You probably know people who sneeze a little when they encounter plant pollens, pet dander, or other everyday allergens. For others, however, these same allergens can trigger a serious asthma attack that can make breathing a life-or-death struggle. Now, two NIH-funded research groups have teamed up to help explain the differences in severity underlying the two types of reactions.
In the studies, researchers at Massachusetts General Hospital, Boston, used an innovative imaging tool to zoom in on a person’s airways safely in real time to gain an unprecedented view of how his or her body reacts to allergens [1,2]. The imaging revealed key differences between the asthma and non-asthma groups in the smooth muscle tissue that surrounds critical airways, and is responsible for constriction. In a complementary series of experiments, researchers also uncovered heightened immune responses in the airways of folks with allergic asthma. The findings offer important new clues in the quest to better understand and guide treatment for asthma, a condition that affects more than 300 million people around the world.
The factors driving airway constriction in people with asthma have been poorly understood in part because, until now, there hasn’t been a way to view airway smooth muscle in action. As described in the journal Science Translational Medicine, Melissa Suter and colleagues adapted an established form of imaging called optical coherence tomography (OCT) to help fill this gap. Standard OCT produces an image by measuring the amount of light reflected back from body tissues, but such images aren’t sufficient to distinguish airway smooth muscle from other tissues.
The breakthrough came when Suter realized that smooth muscle’s highly organized cellular structure, which she likens to strands of rope, presented an opportunity. She could obtain an additional layer of information by measuring not just the amount of light reflected back from the surface of airways, but also differences in the direction and speed of that light as it scatters. She and her colleagues used this approach to develop a new imaging method that they’ve dubbed orientation-resolved OCT (OR-OCT).
According to Suter, OR-OCT images can be taken during a traditional bronchoscopy procedure in which a flexible scope is used to observe a patient’s airways and lungs. The OR-OCT-imaging procedure itself takes less than a minute to complete and is done without exposing patients to ionizing radiation.
With this new tool in hand, Suter joined forces with Andrew Luster and his colleagues, also at Mass General, who were already engaged in an effort to define the airway immune responses of 84 people known to be allergic to cats or dust mites. Thirty-six volunteers had mild allergic asthma, while 48 had allergies but no history of asthma. Besides those suffering from allergies, the study included five controls—healthy people without allergies or asthma.
The OR-OCT images obtained during bronchoscopy showed that the smooth muscle tissue in the airways of allergy sufferers with asthma is arranged in bands that are both thicker and wider than in those without asthma. Luster says it’s not yet clear if individuals with more smooth muscle tissue in their airways are at increased risk for developing asthma, or if individuals predisposed to developing asthma experience a type of airway inflammation that bulks up smooth muscle.
To explore the issue further, Luster introduced a dilute extract of dust mite or cat hair into a small portion of the study participants’ lungs. They then obtained a sample of immune cells and immune cell mediators present in patients’ airways. Allergy sufferers showed signs of an inflammatory immune response whether or not they had asthma. However, only the airways of people with both allergies and asthma showed increased levels of receptors on allergen-specific T cells and increased inflammation. Their airways also stepped up production of mucus, as well as of a protein that thickens mucus and may cause the airways to become hyper-reactive.
It will now be important to examine these features in people with more severe allergic asthma and for longer periods of time. For instance, it will be interesting to learn how these airway characteristics and immune responses change as a person’s asthma symptoms grow more or less severe.
The hope is that this newfound ability to study the airways of living humans in greater detail in real time will transform not only our understanding of allergic asthma, but of other airway diseases. As it is for so many other disorders, such fundamental knowledge is crucial to NIH’s ongoing efforts to develop better strategies for diagnosing, treating, and, ultimately, preventing respiratory conditions.
 Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation. Cho JL, Ling MF, Adams DC, Faustino L, Islam SA, Afshar R, Griffith JW, Harris RS, Ng A, Radicioni G, Ford AA, Han AK, Xavier R, Kwok WW, Boucher R, Moon JJ, Hamilos DL, Kesimer M, Suter MJ, Medoff BD, Luster AD. Sci Transl Med. 2016 Oct 5;8(359):359ra132.
 Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo. Adams DC, Hariri LP, Miller AJ, Wang Y, Cho JL, Villiger M, Holz JA, Szabari MV, Hamilos DL, Scott Harris R, Griffith JW, Bouma BE, Luster AD, Medoff BD, Suter MJ. Sci Transl Med. 2016 Oct 5;8(359):359ra131.
What is asthma? (National Heart, Lung, and Blood Institute/NIH)
Suter Pulmonary Optical Imaging Lab (Massachusetts General Hospital, Boston)
Luster Lab (Massachusetts General Hospital, Boston)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering