Chest

Chest

Volume 135, Issue 3, March 2009, Pages 842-848
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Selected Report
Quantitative Analysis of Longitudinal Response to Aerosolized Granulocyte-Macrophage Colony-Stimulating Factor in Two Adolescents With Autoimmune Pulmonary Alveolar Proteinosis

https://doi.org/10.1378/chest.08-1317Get rights and content

Background

Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood and tissues, resulting in alveolar surfactant protein accumulation. Patients with APAP present with ground-glass opacities (GGOs) and interlobular septal thickening on thin-slice chest CT scans. Aerosolized GM-CSF therapy (aeroGM-SCF) has qualitatively improved the clinical condition of patients with APAP. This report details quantitative chest CT responses to aeroGM-CSF.

Methods

Two adolescent patients (aged 16 and 19 years) with APAP were treated with aeroGM-CSF. Clinical parameters, including pulmonary function tests and chest CT scans, were obtained before and after aeroGM-CSF therapy. To evaluate the effect of the therapy, serial chest CT scans were analyzed using a novel approach permitting quantitative assessment of improvement in GGOs, lung weight, and gas volume.

Results

In association with GM-CSF treatment, nutritional status and pulmonary function improved. Quantitative analysis of the CT scans demonstrated reduction in GGOs and lung weight, concomitant with an increase in airspace volume and lung inflation. The findings were consistent with a qualitative reduction in GGOs on chest CT imaging.

Conclusions

Quantitative analysis of CT holds promise as a sensitive diagnostic tool permitting longitudinal and objective analysis of the therapeutic response to aeroGM-CSF in patients with APAP.

Section snippets

Case 1

In August 2004, a 16-year-old girl presented with a 10-week history of mild shortness of breath. Fifteen weeks prior to presentation, the patient underwent appendectomy. The hospital course was complicated by a pelvic abscess, bilateral pneumonia, and hypoxemia. She was treated with IV antibacterial therapy and discharged home. She had persistent symptoms at home and bilateral lung infiltrates on a chest radiograph. Her oxygen saturation was 97% at rest by pulse oximetry measurements. Her chest

Materials and Methods

Inspiratory thin-slice spiral chest CT scans (Sensation 64 Scanner; Siemens; Erlangen, Germany) were performed on the two female adolescents, in the supine position, before and after long-term aeroGM-CSF therapy. The CT scans were performed using the standard clinical settings of 120 kVp, 200 to 310 mA for patient 1 and 200 mA for patient 2, rotation time 0.5 s, and lung (B60F) reconstruction kernel. Levels of serum lactate dehydrogenase, GM-CSF autoantibody, and surfactant protein D (SP-D)

Results

The characteristics of the two female adolescents (ages 16 and 19 years) before and after treatment with aeroGM-CSF are presented in Table 1. AeroGM-CSF was well tolerated by both patients, without untoward sequelae. For both patients, serum GM-CSF autoantibody levels increased after aeroGM-CSF therapy, while serum SP-D decreased in patient 1; T1 and T2 comparisons for SP-D were not available for patient 2. Both patients had a favorable response to therapy with increases in body weight, resting

Discussion

This report describes two cases of APAP demonstrating the benefits of quantitative CT measurements in ascertaining precise improvements in lung parenchyma as a result of aeroGM-CSF therapy. In both patients significant improvements were noted in all quantitative CT parameters after 8 months of aeroGM-CSF. These changes were consistent with improvements in clinical parameters, PFTs, and pulse oximetry during the 6-min walk test. In our assessment of changes in GGOs, we evaluated histograms in HU

References (18)

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The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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Copyright © 2009 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.