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PubMed1998

Effects of inhaled nitric oxide during permissive hypercapnia in acute respiratory failure in piglets.

OBJECTIVE: To look for the effects of inhaled nitric oxide on oxygenation and pulmonary hemodynamics during acute hypercapnia in acute respiratory failure. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Ten piglets, weighing 9 to 13 kg. INTERVENTIONS: Acute respiratory failure was induced by oleic acid infusion and repeated lung lavages with 0.9% sodium chloride. The protocol consisted of three randomly assigned periods with different PaCO2 levels. Tidal volume was reduced to induce hypercapnia. Inspiratory time was prolonged to achieve similar mean airway pressures. During permissive hypercapnia, pH was not corrected. At each PaCO2 period, the animals were ventilated with inhaled nitric oxide of 10 parts per million and without nitric oxide inhalation. MEASUREMENTS AND MAIN RESULTS: Continuous hemodynamic monitoring included right atrial, mean pulmonary arterial, and mean systemic arterial pressures, arterial and mixed venous oxygen saturations, and continuous flow recording at the pulmonary artery. In addition, airway pressures, tidal volumes, dynamic lung compliance and airway resistance, end-tidal CO2 concentrations, and arterial and mixed venous blood gases were measured. Data were obtained at baseline and after lung injury, at normocapnia, at two levels of hypercapnia with and without nitric oxide inhalation. Acute hypercapnia resulted in a significant decrease in blood pH and a significant increase in mean pulmonary arterial pressure. There was no significant change in PaO2 during normocapnia and hypercapnia. Inhaled nitric oxide significantly decreased the mean pulmonary arterial pressure during both hypercapnic periods. It significantly improved oxygenation during both normocapnia and hypercapnia. CONCLUSIONS: Acute hypercapnia resulted in a significant increase in pulmonary arterial pressure without influencing oxygenation and cardiac output. Inhaled nitric oxide significantly reduced the pulmonary hypertension induced by acute permissive hypercapnia but did not influence the flow through the pulmonary artery. Inhaled nitric oxide significantly improved oxygenation in this model of acute lung injury during normocapnia and acute hypercapnia.

Administration, Inhalation↗
PubMed1998

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

Administration, Inhalation↗
PubMed2000

Short-term effect of inhaled nitric oxide and prone positioning on gas exchange in patients with severe acute respiratory distress syndrome.

OBJECTIVE: To compare the short-term effects of inhaled nitric oxide (NO) and prone positioning in improving oxygenation in acute respiratory distress syndrome (ARDS). METHODS: Charts of consecutive ARDS patients (lung injury score >2) during a 2-yr period, tested for both inhaled NO and prone positioning efficacy were retrospectively reviewed. Variations in the Pao2/Fio2 ratio induced by inhaled NO and prone positioning were evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (age, 42+/-17 yrs) were included. Simplified Acute Physiology Score II was 45+/-14. Mortality rate in the intensive care unit was 63%. The causes of ARDS were pneumonia (n = 14), extra-lung infection (n = 5), and noninfectious systemic inflammatory response syndrome (n = 8). Lung injury score was 2.7+/-0.3. At baseline, before the initiation of inhaled NO, the Pao2/Fio2 ratio was 97+/-46 torr and before prone positioning, 92+/-26 torr. Variations in the Pao2/Fio2 ratio were lower at start of NO therapy (11+/-4 ppm) than that observed at prone positioning initiation (23+/-31 vs. 62+/-78 torr, p<.05). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with prone positioning in 16 patients (59%) and with NO inhalation in 13 patients (48%) (not significant). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with both techniques in only six patients (22%). There was no correlation between the response to prone positioning and the response to inhaled NO (r2 = .005; p = .73). CONCLUSIONS: Prone positioning improves hypoxemia significantly better than does inhaled NO. The response to one technique is not predictive of the response to the other technique.

APACHE↗
PubMed2000

Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury.

OBJECTIVE: Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity. DESIGN: A randomized, prospective interventional study. SETTING: A university hospital's general intensive care unit. PATIENTS: Thirty-two patients with acute lung injury. INTERVENTIONS: Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%. MEASUREMENTS AND MAIN RESULTS: Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter. CONCLUSIONS: The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.

