Pulmonary function responses to ozone in smokers with a limited smoking history.

In non-smokers, ozone (O3) inhalation causes decreases in forced expiratory volume (FEV1) and dead space (VD) and increases the slope of the alveolar plateau (SN). We previously described a population of smokers with a limited smoking history that had enhanced responsiveness to brief O3 boluses and aimed to determine if responsiveness to continuous exposure was also enhanced. Thirty smokers (19M, 11F, 24±4 years, 6±4 total years smoking,4±2 packs/week) and 30 non-smokers (17M, 13F, 25±6 years) exercised for 1h on a cycle ergometer while breathing 0.

Comparison of ozone-specific (OZAC) and oxygen radical (ORAC) antioxidant capacity assays for use with nasal lavage fluid.

Antioxidants in respiratory mucus protect the underlying airway epithelium from damage by ozone (O(3)), a common outdoor air pollutant. To understand O(3)-antioxidant interactions and the variation of these interactions among individuals, in vitro assays are needed to measure the total antioxidant capacity of airway lavage fluid, a convenient source of (diluted) mucous samples. Here, we compare the oxygen radical absorbance capacity (ORAC), a general method that uses peroxyl radicals as a reactive substance, to the recently developed ozone specific antioxidant capacity (OZAC), a procedure that directly employs O(3).

Longitudinal distribution of ozone absorption in the lung: comparison of cigarette smokers and nonsmokers.

In nonsmokers, ozone (O(3)) is removed primarily by the epithelial lining fluid (ELF) of the conducting airways. We hypothesized that cigarette smokers, whose ELF antioxidant capacity may be limited by smoking, would remove less O(3) from their conducting airways than nonsmokers. We recruited 29 nonsmokers (17M, 12F) and 30 smokers (19M, 11F, 4+/-4 pack-years) with similar anthropometric characteristics and measured the longitudinal distribution of O(3) using the bolus inhalation method.

Kinetics of ozone reaction with uric acid, ascorbic acid, and glutathione at physiologically relevant conditions.

This study quantified the reaction kinetics of O3 with three low molecular weight antioxidants-uric acid (UA), ascorbic acid (AH2), and glutathione (GSH)-found in respiratory mucous. Using a semi-batch reactor in which a 500 ml/min flow of air containing 1-5 parts per million of O3 contacted 3 ml of well-stirred physiological saline solution containing 100-200 microM antioxidant, we found that: (1) mass transfer resistances in the gas and liquid phases were successfully eliminated by the reactor design; (2) the reaction of O3 with UA, AH2 and GSH had stoichiometries of 1:1, 1:1, and 1:2.5, respectively; (3) the reactivity between O3 and antioxidants was in the order UA approximately AH2>GSH.

Reduced airway hyperresponsiveness and tracheal responses during allergic asthma in mice lacking tyrosine kinase inducible T-cell kinase.

Background: Patients with allergic asthma have symptoms of a predominant T(H)2 response, including airway eosinophilic inflammation and increased mucous production in the lungs. This accompanies increased airways responsiveness, which can be life threatening. Because T(H)2 cells and cytokines have been implicated in contributing to these symptoms, pathways that control the development of these cells or that regulate their cytokine production represent good targets for controlling this disease.

Changes in the carbon dioxide expirogram in response to ozone exposure.

The objectives of this study were to quantify pulmonary responses to ozone (O3) exposure by parameters computed from the carbon dioxide expirogram and to compare these responses to decrements in forced expired spirometry. Anatomical dead space (VD) was determined from the pure dead space and transition regions of the expirogram. Four alternative parameters were computed from the alveolar plateau: slope (S), normalized slope (NS), peripheral cross-sectional area (AP) and well-mixed peripheral volume (VMP).

Uptake of ozone in human lungs and its relationship to local physiological response.

To investigate whether intersubject variations in the dose of inhaled ozone (O(3)) cause corresponding variations in the physiological response, 28 female and 32 male nonsmokers participated in a 1-h continuous inhalation of clean air or 0.25 ppm O(3) while exercising on a cycle ergometer at a constant ventilation rate of 30 L/min. The exposure protocols included continuous monitoring of respiratory flow rate and O(3) concentration from which O(3) uptake (OZU) and fractional uptake efficiency (UE) were computed.

Uptake distribution of ozone in human lungs: intersubject variability in physiologic response.

The primary hypothesis of this study was that intersubject variation in uptake of inhaled ozone causes corresponding variation in the resulting physiologic response. The second hypothesis was that differences in breathing pattern and lung anatomy induce differences in ozone uptake. Sixty healthy nonsmokers participated in three exposure protocols during which their minute ventilation was 30 L/min, corresponding to moderate exercise.

Modulation of tracheal smooth muscle responses in inducible T-cell kinase knockout mice.

It has been shown that the Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) plays a role in the activation of naive T cells and in the differentiation of T helper (TH2)-type cells producing cytokines in a model of allergic inflammation, thereby possibly indirectly mediating hyperresponsivenes of airway smooth muscle tone. Using excised tracheae from wild type (WT) mice and those lacking ITK, we conducted a series of in vitro experiments in which isometric smooth muscle tones were assessed in response to several agonists to determine whether the absence of ITK would affect the responsiveness of tracheal smooth muscle cells. The resulting change in contractile responses was evaluated by measuring agonist cumulative concentration-response curves (CCRC).

Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application.

Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance).

Development of an assay for ozone-specific antioxidant capacity.

A method of determining the ozone-specific antioxidant capacity (OZAC) of lavage samples from the respiratory system was developed: Gaseous ozone (O(3)) was produced in cuvettes by irradiation with an ultraviolet lamp; aliquots of sample or of a saline control were then added and sufficient time was allowed for ozonation to reach completion; and an aliquot of indigo trisulfonate (ITS) was added to react with excess O(3). Because each molecule of O(3) rapidly bleaches one molecule of the deeply colored ITS, an OZAC value in concentration units was computed from the difference in light absorbance between the sample and the saline control multiplied by the extinction coefficient of ITS. Experiments in 0-40 micro M antioxidant solutions indicated that the OZAC values of uric acid and ascorbic acid were close to their actual concentrations and were independent of O(3) concentration.