MEDICINE
ORIGINAL ARTICLE
Whole-Body Plethysmography in Suspected Asthma A Prospective Study of Its Added Diagnostic Value in 302 Patients Antonius Schneider, Johannes Schwarzbach, Bernhard Faderl, Hubert Hautmann, Rudolf A. Jörres
SUMMARY Background: Whole-body plethysmography (WBP) with bronchial challenge testing to measure the (specific) airway resistance, (s)RAW, is considered to be a more sensitive diagnostic procedure than spirometry, which can only measure the forced expiratory volume in one second (FEV1). The evidence for the added diagnostic value of WBP is not yet conclusive. Methods: In a prospective diagnostic study, we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011. The bronchial provocation test was considered positive if the FEV1 fell by at least 20% and/or the airway resistance doubled, with an increase of the sRAW to at least 2.0 kPA × s and/or of the RAW to 0.5 kPA × s/L. Follow-up evaluation was performed one year later. Results: The prevalence of asthma in the 302 patients who completed followup was 27.5%. The sensitivity of WBP with sRAW measurement for asthma was 95.2% (95% confidence interval [CI] 88.3%–98.1%), and its specificity was 81.7% (95% CI 76.1%–86.3%). The sensitivity of FEV1 was 44.6% (95% CI 34.4%–55.3%), and its specificity was 91.3% (95% CI 86.6%–94.4%). The negative predictive value (NPV) of WBP with sRAW measurement was 97.8% (95% CI 94.5%–99.1%), while that of FEV1 was 81.3% (95% CI 76.0%–85.7%). The positive predictive value (PPV) of WBP with sRAW measurement was 66.4% (95% CI 57.5%–74.2%), while that of FEV1 was 66.1% (95% CI 53.0%–77.1%). Conclusion: With sRAW measurement, asthma can be ruled out with high certainty. Improving the positive predictive value of testing for asthma remains a challenge, however, as sRAW measurement does not yield any increase in specificity. ►Cite this as: Schneider A, Schwarzbach J, Faderl B, Hautmann H, Jörres RA: Whole-body plethysmography in suspected asthma—a prospective study of its added diagnostic value in 302 patients. Dtsch Arztebl Int 2015; 112: 405–11. DOI: 10.3238/arztebl.2015.0405
Institute of General Practice, Klinikum rechts der Isar der TU München: Prof. Dr. med. Schneider, Schwarzbach, Faderl 1st Medical Clinic, Klinikum rechts der Isar, Technische Universität München: Prof. Dr. med. Hautmann Institute of Occupational, Social and Environmental Medicine, Ludwig-Maximilian-University, Munich: PD Dr. rer. nat. Jörres
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2015; 112: 405–11
hole-body plethysmography (WBP) has been widely in use in Germany since the 1980s. It is available for everyday routine diagnostic evaluation not only in hospitals but also in every chest physician’s practice. WBP provides more diagnostic information than spirometry; it measures intrathoracic gas volume, total lung capacity, functional residual capacity, and (specific) airway resistance RAW (sRAW), which requires no active cooperation of the patient to be captured (1). Especially sRAW is regularly used in routine diagnostics, since it responds very sensitively to nonspecific bronchial provocation using methacholine or histamine. The provocation test is required to reach a guideline-conform diagnosis of bronchial asthma or rule this out, where spirometry results are normal—which is very often the case in mild asthma (2). The results of the bronchial challenge test are usually interpreted on the basis of the drop in FEV1 and/or rise in RAW or sRAW. The wide availability of WBP in Germany is in direct contrast to the available evidence for any additional diagnostic benefit compared with spirometry. One reason for this may be the fact that in earlier years, the need for systematic evaluations of diagnostic instruments was not seen as an issue (3). Accordingly, wholebody plethysmography is regarded as highly important in routine clinical practice for the diagnostic evaluation in asthma (4) and chronic obstructive pulmonary disease (COPD) (5), which is also reflected in German guidelines (6, 7), whereas it is barely mentioned in international guidelines. Renowned scientists in international pneumology keep casting doubt on its diagnostic usefulness (8). However, Decramer et al. showed recently on the basis of decision scenarios in focus groups that whole-body plethysmography contributed significantly to establishing the diagnosis (9). The specific role of WBP in the diagnosis of bronchial asthma has remained unclear, however, especially with regard of bronchial challenge testing. This is important because sRAW is occasionally categorized as particularly sensitive to measuring artifacts (8). Some studies found that sRAW may be superior to FEV1 in assessing bronchial challenge, but the focus was either not on asthma (10) or the patients were preselected (11, 12),
W
405
MEDICINE
TABLE 1 Characteristics of patients at baseline (study inclusion) (t0) Asthma n (%)
COPD n (%)
No obstructive respiratory disease n (%)
which may lead to bias in assessing diagnostic accuracy (13). The present study aimed to determine the addeddiagnostic value of sRAW in bronchial challenge testing in patients who presented to a specialist chest physician for the first time for the purpose of routine diagnostic evaluation of suspected bronchial asthma.
n
154 (39.2)
5 (1.3)
234 (59.5)
Female sex
91 (59.1)
2 (40.0)
142 (60.7)
Methods
Are you experiencing dyspnea? (yes)
98 (63.6)
5 (100.0)
123 (52.6)
During the past 12 months, have you noticed a wheezing in your chest while breathing? (yes)
97 (63.0)
5 (100.0)
79 (33.8)
Do you often have a cough? (yes)
65 (42.2)
3 (60.0)
112 (47.9)
Do you often cough up sputum? (yes)
44 (28.6)
3 (60.0)
58 (24.8)
In the past 12 months, have you woken up at night with a sensation of tightness around your chest? (yes)
54 (35.1)
1 (20.0)
59 (25.2)
Study design The prospective data collection in the sense of a delayed-type diagnostic study (14) was undertaken between June 2010 and October 2011 in a private practice of chest physicians in Augsburg (15, 16). The present analysis aimed to determine the added diagnostic-prognostic value of WBP and sRAW in the diagnostic evaluation of bronchial asthma.
In the past 12 months, have you woken up because of dyspnea attacks? (yes)
35 (22.7)
1 (20.0)
28 (12.0)
Do you often have allergic rhinitis (for example, hay fever)? (yes)
76 (49.4)
0 (0)
47 (20.1)
Do you smoke? (yes)
19 (12.3)
0 (0)
20 (8.5)
Have you smoked in the past? (yes)
56 (36.4)
4 (80.0)
79 (33.8)
MV [SD]
MV [SD]
MV [SD]
40.5 [15.4]
60.8 [17.0]
44.6 [16.5]
3.3 [0.9]
2.0 [1.1]
3.4 [1.0]
Age FEV1 in liters FEV1 as % of expected
101.3 [17.0] 74.1 [12.3]
107.7 [16.3]
FEV1/VC as %
81.8 [8.4]
66.8 [9.8]
85.6 [7.3]
How much do you smoke/did you smoke? (In pack years)
10.1 [10.7]
42.5 [3.5]
12.9 [15.8]
COPD, chronic obstructive pulmonary disease; MV, mean value; SD, standard deviation
Population 400 patients were entered into the study consecutively, who presented with suspected bronchial asthma to a specialist chest physician for the first time (indicated population [3]). Our inclusion criteria were the description of typical symptoms, such as dyspnea and a productive cough lasting longer than two months, which raised suspicion of the presence of a respiratory disease and required extensive examination including WBP. Our exclusion criteria were: infections of the respiratory tract within the preceding six weeks and contraindications to bronchial challenge testing—such as pregnancy, cardiac arrhythmias, or coronary heart disease. The study was approved by the ethics committee of the Medical Faculty of the University Hospital Klinikum rechts der Isar/Technische Universität München. Information on participants’ medical histories were documented using a structured questionnaire (Table 1). Diagnostic examination using whole-body plethysmography Patients were instructed not to smoke on the day of their examination (t0). They were asked to stop taking anti-obstructive medication that they may previously have been prescribed, 12 hours before the examination. Lung function tests were undertaken according to a standardized protocol, adjusted for sex, age, and body height (17). In case of FEV1/VC (=vital capacity)
ORIGINAL ARTICLE
Whole-Body Plethysmography in Suspected Asthma A Prospective Study of Its Added Diagnostic Value in 302 Patients Antonius Schneider, Johannes Schwarzbach, Bernhard Faderl, Hubert Hautmann, Rudolf A. Jörres
SUMMARY Background: Whole-body plethysmography (WBP) with bronchial challenge testing to measure the (specific) airway resistance, (s)RAW, is considered to be a more sensitive diagnostic procedure than spirometry, which can only measure the forced expiratory volume in one second (FEV1). The evidence for the added diagnostic value of WBP is not yet conclusive. Methods: In a prospective diagnostic study, we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011. The bronchial provocation test was considered positive if the FEV1 fell by at least 20% and/or the airway resistance doubled, with an increase of the sRAW to at least 2.0 kPA × s and/or of the RAW to 0.5 kPA × s/L. Follow-up evaluation was performed one year later. Results: The prevalence of asthma in the 302 patients who completed followup was 27.5%. The sensitivity of WBP with sRAW measurement for asthma was 95.2% (95% confidence interval [CI] 88.3%–98.1%), and its specificity was 