Background
Asthma is a common chronic disease with a high prevalence of approx. 5% in industrialized nations. It is characterized by a chronic inflammation process which induces bronchial hyper-responsiveness and in most cases, reversible airway obstruction [
1]. Another common pulmonary disease is chronic obstructive pulmonary disease (COPD) which shows irreversible airway obstruction, and which is mostly caused by inhaling tobacco smoke [
2]. The prevalence of COPD is estimated to be around 10% and expected to be the fourth most important cause of death in 2020 [
3]. Due to this high morbidity, general practitioners play a key role in detecting the disease as they see patients during the earlier stages of disease. Spirometric investigation is seen as a gold standard for diagnosing airway obstruction. Therefore, office spirometry is increasingly seen as a quality standard in general practice [
4,
5].
The efficacy of spirometry in diagnosing COPD was demonstrated by a specialist team, which received referrals for performing spirometry and bronchodilator reversibility testing in patients suspected of having COPD [
6]. The DIDASCO Study revealed the difficulty of diagnosing COPD with screening questionnaires only and concluded that spirometry is essential for early diagnosis [
7]. These investigations focused on COPD only, which is marked by irreversible airway obstruction. The diagnostic value of spirometry for diagnosing asthma marked by reversible airway obstruction remains unclear. This is of importance, as asthma needs to be diagnosed by bronchial provocation testing when spirometry shows no airway obstruction [
8]. One diagnostic study in primary care used spirometry and bronchial provocation testing for identifying patients with asthma and COPD [
9]. However, this was only carried out in patients complaining of suffering from a cough; and spirometry was performed by a single specialist. Spirometry and bronchial provocation testing were also used in the DIMCA study [
10]. Indeed this was a screening study performed in a specialist center to detect patients in early stadiums of asthma or COPD.
Due to the design of these asthma and COPD trials, there is no evidence of the diagnostic accuracy of spirometry itself. Therefore, the true degree of the associated diagnostic uncertainty for patients with complaints suspected of having an airway obstruction remains unclear. The need for closing this gap of knowledge has been pointed out several times [
11,
12]. The difficulty is that the pretest probability of a disease and its severity in primary care is lower when compared to a hospital setting, thus hampering the predictive values of diagnostic tests [
13,
14]. Therefore, test results evaluated in hospital settings can not easily be transferred into general practice [
15]. The aim of this study was to investigate the sensitivity, specificity and predictive values of spirometry for diagnosing airway obstruction in asthma and COPD in general practice.
Discussion
To our knowledge, this is the first study evaluating the diagnostic accuracy of spirometry for diagnosing airflow obstruction in patients with asthma or COPD in primary care. We found that the use of spirometry is feasible within general practice after training GPs and practice nurses. Under these conditions, the presence or absence of COPD can be estimated with a comparatively high diagnostic accuracy. It is also possible to rule in asthma. However, it was impossible to rule out asthma as the sensitivity was too low.
The prevalence of COPD is increasing in nearly all countries of the world and a high diagnostic accuracy is a prerequisite of optimal therapeutic management. The important role of spirometry for diagnosing airway obstruction has already been demonstrated [
6,
7,
30,
31]. However, the diagnostic accuracy of spirometry for diagnosing COPD has been unknown up to now, thus leading to diagnostic uncertainty in suspected cases of COPD. Our results demonstrate that the pretest-probability of 22% of patients presenting themselves with complaints suggestive of airway obstruction can be increased up to a post-test probability of 63% for having COPD. This comparatively low PPV might be surprising, as the sensitivity was 84% and specificity was 92%. However, this is explainable by the low pretest probability. Another reason might be due to sub-maximal maneuvers, leading to false positive results by underestimation of FEV
1 [
11]. As a consequence, more efforts in terms of continuous education would be necessary for an improvement of performance and an interpretation of spirometry. Nevertheless, COPD can be definitively excluded (NPV 97%) when spirometry is performed optimally. For these reasons, spirometry should be used regularly for diagnosing and managing COPD in primary care.