Acute Disease↗
PubMed1998

An improved mouth-piece to prevent environmental contamination during radioaerosol inhalation procedures.

The literature suggests that environmental contamination is common during labeled aerosol inhalation procedures in nuclear medicine. We have tested an adherent mask to prevent environmental contamination in 70 procedures. Two groups of patients were evaluated. Group 1 (60 inhalation cases in which the mask was used) presented no environmental contamination in 95% of the procedures (means of 553 dpm and 596 dpm before and after inhalation, p > 0.05, mean of the differences before/after inhalation 6.95, SD = 21.2 dpm) and the only 3 cases in which contamination did occur concerned bearded men; Group 2 (10 inhalation cases in which the mask was not used) showed large increases of environmental radioactive levels in 70% of the procedures (means of 601 dpm and 2,756 dpm before and after inhalation, p < 0.05, mean of the differences 3,066, SD = 2,98 dpm). We conclude that such a mask is very helpful in avoiding environmental contamination during radioaerosol inhalation procedures.

Administration, Inhalation↗
PubMed2000

Effect of inhaled nitric oxide on cardiovascular response to catecholamine in heart failure.

We examined the dose responses to continuous infusion of isoproterenol (ISO) and norepinephrine (NE) in normal (control) and procainamide-induced heart failure dogs with or without inhalation of 70 ppm nitric oxide (NO). Inhaled NO affected neither left ventricular (LV) function nor hemodynamics at baseline in both control and heart failure dogs. There were no significant differences in the responses to ISO and NE with or without inhaled NO in the control. The responses of LV dP/dt to ISO and NE were significantly enhanced in heart failure; however, they were not affected by inhaled NO. In contrast, LV pressure and dimension at end diastole were significantly increased, and pulmonary vascular resistance (PVR) was significantly decreased by inhaled NO during infusion of both ISO and NE in heart failure. In conclusion, the positive inotropic response to cathecholamine is not affected by inhaled NO even in heart failure. Inhaled NO decreases PVR, but potentially increases LV preload in the presence of additional stress of cathecholamine in heart failure.

Administration, Inhalation↗
PubMed2000

Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit.

Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.

Administration, Inhalation↗
PubMed1996

Impact of inhaled corticosteroids on acute asthma hospitalization in Sweden 1978 to 1991.

OBJECTIVES: In clinical studies, it has been found that treating asthmatic patients with inhaled corticosteroids can reduce the need for in-patient care. The purpose of this study was to determine if such a relationship could be observed in available health-care statistics in Sweden and, if such a relationship could be established, what health economic consequences it implied. METHODS: A retrospective study was conducted using regional data on acute hospitalization-ie, number of bed-days in acute somatic in-patient care clinics-and sales of anti-asthmatic drugs from 14 health-care administrative regions, covering 6 million people (71% of the Swedish population) between 1978 and 1991. The data were analyzed in multiple regression analyses where time- and cross-section data were pooled. The variation in bed-days was explained by three variables: (1) the sales of inhaled corticosteroids, (2) the total number of bed-days within acute somatic in-patient care, and (3) the sales of inhaled bronchodilators, which were used as a proxy variable for asthma prevalence. RESULTS: The total number of bed-days due to asthma in the 14 county councils did not show any upward or downward trend between 1978 and 1985. However, after 1985, there was a significant downward trend despite an increase in estimated asthma prevalence. Increased sales of inhaled corticosteroids were significantly correlated (P < 0.01) with a reduction in bed-days due to asthma. The model used indicated that an increase in sales of inhaled corticosteroids by 1 defined daily dose (DDD) per day and 1,000 inhabitants gave, on average over the study period, a reduction of 1.5 bed-days for asthma in acute in-patient care per 1,000 inhabitants. CONCLUSIONS: Clinical trial findings that treating asthmatic patients with inhaled corticosteroids improves asthma control and reduces the need for hospitalization, seem to be realized in clinical practice. The increased costs of inhaled corticosteroids to the health-care system were more than offset by a reduction in the costs for acute somatic hospital care.

Administration, Inhalation↗
PubMed2005

Inhaled alternatives to nitric oxide.