81.7% (95% CI 76.1%–86.3%). The sensitivity of FEV1 was 44.6% (95% CI 34.4%–55.3%), and its specificity was 91.3% (95% CI 86.6%–94.4%). The negative predictive value (NPV) of WBP with sRAW measurement was 97.8% (95% CI 94.5%–99.1%), while that of FEV1 was 81.3% (95% CI 76.0%–85.7%). The positive predictive value (PPV) of WBP with sRAW measurement was 66.4% (95% CI 57.5%–74.2%), while that of FEV1 was 66.1% (95% CI 53.0%–77.1%). Conclusion: With sRAW measurement, asthma can be ruled out with high certainty. Improving the positive predictive value of testing for asthma remains a challenge, however, as sRAW measurement does not yield any increase in specificity. ►Cite this as: Schneider A, Schwarzbach J, Faderl B, Hautmann H, Jörres RA: Whole-body plethysmography in suspected asthma—a prospective study of its added diagnostic value in 302 patients. Dtsch Arztebl Int 2015; 112: 405–11. DOI: 10.3238/arztebl.2015.0405
Institute of General Practice, Klinikum rechts der Isar der TU München: Prof. Dr. med. Schneider, Schwarzbach, Faderl 1st Medical Clinic, Klinikum rechts der Isar, Technische Universität München: Prof. Dr. med. Hautmann Institute of Occupational, Social and Environmental Medicine, Ludwig-Maximilian-University, Munich: PD Dr. rer. nat. Jörres
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2015; 112: 405–11
hole-body plethysmography (WBP) has been widely in use in Germany since the 1980s. It is available for everyday routine diagnostic evaluation not only in hospitals but also in every chest physician’s practice. WBP provides more diagnostic information than spirometry; it measures intrathoracic gas volume, total lung capacity, functional residual capacity, and (specific) airway resistance RAW (sRAW), which requires no active cooperation of the patient to be captured (1). Especially sRAW is regularly used in routine diagnostics, since it responds very sensitively to nonspecific bronchial provocation using methacholine or histamine. The provocation test is required to reach a guideline-conform diagnosis of bronchial asthma or rule this out, where spirometry results are normal—which is very often the case in mild asthma (2). The results of the bronchial challenge test are usually interpreted on the basis of the drop in FEV1 and/or rise in RAW or sRAW. The wide availability of WBP in Germany is in direct contrast to the available evidence for any additional diagnostic benefit compared with spirometry. One reason for this may be the fact that in earlier years, the need for systematic evaluations of diagnostic instruments was not seen as an issue (3). Accordingly, wholebody plethysmography is regarded as highly important in routine clinical practice for the diagnostic evaluation in asthma (4) and chronic obstructive pulmonary disease (COPD) (5), which is also reflected in German guidelines (6, 7), whereas it is barely mentioned in international guidelines. Renowned scientists in international pneumology keep casting doubt on its diagnostic usefulness (8). However, Decramer et al. showed recently on the basis of decision scenarios in focus groups that whole-body plethysmography contributed significantly to establishing the diagnosis (9). The specific role of WBP in the diagnosis of bronchial asthma has remained unclear, however, especially with regard of bronchial challenge testing. This is important because sRAW is occasionally categorized as particularly sensitive to measuring artifacts (8). Some studies found that sRAW may be superior to FEV1 in assessing bronchial challenge, but the focus was either not on asthma (10) or the patients were preselected (11, 12),
W
405
MEDICINE
TABLE 1 Characteristics of patients at baseline (study inclusion) (t0) Asthma n (%)
COPD n (%)
No obstructive respiratory disease n (%)
which may lead to bias in assessing diagnostic accuracy (13). The present study aimed to determine the addeddiagnostic value of sRAW in bronchial challenge testing in patients who presented to a specialist chest physician for the first time for the purpose of routine diagnostic evaluation of suspected bronchial asthma.
