Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions

Area of Science:

• Pulmonary Medicine
• Respiratory Pathology
• Asthma Research

Background:

• Distal lung inflammation and structural changes in asthma, particularly in uncontrolled cases, are not well understood.
• Patients with uncontrolled asthma may exhibit distinct tissue compositions in central and distal lung compartments.

Purpose of the Study:

• To investigate structural differences in lung tissue, including the alveolar parenchyma, between healthy individuals, controlled asthmatics, and uncontrolled asthmatics.
• To test the hypothesis that uncontrolled asthma is associated with unique tissue composition in both central and distal airways.

Main Methods:

• Bronchial and transbronchial biopsies were obtained from healthy controls, controlled atopic asthma patients, and uncontrolled atopic asthma patients.
• Immunohistochemical analysis was performed to quantify fibroblasts and extracellular matrix molecules, including collagen, versican, biglycan, decorin, fibronectin, MMP-9, and TIMP-3.

Main Results:

• Uncontrolled asthma showed increased versican and decorin in central airways, and increased collagen, versican, and decorin in the alveolar parenchyma compared to controlled asthma.
• Biglycan was elevated in both central airways and alveolar parenchyma in uncontrolled asthma versus controlled asthma.
• Myofibroblast numbers were significantly higher in both central airways and alveolar parenchyma of uncontrolled asthmatics.

Conclusions:

• Significant differences in tissue composition exist between uncontrolled and controlled asthma patients, even at equivalent inhaled corticosteroid (ICS) doses.
• Altered lung structure and potential changes in tissue elasticity in uncontrolled asthma may underlie abnormal mechanical properties.
• These structural changes could be a contributing factor to persistent symptoms in patients with uncontrolled asthma.