OBJECTIVE: Inhaled nitric oxide has gained an established place in the management of pulmonary hypertension. However, cost, potential toxicity, and the lack of positive outcome data with inhaled nitric oxide therapy has generated interest in alternative inhaled, selective pulmonary vasodilators. This article describes those alternatives that have been studied to date. DESIGN: Literature review of inhaled, selective pulmonary vasodilators other than nitric oxide. METHODS: A review of the molecular mechanisms, potential side effects, and the studies to date in both animal models and clinical studies describing the physiologic effects of alternative agents to inhaled nitric oxide. CONCLUSION: There are a number of available agents that have comparable physiologic effects as inhaled nitric oxide. The best studied of these are the inhaled prostanoids (prostacyclin and iloprost), and there is growing interest in novel therapies such as phosphodiesterase inhibitors and neuropeptides.

Administration, Inhalation↗
PubMed2006

Healthcare costs and long-term outcomes after acute respiratory distress syndrome: A phase III trial of inhaled nitric oxide.

OBJECTIVE: To determine the costs and long-term outcomes of acute respiratory distress syndrome (ARDS) in previously healthy adults. To determine whether treatment with inhaled nitric oxide affects these costs and outcomes. DESIGN: One-year follow-up of a randomized trial of inhaled nitric oxide. Hospital bills were collected, and follow-up was performed at hospital discharge, 6 months, and 1 year. SETTING: Forty-six U.S. centers. PATIENTS: Three hundred and eighty-five previously healthy adults with ARDS. INTERVENTIONS: Subjects were randomized to 5 ppm inhaled nitric oxide or placebo gas. MEASUREMENTS AND MAIN RESULTS: One-year survival was 67.8%, with no difference by treatment arm (67.3% vs. 68.3% for inhaled nitric oxide vs. placebo, p = .71). Hospital costs from enrollment to discharge were high and similar in the inhaled nitric oxide and placebo arms ($48,500 vs. $47,800, p = 0.8). There were also no differences in length of stay or Therapeutic Intervention Scoring System points. Almost half (43.4%) of subjects were discharged to another healthcare facility or to home with professional help, and 24.1% were readmitted in 6 months, with no differences between groups. At 1 year, survivors reported low quality of life with no differences by treatment arm (Quality of Well-Being score [range 0-1], 0.61 vs. 0.64 for inhaled nitric oxide vs. placebo, p = .11) and poor function with no differences by treatment arm (32.5% returned to </=5 points of baseline Activities of Daily Living [range 0-100], 63.3% returned to </=10 points, and the remaining 36.7% suffered a mean decrement of 27 points). CONCLUSIONS: ARDS, even in previously healthy adults, not only is followed by poor survival, quality of life, and function but also is associated with high costs of care and postdischarge resource use. Inhaled nitric oxide at 5 ppm had no effect on these outcomes.

Administration, Inhalation↗
PubMed2004

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome.

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Administration, Inhalation↗
PubMed1994

Time course of effects of brief inhalations of nitrous oxide in normal volunteers.

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psychomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or "trial", subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of "anxious", "stimulated", "coasting (spaced out)", "lightheaded", "confused", and "high". Free recall of wards that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p = 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.

Administration, Inhalation↗
PubMed1989

L-648,051, a novel cysteinyl-leukotriene antagonist is active by the inhaled route in man.

1. We have studied some of the pharmacological properties of inhaled L-648,051 which has been shown to be a selective cysteinyl-leukotriene (LT) antagonist in vitro and in vivo in various animal models. 2. The effects of three different doses (1.6, 6.0 and 12.0 mg) on the bronchoconstriction induced by inhaled LTD4 have been investigated in normal male subjects in a series of double-blind, placebo controlled studies. Furthermore, the specificity of the drug has been investigated by challenging subjects with histamine after pre-inhalation of 12.0 mg L-648,051. 3. At all doses L-648,051 partially blocked the bronchoconstriction induced by LTD4 inhalation in a dose related manner. At a dose of 12.0 mg, L-648,051 decreased the maximum fall in specific airways conductance (sGaw) (placebo, 49% vs L-648,051, 21%, P less than 0.01) and shortened the time to recovery from LTD4-induced bronchoconstriction (placebo, 41 min vs L-648,051, 19 min, P less than 0.01). 4. There was no evidence of partial agonist activity, and no effect on histamine-induced bronchospasm. Inhaled L-648,051 at all doses was well tolerated. 5. We conclude that LT antagonism is possible by the inhaled route in man. Inhaled L-648,051 is an active and selective LT-antagonist in man which is well tolerated and may prove to be a useful drug for assessing the role of leukotrienes in asthma and other lung diseases.

