Validation of Lung Age Measured by Spirometry and Handy Electronic FEV1/FEV6 Meter in Pulmonary Diseases

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1 ORIGINAL ARTICLE Validation of Lung Age Measured by Spirometry and Handy Electronic FEV1/FEV6 Meter in Pulmonary Diseases Reiko Toda 1, Tomoaki Hoshino 1, Tomotaka Kawayama 1, Haruki Imaoka 1, Yuki Sakazaki 1, Toru Tsuda 2, Shohei Takada 3, Masaharu Kinoshita 1, Tomoaki Iwanaga 1 and Hisamichi Aizawa 1 Abstract Objective The concept of lung age is thought to be useful for understanding pulmonary function. In this study, we validated lung age to detect pulmonary function abnormalities in pulmonary diseases. Methods We used both spirometry and an electronic FEV1/FEV6 meter (FEV6 meter) to perform pulmonary function tests. We evaluated the sensitivity and specificity of FEV6 and FEV1/FEV6, and calculated lung age in Japanese subjects including those with chronic obstructive pulmonary disease (COPD), bronchial asthma (BA), and interstitial lung diseases (ILD). Results FEV1 (spirometer) vs. FEV1 (FEV6 meter), FVC (spirometer) vs. FEV6 (FEV6 meter), and FEV1/ FVC (spirometer) vs. FEV1/FEV6 (FEV6 meter) measurements were all significantly and closely correlated. For the difference of lung age and actual age, the area under the receiver operating characteristic curve (ROC-AUC) for detecting obstructive impairment was (spirometer) and (FEV6 meter), respectively. The corresponding ROC-AUC for detecting restrictive impairment was and 0.836, respectively, and that for detecting both obstructive and restrictive impairment was and 0.853, respectively. For detection of both obstructive and restrictive impairment, the difference of the lung age and actual age cutoff value, corresponding to the greatest sum of sensitivity and specificity, was 18.3 years (spirometer) and 19.8 years (FEV6 meter), respectively. The sensitivity was (spirometer) and (FEV6 meter), and the specificity was (spirometer) and (FEV6 meter), respectively. Conclusion Lung age can provide an easy interpretation of the results, and can detect pulmonary function abnormalities in pulmonary diseases. Key words: FEV6, spirometry, obstructive impairment, restrictive impairment, COPD, lung age (Inter Med 48: , 2009) () Introduction Spirometry is indispensable for the evaluation of pulmonary functional disorders. The diagnosis of chronic obstructive pulmonary disease (COPD) requires spirometry, and spirometry is also required to evaluate pulmonary function in almost all other pulmonary diseases, such as bronchial asthma (BA) or conditions of restrictive impairment such as idiopathic interstitial fibrosis (IPF). COPD has high prevalence and mortality, both of which are generally underestimated because many COPD patients are not diagnosed (1-3). A NICE (Nippon COPD Epidemiology) Study estimated the prevalence of COPD in Japan to be 5,300,000, but the number of patients treated yearly is only 220,000 (2). Underdiagnosis is thought to result from patients being unaware of the disease until it is advanced, and also from the fact spirometry, the most important tool Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Department of Medicine, Kirigaoka Tsuda Hospital, Kitakyushu and Division of Respirology, Department of Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Fukuoka Received for publication October 15, 2008; Accepted for publication December 15, 2008 Correspondence to Dr. Tomoaki Hoshino, hoshino@med.kurume-u.ac.jp. 513