In contrast to these promising results is the limited value of spirometry in excluding asthma. This might be explained by the reversibility of airway obstruction in asthma. It proved possible to speculate that patients with mild or moderate asthma show no airway obstruction when spirometry is performed. In these cases, it was necessary for the GP to estimate the presence or absence of asthma on the basis of the patient history and inconclusive spirometry. This was misleading in 53 (24.2%) of cases (46 patients false positive and 7 patients false negative). Therefore, alternative methods need to be found for diagnosing asthma in primary care. Guidelines recommend using the measurement of peak-flow-variability to diagnose asthma in case of inconclusive spirometry. However, the low diagnostic value of peak-flow-variability in primary care has already been demonstrated [
32]. The SAPALDIA study, which used an epidemiologic approach, has also shown a poor diagnostic value [
33]. The measurement of exhaled nitric oxide (NO) which is elevated in eosinophilic airway inflammation [
34] has been shown to be more promising [
35], although the technology is expensive. Therefore, patients suspected of having asthma might be tested with NO measurement or should be referred for bronchial provocation if possible to guarantee accurate diagnosis. Nevertheless, spirometry should be used in diagnosing asthma, as the positive predictive value has been comparatively high in general practice.
One important limitation was that 22% of the spirometric maneuvers were not performed correctly in general practice. However, with the analysis of the spirometric maneuvers as part of the WBP investigation in the lung function laboratory, we received accurate diagnostic values of spirometry. Our results revealed that the predictive values of general practice were slightly lower than in the lung function laboratory. In addition to this, it was not possible to include all patients consecutively, as some patients were not willing to travel to the lung function laboratory of the Medical Hospital. This might have led to an overestimation of the diagnostic accuracy of spirometry [
36]. However, that would also emphasize the impossibility of excluding asthma solely with spirometry. Another limitation is due to the choice of the cut-off points. Our use of the ratio FEV
1/VC ≤ 0.70 as is still recommended by GOLD [
5] may have led to some overestimation of airway obstruction in older patients [
37] and underestimation in younger patients [
38]. The ATS/ERS guideline therefore suggests using lower limits of normal, which is statistically defined by the 5
th lower percentile of a reference population, to provide more accurate diagnoses [
19]. This diagnostic algorithm was not integrated in the spirometric software at the time of our study. Moreover, we are aware of the limitations of a one-off lung function test to determine a final diagnosis, as a negative bronchodilator response can occur due to fixed airway obstruction in asthma. A trial of steroids might have been necessary to differentiate between asthma and COPD in some patients. Nevertheless, these limitations do not hamper our finding that asthma cannot be excluded solely with spirometry. The WBP showed little added value on top of spirometry. We used it as a reference standard to distinguish between overlapping diseases, COPD and restrictive lung disorder. However, we only experienced two changes in making the diagnosis with the added information of WBP. In two patients suffering from dyspnea attacks, the airway resistance was very high during bronchial provocation, but FEV
1 remained normal. Moreover, we found no patient with restrictive lung disorder, which indicates a low prevalence in primary care settings. Therefore, the added value of WBP for primary care is limited and it should be reserved for patients who are difficult to diagnose and show persistent complaints.
It was not possible to specify the alternate diagnosis of the patients with no OAD, which is a typical problem of diagnostic studies in primary care. It was impossible to perform every investigation (e.g. gastroscopy to determine gastro-oesophageal reflux; x-ray) until a definite diagnosis could be made. This would not have been allowed by the Ethics Committee. However, this limitation does not alter the results of spirometric investigation. Finally, the participating GPs and practice assistants were highly motivated and received intensive training. Nevertheless, 22% of the spirometric maneuvers showed no guideline adherence. In particular bronchodilation testing was not performed regularly which might be due to organisational reasons and time constraints in general practice. The GPs estimated fourteen patients to suffer from COPD. However, the final pneumologists' diagnosis of these patients was asthma due to positive bronchodilator testing. Therefore, this lack of performance led the GPs to over-estimate COPD and under-estimate asthma in patients with airway obstruction. This is of importance as patients with asthma need to be treated preferably with inhaled steroids. However, our results are better than demonstrated by Miravitlles et al. [
39], which might be due to the repeated education of the whole practice team. Nevertheless, these results are not satisfying enough. Further efforts are necessary to improve the performance of spirometry, as this could enhance the diagnostic accuracy. It has already been established that GPs are able to perform and interpret spirometry after educational meetings [
40] and that performing spirometry has a positive impact on medical decision making [
6,
30,
41]. It therefore seems reasonable and valuable to implement high quality spirometry in primary care.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AS designed the study, performed the analyses and wrote the manuscript. LG trained the practice assistants, managed the data and helped to write the manuscript. LT helped to manage the data and to write the manuscript. TS and GJ helped to interpret the data and with writing. FJM made the final diagnoses as pneumologist and helped to write the manuscript. JS helped to write the manuscript. All authors read and approved the final manuscript.