Biomedical subjects

A Harf

Publications and source records attributed to A Harf.

At least 109 records · Page 6Linked to original sources

PubMed1996

Evaluation of an auto-nCPAP device based on snoring detection.

We evaluated an auto-nasal continuous positive airway pressure (nCPAP) prototype (MC+; SEFAM, Nancy, France) in which apnoea/hypopnoea detection was disabled and nasal mask pressure vibration detection was the only mode of pressure setting. The device was tested in 15 previously untreated obstructive sleep apnoea patients during a night with polysomnography. We observed that a single night of auto-nCPAP improved the apnoea/hypnoea index (AHI) (12 +/- 21 vs 51 +/- 31 disordered breathing events.h-1 of sleep (mean +/- SD)), the awakening-arousal index (13 +/- 20 vs 40 +/- 26 arousals.h-1 of sleep), and duration of slow wave sleep (102 +/- 49 vs 71 +/- 56 min) but not of rapid eye movement (REM) sleep (55 +/- 31 vs 64 +/- 38 min). Auto-nCPAP was effective (apnoea/hypopnoea and arousal indices < 10 events.h-1) in all but three patients. Auto-nCPAP was ineffective in one patient, whose obstructive respiratory events were not preceded by nasal mask pressure vibration detection, and in two patients who were quasi-permanent mouth breathers. Snoring detection may be effective in sleep apnoea syndrome with heavy snoring and without permanent mouth breathing, during the first night of nasal continuous positive airway pressure treatment.

Airway Obstruction↗

PubMed1996

Oxidant-antioxidant balance in alveolar macrophages from newborn rats.

An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may contribute to the increased susceptibility to lung injury described in the neonatal period. We therefore evaluated oxygen radical production by rat AMs at various postnatal ages, and measured in parallel cellular antioxidant enzyme activities. AMs were obtained by bronchoalveolar lavage from rats aged < 24 h, 21 days and 5 weeks, and results were compared to those obtained with adult rat AMs. Intracellular production of oxygen radical species, estimated fluorometrically using 2',5'-dichlorofluorescein diacetate as the substrate, was significantly reduced in neonates as compared with adults, both in the presence and in the absence of cell stimulation with phorbol myristate acetate (PMA) or opsonized zymosan. A similar pattern was observed for the extracellular release of oxygen radical species, evaluated by lucigenin-enhanced chemiluminescence (CL) or peroxidase-catalysed CL oxidation of luminol: peak CL values measured after cell stimulation with PMA or opsonized zymosan remained significantly lower for AMs from newborn rats than for AMs from adults. By contrast, high values for antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) in AMs were demonstrated in newborns as compared to adults. We conclude that high antioxidant activity in rat AMs after birth may be at least partly responsible for the low production of oxygen metabolites observed during the same period.

Aging↗

PubMed1996

Sleep fragmentation as a risk factor for hypertension in middle-aged nonapneic snorers.

Although a high prevalence of hypertension has been observed in snorers, whether there is a direct link between hypertension and snoring remains controversial. It has recently been demonstrated that an abnormal amount of breathing effort during snoring is responsible for sleep fragmentation even in the absence of sleep apnea syndrome criteria. We hypothesized that sleep fragmentation during snoring may be a direct risk factor for the development of hypertension. On the basis of polysomnographic data, 105 nonapneic patients between 40 and 65 years of age referred for snoring with social impairment were selected and categorized as snorers with (n=55) or without sleep fragmentation (n=50) based on whether the arousals index was 10 or greater or less than 10/h of sleep, respectively. Sleep distribution did not differ between the two groups, except for a longer duration of wake after sleep onset (58 +/- 43 min vs 42 +/- 38 min) and a shorter duration of slow-wave sleep in the group with sleep fragmentation (72 +/- 34 min vs 97 +/- 34 min). Although there were no statistically significant differences between the snorers with and without sleep disruption in terms of age (51.3 +/- 7.7 vs 48.6 +/- 6.0 years), body mass index (26.9 +/- 4.0 vs 27.2 +/- 5.5 kg/m2), sex ratio, respiratory indexes during sleep, daytime sleepiness, and daytime tiredness, prevalence of systemic hypertension was significantly higher in the sleep-fragmented group (20/55 vs 7/50). This significant difference persisted (16/51 vs 6/49) when patients using antihypertensive drugs with possible effects on the CNS were excluded. Our data suggest that sleep fragmentation is common in patients who seek medical help for snoring with social impairment and may play a role in the development of hypertension.

