Severe asthma NHLBI update: Your tax dollars at work (Review, AJRCCM)

Can someone tell me why asthma gets no respect in academic pulmonology? I repeatedly hear otherwise intelligent physicians call asthma “boring,” as if we’ve conquered the disease (or maybe they think they have). In fact, severe asthma is a perenially humbling adversary that has proven largely resistant to a decades-long onslaught by both Pharma and the NIH. Severe asthma is a common cause of severe disability and repeated need for urgent medical care, but despite huge outlays of time, toil and treasure, we have a poor understanding of its pathophysiology and no proven therapies besides bronchial thermoplasty.

In response to the generalized confusion, 12 years ago the National Heart, Lung, and Blood Institute created a severe asthma research program (SARP) that has since followed 583 people with severe asthma, and coordinated sharing of their research data (pulmonary function, radiography, bronchoscopice biopsies, genomics, etc) among research centers.

Progress has been slow; in ten years, SARP made a few interesting discoveries (exhaled nitric oxide can predict asthma phenotype; obesity and several other risk factors are associated with severe asthma; activation of certain protein kinases is associated with corticosteroid insensitivity), but none of these significantly changed the understanding of severe asthma or shone light on a path to a new ”translational” therapy.

However, SARP was a resounding success in laying the groundwork for a systematic, ongoing, national effort to better understand and treat severe asthma. These successes have been in two areas:

• Defining “reality-based” phenotypes of disease. Using the breadth of data collected (onset, patient factors, FEV1 reduction and reversibility, exacerbation frequency, etc.), investigators were able to define 5 phenotypes of asthma not based on gestalt or medical lore, but on observed clustering of patients with shared characteristics. They first published their classification system in AJRCCM in 2010. Future studies can now more profitably focus on identifying why these patients are different (e.g., late adult vs. childhood onset; more severe airway remodeling vs. reversibility; etc) and what might be done about it.
• Creating the template for competitive investigators and institutions to collaborate and cooperate on a national scale. This took considerable time and effort — as a single example, consider getting everyone at U. of Colorado, Harvard, and the Cleveland Clinic to perform bronchoscopies and share data in a standardized way. (Creating these standards took 2 years.) In so doing, however, SARP and the NIH have sparked a glimmer of hope of transcending the core problem hampering scientific medical research in the U.S. today: the hidebound tradition in which single, competing, underfunded university centers enroll handfuls of patients, perform uncoordinated, un-ambitious (“feasible”) short-term studies, and publish interesting but ultimately inconclusive findings that with only a few exceptions, do not bring us closer to a holistic understanding of the disease, nor help patients or the physicians caring for them.

The NIH and its investigators in programs like SARP and the Alzheimer’s Disease Neuroimaging Initative show that this kind of national collaboration can be the future of academic medicine, and yield a better return on taxpayers’ research dollars in an era characterized both by increasing expectations that research should actually lead to improvements in Americans’ health, and a tightening squeeze on funding.

SARP’s future efforts will include medication adherence in their data collection and analysis, and also follow children from an early age (SARP’s first stage mainly followed adults).

Jarjour NN et al (for the SARP investigators). Severe Asthma: Lessons Learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am J Respir Crit Care Med 2012;185:356-362.