Automated Computed Tomography Lung Densitometry in Bronchiectasis Patients

Rationale: Bronchiectasis is a complex and heterogeneous disease. Visual computed tomography (CT) scoring systems are used to assess disease severity, disease progression and predict outcomes in bronchiectasis although they have some limitations such as subjectivity, requirement of previous training and are time-consuming. Objective: To correlate quantitative CT lung densitometry measurements with pulmonary function test (PFT) and multidimensional prognostic scores in patients with bronchiectasis.Materials and methods: From 2014 to 2017, 100 consecutive adult patients with non-cystic fibrosis bronchiectasis underwent inspiratory and expiratory volumetric chest CT and PFT (spirometry, plethysmograph, diffusing capacity of carbon monoxide measurement [DLCO]). Visual CT score (CF-CT score), CT lung densitometry parameters (kurtosis, skewness and expiratory/inspiratory mean lung density [E/I MLD]) and multidimensional prognostic scores (BSI and FACED) were calculated in all patients and correlated to PFT.Results: CT lung densitometry parameters (kurtosis and skewness), correlated with forced expiratory volume in 1 second (FEV1) (R=0.32; p=0.001 and R=0.34; p<0.001) and DLCO (R=0.41 and R=0.43; p<0.001). Automated CT air trapping quantification (E/I MLD) showed correlation with residual volume (RV), multidimensional score FACED (R=0.63 and R=0.53; p<0.001) and performed better than the CF-CT score in the diagnosis of high-risk patients and severe air trapping. Conclusion: CT lung densitometry parameters showed correlations with PFT in non-cystic fibrosis bronchiectasis patients. Automated CT air trapping quantification performed better than visual CT score in the identification of high-risk patients and severe air trapping, suggesting it could be a useful tool in the evaluation of these patients, although further studies are needed to confirm these findings.

Implications of a Change of Paradigm in Alpha1 Antitrypsin Deficiency Augmentation Therapy: From Biochemical to Clinical Efficacy

Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field.

α1-Antitrypsin deficiency and chronic respiratory disorders

α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.

Short-term Physiologic Consequences of Regional Pulmonary Vascular Occlusion in Pigs

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Acute unilateral pulmonary arterial occlusion causes ventilation–perfusion mismatch of the affected lung area. A diversion of ventilation from nonperfused to perfused lung areas, limiting the increase in dead space, has been described. The hypothesis was that the occlusion of a distal branch of the pulmonary artery would cause local redistribution of ventilation and changes in regional lung densitometry as assessed with quantitative computed tomography. Methods In eight healthy, anesthetized pigs (18.5 ± 3.8 kg) ventilated with constant ventilatory settings, respiratory mechanics, arterial blood gases, and quantitative computed tomography scans were recorded at baseline and 30 min after the inflation of the balloon of a pulmonary artery catheter. Regional (left vs. right lung and perfused vs. nonperfused area) quantitative computed tomography was performed. Results The balloon always occluded a branch of the left pulmonary artery perfusing approximately 30% of lung tissue. Physiologic dead space increased (0.37 ± 0.17 vs. 0.43 ± 0.17, P = 0.005), causing an increase in Paco2 (39.8 [35.2 to 43.0] vs. 41.8 [37.5 to 47.1] mmHg, P = 0.008) and reduction in pH (7.46 [7.42 to 7.50] vs. 7.42 [7.38 to 7.47], P = 0.008). Respiratory system compliance was reduced (24.4 ± 4.2 vs. 22.8 ± 4.8 ml · cm H2O−1, P = 0.028), and the reduction was more pronounced in the left hemithorax. Quantitative analysis of the nonperfused lung area revealed a significant reduction in lung density (−436 [−490 to −401] vs. −478 [−543 to −474] Hounsfield units, P = 0.016), due to a reduction in lung tissue (90 ± 23 vs. 81 ± 22 g, P &lt; 0.001) and an increase in air volume (70 ± 22 vs. 82 ± 26 ml, P = 0.022). Conclusions Regional pulmonary vascular occlusion is associated with a diversion of ventilation from nonperfused to perfused lung areas. This compensatory mechanism effectively limits ventilation perfusion mismatch. Quantitative computed tomography documented acute changes in lung densitometry after pulmonary vascular occlusion. In particular, the nonperfused lung area showed an increase in air volume and reduction in tissue mass, resulting in a decreased lung density.