2 for the diagnosis of COPD, is not widely available (4-6). For early diagnosis and treatment of COPD we need to increase the use of spirometer in primary care institutions. Pulmonary function test is indispensable for evaluating the progress and treatment of many pulmonary diseases besides COPD (1). However, the rate of uptake of the pulmonary function test by primary care physicians has been lower than those of the electrocardiogram or sphygmomanometer. One very important reason may be that spirometry is not familiar to general practitioner, medical staff or patients (4-6). Also, the parameters used in spirometry including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio are difficult for both the patients and co-medical staffs to understand. Forced expiratory volume in 6 s (FEV6) is used as a surrogate for FVC (7-9). It may reduce test time and frustration (10). There is much evidence that FEV6 is equivalent to FVC and is easier to measure (11-14). Furthermore, FEV6 may improve reproducibility with no significant loss of sensitivity or specificity (15). An electronic device for FEV1 measurement (FEV1 meter) is the same size as a peak flow meter and can be used for examination anywhere. Measurement can be performed easily and immediately; the device can be used to promote pulmonary function test and for screening purposes. The precision of the device has been assessed for FEV1 in pulmonary diseases (16-18). Recently, an electronic handy device for FEV1 and FEV6 measurement (FEV1/FEV6 meter) has been developed. However, there have been very few reports concerning FEV6 and FEV1/FEV6 ratio with this electronic FEV1/FEV6 meter (19, 20). In addition, it has reported that there are racial differences in the normal values of pulmonary function tests (21). We therefore used the new FEV 1/FEV6 meter to perform pulmonary function test and thus elucidate the FEV1/FEV6 meter s utility in FEV1, FEV6, and FEV1/FEV6 ratio in Japanese subjects. The concept of lung age has been proposed as a way of making the results of pulmonary function test more familiar to the public (22-24). Lung age enables both the general public and pulmonary disease patients to better understand otherwise incomprehensible pulmonary functional abnormalities. It motivates patients to stop smoking and helps encourage patients with potential COPD to seek consultation (22-24). Therefore, we wish to use the concept of lung age to express pulmonary function by age so that participants could understand their pulmonary function easily and clearly. However, no study has been performed to evaluate lung age scientifically to detect impairment of pulmonary functions in pulmonary diseases. In this study, we reviewed the sensitivity and specificity of lung age as measured by both conventional spirometer and the handy electronic FEV1/ FEV6 meter in Japanese subjects including non-smokers, smokers, COPD, BA, and interstitial lung diseases (ILD). We evaluated whether lung age and the FEV1/FEV6 meter detect pulmonary function abnormalities in pulmonary diseases. Methods Conventional spirometer and electronic FEV1/FEV6 meter We measured FEV1, FVC with a conventional spirometer (Chestgraph Jr. 101, Chest Co., Tokyo) according to a recommendation of the American Thoracic Society (25). After the spirometry, we used an electronic FEV1/FEV6 meter (Piko-6, Ferraris Co., London, hereafter FEV6 meter ) on the same subject to measure FEV1 and FEV6. In this study, obstructive impairment was assumed to be indicated by FEV1/FVC < 0.7, and restrictive impairment was assumed to be %FVC < 80% by spirometry. Subjects We used both a conventional spirometer and FEV6 meter to perform pulmonary function test in all 768 subjects. Of these, 272 subjects (113 with %FVC < 80% plus 159 with %FVC 80%) had obstructive impairment (FEV1/FVC < 0.7) and 247 subjects (134 with FEV1/FVC 0.7 plus 113 with FEV1/FVC < 0.7) had restrictive impairment (%FVC < 80%) (Table 1). All patients with BA and COPD were diagnosed as previously reported (26). We carefully excluded individuals with chronic lung conditions such as BA, bronchiectasis, and ILD from COPD patients as previously reported (26). All ILD patients were diagnosed according to the clinical criteria for diagnosis of ILD by ATS/ERS (27) as we previously reported (28). Table 2 give details of nonsmokers without disease, smokers without disease, and patients with pulmonary diseases (number, age, sex). All procedures were approved by the ethics committees of Kurume University. We obtained informed written consent from each subject. Calculation of lung age We used the Japanese Respiratory Society s normal prediction equation for FEV1 (29) and then substituted the measured FEV1 and the patient s height to calculate the functional age, which has been termed the lung age as follows. Male: Lung age = (0.036 height (cm) fev1 (L))/0.028 Female: Lung age = (0.022 height (cm) fev1 (L))/0.022 Statistical analysis Results were expressed as means ± standard error of the mean (SEM). Correlations were analyzed by simple regression. The sensitivity and specificity of the FEV1/FEV6 meter for identifying obstructive and restrictive impairment were analyzed by using a receiver operating characteristic (ROC) curve generated by logistic regression. SAS software, Japanese edition (SAS Institute, Cary, NC, USA) was used to determine positive predictive values (PPVs) and negative 514

3 Table1. PulmonaryFunctionsinSubjectsUsedinThisStudy Sex No. Age (years) Male ± 0.9 Female ± 0.9 Total ± 0.6 Height (cm) FEV 1 /FVC 0.7 FEV 1 /FVC < 0.7 %FVC 80% %FVC < 80% %FEV 1 80% 50% %FEV 1 < 80% 30% %FEV 1 < 50% %FEV 1 < 30% 165.4± ± ± a Seven hundred sixty-eight subjects (15 to 89 years old, mean age 58 years; 366 female, 402 male) were monitored at Kurume University Hospital (Kurume Japan), National Hospital Organization Fukuoka-Higashi Medical Center (Fukuoka, Japan), Nagata Hospital (Yanagawa, Japan), and Kirigaoka Tsuda Hospital (Kitakyushu, Japan). We used both conventional spirometry and FEV 6 meter to perform pulmonary function test in all 768 subjects. a. 113 with %FVC < 80% and 159 with %FVC 80% Table2. ClinicalCharacteristicsofSubjectsUsedinThisStudy Male (age) Female (age) Total (age) Nonsmokers 16 (36.8 ± 4.1) 55 (44.0 ± 2.3) 71 (42.4 ± 2.0) Smokers BA COPD ILD LC Other pulmonary diseases a (46.4 ± (57.6 ± (71.7 ± (69.9 ± (65.6 ± (60.7 ± 1.8) 2.5) 1.6) 1.4) 2.3) 1.7) (41.4 ± (56.0 ± (61.3 ± (63.1 ± (60.5 ± (60.5 ± 1.6) 4.6) 1.4) 4.5) 2.2) 2.8) (45.0 ± (56.7 ± (70.3 ± (67.2 ± (63.8 ± (60.6 ± 1.2) 2.2) 1.1) 1.4) 1.7) 1.5) a. Includes tuberculosis, nontuberculous mycobacteriosis, pneumonia, sarcoidosis, bronchiectasis, pneumoconiosis, sleep apnea syndrome, chronic eosinophilic pneumonia, bronchitis and/or diffuse panbronchiolitis. BA: bronchial asthma, COPD: chronic obstructive pulmonary disease ILD: interstitial lung diseases, LC: lung cancer predictive values (NPVs) and to calculate the area under the ROC curve (ROC-AUC). The sensitivity and specificity of the difference between the lung age and the actual age for identifying pulmonary function abnormality were also analyzed from the ROC curve. Nonparametric tests (Kruskal-Wallis test) were used to compare differences between the groups. A p value of < 0.05 was considered to indicate a statistically significant difference. Results Comparison of data obtained by spirometer and electronic FEV1/FEV6 meter We used both a conventional spirometer and a FEV6 meter in 768 subjects. We observed close correlations between FEV1 (spirometer) vs. FEV1 (FEV6 meter) (r = 0.933, p < ), FVC (spirometer) vs. FEV6 (FEV6 meter) (r = 0.897, p < ), and FEV1/FVC (spirometer) vs. FEV1/ 515

4 Figure1. CorrelationbetweenFEV1measuredbyaspirometerandbyelectronicFEV1/FEV6me ter(a).correlationbetweenfvcmeasuredbythespirometerandfev6bytheelectronicfev1/ FEV6meter(b).CorrelationbetweenFEV1/FVCmeasuredbythespirometerandFEV1/FEV6by theelectronicfev1/fev6meter(c).closeandsignificantcorrelationswereobtainedinalthree comparisons. FEV6 (FEV6 meter) (r = 0.733, p < ) in all subjects (n = 768) (Fig. 1a, b, c, respectively). The correlations were all significant. Next, we evaluated the sensitivity and specificity of a conventional spirometer and FEV1/FEV6 meter for assessment of obstructive impairment. Using ROC analysis, we reviewed whether the FEV1/FEV6 ratio can detect obstructive impairment (FEV1/FVC < 0.7) judged by spirometry (Fig. 2a). The ROC-AUC was At a cutoff value of corresponding to the greatest sum of sensitivity and specificity, the sensitivity of the FEV1/FEV6 for detecting obstructive impairment was and the specificity was The PPVs and NPVs were 75.8% and 88.4%, respectively. For restrictive impairment (%FVC < 80%), the ROC- AUC was in the