Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic asthmatic patients with normal spirometric values, and to be correlated with airways hyperresponsiveness to methacholine. We investigated whether Rp in asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in response to cool, dry air. Using a wedged bronchoscope technique, we challenged an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22 degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and eight normal subjects. Baseline Rp and Rp following challenge were measured with saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min; median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07] cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03 to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We conclude that the peripheral airways of asthmatic individuals with EIB are responsive to cool, dry air, and may play an important role in EIB.
The effects of hyperpnea on parenchymal lung mechanics are unknown, but they may contribute to the resultant airflow limitation commonly seen in asthma. To investigate these effects, we measured the following parameters in seven asthmatic and six normal subjects before and after 5 min of hyperpnea: specific conductance, upstream resistance, static compliance, the coefficient of retraction, lung volumes, lung hysteresis, and the ratio of maximal to partial flow rates (the M:P ratio, an indicator of the effect of deep inhalation on airflow, and a measure of relative airway and parenchymal hysteresis). In addition to a central effect on the airways, as shown by significant falls in specific conductance, hyperpnea in asthmatics, but not in normal subjects, resulted in significant increases in residual volume and pressure-volume hysteresis, suggestive of changes in parenchymal lung mechanics. The M:P ratio also increased in the asthmatics, consistent with greater increases in airway than in parenchymal hysteresis after hyperpnea. We conclude that hyperpnea has significant effects on the lung parenchyma that contribute to airflow limitation in asthmatics, and we hypothesize that these effects may be due to alterations in peripheral airway smooth muscle tone and surfactant function.
Interstitial lung disease is thought to result from progression of an initial lung injury and alveolitis into a chronic inflammatory process that produces fibrosis. However, the relationship between the severity of the initial phase of acute injury and alveolitis and the amount of subsequent chronic inflammation and fibrosis remains unclear. We induced a wide spectrum of acute lung injury in rabbits by using various amounts of intratracheal bleomycin (5 or 10 U/kg) with and without oxygen supplementation (100% O2 for 2 min). The arterial oxygen tension on Day 12 after the bleomycin correlated with the extent of acute lung injury, as well as with the amount of chronic inflammation and fibrosis present on Day 56, as determined by physiologic parameters (lung volume, DLCO/VA, and PO2), and morphometry (volume proportions abnormal parenchyma made up of intra-alveolar macrophages, intra-alveolar granulocytes, abnormal alveoli, abnormal airways, fibrosis, consolidation, and honeycombing). We conclude that in bleomycin-induced interstitial lung disease in the rabbit, there is a direct relationship between the severity of acute lung injury after intratracheal bleomycin and the amount of subsequent chronic inflammation and fibrosis. This suggests that the mechanisms regulating the development of fibrosis are directly influenced by the extent of initial injury.
Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung "region of interest" (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.