n
154 (39.2)
5 (1.3)
234 (59.5)
Female sex
91 (59.1)
2 (40.0)
142 (60.7)
Methods
Are you experiencing dyspnea? (yes)
98 (63.6)
5 (100.0)
123 (52.6)
During the past 12 months, have you noticed a wheezing in your chest while breathing? (yes)
97 (63.0)
5 (100.0)
79 (33.8)
Do you often have a cough? (yes)
65 (42.2)
3 (60.0)
112 (47.9)
Do you often cough up sputum? (yes)
44 (28.6)
3 (60.0)
58 (24.8)
In the past 12 months, have you woken up at night with a sensation of tightness around your chest? (yes)
54 (35.1)
1 (20.0)
59 (25.2)
Study design The prospective data collection in the sense of a delayed-type diagnostic study (14) was undertaken between June 2010 and October 2011 in a private practice of chest physicians in Augsburg (15, 16). The present analysis aimed to determine the added diagnostic-prognostic value of WBP and sRAW in the diagnostic evaluation of bronchial asthma.
In the past 12 months, have you woken up because of dyspnea attacks? (yes)
35 (22.7)
1 (20.0)
28 (12.0)
Do you often have allergic rhinitis (for example, hay fever)? (yes)
76 (49.4)
0 (0)
47 (20.1)
Do you smoke? (yes)
19 (12.3)
0 (0)
20 (8.5)
Have you smoked in the past? (yes)
56 (36.4)
4 (80.0)
79 (33.8)
MV [SD]
MV [SD]
MV [SD]
40.5 [15.4]
60.8 [17.0]
44.6 [16.5]
3.3 [0.9]
2.0 [1.1]
3.4 [1.0]
Age FEV1 in liters FEV1 as % of expected
101.3 [17.0] 74.1 [12.3]
107.7 [16.3]
FEV1/VC as %
81.8 [8.4]
66.8 [9.8]
85.6 [7.3]
How much do you smoke/did you smoke? (In pack years)
10.1 [10.7]
42.5 [3.5]
12.9 [15.8]
COPD, chronic obstructive pulmonary disease; MV, mean value; SD, standard deviation
Population 400 patients were entered into the study consecutively, who presented with suspected bronchial asthma to a specialist chest physician for the first time (indicated population [3]). Our inclusion criteria were the description of typical symptoms, such as dyspnea and a productive cough lasting longer than two months, which raised suspicion of the presence of a respiratory disease and required extensive examination including WBP. Our exclusion criteria were: infections of the respiratory tract within the preceding six weeks and contraindications to bronchial challenge testing—such as pregnancy, cardiac arrhythmias, or coronary heart disease. The study was approved by the ethics committee of the Medical Faculty of the University Hospital Klinikum rechts der Isar/Technische Universität München. Information on participants’ medical histories were documented using a structured questionnaire (Table 1). Diagnostic examination using whole-body plethysmography Patients were instructed not to smoke on the day of their examination (t0). They were asked to stop taking anti-obstructive medication that they may previously have been prescribed, 12 hours before the examination. Lung function tests were undertaken according to a standardized protocol, adjusted for sex, age, and body height (17). In case of FEV1/VC (=vital capacity)
