Monitoring of airway inflammation in asthma

EDITORIAL

Monitoring of Airway Inflammation in Asthma

Mark D. Inman, MD, PhD

Firestone Institute for Respiratory Health

^{Correspondence}

While asthma continues to be defined based on the presence of variable and reversible airflow obstruction, our understanding of the diseases has increased considerably since the original clinical description. It is now known that there is both a hyperresponsiveness of the airways as well as a characteristic pattern of airway wall inflammation. While the exact nature of the link is not clear, it is currently believed that the airway dysfunction in asthma is a result of both acute and chronic consequences of this inflammatory processes. Thus, one of the recommendations from the Global Initiative in Asthma (GINA) is that the assessment of the patient with asthma should be expanded to include some measure of the extent of ongoing airway inflammation in addition to standard clinical assessment. This recommendation seems justified, based on evidence that incorporating measurements of indirect airway responsiveness1, or quantitative and qualitative assessment of induced sputum 2 into patient management strategies can result in decreased morbidity associated with asthma.

In a manuscript published here, van de Sande Lee et al. describe the pattern of inflammatory cells assessed from induced sputum induced from steroid naïve asthmatic individuals from a city in the South of Brazil, Florinopolis. The chief observation was that the percentage of eosinophils in the sputum from asthmatic individuals was increased (mean value, 6.4%) in comparison to those in a cohort of healthy subjects (normal < 2%)3. Moreover the examination of induced sputum can discriminate two patterns of airway inflammation in steroid naïve asthmatics, one with an increased proportion of sputum eosinophils (eosinophilic group, mean eosinophils, 14,4 %) and a group of asthmatics without sputum eosinophilia (mean eosinophils, 0,4%). This finding supports many previous observations that eosinophilic inflammation is a prominent feature in asthma. It further indicates that many steroid naïve asthmatic individuals have markedly inflamed airways.

A second, and perhaps more important observation in this manuscript was that clinical assessment alone, could not be used to identify those individuals with asthma in whom eosinophilic airway inflammation was the most marked. This finding supports the recommendation from GINA that direct monitoring of airway inflammation would add information that is not available to the physician through standard clinical assessment. Clearly however, this would only be of value if this new information was useful in guiding patient care. Given that specific treatment aimed against the eosinophil appears to have limited clinical value4 , it is worth questioning how monitoring sputum eosinophils would be useful in guiding patient management.

However, there is strong evidence to suggest that presence of eosinophils in the sputum is a good indicator of whether patients with chronic cough or asthma will respond favorable to inhaled steroids5;6. More recently, it has been shown that when normalization of sputum eosinophils as the treatment target was compared to standard clinical practice, those patients in whom sputum eosinophils had been used to guide treatment had fewer exacerbation and hospitalizations over the course of a year2. In both groups, the primary therapy was with inhaled steroids, and there were not mean differences in steroid use between the two groups. While it may appear discrepant that inhaled steroid treatment aimed at normalizing eosinophils is efficacious at improving patient morbidity, while specific anti-IL-5 therapy failed to demonstrate significant efficacy, these observations are perhaps explainable. The most obvious explanation is that specific anti-IL-5 treatment is efficacious at normalizing sputum4, but not tissue eosinophils7, while inhaled steroid therapy has been shown to normalize eosinophils in both of these compartments. A second, and perhaps more intriguing explanation is that the eosinophil may be acting simply as a marker of TH2 diseases activity, but that clinically effective therapy must cover a broader spectrum than simply clearing eosinophilic inflammation. Thus, the reason for the success in the trial where sputum eosinophil counts were used to determine steroid dose, were not a result of controlling eosinophilia, but rather a result of applying broad spectrum anti-inflammatory therapy to those patient from whom it was needed. In conclusion, the findings of the manuscript by van de Sande Lee et al suggest that there are steroid naive patients in Florinopolis in whom eosinophil counts are markedly elevated in comparison to healthy individuals. While it is not possible to say that the eosinophil proportions are dangerous in and by itself, this likely reflects that there is a TH2 process in these individuals such that they would receive clinical benefit from inhaled steroid therapy. That this information would not have been available without the use of induced sputum analysis strongly supports the regular use of this analytic technique in guiding patient management. There is a need to further study the response to intervention using anti-inflammatory drugs in these individuals and determine whether the presence of sputum eosinophilia in steroid naïve asthmatics is able to identify a group with better response to treatment.

References

1. Sont JK, Willems LN, Bel EH, Van Krieken JH, Vandenbroucke JP, Sterk PJ. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med 1999; 159:1043-51.

2. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002; 360:1715-21.

3. Belda J, Leigh R, Parameswaran K, O'Byrne PM, Sears MR, Hargreave FE. Induced sputum cell counts in healthy adults. Am J Respir Crit Care Med 2000; 161:475-8.

4. Leckie MJ, Ten Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356:2144-8.

5. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet 1999; 353:2213-4.

6. Pizzichini E, Pizzichini M, Gibson P, Parameswaran K, Gleich GJ, Berman L,et al. Hargreave. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med 1998; 158:1511-7.

7. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. 2003. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 167:199-204.

Publication Dates

• Publication in this collection
  02 Dec 2003
• Date of issue
  Aug 2003