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Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration

Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration

Published on: May 4, 2017

Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function

Nurdan Kokturk^1,2, Nazli Khodayari¹, Jorge Lascano¹

¹Division of Pulmonary, Critical Care and Sleep Medicine, J. Hillis Miller Health Science Center, University of Florida College of Medicine, P.O. Box 100225, Gainesville, FL, 32610-0225, USA.

Respiratory Research

|February 3, 2023

Insights

Alpha-1-antitrypsin deficiency (AATD) individuals show mild airway inflammation and elevated protease levels even with normal lung function. This inflammation correlates with a declining lung function, suggesting early anti-inflammatory treatment could prevent COPD progression in AATD patients.

Area of Science:

Pulmonary Medicine
Genetics
Immunology

Background:

Alpha-1-antitrypsin deficiency (AATD) predisposes individuals to early-onset, severe chronic obstructive pulmonary disease (COPD).
Understanding pre-symptomatic lung changes in AATD is crucial for early intervention.
This study investigates the lower respiratory tract characteristics in AATD individuals before significant COPD onset.

Purpose of the Study:

To characterize airway inflammation in AATD individuals with normal lung function.
To identify inflammatory markers and immune cell profiles in the lower respiratory tract of AATD patients.
To correlate airway inflammation with lung function decline in AATD.

Main Methods:

Bronchoalveolar lavage and bronchial biopsies were performed on AATD individuals and healthy controls.
Analysis included cell counts, protease concentrations, and inflammatory mediators (IL-8, IL-6, IL-1β, LTB4).
Immunohistochemistry assessed immune cell components; lung function was monitored over one year.

Main Results:

AATD individuals exhibited 3x higher neutrophils, increased proteases, and elevated IL-8, IL-6, IL-1β, LTB4 in epithelial lining fluid.
Neutrophil elastase positively correlated with IL-8 and neutrophils.
AATD patients showed increased lymphocytes, macrophages, neutrophils, and mast cells, with FEV1 negatively correlating with inflammation markers.

Conclusions:

Mild inflammation and a pro-inflammatory phenotype are present in the airways of AATD individuals, even with normal lung function.
A declining lung function trend was observed in AATD, linked to this pro-inflammatory state.
Early anti-inflammatory therapies are proposed as a strategy to prevent lung disease progression in AATD.

Read full analysis

Abstract

Background:

Alpha-1-antitrypsin deficient (AATD) individuals are prone to develop early age of onset chronic obstructive pulmonary disease (COPD) more severe than non-genetic COPD. Here, we investigated the characteristics of lower respiratory tract of AATD individuals prior to the onset of clinically significant COPD.

Methods:

Bronchoalveolar lavage was performed on 22 AATD with normal lung function and 14 healthy individuals. Cell counts and concentrations of proteases, alpha-1-antitrypsin and proinflammatory mediators were determined in the bronchoalveolar lavage fluid from study subjects. In order to determine the airway inflammation, we also analyzed immune cell components of the large airways from bronchial biopsies using immunohistochemistry in both study subjects. Finally, we made comparisons between airway inflammation and lung function rate of decline using four repeated lung function tests over one year in AATD individuals.

Results:

AATD individuals with normal lung function had 3 folds higher neutrophil counts, 2 folds increase in the proteases levels, and 2-4 folds higher levels of IL-8, IL-6, IL-1β, and leukotriene B4 in their epithelial lining fluid compared to controls. Neutrophil elastase levels showed a positive correlation with the levels of IL-8 and neutrophils in AATD epithelial lining fluid. AATD individuals also showed a negative correlation of baseline FEV₁ with neutrophil count, neutrophil elastase, and cytokine levels in epithelial lining fluid (p < 0.05). In addition, we observed twofold increase in the number of lymphocytes, macrophages, neutrophils, and mast cells of AATD epithelial lining fluid as compared to controls.

Conclusion:

Mild inflammation is present in the lower respiratory tract and airways of AATD individuals despite having normal lung function. A declining trend was also noticed in the lung function of AATD individuals which was correlated with pro-inflammatory phenotype of their lower respiratory tract. This results suggest the presence of proinflammatory phenotype in AATD lungs. Therefore, early anti-inflammatory therapies may be a potential strategy to prevent progression of lung disease in AATD individuals.

Keywords:

Epithelial lining fluid Neutrophil elastase Protease inhibitor Pulmonary function

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