Adrenergic beta-Antagonists↗

PubMed1995

Assessment of neonatal ventilator performances.

OBJECTIVE: To analyze efficiency and reliability of 4 modern neonatal ventilators under difficult test conditions. The ventilators tested were: Babylog 8000 (Dräger Medical), BP 2001 (Bear Medical Systems), Sechrist IV 100 B (Sechrist Industries), Infant Star (Infrasonics INC). MEASUREMENTS AND RESULTS: Gas flow generation was tested by comparison of preset flow values with no resistance in the circuit to flow values obtained during interposition of a resistance in the inspiratory circuit. A decrease in gas flow was observed when interposition of a resistance in the inspiratory circuit increased peak inspiratory pressure to 60 cmH2O (gas flow decreased by 8% to 24% depending on the ventilator tested). The pressure limiting valve and the positive end-expiratory pressure valve were also evaluated in order to test their behaviour under different flow conditions. Flow-dependence of the pressure was noted for all ventilators except Babylog 8000. Assessment of the reliability of pressure monitoring revealed either 'under' or 'over' estimation of peak inspiratory pressure and positive end-expiratory pressure depending on the ventilator tested. CONCLUSION: For the best clinical use of mechanical ventilators, neonatologists should be aware of these limitations. Therefore a regular assessment of ventilator performance and monitoring reliability is recommended.

Equipment Failure↗

PubMed1995

Tachykinins induce gelatinase production by guinea pig alveolar macrophages: involvement of NK2 receptors.

To determine whether tachykinins induce gelatinase production by guinea pig alveolar macrophages (AM), and to characterize the mechanism involved, we incubated AM with substance P (SP), neurokinin A (NKA), or the NH2-terminal fragment of SP, SP(1-7). The effects of increasing concentrations of selective NK1 and NK2 agonists on tachykinin-induced gelatinase production were also evaluated, as were the effects of a selective NK2 antagonist. Gelatinase activity in conditioned culture media (CCM) was assessed by zymography and quantified by image analysis. SP increased 92-kDa gelatinase activity in CCM of AM in a concentration-dependent manner, with a maximum increase at 10(-4) M. NKA, the NH2-terminal fragment of SP, and an NK1-selective agonist had no effect. In contrast, a selective NK2 agonist induced a concentration-dependent increase in gelatinase activity. The increase in this activity induced by SP and the selective NK2 agonist was inhibited by a selective NK2 antagonist. We conclude that SP induces gelatinase production by AM through NK2 receptor activation. The release of gelatinase may constitute one mechanism through which SP contributes to the epithelial lesions observed in bronchial hyperreactivity and asthma.

Animals↗

PubMed1995

Alveolar endotoxin increases alveolar liquid clearance in rats.

Under some pathological conditions, ion transport across alveolar epithelial cells is downregulated, whereas under other pathological conditions, it may be upregulated. Because endotoxin is a biologically relevant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotoxin (220 micrograms/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liquid clearances were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar liquid clearance was significantly greater at 24 h (36 +/- 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-instilled controls (27 +/- 6%). Although there was an influx of neutrophils into the air space, there was no increase in lung epithelial permeability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium channel inhibitor, significantly reduced alveolar liquid clearance in the rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upregulates net alveolar fluid clearance in vivo for up to 40 h, a potentially important mechanism for accelerating alveolar fluid clearance under some pathological conditions. The increase in alveolar liquid clearance 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.

Amiloride↗

PubMed1995

Increased 92 kD gelatinase activity from alveolar macrophages in newborn rats.

