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What Is New In Small Airways Research

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Ves Dimov, M.D.
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine

“Small airway-on-a-chip” enables in vitro research on human lung inflammation and drug responses.

A human lung “small airway-on-a-chip” was developed at Harvard University with sponsorship by Pfizer and Merck.

The chip contained a differentiated, mucociliary bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which allows for analysis of organ-level lung pathophysiology in vitro. After the normal physiology was established in the chip, the researchers induced a pathology: exposure to interleukin-13 (IL-13) reconstituted the goblet cell hyperplasia and cytokine hypersecretion and decreased ciliary function of asthmatics.

Small airway chips lined with epithelial cells from individuals with chronic obstructive pulmonary disease (COPD) recapitulated features of the disease such as selective cytokine hypersecretion, increased neutrophil recruitment and clinical exacerbation by exposure to viral and bacterial infections.

With this in vitro method for modeling human lung inflammatory disorders, it would be feasible to:

  • detect synergistic effects of lung endothelium and epithelium on cytokine secretion
  • identify new biomarkers of disease exacerbation and
  • measure responses to anti-inflammatory compounds.

Source: Benam KH, Vilenave R, Lucchesi C, Varone A, Hubeau C et al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nature Methods 2015; published ahead of print, December 21. (doi:10.1038/nmeth.3697)

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Image Source: Flow Chart, Open Clipart, free to use

Small airways function in young children is linked to obstructive symptoms.

Frequency dependence of resistance (R5-20) assessed by impulse oscillometry (IOS) is suggested to be a measure of small airways. Small airways involvement during induced bronchoconstriction has been shown to reflect severity of asthma in adults.

The researchers from Finland evaluated if methacholine (Mch) induced changes in R5-20 are associated with the severity of exercise induced bronchoconstriction (EIB) in 109 young children, aged 3-8 years (95 with obstructive symptoms; 14 healthy controls).

R5-20 was measured at baseline and after the Mch challenge. In a standardized exercise test, the children were grouped according to the severity of EIB expressed as the percentage increase in resistance at 5 Hz (ΔR5).

The baseline R5-20 was not associated with the severity of EIB. However, the change in R5-20 during Mch induced bronchoconstriction was significantly higher in children with severe EIB.

Frequency dependence of resistance (R5-20) measured by IOS during the Mch induced bronchoconstriction is associated with severe EIB in young children.

Source: Kalliola S, Malmberg LP, Pelkonen AS, Makela MJ. Aberrant small airways function relates to asthma severity in young children. Respiratory Medicine 2015; Article in press; published online ahead of print, December 19. (doi:10.1016/j.rmed.2015.12.006)

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FEF25-75 gets another look: Forced midexpiratory flow between 25% and 75% linked to asthma persistence

This French study assessed if forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1.

The study included 337 patients with asthma (asthma attacks or treatment in the past year, 142 children and 225 adults). The patients were followed up at the 12- and 20-year surveys.

Decreased FEF25-75 at the onset of the study increased the risk of:

  • long-term asthma persistence, but only slightly (adjusted odds ratio (OR), 1.14)
  • more severe bronchial hyperresponsiveness and current asthma a decade later (OR between 1.21 and 1.44)

Small-airway obstruction, as assessed based on FEF25-75, might contribute to the long-term persistence of asthma and subsequent risk for poor asthma outcomes, independently from FEV1.

Source: Siroux V, Boudier A, Dolgopoloff M, Chanoine S, Bousquet J at al. Forced midexpiratory flow between 25% and 75% of forced vital capacity is associated with long-term persistence of asthma and poor asthma outcomes. Journal of Allergy and Clinical Immunology 2015; Article in press; published online ahead of print, December 11. (doi:10.1016/j.jaci.2015.10.029)

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Last updated: Tuesday, January 12th, 2016