My asthma patient has normal spirometry. Should I test for bronchodilator responsiveness?

Dear Editor, According to the Global Initiative for Asthma (GINA) guidelines, the diagnosis of asthma is established by a variable pattern of respiratory symptoms and variable expiratory airflow. Variable expiratory airflow is usually confirmed by the finding of airways obstruction on spirometry and a significant response to bronchodilator.1,2 A bronchodilator responsiveness (BDR) test is considered positive if the FEV1 or FVC increases by 12% and 200 ml after inhalation of a bronchodilator.3 GINA has recommended continued use of this method over the new recommendations, expressing change as a percent of predicted, with a value of >10% considered as positive.4 However, airways obstruction may not always be present in suspected asthmatics, especially in those with mild episodic symptoms. Confirmation of diagnosis in such patients can be challenging. Intuitively, it may appear that a BDR test would be negative in such patients. Should the BDR test be done in such patients or should one proceed with other tests of demonstrating variable expiratory airflow, such as bronchial challenge tests, suggested in the GINA guidelines.4 The objective of this brief note is to highlight that normal spirometry does not preclude a positive BDR. We present data of two patients with normal spirometry showing a positive and negative BDR test to illustrate the concept of personal-best lung function to understand how a BDR test may be positive even when spirometry is normal. Data are shown in Table 1 and Figure 1. In the first case, the post-bronchodilator increase in both FVC and FEV1 was more than 12% and 200 ml. The BDR test was positive. In the second case, the change in both parameters was less than 12% and 200 ml. The BDR test was thus negative.Table 1: Spirometry data pre- and post-bronchodilatorFigure 1: Bronchodilator response in FEV1, expressed in terms of z scores, in two patients. A1 and A2 are pre-bronchodilator, and B1 and B2 are post-bronchodilator values, respectively. Predicted line (solid line) and lower and upper limits of normal, LLN, and ULN (dashed-dotted line) are shown 5 CONCEPT OF PERSONAL-BEST AND THE BDR The range of normal lung function is wide, from the 5th percentile (lower limit of normal, LLN) to the 95% percentile (upper limit of normal, ULN). The predicted value is the 50th percentile. For spirometry, ULN is not clinically meaningful. An observed FEV1 in the normal range may or may not be the highest possible value a patient may attain. The latter value is called ‘personal-best’. Personal-best is the highest achievable value in health or in the best state of asthma control. If a normal baseline FEV1 is substantially short of the personal-best, it is likely to improve further after bronchodilator yielding a positive BDR test. In the first case, baseline FEV1 is at point A1, that is substantially short of the personal-best at B1 indicating a relatively lower lung function than the best possible. Post-bronchodilator, it therefore improved significantly from A1 to B1. On the other hand, if the baseline FEV1 is already close to the personal-best, there will be a ceiling effect limiting further improvement. This was observed in the second case where baseline FEV1 (point A2) is close to the personal best value at B2 and thus the BDR test was negative. Thus, the outcome of the BDR test in a patient with normal spirometry depends on how close the baseline value is to the personal-best. Usually, the personal-best value is not known unless previous records are available and can be found only by doing the test. The test therefore should be done. In patients with normal baseline spirometry, the frequency of a positive bronchodilator response is low with one study reporting a 3.1% positive response.6 However, this is valuable as it confirms a diagnosis of asthma. Supernormal FEV1 or FVC values (above the ULN) have been observed in 3–5% of the general population and are associated with better health markers.7,8 The reasons for the ultimate lung size attained in adults are speculative and may relate to individual genetic makeup, optimal lung growth, freedom from significant early-life adverse exposure like smoking (active or passive) and other significant environmental exposures, fewer lower respiratory infections, and regular physical activity.8,9 When such persons develop asthma, they can have a substantial fall in spirometry values while still being in the normal range and show a significant BDR. In conclusion, BDR should be performed in all patients in whom asthma is clinically suspected, irrespective of whether they show the presence of airflow obstruction or not. A BDR test, if positive, confirms variable expiratory airflow and will rule in the diagnosis of asthma and avoid the need for alternative methods that are more time-consuming or require greater resources. These other options can be used if the BDR test is negative. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.