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV collagenase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages. Total gelatinase activity was measured by zymography in AM-conditioned media. Spontaneous secretion of gelatinase from AMs varied significantly with age, the highest levels being found immediately after birth. Stimulation of AMs by PMA induced a four- to fivefold greater increase in total gelatinase activity during the first 10 d of postnatal life compared with adulthood. Using [3H]gelatin as the substrate, we found high free gelatinase activity only within 24 h after birth; data obtained after exposing cells to natural surfactant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of metalloproteinases (TIMP) by AMs was detectable in newborns within 24 h after birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profile during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradation.

Animals↗

PubMed1995

Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.

Adolescent↗

PubMed1995

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

PubMed1995

Forced oscillation technique vs spirometry to assess bronchodilatation in patients with asthma and COPD.

The forced oscillation technique (FOT) is a noninvasive test used to characterize the mechanical impedance of the respiratory system. The aim of the study was to compare the changes in respiratory conductance (Grs) measured with FOT to those in FEV1 in 22 patients with asthma and 20 patients with chronic obstructive pulmonary diseases (COPD) after salbutamol inhalation. FEV1 and Grs indexes, computed as the ratio of the difference between postbronchodilator and prebronchodilator values over the predicted value, were used to express reversibility of airway obstruction. After inhalation of salbutamol in cumulative doses up to 1,200 micrograms in ten patients of each group, FEV1 and Grs indexes showed parallel changes, and most of the increase was observed after the first dose of 200 micrograms of salbutamol for the two indexes. In all the 42 patients, we found a linear relationship between the two indexes after inhalation of 200 micrograms of salbutamol (r = 0.7, p < 0.0001). We evaluated FEV1 and Grs indexes in terms of sensitivity and specificity for identifying asthmatics among patients with COPD: using a 10% change as the cut-off value, these indexes proved of similar value (sensitivity, 0.91 and 0.95; specificity, 0.95 and 0.85, respectively). We conclude that the use of FOT can be considered as an alternative to forced expiration for detecting bronchodilatation in asthmatics and patients with COPD.

Airway Resistance↗

PubMed1995

Evaluation of carbon dioxide rebreathing during pressure support ventilation with airway management system (BiPAP) devices.

The purpose of this study was to evaluate whether carbon dioxide (CO2) rebreathing occurs in acute respiratory failure patients ventilated using the standard airway management system (BiPAP pressure support ventilator; Respironics; Murrysville, Pa) with positive inspiratory airway pressure and a minimal level of positive end-expiratory pressure (PEEP) and whether any CO2 rebreathing may be efficiently prevented by the addition of a nonrebreathing valve to the BiPAP system circuit. In the first part of the study, the standard device was tested on a lung model with a nonrebreathing valve (BiPAP-NRV) and with the usual Whisper Swivel connector (BiPAP-uc). With the BiPAP-uc device, the resident volume of expired air in the inspiratory circuit at the end of expiration (RVEA) was 55% of the tidal volume (VT) when the inspiratory pressure was 10 cm H2O and the frequency was at 15 cycles per minute. The BiPAP-NRV device efficiently prevented CO2 rebreathing but resulted in a slight decrease in VT, which was due to a significant increase in external PEEP (2.4 vs 1.3 cm H2O) caused by the additional expiratory valve resistance. For similar reasons, both the pressure swing necessary to trigger pressure support and the imposed expiratory work were increased in the lung model when the nonrebreathing valve was used. In the second part of the study, seven patients weaned from mechanical ventilation were investigated using a randomized crossover design to compare three situations: pressure support ventilation with a conventional intensive care ventilator (CIPS), BiPAP system use, and BiPAP-NRV. When we compared the BiPAP system use with the other two systems, we observed no significant effect on blood gases but found significant increases in VT, minute ventilation, and work of breathing. These findings are experimental and are clinical evidence that significant CO2 rebreathing occurs with the standard BiPAP system. This drawback can be overcome by using a non-rebreathing valve, but only at the expense of greater expiratory resistance.

Adult↗

PubMed1995

[Non-invasive ventilation in acute respiratory insufficiency in chronic obstructive bronchopneumopathy].

