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Inhalation OCTOBER2016 19 Over the years, more attention has been given to patients' quality of life, measured via patient-reported outcome parameters (PRO). Yet these PRO are often confounded by comorbidities and psychological elements. From a res- piratory point of view, different parameters probably play an important role. Not only lung volume parameters such as hyperinflation, or airway characteristics such as airway resistance, determine the patient's perception of their condition; the regional vasculature and the associ- ated ventilation/perfusion ratio likely also impact patients' quality of life. For example, patients suffering from pulmonary hypertension (elevated blood pressure in the pulmonary vessels) may benefit from the adminis- tration of vasodilators that lower blood pressure and enhance oxygen transport. In another recent study, Fluidda explored the potential of FRI to assess the effect of pulsed inhaled nitric oxide (iNO) on blood vessel caliber. 5 It was observed that iNO increased FRI-derived blood vessel volume to signifi- cantly more than the natural variability level of the blood vessel volume (Figure 2). This not only demonstrated the mode of action of the drug itself but also showed that FRI can be a sensitive tool for detection of relevant changes. Regional vasodilation correlated well with regional ventilation, thereby improving the ventila- tion/perfusion (V/Q) ratio while limiting the risk for shunting. Following treatment, patients also reported an improvement in perceived wellbeing. FRI, lung health and patients with IPF Idiopathic pulmonary fibrosis (IPF) is a chronic lung dis- ease characterized by progressive loss of the ability of the lungs to absorb oxygen due to scarring (fibrosis). As a result, patients with IPF can experience shortness of breath and cough and have difficulty participating in everyday physical activities. The cause is unknown and there is no known cure. The median survival time from diagnosis is two to five years and the five-year survival rate is approximately 20 to 40 percent. IPF typically occurs in people over the age of 45 and tends to affect slightly more men than women. Forced vital capacity (FVC) was used as the primary end- point for efficacy evaluation of the two drugs approved in the US for IPF. 6 FVC is a functional measurement of the lungs as a whole and does not capture local information about deterioration and potential compensation by healthier areas of the lung. In addition, FVC depends on a forced maneuver to be performed by the patient, which can further increase the potential for variability of the mea- surement. During their development processes, the FDA voiced concerns about the applicability of this measure- ment given, among other aspects, that the clinically mean- ingful effect size is unclear. 2 In a range of studies, 7-11 it was observed that IPF is expressed in terms of FRI parameters by smaller lungs and lobe vol- umes but larger airway radii (Figure 3). It seems that while fibrosis reduces the lobe volume, the airway volumes are Figure 2. Changes in blood vessel volume determined using functional respiratory imaging (FRI) in a COPD patient with pulmonary hypertension after the administration of pulsed inhaled nitric oxide (iNO). Green areas indicate an increase in blood vessel volume, i.e., vasodilation, which induces a reduction in pulmonary pressures. This demon- strates the ability of FRI to provide relevant information in a significantly less invasive way compared to catheteri- zation, thereby greatly reducing burden on the patient. Figure 2 Improvement 20 18 16 14 12 10 8 6 4 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 Worsening