American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Aug 2019
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.
Rationale: Histologic stains have been used as the gold standard to visualize extracellular matrix (ECM) changes associated with airway remodeling in asthma, yet they provide no information on the biochemical and structural characteristics of the ECM, which are vital to understanding alterations in tissue function. Objectives: To demonstrate the use of nonlinear optical microscopy (NLOM) and texture analysis algorithms to image fibrillar collagen (second harmonic generation) and elastin (two-photon excited autofluorescence), to obtain biochemical and structural information on the remodeled ECM environment in asthma. Methods: Nontransplantable donor lungs from donors with asthma (n = 13) and control (n = 12) donors were used for the assessment of airway collagen and elastin fibers by NLOM, and extraction of lung fibroblasts for in vitro experiments. ⋯ Packaging of collagen fibrils was found to be more disorganized in asthmatic airways compared with control subjects, using transmission electron microscopy. Conclusions: NLOM imaging enabled the structural assessment of the ECM, and the data suggest that airway remodeling in asthma involves the progressive accumulation of disorganized fibrillar collagen by airway fibroblasts. This study highlights the future potential clinical application of NLOM to assess airway remodeling in vivo.
-
Am. J. Respir. Crit. Care Med. · Aug 2019
Observational StudyArterial Vascular Pruning, Right Ventricular Size and Clinical Outcomes in COPD.
Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes. Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study. ⋯ An increased RVEV was associated with reduced 6-minute-walk distance and in those with arterial pruning an increased mortality. Conclusions: Pulmonary arterial pruning is associated with clinically significant increases in RV volume in smokers with COPD and is related to exercise capacity and mortality in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
-
Am. J. Respir. Crit. Care Med. · Aug 2019
Glutathione S-Transferase Genotype Protects Against In Utero Tobacco Linked Lung Function Deficits.
Rationale:In utero tobacco exposure is associated with reduced lung function from infancy. Antioxidant enzymes from the glutathione S-transferase (GST) family may protect against these lung function deficits. Objectives: To assess the long-term effect of in utero smoke exposure on lung function into adulthood, and to assess whether GSTT1 and GSTM1 active genotypes have long-term protective effects on lung function. ⋯ In utero tobacco exposure was associated with deficits in lung function among those with both GSTT1-null and GSTT1-active genotypes. Conclusions: Certain GST genotypes may have protective effects against the long-term deficits in lung function associated with in utero tobacco exposure. This offers potential preventative targets in antioxidant pathways for at-risk infants of smoking mothers.