Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

Abstract

Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q ) to such ventilation defects have not been well studied. Methods: We used positron emission tomography to assess the intrapulmonary kinetics of intravenously infused tracer nitrogen-13 ( 13 NN), and measured the regional distributions of ventilation and perfusion in 11 patients with mild asthma. For each subject, the regional washout kinetics of 13 NN before and during methacholineinduced bronchoconstriction were analyzed. Two regions of interest (ROIs) were defined: one over a spatially contiguous area of high tracer retention (TR) during bronchoconstriction and a second one covering an area of similar size, showing minimal tracer retention (NR). Results: Both ROIs demonstrated heterogeneous washout kinetics, which could be described by a two-compartment model with fast and slow washout rates. We found a systematic reduction in regional Q to the TR ROI during bronchoconstriction and a variable and nonsignificant change in relative Q for NR regions. The reduction in regional Q was associated with an increase in regional gas content of the TR ROI, but its magnitude was greater than that anticipated solely by the change in regional lung inflation. Conclusion: During methacholine-induced bronchoconstriction, perfusion to ventilation defects are systematically reduced by a relative increase in regional pulmonary vascular resistance.Keywords: emission computed tomography; pulmonary gas exchange; vascular resistance; vasoconstriction; ventilation-perfusion ratio It is well established that severe heterogeneity of regional ventilation contributes significantly to gas exchange impairment in asthma. However, the extent to which regional pulmonary perfusion adapts to match changes in ventilation during an asthma attack is unknown. Evidence for severe heterogeneity of regional ventilation in patients with asthma has come from measurements with external scintillation counters (1, 2), single-photon emission computed tomography (CT) of Technegas (3), nuclear magnetic resonance imaging after a single-breath inhalation of hyperpolarized helium (4), and high-resolution CT (5-10). Most of these studies, however, did not quantify regional ventilation during normal breathing and did not evaluate the effect of bronchoconstriction on regional pulmonary perfusion.Changes in regional perfusion during bronchoconstriction (BC) have been measured using technetium ( 99m Tc)-labeled macroaggregated albumin (11,12). In one study, perfusion defects of segmental or smaller size were reported mainly at the periphery of middle or lower lung zones in children with asthma, despite normal chest X-rays, blood gases, and peak expiratory flows (13). That study, however, did not assess whether these perfusion defects corresponded to defects in ventilation. Another study assessed ventilation with krypton ( 81m Kr) gas and perfusion with 99m Tc ...

Airway Hyperresponsiveness in Allergically Inflamed Mice

“…This region was also the dependent part of the lung because the animals were studied supine, which raises the possibility that gravity could have played a role in our observations. Certainly, humans with asthma during bronchoconstriction exhibit poorer ventilation in dependent lung regions (10,11). On the other hand, it is perhaps doubtful that gravity could have a significant effect in a lung as small as that of the mouse.…”

“…Single-photon emission CT with inhaled Technegas has shown that, even though airway closure appears to be a normal feature in a healthy lung, the pattern by which closure occurs is altered in subjects with asthma (11). It has also recently been shown that humans with asthma challenged with methacholine have clusters of underventilated alveoli adjacent to normally ventilated areas, and that this pattern can be understood in terms of self-organized clusters of small airway closures (10). Similarly, a correlation has been reported between the amount of air trapped in the lungs and the reversibility of small airway constriction (25), again suggesting that it is the small airways that close during bronchoconstriction in human lungs.…”

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…Washout was poor in areas of low perfusion. Because of perfusion redistribution, the V/Q mismatch was reduced (Harris et al, 2006). Compared with healthy volunteers, perfusion heterogeneity was also greater in patients with mild to moderate COPD, as was the heterogeneity in V/Q, which was primarily caused by the heterogeneity in perfusion and not so much in ventilation (Vidal Melo et al, 2010).…”

Evaluation of Structure-Function Relationships in Asthma using Multidetector CT and Hyperpolarized He-3 MRI

“…Regional patterns of ventilation in asthma have also been explored using inhaled gas contrast agents in conjunction with imaging (11)(12)(13)(14), including hyperpolarized helium-3 magnetic resonance imaging (HP MRI) (15). Like MDCT measures of parenchymal density, whole lung measures of ventilatory defect number on HP MRI correlate with obstructive physiology (7,14,16).…”