262 million people world-wide have asthma. 25 million Americans have asthma. Ten people die each day in the United States from an asthma exacerbation. It is a heterogenous disease that can be difficult to diagnose and manage. There are objective tests which can be utilized to accurately diagnose and manage asthmatic patients. Unfortunately, a high number of patients are still diagnosed based on symptoms alone. Research has shown as few as half of patients with an asthma diagnosis had their disease confirmed with objective testing like spirometry. Far fewer, 19%, have spirometry monitored on a yearly basis. Why is objective testing so important in diagnosing asthma? A study in 2017 which reevaluated patients with an asthma diagnosis from their physician, found that 33% of the patients did not have asthma. What did they have? The study uncovered twenty-two different diagnoses including: congestive heart failure, vocal cord dysplasia, GERD, sinusitis, and bronchiectasis. In this study 44% of those misdiagnosed had not had pre and post bronchodilator spirometry. When a patient reports shortness of breath, chest tightness, wheezing, cough, yes, these may indicate asthma. They are also reported with COPD, IPF, anxiety, VCD, and more, none of which are managed the same as asthma. This highlights the importance of using objective testing along with the patients’ reported symptoms, history and physical to determine a diagnosis. All of these are pieces in the diagnostic puzzle.

Spirometry is recommended in the diagnosis of asthma. It is widely available and reimbursed. Yet it is under-utilized. Why this is, seems to be the unanswerable question. When spirometry does not guide to a diagnosis, why is bronchial challenge testing not the next step for so many patients? There are a variety of bronchial challenge tests which can be used and are recommended to help complete the diagnostic puzzle. There are two categories of bronchial challenge tests, or bronchoprovocation challenge tests: Direct and Indirect. Direct challenge tests include methacholine and histamine. Methacholine is the most utilized direct challenge test in the USA. Simply put, direct challenge tests work directly on the smooth muscle receptors of the airways to cause bronchoconstriction in hyperresponsive airways. The strength of the direct challenges is to rule out airway hyperresponsiveness as seen in asthma. There are strict parameters PFT labs should follow for dosing and timing of the methacholine challenge. Historically, a lack of standardization has led to a variety of methods for executing the methacholine challenge. The 2017 ERS/ATS technical standards on bronchial challenge testing: general considerations and performance for the methacholine challenge test is the most recent set of standards pulmonary function labs should look to when updating or starting the challenge. Typically, direct challenge tests are used to rule asthma out. Conversely, indirect challenge tests are used to confirm airway inflammation and hyperresponsiveness. A condensed explanation is that they cause the release of inflammatory mediators which can cause bronchoconstriction as seen in asthma. The action of the indirect challenge tests helps to identify patients who may respond well to anti-inflammatory treatment with inhaled corticosteroids. There are a variety of indirect challenge tests which can be used to identify hyperresponsive airways, as seen in asthma, and particularly to identify the phenotype of exercise induced bronchoconstriction. The indirect challenge test provocative agents include mannitol, eucapnic voluntary hyperventilation, exercise on a treadmill or stationary bike, and hypertonic saline.

Determining which challenge test to utilize can be…challenging. If looking to rule asthma out for occupational safety reasons or in military recruits, the direct challenges have high sensitivity and are the appropriate test. The indirect challenges are the correct choice to confirm asthma or provide objective proof that an athlete has EIB. Since the tests answer different questions and challenge the airway differently, it may make sense for PFT laboratories to offer each type of challenge. Management of asthma needs to be personalized and targeted for each patient. Utilizing the tests available will allow for precision management of this common, yet complicated, disease.

Heather Murgatroyd, BA, RRT, CPFT

Senior Clinical Specialist, Methapharm Respiratory

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Coates AL, Wanger J. Cockcroft DW, et al. ERS technical standard on bronchial challenge testing:  general considerations and performance of Methacholine challenge tests. Eur Respir J 2017:49:1601526

Hallstrand TS, Leuppi JD, Joos G, et al. ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challenge testing. Eur Respir J 2018

Numragambetov, T, Kuwahara, and P Garbe. The Economic Burden of Asthma in the United States, 2008-2013