation of age with change in FEV, might also be explained by the diminished coordination and fatigue of elderly subjects, resulting more frequently in the decreasing FEV, found in bronchodilation test results. The role of baseline FVC was slightly more pronounced in our

35 40 Bhll Iklim'lJ

45

50

55

-10

1

-I5 J

I

14

15

1.6

17 1.8 bsighl [m]

1.9

20

21

FIGURE3. Distribution of change of FEV, in the bronchodilation test related to age (left, a ) , BMI (center, b ) ,and height (right, c) in the population sample. www.chestjournal.org

CHEST I 134 I 2 I AUGUST, 2008

391

Table 3-Linear Regression Model of Change in FEV, in Bronchodilation Test in Population dFEV,, L (Rz = 26.5%) Predictors Female gender Age Height Log pack-yr of smoking Baseline FEV, Baseline FVC Baseline FEV,/FVC ratio Constant

*NS

=

I

Estimate

SE

t Statistic

-0.034 -0.003 0.092 -0.005 -0.140 0.103 -0.138 0.211

0.013 0.000 0.078 0.004 0.052 0.040 0.204 0.200

-2.587 -7.371 1.180 - 1.379 -2.683 2.578 -0.680 1.054

p Value 0.01

< 0.01 NS NS < 0.01 0.01 NS NS

I

I

Estimate

SE

t Statistic

p Value

-0.014 -0.001 0.034 -0.001 0.013 -0.021 -0.370 0.356

0.004 0.000 0.027 0.001 0.018 0.014 0.070 0.068

-3.056 -7.617 1.286 -0.843 0.754 - 1.548 -5.318 5.205

< 0.01 < 0.01 NS NS NS NS < 0.01 < 0.01

not significant. See Table 2 for abbrevkation not used in the text.

study than in earlier reports.7J6 In larger lungs, transectional airway areas at different levels of the bronchial tree are larger and thus can offer a greater absolute change for FEV, in the bronchoddation test results. When considering the lower limits of clinically significant change, the criteria for bronchodilation response are also restricted by inherent measurement variability (ie, the expected intraindividual variation between two measurements either at the same time or on different occasions). In a large patient pool of 18,000 individuals, the within-test FEV, repeatability was 58 mL (95th percentile, 150 mL), and relative to baseline it was 3.0% (95th percentile, 8.2%).25When using criteria based on the relative change in FEV,, individuals with low initial FEV, levels and the greatest pulmonary impairment would appear to have the greatest reversibility7.9and also the poorest reproducibility.2”26 Therefore, the relative change in FEV, cannot be used as the only criterion for a clinically significant bronchodilation response, but a concurrent absolute change criterion is also needed. The current ATS/ERS standard2 for a significant bronchodilation response requires a 12% relative increase over baseline and an absolute increase of 200 mL. This reflects in part the fact that an intrasession repeatability of FEV, or FVC is considered to be acceptable if it is < 200 mL. Repeatability studies in population samples are necessary to validate this value. This population study was conducted with individuals receiving their regular therapeutic medication. Individuals with physician-diagnosed asthma showed dampened bronchodilation responses. Test results with decreased FEV, in bronchodilation testing have sometimes been excluded from analyses.18,27,28 We found that small negative changes were also more frequent than have been previously reported in healthy asymptomatic nonsmokers and believe that these changes should be considered when assessing the upper limits of the normal variation in bronchodilation tests. 392

dFEV,, % (R2 = 33.5%) I

This study was conducted in Helsinki, the capital city of Finland, which is an urban center with medium low levels of air pollution and a predominantly white population. Air pollution has been shown to increase respiratory symptoms and to affect lung function.2” We believe that our results represent the normal status without excessive air pollution and could be generalized also to other white populations. Our results indicate that the limit for a significant increase in FEV, from baseline in bronchodilation test results is close to 9% in a randomly selected adult population. These findings suggest that the limit of 12% presented in the most recent ATS/ERS guidelines2J” may be slightly overestimated. The main determinants for the bronchodilation response were age and, in particular, the FEV,/FVC ratio, reflecting airflow limitation. The level of the significant absolute increase in FEV, seems to depend on FVC. ACKNOWLEDGMENT: The authors thank the personnel at the Research Unit of Pulmonary Diseases for excellent assistance.

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