FEV6/FVC predicted (Fig. 2b). At a cutoff value of 80.6% corresponding to the greatest sum of sensitivity and specificity in the FEV1/FEV6 for detecting restrictive impairment, the sensitivity was and the specificity was The PPVs and NPVs were 65.2% and 96.4%, respectively. Detection of pulmonary function abnormalities by lung age First, we pointed out the difference of lung age and actual age, and examined whether pulmonary function abnormalities can be detected by lung age calculated from the spirometry values. For the difference of lung age and actual age, ROC-AUC was for detection of obstructive impairment (Fig. 3a). Next, we used lung age calculated from the FEV6 meter values. For the difference of lung age and actual age, ROC-AUC was for detection of obstructive impairment (Fig. 3b). For the difference of lung age and actual age, ROC-AUC for detection of restrictive impairment was (spirometer) and (FEV6 meter) (Fig. 4a, b). For the difference of lung age and actual age, ROC-AUC for detection of both obstructive and restrictive impairment was (spirometer) and (FEV6 meter) (Fig. 5a, b). To detect obstructive impairment, the difference in the lung age and actual age cutoff value, corresponding to the greatest sum of sensitivity and specificity, was 18.3 years old (spirometer) and 19.6 years old (FEV6 meter), respectively. If lung age was more than 20 years greater than actual age, then the sensitivity of this calculation for detecting obstructive impairment was (spirometer) and (FEV6 meter) and the specificity was (spirometer) and (FEV6 meter), respectively. To detect restrictive impairment, the difference in the lung age and actual age cutoff value, corresponding to the greatest sum of sensitivity and specificity, was 23.3 years (spirometer) and 24.9 years (FEV6 meter), respectively. At a cutoff value of 20 years, the sensitivity was and and the specificity 516

5 Figure2.ReceiveroperatingcharacteristiccurveforFEV1/FEV6.Receiveroperatingcharacteris ticcurve(roc)curveforfev1/fev6infev1/fvc(measuredbyspirometer)<0.7asobstructive impairment(a).roccurveforfev6/fvcpredictedin%fvc(measuredbyspirometer)<80% as restrictiveimpairment(b). (a) (b) Figure3. Receiveroperatingcharacteristiccurveforthediferencebetween lungage and ac tualage fordetectingobstructiveimpairment.obstructiveimpairmentwasdefinedasfev1/fvc (measuredbyspirometer)<0.7.roccurveforthediferencebetween lungage and actualage calculatedfrom valuesobtainedusingthespirometer(a)andthefev1/fev6meter(b). was and 0.655, respectively. To detect both obstructive and restrictive impairment, the difference of lung age and actual age cutoff value, corresponding to the greatest sum of sensitivity and specificity, was 18.3 years (spirometer) and 19.8 years (FEV6 meter), respectively. At a cutoff value of 20 years, the sensitivity of this method for detecting pulmonary function abnormality was and and the specificity was and 0.790, respectively. Tables 3 and 4 show the PPVs and NPVs at different cutoff values for spirometry and FEV1/FEV6 meter analysis, respectively. We calculated lung age from the spirometry values, and examined the differences between lung age and actual age in non-smokers without disease (n = 71), smokers without disease (n = 54), BA (n = 285), COPD (n = 69), ILD (n = 43), and lung cancers (n = 50). In smokers, BA, COPD, ILD, and lung cancers, the difference of between lung age and actual age was significantly higher than seen in non-smokers. A similar result was obtained when we calculated lung age from the FEV6 meter values (Fig. 6). Interestingly, the pulmonary function test using the spirometer and the FEV6 meter revealed that even normal subjects that had a history of cigarette smoking but showed no obstructive impairment had a lung age significantly greater by 2 and 11 years than their average actual age, respectively. 517

