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

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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].”

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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.


  1. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.
  2. Barnes PJ. Mechanisms and resistance in glucocorticoid control of inflammation. J Steroid Biochem Mol Biol. 2010;120(2-3):76-85.
  3. World Health Organization (WHO). Bronchial Asthma Fact Sheet, 2016. Accessed August 10, 2017.
  4. Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG. Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples. J Allergy Clin Immunol. 2011;127(1):53-160 e151-159.
  5. Baines KJ, Simpson JL, Bowden NA, Scott RJ, Gibson PG. Differential gene expression and cytokine production from neutrophils in asthma phenotypes. Eur Respir J. 2010;35(33):522-531.
  6. Stokes JR, Casale TB. Characterization of asthma endotypes: Implications for therapy. Ann Allergy Asthma Immunol. 2016;117(2):121-125.
  7. Hansbro PM, Kim RY, Starkey MR, et al. Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma. Immunol Rev. 2017;278(1):41-62. 
  8. Ito K, Chung KF, Adcock IM. Update on glucocorticoid action and resistance. J Allergy Clin Immunol. 2006;117(3):522-543. 
  9. Adcock IM, Ford PA, Bhavsar P, Ahmad T, Chung KF. Steroid resistance in asthma: mechanisms and treatment options. Curr Allergy Asthma Rep. 2008;8(2):171-178.
  10. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140(6):900-917.
  11. Bauer RN, Diaz-Sanchez D, Jaspers I. Effects of air pollutants on innate immunity: The role of Toll- like receptors and nucleotide- binding oligomerization domain- like receptors. J Allergy Clin Immunol. 2012;129(1):14-24; quiz 25-16.
  12. Hirota JA, Hirota SA, Warner SM, et al. The airway epithelium nucleotide- binding domain and leucine- rich repeat protein 3 inflammasome is activated by urban particulate matter. J Allergy Clin Immunol. 2012;129(4):1116-1125.e6.