In both experimental and clinical studies, air pollution has been associated with the induction of “immune responses in the respiratory mucosa that is consistent with the development of allergic sensitization and augmentation of inflammation associated with asthma pathology,” according to the investigators. Many of these processes overlap with the processes found in severe, steroid-resistant asthma that is induced by infection.
“Air pollution activates innate immune receptors, including the TLRs and NLRs, expressed by these cells leading to the production of a variety of immune mediators that are important in allergic sensitization, exacerbations, and severe asthma.”11 The activation of TLR2 and TLR4 leads to the induction of IL-6 and IL-8, and activation of the NLRP3 inflammasome leads to the release of IL-1β.12
Additional research is needed to further explore these various mechanisms, including the roles of obesity and pollution in the pathogenesis of the disease. Andrea J. Apter, MD, MSc, MA, professor of medicine, chief, and program director of the section of allergy & immunology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, notes that is also important to have real-world studies examining the effects of these factors and others, such as poor housing and climate change, on asthma.
In terms of immediate clinical implications, Dr Apter emphasized the importance of confirming an asthma diagnosis before labeling the patient as steroid-resistant. In addition, the clinician should “make sure [the] patient is taking medications, using inhalers properly, and that there are no environmental precipitants exacerbating the patient’s respiratory status,” she told Pulmonology Advisor. “If all of these elements have been considered and an immunologic mechanism is still under consideration, a targeted biologic could be [examined].”
Dr Hansbro and colleagues report no conflicts of interest.
Summary and Clinical Applicability
Emerging evidence highlights potential roles of infection, obesity, and air pollution in severe, steroid-resistant asthma.
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