Mouse allergen exposure associated with air trapping among urban children with asthma

Angela Duff Hogan, MD, FAAAAI, FACAAI, FAAP

One of the cardinal components of asthma is airflow obstruction. When airflow obstruction involves the small airways, it can lead to hyperinflation in some areas of the lung and to air trapping with an increase in the residual volume in other areas. Air trapping can be demonstrated by measuring the percent change in the FVC following a bronchodilator. A 10% change or greater in FVC is associated with air trapping.

These patients are often referred to as the air-trapping obstructive phenotype. This phenotype has been associated with more asthma exacerbations during a 12-month study period, higher asthma severity index scores, higher asthma treatment steps and greater variability in FEV₁ over time. The air-trapping phenotype was also found to have high serum IgE levels, high levels of allergen sensitization and elevated blood eosinophil counts compared with other obstruction phenotypes.

Researchers of this study looked at children aged 5 to 17 years who had asthma and lived in poor urban neighborhoods in Baltimore. It states that allergen exposures lead to sensitization to specific allergens and that subsequent exposures lead to airway inflammation and, in some individuals, air trapping.

The researchers evaluated airborne and bedroom floor allergen levels for mouse, cockroach, cat, dog, particulate matter size and nicotine. Mouse allergen was the only particle that was associated with air trapping. Sensitization was determined by positive skin prick tests greater than 2 mm. Using these criteria, 66% of the participants were sensitized to mice, which is certainly in the range of what previous intercity asthma studies have shown.

Mouse allergen levels measured on the floor of the homes of these asthmatic children were elevated with a mean value of 0.61 µg/g. Most airborne mouse allergens are associated with small particles less than 5 µm, which means these particles can penetrate the smaller parts of the airway. Exposure to greater than 0.5 µg of mouse allergen in home dust samples has been associated with increased asthma symptoms among sensitized individuals.

This study suggests that adequate exposure to mouse allergens among sensitized children is associated with more significant air trapping, an asthma phenotype associated with more severe asthma. It also states that the mechanism of increased air trapping is unknown, but exposure reduction might improve asthma outcomes.

Routinely when spirometry is completed on asthmatics, significant reversibility in FEV₁ demonstrates hyperresponsiveness, which has been associated with greater lability in asthma and increased risk for more severe exacerbations. Perhaps also evaluating the percentage change in FVC more routinely may help identify more severe asthmatics at risk with air trapping. However, most studies would not consider a 2 mm positive skin test to mouse allergen as significant sensitization. Measuring exposure, sensitization and particle size are probably related, but this study did not connect all the dots.  

Reference:

Sorkness RL, et al. J Allergy Clin Immunol. 2018;doi:10.1016/j.jaci.2017.09.047.

Barbara P. Yawn, MD, MSc, FAAFP

Compared with the overall group, the 14% of children who had air trapping at baseline were more likely to have had oral prednisone in the past 6 months, but it was not a huge difference. Those with air trapping did not appear to require more intense asthma therapy (same National Asthma Education and Prevention Program level) compared with others. They also were more likely to be sensitized to mouse as an allergen but, again, it was not a huge difference. 

We have to consider what this means for clinical practice.

Although the authors commented that these children may have more severe asthma or greater risk for exacerbations, what type of treatment, if any, makes a difference? Although making diagnoses of phenotypes is intellectually satisfying, we need to know that we have some treatment that makes a difference for it to be useful in practice.

The phenotype was not stable over the time period, so do I have to assess the patient multiple times to identify it? The study also does not suggest that I would look for this phenotype in the children with the worst outcomes or poorest asthma control based on the data.

Although it is true that pre- and post-spirometry should be completed in all children with asthma, it is not universal. Would identifying these 14% be an inducement to complete pre- and post-spirometry? Probably not, without some indication of what can be done to treat this issue. Do we work on decreasing mouse exposure or providing different pharmacotherapy?

Of interest to me are some of the negative findings. Cockroach has been a significant concern for many years, but this study showed air trapping was not associated with levels of cockroach exposure, which I find surprising.

The next steps are to repeat these findings in a larger sample across multiple races and ethnicities. We need to confirm these hypothesis-generating results. 

It also is important to address the stability of air trapping over time. What does it mean if it comes and goes? This may suggest less long-term impact if it is not chronic.

Most importantly, what am I as a clinician supposed to do with this information? How would treatment change? How do I decide who to assess for air trapping?

This is interesting use of data from a study done for another reason. Currently, it probably is most important for helping to design and getting funding for long-term and larger studies to confirm the findings and address potential therapeutic approaches.