Administration, Inhalation↗
PubMed1992

Inhaled beta 2-adrenoceptor agonists in asthma: help or hindrance?

Conventional low doses of inhaled beta 2-adrenoceptor agonists produce effective bronchodilation without systemic effects. Higher doses of inhaled beta 2-adrenoceptor agonists may produce substantial improvements in bronchodilator response, which may be helpful to patients with more severe airway obstruction. At higher than recommended doses, in asthmatic patients, fenoterol appears to cause greater dose-related systemic beta 2-responses compared with salbutamol or terbutaline, although there is no evidence to suggest that fenoterol is any less beta 2-selective in vivo. Furthermore, tolerance develops to systemic but not to bronchodilator effects during chronic treatment with inhaled beta 2-adrenoceptor agonists. The link between asthma mortality and systemic adverse effects of inhaled beta 2-adrenoceptor agonists at present remains unproven. A critical reappraisal of the regular use of inhaled beta 2-adrenoceptor agonists including long-acting drugs is now indicated in the light of their possible adverse effects on disease control. Patients requiring regular use of inhaled beta 2-adrenoceptor agonists should be given additional anti-inflammatory therapy with inhaled corticosteroids.

Administration, Inhalation↗
PubMed2006

Prescribed doses of inhaled steroids in Dutch children: too little or too much, for too short a time.

AIMS: To investigate the dosage and duration of inhaled steroids prescribed to children and to compare the prescribed doses with recommended doses for the treatment of asthma in children. METHODS: For 2514 Dutch children aged 0-12 years who had used inhaled steroids in 2002, pharmacy dispensing data were obtained from the InterAction database, type of steroid (beclomethason, budesonide, fluticasone) and type of user (first time or existing) and the average prescribed doses according to age were determined and compared with the doses as recommended in the national Dutch Nederlands Huisartsen Genootschap (NHG) guideline. Furthermore, for all first-time users the duration of therapy with inhaled steroids was determined using a Kaplan-Meier analysis. RESULTS: The major findings were that: (i) overall 43% of children starting inhaled steroids were prescribed doses that are half the recommended dose or less; (ii) overall 8% of the children starting inhaled steroids were prescribed doses that were twice the recommended dose or more, up to 50% in the 12-year-olds fluticasone group; and (iii) only 8% of the children who started with inhaled steroids used them continuously for a full year. CONCLUSIONS: Doses of inhaled steroids for many children deviate from those recommended, with lower doses more frequently occurring than higher doses. Less than 10% of the children receive prescriptions for a prolonged period of time.

Administration, Inhalation↗
PubMed1992

Effects of single and multiple inhalations of platelet-activating factor on airway cell composition and responsiveness in monkeys.

Platelet-activating factor (PAF) is a potent pro-inflammatory mediator that may play a role in the pathogenesis of airway hyper-responsiveness and asthma. In man, a single inhalation of PAF induces a small but prolonged increase in airway responsiveness in some individuals. The purpose of this study was to determine the effects of single and multiple inhalations of PAF on airway cell composition and responsiveness in monkeys. Anaesthetized and intubated adult male cynomolgus monkeys were studied. Airway cell composition was measured by bronchoalveolar lavage (BAL). Airway responsiveness was measured by determining the concentration (PC100) of inhaled methacholine that caused a 100% increase in respiratory system resistance (Rrs). Airway cell composition (BAL) and responsiveness (PC100) were determined 1 day before and 20 hr after a single inhalation of PAF (approximately 200 micrograms) or 3 days before (Day 0) and 3 days after (Day 10) 3-alternate-day (Days 3, 5 and 7) inhalations of PAF (each approximately 600 micrograms). The single inhalation of PAF (n = 8) caused an acute increase in Rrs (147 +/- 69%), an increase in BAL granulocytes, and a decrease in PC100 in four of eight animals that was moderate (greater than eight fold) in only one animal. The mean +/- s.e. change in log PC100 was -0.29 +/- 0.18. The multiple inhalations of PAF (n = 8) caused acute increases in Rrs (143 +/- 38%, 175 +/- 44% and 156 +/- 39%, respectively), an increase in BAL granulocytes, and a decrease in PC100 in four of eight animals that was moderate in two animals. The mean +/- s.e. change in log PC100 was -0.43 +/- 0.22.

Administration, Inhalation↗
PubMed2005

Early- and late-phase bronchoconstriction, airway hyper-reactivity and cell influx into the lungs, after 5'-adenosine monophosphate inhalation: comparison with ovalbumin.

BACKGROUND: Antigen inhalation in atopic asthmatic patients results in an early asthmatic response (EAR), accompanied by a late asthmatic response (LAR) in 60% of patients. Inhaled 5'-adenosine monophosphate (5'-AMP) causes immediate bronchoconstriction in asthmatics but not in normal subjects. OBJECTIVES: The aims of this study were to investigate whether 5'-AMP can produce a LAR, airway hyper-reactivity (AHR) and cell influx to the lungs, in a sensitized guinea-pig model of asthma, and to compare with the profile of activity after ovalbumin (OVA) inhalation. METHODS: Airway responses to inhaled OVA (10 microg/mL) and 5'-AMP (3 and 300 mm) of actively sensitized, conscious guinea-pigs were determined by whole body plethysmography as the change in specific airway conductance (sGaw). Inhaled histamine (1 mm) was used to investigate AHR, and cell influx was determined by bronchoalveolar lavage (BAL). RESULTS: Exposure to OVA revealed an EAR, and LAR at 6 h post-challenge. AHR to histamine occurred 24 h after challenge together with a significant increase in total and differential (eosinophils and macrophages) cell counts. Low dose 5'-AMP (3 mm) produced an EAR, LAR at 6 h after challenge, and AHR to histamine 12 h post-challenge. No AHR occurred 24 h after inhalation. Total and macrophage cell counts were increased significantly 6, 12 and 24 h after exposure. Bronchodilatation followed high dose 5'-AMP (300 mm), followed by a LAR at 6 h. AHR to histamine occurred 12 h after challenge, but not at 24 h. A significant increase in total and differential (eosinophils and macrophages) cell counts occurred 6, 12 and 24 h post-exposure. No changes were observed in non-sensitized guinea-pigs. CONCLUSION: OVA challenge revealed an EAR, LAR, cell influx and AHR in a guinea-pig model of asthma. This study demonstrated for the first time that a LAR and AHR to histamine can be revealed following 5'-AMP inhalation, in sensitized but not unsensitized guinea-pigs. Cell influx at 6, 12 and 24 h post-challenge suggests that it may be associated with the LAR and AHR.

Adenosine Monophosphate↗
PubMed2006

Alveolar-capillary membrane permeability for early prediction of response of inhaled steroid on patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Glucocorticosteroid reversibility-testing is undertaken over a period of 3 months to identify whether patients with chronic obstructive pulmonary disease (COPD) would benefit from long-term inhaled corticosteroids. This study assessed whether alveolar-capillary membrane (a/c) permeability testing can be used as an early alternative test method for the same purpose. METHODS: Fourteen patients with severe and symptomatic moderate COPD (group S) were prescribed inhaled steroid 800 microg/day for 3 months. Before inhalation and 4 weeks after inhalation therapy, forced expiratory volume in 1 s (FEV(1)) and a/c permeability using (99m)Tc-DTPA were performed. FEV(1) was recorded again at the end of the third month. Another 10 patients with COPD of comparable severity (group B) prescribed with inhaled bronchodilators were examined and studied as controls. RESULTS: In group S, the permeability decreased in eight patients (group D) and increased in six patients (group I). No significant change was noted in FEV(1) at the end of the first month. However, seven patients in group D showed significant improvement in FEV(1) at the end of the third month, whereas in patients in group I no significant changes were observed. In group B, no significant change in a/c permeability was observed, although the FEV(1) increased by 12-17%. CONCLUSION: With steroid inhalation, the a/c permeability at 4 weeks predicts future changes in lung functions. Long-term inhaled corticosteroids are likely to be useful if permeability decreases. This test, which needs further validation, appears to provide much earlier prediction of response than glucocorticoid reversibility testing.

Administration, Inhalation↗