Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study

Background: the concept that the small conducting airways <2mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the literature. It has also been shown that the last generation of small conducting airways, terminal bronchioles, are significantly destroyed in patients with very-severe COPD. What is not known is at what stage in the development of COPD the loss of small airways occurs, or how loss of terminal and transitional (first generation of respiratory airways) bronchioles - relates to the loss alveolar surface area that characterizes emphysema. Methods: a novel multi-resolution computed tomography (CT) imaging protocol was applied to systematically, randomly sampled whole lungs or lobes of smokers with normal lung function (n=10), mild (n=10), moderate (n=8), and very-severe COPD (n=6). The 34 lung specimens provided 262 lung tissue samples for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (Lm), alveolar surface area. Findings: the new data demonstrate that 41% of terminal bronchioles, 57% of transitional bronchioles, and 37% of the alveolar surface area is lost in patients with mild and moderate COPD compared to control smokers, before any emphysematous changes can be detected by CT. We also show these pathological changes correlate with lung function decline. Importantly, we demonstrate that loss of terminal and transitional bronchioles occurs in regions of the lung that have no loss of alveolar surface area. Further, we validated using histology, that the surviving small airways have thickened walls and narrowed lumens which become more obstructed as the disease progresses. Interpretation: these data demonstrate that small airways disease is an early pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention in mild and moderate COPD patients is most likely required for disease modification

Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma

In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coate

Genomewide Clonal Analysis of Lethal Mutations in the Drosophila melanogaster Eye: Comparison of the X Chromosome and Autosomes

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes