American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 1997
Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.
Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. ⋯ Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.
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Am. J. Respir. Crit. Care Med. · Aug 1997
Comparative StudySignificance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. An immediate postmortem histologic study.
The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (> 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. ⋯ The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.
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Am. J. Respir. Crit. Care Med. · Aug 1997
D-dimer testing for suspected pulmonary embolism in outpatients.
The plasma level of D-dimer, a fibrin degradation product (FDP), is nearly always increased in the presence of acute pulmonary embolism (PE). Hence, a normal D-dimer level (below a cutoff value of 500 micrograms/L by enzyme-linked immunosorbent assay [ELISA]) may allow the exclusion of PE. To assess the negative predictive value of a D-dimer concentration below 500 micrograms/L in outpatients with suspected PE, and the safety of withholding anticoagulant treatment from such patients, we performed D-dimer assays, lower limb venous compression ultrasonography, and lung scans in 671 consecutive outpatients presenting in the Emergency Center of the Geneva University Hospital with suspected PE. ⋯ Using a cutoff value of 4,000 micrograms/L, the overall specificity of D-dimer concentration for PE was 93.1%. In conclusion, a plasma D-dimer concentration below 500 micrograms/L allows the exclusion of PE in 29% of outpatients suspected of having PE. Withholding anticoagulation from such patients is associated with a conservative 1% risk of thromboembolic events during follow-up.
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Am. J. Respir. Crit. Care Med. · Aug 1997
Expression of mRNA for gastrin-releasing peptide receptor by human bronchial epithelial cells. Association with prolonged tobacco exposure and responsiveness to bombesin-like peptides.
Bombesin-like peptides (BLPs) are important regulators of lung development and may also act as autocrine growth factors in lung tumors. We have previously demonstrated expression of mRNA for the three BLP receptor subtypes (neuromedin B [NMB]) receptor, gastrin-releasing peptide [GRP] receptor, and bombesin receptor subtype 3 [BRS-3]) in human non-small cell lung carcinoma (NSCLC) cell lines and bronchial biopsies using the reverse transcription-polymerase chain reaction (RT-PCR; DeMichele, et al. Am. ⋯ Cultures of HBE cells from four of the five subjects with severe obstructive lung disease gave a positive response to GRP and NMB in proliferation assays, compared to five of fifteen without severe obstructive lung disease, but this difference was not significant (p = 0.13). These results suggest there is an increased likelihood of expression of the GRP receptor mRNA in the respiratory epithelium of some individuals with a history of prolonged tobacco exposure, and that expression of the GRP receptor mRNA is accompanied by responsiveness to the mitogenic effects of BLPs. These effects appear to persist after smoking cessation.
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Am. J. Respir. Crit. Care Med. · Jul 1997
Randomized Controlled Trial Clinical TrialNasal inhalation of l-menthol reduces respiratory discomfort associated with loaded breathing.
To test the hypothesis that stimulation of cold receptors in the upper airway may alleviate the sensation of respiratory discomfort, we investigated the effects of nasal inhalation of l-menthol (a specific stimulant of cold receptors) on the respiratory sensation and ventilation during the loaded breathing in 11 normal subjects. Subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (VAS) while breathing on a device with a flow-resistive load (180 cm H2O/L/s) or with an elastic load (75.5 cm H2O/L). The effects of inhalation of l-menthol on ventilation and respiratory sensation were evaluated by comparing the steady-state values of ventilatory variables and VAS scores obtained before, during, and after l-menthol inhalation. ⋯ Inhalation of strawberry-flavored air caused neither changes in VAS score nor changes in breathing pattern and ventilation, indicating that olfaction is not a contributing factor in the relief of respiratory discomfort. We concluded that stimulation of cold receptors in the upper airway with nasal inhalation of l-menthol reduces the sensation of respiratory discomfort associated with loaded breathing. This effect is more effective during the flow-resistive loading than during the elastic loading.