At the time of acute exacerbations of chronic airflow obstruction (BPCO) non-invasive ventilation represents an alternative to endotracheal intubation. In patients with respiratory distress, the use of a face mask is often preferable to a nasal mask alone, by avoiding the escape of oxygen which occurs around the mouth in nasal ventilation. The inspiratory aid is a type of ventilation which permits good synchronisation with the spontaneous activity of the patient; it leads to a reduction of respiratory effort developed by the patient and at the same time improves oxygenation and alveolar ventilation. In a recent randomised multicentre trial in 85 BPCO patients with severe respiratory distress, the level of intubation was reduced from 74 to 26 per cent by ventilation with an inspiratory mask. The consequences were a significant reduction of the complications of acute respiratory failure which were linked to artificial ventilation (p < 0.05) with a reduction of the hospital stay (p < 0.05) and finally a significant reduction in mortality (29 per cent - 9 per cent, p < 0.005). From now on, this technique could be used in many centres as the first treatment in acute exacerbations of BPCO patients to avoid the use of endotracheal intubation.

Acute Disease↗

PubMed1994

A synthesis of the Otis, Mead, and Mount mechanical respiratory models.

We propose a unified approach of the viscoelastic models introduced by Otis, Mead and Mount to describe the mechanical behaviour of the respiratory system. A single equation of motion is developed for these two-compartment models and solved in response to typical pressure and volume inputs. The analytic expression of the pressure response to rapid airway occlusion following constant flow inflation, and of the volume response to single breath following end-inspiratory pause are more particularly analysed. The lumped respiratory parameters derived from these responses are expressed as functions of the parameters characterising the constitutive mechanical elements of each model. Different combinations of respiratory models and of methods for measuring respiratory mechanics are examined. For each model, the physiological interpretation of the lumped mechanical parameters is summarised in terms of gas redistribution or tissue viscoelastic properties.

Humans↗

PubMed1994

Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.

Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). The control group was given 0.9% NaCl. 24 h after instillation, a BAL was performed, the BAL fluid was separated from the cells by centrifugation, and AMACs and PMNs were separately cultured for 24 h. In BAL fluid from LPS-treated guinea pigs, we found 1) an increase in free gelatinase activity, tested on [3H]gelatin (0.7 +/- 0.2 micrograms.200 microliters BAL fluid-1.48 h-1 vs. 0.2 +/- 0.1 in controls, P < 0.05), and 2) increased total gelatinase activities, as assessed by zymography. The molecular masses of the major gelatinase species found in BAL fluid by zymography were 92 and 68 kDa. The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.

Animals↗

PubMed1994

Acute and chronic respiratory effects of sulfur mustard intoxication in guinea pig.

Sulfur mustard (SM) has been used as a vesicant chemical warfare agent. To investigate the respiratory damages it causes, we studied the effects on guinea pigs of an intratracheal injection of 0.3 mg/kg of SM 5 h and 14 days after injection. Five hours after SM intoxication, respiratory system resistance and microvascular permeability were increased. These alterations were not prevented by pretreatment with 50 mg/kg sc of capsaicin 2 wk before SM intoxication. Histological studies showed columnar cell shedding all along the tracheal epithelium, bronchoconstriction, and peribronchial edema. Fourteen days after SM intoxication, guinea pigs demonstrated airway hyperreactivity to aerosolized substance P and histamine. Pretreatment with phosphoramidon caused a further increase in airway responsiveness to substance P. Neutral endopeptidase activity in the tracheal epithelium was decreased by twofold in SM-intoxicated guinea pigs. At this stage, the tracheal epithelium was disorganized and atrophic. These results demonstrate that in guinea pigs SM intoxication induces severe lesions to the tracheal epithelium, which might account for the airway hyperresponsiveness observed 14 days after intoxication.

Acetylcholine↗

PubMed1994

Respiratory response to inhaled CO2 during positive inspiratory pressure in humans.