6 (a) (b) Figure4. Receiveroperatingcharacteristiccurveforthediferencebetween lungage and ac tualage fordetectionofrestrictiveimpairment.restrictiveimpairmentwasdefinedas%fvc (measuredbyspirometer)<80%.theroc curveforthediferencebetween lungage and ac tualage wascalculatedfrom thevaluesobtainedusingthespirometer(a)andthefev1/fev6me ter(b). (a) (b) Figure5. Receiveroperatingcharacteristiccurveforthediferencebetween lungage and lac tualage fordetectingbothobstructiveandrestrictiveimpairment.obstructiveimpairmentwas definedasfev1/fvc (measuredbyspirometer)<0.7.restrictiveimpairmentwasdefinedas %FVC(measuredbyspirometer)<80%.TheROC curveforthediferencebetween lungage and actualage calculatedfrom thevaluesobtainedusingthespirometer(a)andthefev1/fev6 meter(b). Discussion This is the first study to show the sensitivity and specificity of the lung age to detect pulmonary function abnormalities. The difference between lung age and actual age in smokers was significantly higher than that in nonsmokers, even in healthy subjects. The concept of lung age may offer opportunities to increase the frequency of early discovery of disorders such as COPD. Previous studies have used lung age as an incentive to stop smoking and this can be motivation enough to stop smoking (30). Lung age also appears useful for consultation with patients and therapeutic approaches to treatment of patients who do not have subjective symptoms, because lung age could be decreased by the treatment of pulmonary diseases. For example, FEV1 has been shown to be increased by 150 to 200 ml after treatment of Japanese COPD patients with tiotropium (31, 32). This means that, by the Japanese normal equation of lung age (see Material and Methods section), lung age decreased by approximately 6 to 8 years; this fact can be expected to motivate patients to seek treatment. We are currently investigating this issue. However, the degree of pulmonary function abnormality 518

7 Table3. CutofValuesinSpirometryAnalysis Diagnosis Cutoff value of Sensitivity Specificity PPVs NPVs lung age - actual age Obstructive impairment 18.3a Restrictive impairment a Obstructive and restrictive 18.3a impairment a: The greatest sum of sensitivity and specificity. PPV: positive predictive values NPV: negative predictive values Table4. CutofValuesinFEV1/FEV6MeterAnalysis Diagnosis Cutoff value of Sensitivity Specificity PPVs NPVs lung age - actual age Obstructive impairment 19.6a Restrictive impairment a Obstructive and restrictive 19.8a impairment a: The greatest sum of sensitivity and specificity. PPV: positive predictive values NPV: negative predictive values indicated by the difference between lung age and actual age needs to be scientifically evaluated. According to our ROC curve for obstructive impairment, the difference of lung age and actual age cutoff value, corresponding to the greatest sum of sensitivity and specificity, was 18.3 years old (spirometer) and 19.6 years old (FEV6 meter), respectively. When the difference of lung age and actual age was greater than 20 years, the sensitivity for detecting obstructive disorder was (spirometer) and (FEV6 meter) and the specificity was (spirometer) and (FEV6 meter), respectively. In contrast, when the difference of lung age and actual age was 10 years, the sensitivity was (spirometer) and (FEV6 meter), and the specificity was (spirometer) and (FEV6 meter), respectively. Furthermore, the sum of sensitivity and specificity was decreased. Our analyses demonstrated that the difference of lung age and actual age by FEV6 meter values was over 11 years in smokers without diseases. Therefore, we propose that subjects whose lung age is more than 20 years greater than actual age might have pulmonary dysfunction and these subjects should undergo further examinations for indications of pulmonary diseases. Many previous studies have shown that %FVC is a potentially good substitute for %VC in evaluating restrictive impairment (33). Therefore, in this study we used %FVC for evaluating restrictive impairment. FEV6 is a useful substitute for FVC in simplifying pulmonary function tests (7, 8). Therefore, we used an electronic FEV1/FEV6 meter (FEV6 519

