The cellular and molecular determinants of emphysematous destruction in COPD

COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function. Inflammation is central for the development of COPD. Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways. The contribution of resident airway structural cells to the inflammatory process is also important in COPD. Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia. Persistent airway inflammation might contribute to airway remodeling and small airway obstruction. However, the underlying mechanisms remain unclear. In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.

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“…This suggests that the alveolar destruction observed in COPD is driven by a Th1 response activated by infiltrating ILC1s. 85 …”

Section: Introductionmentioning

confidence: 99%

Role of inflammatory cells in airway remodeling in COPD

Wang¹,

Xu²,

Meng³

et al. 2018

COPD

253

184

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“…There may be differences in the pathogenesis between smoking-induced COPD and subjects with AAT deficiency. Whereas there is little doubt that smoking-induced COPD starts in the terminal bronchioles, 26 emphysema may be more predominant at an early stage in subjects with AAT deficiency. The PiZZ subjects in this study showed evidence of hyperinflation (high FRC/TLC ratios) and air trapping (high RV/TLC ratios), which may offer an explanation for our findings.…”

Section: Discussionmentioning

confidence: 99%

Lung function and CT lung densitometry in 37- to 39-year-old individuals with alpha-1-antitrypsin deficiency

Mostafavi

Diaz

Piitulainen

et al. 2018

COPD

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BackgroundAlpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening program in 1972–1974 and has been followed-up since birth. Our aim was to study whether the cohort has signs of emphysema in pulmonary function tests (PFTs) and computed tomography (CT) densitometry at 38 years of age in comparison with an age-matched control group, randomly selected from the population registry.MethodsForty-one PiZZ, 18 PiSZ, and 61 control subjects (PiMM) underwent complete PFTs, measurement of resistance and reactance in the respiratory system by impulse oscillometry (IOS)/forced oscillation technique (FOT), and CT densitometry. The results were related to self-reported smoking habits.ResultsThe total lung capacity (TLC) % of the predicted value was significantly higher in the PiZZ ever-smokers than in the PiZZ never-smokers (P<0.05), PiSZ never-smokers (P=0.01) and the PiMM never-smokers (P=0.01). The residual volume (RV) % of the predicted value was significantly higher in the PiZZ ever-smokers compared to the PiMM never-smokers (P<0.01). The PiZZ ever-smokers had a significantly lower carbon monoxide transfer coefficient (Kco) than the PiSZ never-smokers (P<0.01) and PiMM never-smokers (P<0.01). Respiratory system resistance at 5 Hz (P<0.01), at 20 Hz (P<0.01), and the area of low reactance (Alx; P<0.05) were significantly lower and respiratory system reactance at 5 Hz (P<0.05) was significantly higher in PiZZ subjects compared to the PiMM subjects. No statistically significant differences in the CT densitometry parameters were found between the Pi subgroups.ConclusionThe physiological parameters in the PiZZ ever-smokers showed evidence of hyperinflation and emphysema before the age of 40 years.

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“…This airways inflammatory response spread to the lung parenchyma resulting in destruction of alveolar walls causing emphysema [11]. Inflammatory mediators resulting in persistent infiltrating immune inflammatory cells and their destructive enzymes have been implicated in the progressive destruction of the lung in COPD [12]. This destruction initiate remodeling that has been described in both the central airways, distal airways, and lung parenchyma.…”

Section: Pathobiology Of Copdmentioning

confidence: 99%

Immune-Modulation in Chronic Obstructive Pulmonary Disease: Current Concepts and Future Strategies

Eeden

Hogg

2019

Respiration

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Chronic obstructive pulmonary disease (COPD) is caused by the chronic inhalation of toxic particles and gases that are primarily but not exclusively derived from cigarette smoke that may be either actively or passively inhaled, which initiates a persistent innate and adaptive immune response in the lung. This immune response is associated with an aberrant tissue repair and remodeling process that results in varying degrees of chronic inflammation with excess production of mucus in the central airways and permanent destruction of the smaller conducting airways and gas exchanging surface in the peripheral lung. Currently, the primary aims of treatment in COPD are bronchodilation (inhaled short-and long-acting β-agonist and antimuscarinic therapies), to control symptoms and nonspecific broad-acting anti-inflammatory agents (inhaled and oral corticosteroids, phosphor-di-esterase inhibitors, and macrolides). That provide symptomatic relief but have little or no impact on either disease progression or mortality. As our understanding of the immune pathogenesis of the COPD improves, available immune modulation therapies have the potential to alter or interfere with damaging immune pathways, thereby slowing relentless progression of lung tissue destruction. The purpose of this brief review is to discuss our current understanding of the immune pathogenesis of both the airways and parenchymal injury as well as the dysfunctional tissue repair process to propose immune modulating interventions in an attempt to stabilize or return these pathological changes to their normal state. The ultimate goal of the immune modulation therapy is to improve both morbidity and mortality associated with COPD.

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The cellular and molecular determinants of emphysematous destruction in COPD

Cited by 57 publications

References 42 publications

Role of inflammatory cells in airway remodeling in COPD

Role of inflammatory cells in airway remodeling in COPD

Lung function and CT lung densitometry in 37- to 39-year-old individuals with alpha-1-antitrypsin deficiency

Immune-Modulation in Chronic Obstructive Pulmonary Disease: Current Concepts and Future Strategies

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