TABLE 3.

KEY RECOMMENDATIONS OF THE INFLAMMATORY BIOMARKERS WORKING GROUP

Procedural Issue	Outstanding Questions
Sputum collection	The influence of different nebulizer systems (high-output ultrasonic, low-output ultrasonic, jet) on quantity of sputum induced, sputum cell counts, and biochemical mediators
Sputum processing	The effect of dithiothreitol (vs. saline or enzyme mixtures) on many inflammatory mediators
	The effect of delay in processing (i.e., immediate freezing) on many inflammatory mediators
Validation of sputum biomarkers	Short-term reproducibility (weeks) of measurements of many inflammatory mediators
	Longer term variability (months) of measurements of many inflammatory mediators
	Further evaluate how biomarkers relate to disease severity, and to longitudinal changes in lung function and lung structure
	Need to establish the minimal clinically meaningful difference in sputum neutrophil counts or inflammatory mediators
	Identify reliable markers of airway structural change such as elastin or collagen breakdown products
	Develop a CF lung injury biomarker panel consisting of three to five proteins with proposed cutoff ranges
Other biomarker sources	The value of systemic (plasma, serum, urine) markers of inflammation to evaluate response to treatment or predict disease progression
	The value of exhaled gases (nitric oxide) or breath condensate to evaluate response to treatment or predict disease progression

Definition of abbreviation: CF = cystic fibrosis.