8 Figure6. Diferencesbetween lungage and actualage for each finaldiagnosis.ba:bronchialasthma;copd: chronicobstructivepulmonarydisease;ild:interstitiallung diseases;lc:lungcancer. *p<0.05,**p<0.004,***p<0.0001(vs.non-smokers) meter) to measure FEV1 and FEV6, and we validated FEV1, FEV1/FEV6, and FEV6 to evaluate the accuracy of the FEV6 meter. Next, we used both a conventional spirometer and a FEV1/FEV6 meter, and evaluated the sensitivity and specificity of lung age in patients with COPD, asthma, ILD, lung cancers, smokers, and non-smokers. This is the first study to validate lung age in pulmonary disease using a FEV1/ FEV6 meter. If the objective is only to determine the cutoff value for detection of pulmonary dysfunction, a conventional spirometer can be sufficient to calculate lung age. However, the FEV6 meter is a small, inexpensive measurement device with a narrowed functional spectrum: i.e. it measures FEV6. The subject performs maximum-effort expiration through a mouthpiece with a one-way valve; the airflow hits a thin flexible plate with one point of support and is deflected by the plate. The inclination of the plate is converted into an electrical signal via a strain gauge. Because the degree of inclination increases in proportion to the airflow, the airflow can be measured, and data integration automatically gives the volume for 1 s and 6 s. The device is advantageous because measurements can be taken more easily with FEV6 than with FVC, the time taken to access results is short, there is little pain associated with the measurement, and there are minimal complications (9). For these reasons, we used both a conventional spirometer and a FEV6 meter (Piko6) in this study. We obtained good correlations between FEV1 (spirometer) vs. FEV1 (FEV6 meter), FVC (spirometer) vs. FEV6 (FEV6 meter), and FEV1/FVC (spirometer) vs. FEV1/FEV6 (FEV6 meter). We also obtained high ROC-AUC values for sensitivity and specificity in detecting obstructive and restrictive impairment. These results strongly suggest that the device will be useful clinically. The present study showed that an appropriate cutoff value for obstructive impairment was FEV1/FEV6 < 0.749, and that for restrictive impairment was %FEV6 < 80.6%. However, there was one problem in that FEV1/FEV6 tended to be higher than the equivalent spirometric values for FEV1/FVC and there were a considerable number of subjects with 100% FEV1/FEV6. Judgment of the quality of the forced expiration maneuver is possible from the flow-volume curve in spirometry, but the FEV6 meter cannot display a curve. For these reasons, the FEV6 meter should be used for screening, and subjects with abnormalities in this test should then undergo further examination. It is important that these subjects undergo precise testing by spirometry and other pulmonary function test methods. References In summary, the simple FEV6 meter device has superior portability and is conveniently simple to operate. The lung age concept is easy to understand and the results from this instrument can be readily conveyed to the general patient population. However, additional tests, including spirometry, should be performed for a correct diagnosis. These tools improve opportunities for patient consultation and provide incentives to stop smoking, and seek treatment for developing disease. Use of the simple FEV6 meter device and the lung age concept may also help to strongly increase the use of spirometry. Thus, the use of the tools may improve rates of treatment for pulmonary diseases and enhance smoking cessation. Acknowledgement We thank Dr. Howard A. Young (NCI-Frederick, Frederick, MD) for editing, and Drs. M. Okamoto and K. Azuma (Kurume University) for scientific discussion. 