Ventilation Inhomogeneities in Patients with Cystic Fibrosis: Which Target Lung Function Parameters Offer Valuable Evaluation?

Abstract

lowing treatment. Statistically, such a response should be higher than the variability found in repeated baseline measurements, or it should exceed the 2-SD range of values predicted. During the past decade, various groups have been working on multibreath washout (MBW) technology to adapt this noninvasive, practically cooperation-independent technique for use in all age groups of CF patients [2–13] . MBW is performed during tidal breathing by analyzing changes in the concentration of an exhaled inert tracer employing either (i) resident N 2 that is ‘washed out’ using 100% oxygen in a semiopen system or (ii) an inhaled inert gas such as sulfur hexafluoride (SF 6 ), which has to be firstly ‘washed in’ in order to be ‘washed out’ in a second step. Both techniques provide a measure of VIH. In CF patients, such VIH can be defined by various parameters such as the lung clearance index (LCI), the moment ratio (MR = m 2 /m 0 ) [4, 14–18] , curvilinearity indices [1, 19] , and specific phase III slope indices of nonuniform gas mixing, especially in the conducting (S cond ) and acinar (S acin ) airway zones [1, 6, 20–22] . Several commercial devices and test procedures for routine use have been developed during the past decade based on infrared or ultrasonic flowmeter technology. These facilitate more widespread usage of highly sensitive lung function techniques to enable early detection of CF lung disease throughout adulthood [5, 6, 8–13, 23–27] . The course of lung disease in patients with cystic fibrosis (CF) is largely characterized by recurrent episodes of pulmonary exacerbations, the number and severity of which influence the overall rate and deterioration of the disease. The day-to-day success or failure of the management of this disease determines the ultimate fate of most patients. The evaluation of lung function before versus after interventional treatment therefore plays a vital role in the clinical assessment of children and adults with CF. The selection of sound parameters which significantly and specifically determine changes in such interventional treatments is thus of great interest. An example of this selection is the study by Vanderhelst et al. [1] published in this issue of Respiration, which demonstrates the clinical application of selective indices obtained by the nitrogen multibreath washout (N 2 MBW) technique, differentiating the treatment effect between conductive and acinar responses of ventilation inhomogeneities (VIH) following intravenous antibiotic treatment in adult CF patients. CF is a complex, multiorgan disease with manifold interactions between genetic background, lung maturation, nutritional factors, viral and bacterial infections, energy expenditure, lung deterioration, and lung remodeling. The selection of sensitive outcome parameters depends on whether or not the parameters are sensitive enough to demonstrate a biological, clinically relevant response folPublished online: May 1, 2014