American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2019
Observational StudyPhysiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia.
Rationale: A sensitive outcome measure for infants with bronchopulmonary dysplasia would facilitate clinical benchmarking and enhance epidemiologic understanding, evaluation of clinical interventions, and outcome prediction. Objectives: Noninvasive assessment of pulmonary gas exchange in preterm infants with and without bronchopulmonary dysplasia to grade disease severity and to identify determinants of impaired gas exchange. Methods: This is a prospective observational study in very preterm infants. ⋯ Shift was the most sensitive and specific index of the severity of bronchopulmonary dysplasia. Conclusions: Most infants with bronchopulmonary dysplasia have impaired oxygenation quantified by a simple, sensitive bedside test. Shift of the SpO2/PiO2 curve may be useful for prediction and measurement of preterm infant respiratory outcomes.
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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.
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Am. J. Respir. Crit. Care Med. · Aug 2019
Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking. Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes. ⋯ For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma. Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
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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.