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease NHLBI/WHO Workshop report. Rev. ed.2006 (at 2. Fukuchi Y, Nishimura M, Ichinose M, et al. COPD in Japan: the Nippon COPD Epidemiology study. Respirology 9: , Takahashi T, Ichinose M, Inoue H, Shirato K, Hattori T, Takishima T. Underdiagnosis and undertreatment of COPD in primary care settings. Respirology 8: , van Weel C. Underdiagnosis of asthma and COPD: is the general practitioner to blame? Monaldi Arch Chest Dis 57: 65-68, Anthonisen NR, Dik N, Manfreda J, Roos LL. Spirometry and obstructive lung disease in Manitoba. Can Respir J 8: , Ferguson GT, Enright PL, Buist AS, Higgins MW. Office spirometry for lung health assessment in adults: A consensus statement from the National Lung Health Education Program. Chest 117: , Swanney MP, Jensen RL, Crichton DA, Beckert LE, Cardno LA, Crapo RO. FEV (6) is an acceptable surrogate for FVC in the spirometric diagnosis of airway obstruction and restriction. Am J Respir Crit Care Med 162: , Enright RL, Connett JE, Bailey WC. The FEV1/FEV6 predicts lung function decline in adult smokers. Respir Med 96: , Pedersen OF. FEV6: a shortcut in spirometry? Eur Respir J 27: , 520

9 Akpinar-Elci M, Fedan KB, Enright PL. FEV6 as a surrogate for FVC in detecting airways obstruction and restriction in the workplace. Eur Respir J 27: , Swanney MP, Beckert LE, Frampton CM, Wallace LA, Jensen RL, Crapo RO. Validity of the American Thoracic Society and other spirometric algorithms using FVC and forced expiratory volume at 6 s for predicting a reduced total lung capacity. Chest 126: , Vandevoorde J, Verbanck S, Schuermans D, Kartounian J, Vincken W. Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/ FEV6 and FEV6. Eur Respir J 27: , Vandevoorde J, Verbanck S, Schuermans D, et al. Forced vital capacity and forced expiratory volume in six seconds as predictors of reduced total lung capacity. Eur Respir J 31: , Vandevoorde J, Verbanck S, Schuermans D, Kartounian J, Vincken W. FEV1/FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airway obstruction and restriction. Chest 127: , Jensen RL, Crapo RO, Enright P. A statistical rationale for the use of forced expired volume in 6 s. Chest 130: , Dal Negro RW, Micheletto C, Tognella S, et al. PIKO-1, an effective, handy device for the patient s personal PEFR and FEV1 electronic longterm monitoring. Monaldi Arch Chest Dis 67: 84-89, Viejo-Banuelos JL, Pueyo-Bastida A, Fueyo-Rodriguez A. Characteristics of outpatients with COPD in daily practice: The E4 Spanish project. Respir Med 100: , Fonseca JA, Costa-Pereira A, Delgado L, et al. Pulmonary function electronic monitoring devices: a randomized agreement study. Chest 128: , Almeida AG, Duarte R, Mieiro L, et al. [Pulmonary function in Portuguese firefighters]. Rev Port Pneumol 13: , 2007 (in Portuguese). 20. [Capital Souffle: results of a 2005 public awareness campaign about breath measurements in France]. Presse Med 36: , 2007 (in French). 21. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med 159: , Morris JF, Temple W. Spirometric lung age estimation for motivating smoking cessation. Prev Med 14: , Lipkus IM, Prokhorov AV. The effects of providing lung age and respiratory symptoms feedback on community college smokers perceived smoking-related health risks, worries and desire to quit. Addict Behav 32: , Parkes G, Greenhalgh T, Griffin M, Dent R. Effect on smoking quit rate of telling patients their lung age: the Step2quit randomised controlled trial. BMJ 336: , Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med 152: , Imaoka H, Hoshino T, Takei S, et al. Interleukin-18 production and pulmonary function in COPD. Eur Respir J 31: , American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June Am J Respir Crit Care Med 165: , Kitasato Y, Hoshino T, Okamoto M, et al. Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 31: , The Japanese Respiratory Society Statement of the Japanese Pulmonary Function Standard. Rev. ed (Accessed November 25, 2006, at (in Japanese)). 30. Bize R, Cornuz J. Incentives to quit smoking in primary care. BMJ 336: , Akamatsu K, Yamagata T, Takahashi T, et al. Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta (2)-agonist. Pulm Pharmacol Ther 20: , Kawayama T, Hoshino T, Ichiki M, et al. Effect of add-on therapy of tiotropium in COPD treated with theophylline. Int J Chron Obstruct Pulmon Dis 3: , Anonymous. Standardization of spirometry update. Statement of the American Thoracic Society. Am Rev Respir Dis 136: , The Japanese Society of Internal Medicine 521