To investigate ventilatory CO2 sensitivity during inspiratory pressure support (IPS), we administered inspiratory CO2 [fractional concn (FICO2) 0.01, 0.03, or 0.05] in eight normal subjects without (CTRL) or with (Pinsp) positive inspiratory airway pressure (5 or 10 cmH2O). At CTRL and low IPS, CO2 inhalation led to a significant increase in tidal volume (VT) with nearly identical slopes in the plot of VT vs. end-tidal PCO2. At the high IPS level, VT at FICO2 of 0 was significantly above the value at lower Pinsp and did not increase with CO2 unless FICO2 was elevated to > 0.03. There was very little effect of either Pinsp or FICO2 on respiratory frequency and respiratory timing. The data suggest that the CO2 sensitivity of ventilation is similar at low levels of IPS as during CTRL. However, at high levels of IPS, VT is determined largely by the passive inflation and, thus, independent of CO2. CO2 has to be elevated to increase the respiratory drive before VT becomes CO2 sensitive.

Administration, Inhalation↗

PubMed1994

Glucocorticoids inhibit sulfur mustard-induced airway muscle hyperresponsiveness to substance P.

To explore the mechanisms of airway hyperreactivity to aerosolized substance P observed in guinea pigs 14 days after intratracheal injection of sulfur mustard (SM), we studied the effects of epithelium removal and inhibition of neutral endopeptidase (NEP) activity on airway muscle responsiveness. Tracheal rings from SM-intoxicated guinea pigs expressed a greater contractile response to substance P than rings from nonintoxicated guinea pigs. After epithelium removal or incubation with the NEP inhibitor phosphoramidon, the contractile responses of tracheal rings to substance P did not differ in guinea pigs injected with SM or ethanol (SM solvent). Treatment of the guinea pigs with betamethasone for 7 days before measurement abolished the airway muscle hyperresponsiveness observed in untreated SM-intoxicated guinea pigs and partially restored tracheal epithelium NEP activity. In addition, the tracheal epithelium height and cell density of SM-intoxicated guinea pigs treated with betamethasone were significantly greater than in those without betamethasone. These results demonstrate that SM intoxication induces airway muscle hyperresponsiveness to substance P by reducing tracheal epithelial NEP activity and that glucocorticoids might inhibit this hyperresponsiveness by increasing this activity.

Administration, Inhalation↗

PubMed1994

Effects of capsaicin on the airway responses to inhaled endotoxin in the guinea pig.

Inhalation of lipopolysaccharide (LPS) has been associated with increased airway responsiveness and inflammation both in humans and in animals. To investigate the contribution of capsaicin-sensitive nerves to these changes, we compared airway responsiveness and inflammation after intratracheal administration of 10 micrograms/kg LPS (Escherichia coli O55:B5 lipopolysaccharide) or saline in guinea pigs treated 10 days previously with 50 mg/kg capsaicin and in those pretreated with the capsaicin vehicle. Four hours after LPS, airway responsiveness and cell counts in the bronchoalveolar lavage were assessed. To determine airway responsiveness, guinea pigs were anesthetized, tracheotomized, and mechanically ventilated before exposure to increasing concentrations of aerosolized histamine (10(-4) to 10(-3) M). Capsaicin pretreatment prevented the LPS-induced increase in airway responsiveness in response to aerosolized histamine. It significantly reduced total cell recovery in the bronchoalveolar lavage after LPS (1,167 +/- 167 10(3) cells/ml in capsaicin-treated guinea pigs versus 2,171 +/- 184 10(3) in vehicle-treated guinea pigs) by reducing the LPS-induced influx of neutrophils and macrophages. Additional experiments demonstrated that the activity of neutral endopeptidase (NEP) in the tracheal epithelium was not significantly different in guinea pigs injected with LPS from that in the saline-treated control animals, and that the pretreatment with the NEP inhibitor phosphoramidon did not increase the LPS-induced influx of neutrophils into the bronchoalveolar lavage. These results demonstrate that in the guinea pig, capsaicin-sensitive nerves are involved in LPS-induced airway hyperresponsiveness and inflammation.

Administration, Inhalation↗