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. 2018 Jul 1;198(1):39-50.
doi: 10.1164/rccm.201712-2426OC.

Pruning of the Pulmonary Vasculature in Asthma. The Severe Asthma Research Program (SARP) Cohort

Samuel Y Ash  1   2 , Farbod N Rahaghi  1   2 , Carolyn E Come  1   2 , James C Ross  2 , Alysha G Colon  3 , Juan Carlos Cardet-Guisasola  4 , Eleanor M Dunican  5 , Eugene R Bleecker  6 , Mario Castro  7 , John V Fahy  8 , Sean B Fain  9   10   11 , Benjamin M Gaston  12   13 , Eric A Hoffman  14   15   16 , Nizar N Jarjour  17 , David T Mauger  18 , Sally E Wenzel  19 , Bruce D Levy  1 , Raul San Jose Estepar  2 , Elliot Israel  1 , George R Washko  1   2 ; SARP Investigators
Affiliations

Pruning of the Pulmonary Vasculature in Asthma. The Severe Asthma Research Program (SARP) Cohort

Samuel Y Ash et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease.

Objectives: To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations.

Methods: We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5 mm2 in cross-sectional area (BV5) and of vessels less than 10 mm2 (BV10) in cross-sectional area on noncontrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature).

Measurements and main results: Compared with healthy control subjects, patients with severe asthma had more pulmonary vascular pruning. Among those with asthma, those with poor asthma control had more pruning than those with well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted FEV1 and FVC, greater peripheral and sputum eosinophilia, and higher BAL serum amyloid A/lipoxin A4 ratio but not with low-attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had 150% greater odds of reporting an asthma exacerbation (odds ratio, 2.50; confidence interval, 1.05-5.98; P = 0.039 for BV10/TBV) and reported 45% more asthma exacerbations during follow-up (incidence rate ratio, 1.45; confidence interval, 1.02-2.06; P = 0.036 for BV10/TBV).

Conclusions: Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control, and exacerbations, and with lung function and eosinophilia.

Keywords: eosinophilia; pruning; pulmonary vascular; severe asthma.

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Figures

Figure 1.
Figure 1.
Sagittal view of the three-dimensional quantitative reconstruction of the pulmonary vasculature in the right lung of (A) a subject without evidence of pruning and normal lung function (FEV1 percent predicted, 97%), and (B) a subject with evidence of pruning and impaired lung function (FEV1 percent predicted, 75%). The color red corresponds to smaller vessels, and blue corresponds to larger vessels. (C and D) Representative axial computed tomography images from the same two participants. (E) Quantitative profiles of blood volume distribution of the same two participants.
Figure 2.
Figure 2.
Pruning by asthma disease severity. Severe asthma was defined on the basis of American Thoracic Society/European Respiratory Society guidelines, and mild–moderate asthma was defined on the basis of National Asthma Education and Prevention Program guidelines (–23). In box plots, the box portion represents the 25th to the 75th percentile with the solid mid-line representing the mean, and the whisker portion represents the 2.5th to the 97.5th percentile. P values for pairwise comparisons shown below the box plots are based on the Steel-Dwass-Critchlow-Fligner method (53). P trend values are based on the Jonckheere-Terpstra test. BV5 = blood vessel volume of vessels less than 5 mm2 in cross-sectional area; BV10 = blood vessel volume of vessels less than 10 mm2 in cross-sectional area; TBV = total pulmonary blood vessel volume.
Figure 3.
Figure 3.
Pruning by asthma control category. The categories are: well controlled—ACT ≥20 and ACQ ≤0.75 and one or fewer exacerbations in the past year; suboptimally controlled—ACT 16–19 and/or 2–3 exacerbations in the past year; and poorly controlled—ACT ≤15 or ACQ ≥1.5 or three or more exacerbations in the past year. In box plots, the box portion represents the 25th to the 75th percentile with the solid mid-line representing the mean, and the whisker portion represents the 2.5th to the 97.5th percentile. P values for pairwise comparisons shown below the box plots are based on the Steel-Dwass-Critchlow-Fligner method (53). P trend values are based on the Jonckheere-Terpstra test. ACQ = asthma control questionnaire; ACT = asthma control test; BV5 = blood vessel volume of vessels less than 5 mm2 in cross-sectional area; BV10 = blood vessel volume of vessels less than 10 mm2 in cross-sectional area; TBV = total pulmonary blood vessel volume.
Figure 4.
Figure 4.
Pruning and lung function. r values are based on Pearson correlation. For definition of abbreviations, see Figure 2.
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