Consideration of Environmental Factors Associated with Asthma

During the Presidential Plenary session at the 2018 AAAAI Annual Meeting, speakers discussed environmental impacts on asthma. Prior to each presentation, the speakers were presented with an award for their research.

Rachel L. Miller, MD, FAAAAI, of Columbia University Medical Center in New York, discussed epigenetic changes related to pollutant exposures. She was the recipient of the inaugural AAAAI Foundation and Sheldon L. Spector, MD, FAAAAI, Memorial Lectureship award.

“Exposure to pollution is clearly a cause of asthma,” she said and noted there is an increased scientific interest worldwide in studying the importance of epigenetic regulation and asthma and allergy. Environmental exposures include allergens, antibiotics, air pollution, diet, and environmental tobacco smoke. Epigenetic modifications include DNA methylation, post-translational modifications of histones, and non-coding RNA, plus RNA methylation and DNA hydroxymethylation, which are newer concepts, and this list is growing with increasing research, she said. Multiple pollutants are associated with epigenetic consequences, such as smoke, particulate matter, diesel/black carbon, and polycyclic aromatic hydrocarbons. Epigenetic mechanisms may modify metabolism of environmental compounds, strength of the gene and environment interactions, and pro-inflammatory response and disease severity.

“We are gaining more knowledge on dynamic influences of asthma,” she said, which include acute, lagged, chronic, and sustained effects across generations. She noted a 2017 study published by Clifford et al in the Journal of Allergy and Clinical Immunology, which included 17 healthy adults who were exposed to allergen alone, diesel exhaust alone, or allergen and diesel exhaust together (co-exposure) to determine the effect on airway epithelial cells. After 48 hours, the researchers did not observe significant differences among the group, but after four weeks, the effects on the diesel cohort were large, with widespread DNA methylation. “Can we regulate this?” she asked. In a 2017 study published by Shorey-Kendrick in the American Journal of Respiratory and Critical Care Medicine, the researchers found that vitamin C could prevent DNA methylation changes in children born to a mother who smoked during pregnancy. “We can actually do something,” said Dr. Miller. “And hopefully more [options are] coming in the future.”

Elizabeth Matsui, MD, MHS, of Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, discussed home remediations and interventions. She received the inaugural AAAAI Foundation and Gary S. Rachelefsky, MD, FAAAAI, Lectureship Investing Together in Our Future award.

She started by noting results from a survey of the AAAAI membership, which found that just three-fourths reported emphasizing the importance of environmental control. Conflicting clinical trials on environment controls may be the reason, she noted. Dr. Matsui compared the outcomes of three trials that did not find a benefit in environmental control interventions and three studies that did.

The negative studies were:

  • A 2003 study by Woodcock et al published in the New England Journal of Medicine assessed allergen-impermeable bed covers for adults with asthma versus active control. The intervention had a large (>50%), but not sustained impact on reducing allergen exposure.
  • A 2016 study by DiMango published in the Journal of Allergy and Clinical Immunology: In Practiceassessed the effect of adding an environmental intervention (educational and behavioral) in addition to treatment in adults. Both those who received the intervention and those who did not received guidelines-based controller medication titration, and both groups saw similar reductions in allergen exposure.
  • A 2017 study by Matsui et al published in JAMA assessed a mouse allergen and asthma intervention in children, and Dr. Matsui noted that the findings were “frustrating” that children did not have a greater reduction in symptoms, saying, “We need better strategies.”

The positive studies were:

  • A 2004 study by Morgan et al published in the New England Journal of Medicine assessed individually-tailored, multifaceted, home-based environmental intervention (educational and behavioral) for children. The intervention group experienced a fairly rapid decline in symptoms, and the difference persisted both during the year of the intervention and for one year afterward.
  • A 2017 study by Murry published in the American Journal of Respiratory and Critical Care Medicine assessed the use of mite-impermeable bedcovers for children and found a large (>50%) reduction in allergen exposure.
  • A 2017 study by Rabito published in the Journal of Allergy and Clinical Immunology assessed cockroach control in the home for children and found a modest (<50%) decrease in allergen exposure.

Dr. Matsui noted that all positive studies were conducted in children, suggesting that environmental interventions are effective among pediatric populations. She then posited that although there are conflicting data on this topic, does that mean these interventions are useless? “What if the intervention does not lower allergen exposure, but does improve asthma?” she asked. “We may have clinical effect through pathways other than allergen reductions.” There is a need for standardized reporting framework, she noted.

Dr. Matsui concluded by discussing the socioeconomic factors to consider surrounding the issue, especially the endemic exposures in children living in urban and low-income neighborhoods, which are related to high levels of pest and other exposures, high morbidity, poor condition of homes, and shared walls and rooflines. “If we want to make headway in asthma, we need to think about the way we got to the way this problem exists,” she said. She gave an example of the structural racism in the history of Baltimore, Maryland: Segregation began in the city in 1910, with red-lining occurring between the 1930s and 1960s. She showed a map of the current areas with highest emergency department use, and these correlated with areas of red-lining practice in the 20th century.

She outlined the Baltimore MAP program, which was the result of a 1995 lawsuit that found HUD violated fair housing laws. Settlements provided housing vouchers for assisted housing to help families move to less poverty-stricken areas. Researchers are conducting a study to see if moving from a high- to low-poverty neighborhood has an impact on indoor environmental exposures and asthma morbidity. The results are still pending. “If this program is successful, it could have implications for future asthma interventions,” she concluded.

David B. Peden, MD, MS, FAAAAI, of the University of North Carolina Health Care, discussed mitigating pollutant effects on disease. He is the second recipient of the AAAAI Foundation and I. Leonard Bernstein, MD, FAAAAI, Memorial Lectureship award.

Pollutants, such as particulate matter and ozone, are associated with a number of health effects, including asthma. Inhaled ozone pollutants can lead to nociceptive airway restriction, acute airway inflammation, increased permeability, and increased airway reactivity. Particulate matter pollutants are associated with inflammation, increased airway reactivity (for some), decreased lung function (for high doses, and cardiovascular effects.

He discussed a number of potential interventions, including:

  • Inhaled corticosteroids, which can decrease baseline eosinophilic inflammation, CD14 expression on airway monocytes and macrophages, and PMN influx to inhaled endotoxin
  • Cytokine directed agents (IL-1 and IL-8), which can reduce endotoxin-induced airway inflammation
  • Nutraceutical interventions
  • Gamma tocopherol, which can reduce acute inflammation

He also concluded by echoing Drs. Miller and Matsui, noting that policy interventions work and are “things we can do to make a change…Physicians have clout at public hearings, legal actions, and regulatory processes.”

Presentation 1601: Environmental Impacts on Asthma: Biology to Intervention