Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed2001

Increase in inhalable particulates' concentration by commercial and industrial activities in the ambient air of a select Indian metropolis.

Inhalable particulates (particulates less than 10 micron) present in ambient air find passage into the respiratory system due to their small size and impair the health. Surveillance of inhalable particulates is, therefore, essential for assessing an inhalation health hazard. The activity also provides guidance for appropriate protection against the ill effects. Monitoring of inhalable particulates requires a high-volume sampler retrofitted with a size selective inlet (SSI) to separate and sample specified size-range fractions of suspended particulate matter in air. Measurement of inhalable particulates indirectly represents anthropogenic activity. In view of this, surveillance of inhalable particulates was conducted in select metropolitan cities of India during 1995-1997 to find out changes in their concentration. The inhalable particulates were measured by retrofitting a suitably designed SSI to the standard high-volume sampler. The study revealed that the concentration of inhalable particulates in the ambient air increased due to industrial activities up to 320, 168, and 546% and due to commercial activities up to 406, 198, and 140% in Ahmedabad, Mumbai, and Delhi, respectively. An increase in inhalable particulates' concentration during the above period also showed a marked seasonal variation. The increase due to commercial activity, however, did not show a definite tendency.

Air Pollution↗
PubMed1998

Bone mineral density and body composition in patients with airflow obstruction--the role of inhaled steroid therapy, disease and lifestyle.

BACKGROUND: Inhaled steroid therapy has been shown to be associated with low bone mineral density (BMD) in asthmatic patients, but its effect in men has not been specifically studied; and the relative importance of therapy, disease and lifestyle leading to low BMD has not been investigated. OBJECTIVES: The study was designed to compare BMD in women and men who had airflow obstruction (asthma or COAD with or without inhaled steroid therapy) with normal controls. The role of inhaled steroid treatment, disease severity and lifestyle was studied among patients. METHODS: One hundred and fourty-four patients (106 on inhaled steroids and 38 not on inhaled steroids) and 212 age-matched controls were studied. Body composition and BMD (at the total body, hip and spine) were measured by dual-X-ray densitometry (DEXA). Forced expiratory volume (FEV1) was measured in patients. A validated questionnaire was administered to measure lifestyle factors. RESULTS: The body mass indices (BMI) (P < 0.001) and percentage of body fat (P < 0.001) were higher among female patients on inhaled steroids than controls. However, the BMD of the total body (P < 0.05) and spine (P < 0.001) were significantly lower in premenopausal and postmenopausal women than controls, respectively (P < 0.005). The BMD at the spine (P<0.01) and hip (P < 0.01) in male patients were significantly lower than the controls. By multiple regression, age and use of inhaled steroid was negatively associated with BMD at the hip (P < 0.01), but not at the spine (P>0.05). Cigarette smoking was associated with significantly lower BMD at the femoral neck (P < 0.05), and a low dietary calcium intake was associated with lower BMD at the spine (P<0.05). In women, use of inhaled steroid was not associated with significantly lower BMD. CONCLUSION: Men who had asthma and/or COAD had lower BMD, and this was not attributable entirely to steroid use. Cigarette smoking and a low dietary calcium intake may partially account for this difference. The difference in BMD between female patients and controls, even in those taking inhaled steroid, was small.

Absorptiometry, Photon↗
PubMed1997

Inhaled beclomethasone dipropionate suppresses the hypothalamo-pituitary-adrenal axis in a dose dependent manner.

OBJECTIVE: Little is known about the dose-response relationship of potential, unwanted, effects of inhaled beclomethasone (BDP) on the hypothalamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clinic settings. The purpose of our study was to investigate the dose-response relationship of inhaled BDP on the HPA axis in a general practice patient population. We also explored the optimal testing strategy in this population and correlated effects of inhaled BDP on the HPA axis with other systemic corticosteroid side effects. PATIENTS AND DESIGN: Controlled observational study employing 21 patients on inhaled BDP recruited from general practice, with minimal past and no present exposure to other corticosteroids, and 21 age and gender-matched controls. MEASUREMENTS: Twenty-four-hour urinary free cortisol excretion (UFC), serum cortisol before and 30 minutes after injection of 1 microgram and 250 micrograms of tetracosactrin, serum IGF-I and serum osteocalcin were measured. BDP use was estimated by inhaler weighing and prescription count. RESULTS: In subjects on inhaled BDP, 24-hour UFC (P < 0.008), serum cortisol 30 minutes after 250 micrograms tetracosactrin (P < 0.05) and the serum cortisol rise after 250 micrograms tetracosactrin (P < 0.04) were significantly lower when compared with controls. Measurements of HPA function correlated inversely with BDP dose estimated by inhaler weighing (all P < 0.03). Serum IGF-I and osteocalcin levels did not differ. CONCLUSIONS: We have demonstrated hypothalamo-pituitary-adrenal axis suppression in nonspecialist-clinic asthma patients on moderate to large doses of inhaled beclomethasone dipropionate. When accurate measurements of inhaled steroid dose are used, there is an exponential relationship between dose and hypothalamo-pituitary-adrenal axis suppression. There appears to be no 'safe' threshold, and around 15% of patients may have clinically significant suppression. However, the significance of hypothalamo-pituitary-adrenal axis suppression as a marker for concomitant corticosteroid effects on other organ systems remains uncertain.

Administration, Inhalation↗
PubMed2000

Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial).

Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control. Long acting beta2-agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids, a randomized, double-blind, multi-centre, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare utilization, and safety, in approximately 1200 adult asthmatic patients. The requirements for study enrollment include a history of asthma, FEV1 or PEFR values between 50% and 90% of the predicted value together with > or = 12% improvement in FEV1 after beta-agonist administration, a minimum pre-determined level of asthma symptoms and daily beta-agonist medication. The study will include a 4-week run-in period, during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone (200 microg daily), followed by a 48-week double-blind, treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol placebo, or inhaled salmeterol (100 microg daily) and montelukast placebo. All patients will continue with inhaled fluticasone (200 microg daily). During the study, asthma attacks, overnight asthma symptoms, and morning peak expiratory flow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-specific quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids.

Acetates↗
PubMed2001

Can asthma treatment in sports be doping? The effect of the rapid onset, long-acting inhaled beta2-agonist formoterol upon endurance performance in healthy well-trained athletes.

Inhaled beta2-agonists have been subject to restrictions in relationship to sports due to fear of possible improvement in endurance performance. According to the international doping regulations only inhaled salbutamol, terbutaline and salmeterol are allowed for use in sports. Formoterol is a recently introduced rapid onset-long-acting inhaled beta2-agonist. The main aim of the present randomized, double-blind placebo-controlled study was to investigate possible improvement in endurance performance of inhaled formoterol in 24 healthy well-trained competitive male athletes, 21-29 years old. Lung function (flow-volume loops) was measured before, 15 min after each inhaled study drug and before and repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak ventilation (VEpeak) and running time till exhaustion were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running time until exhaustion were determined. Inhaled formoterol did not improve any parameter of endurance performance. On the other hand a statistically significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change was found in estimated difference of VO2max between formoterol and placebo in favour of placebo. Lung function increased significantly after inhaled formoterol, and after exercise also for placebo, but without differences between the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol did not improve endurance performance compared to placebo.

Administration, Inhalation↗
PubMed2003

One-year safety and efficacy of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler) for the treatment of asthma.

BACKGROUND: A budesonide/formoterol single inhaler has been developed for convenient treatment of patients whose asthma is inadequately controlled by inhaled glucocorticosteroids alone. OBJECTIVES: To compare long-term safety and efficacy of budesonide/formoterol single inhaler with budesonide plus formoterol via separate inhalers in adults with asthma. METHODS: In this open, randomized, parallel-group 6-month extension conducted in a subset of centres from a previous 6-month study, patients (n=321) received two inhalations bid of budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg delivered dose or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler) via separate inhalers. RESULTS: Significantly fewer patients receiving budesonide/formoterol single inhaler withdrew compared with budesonide plus formoterol (9 vs. 19%, P=0.008). Incidence and severity of AEs were low and similar in both groups. No clinically important differences between groups, or changes, were identified in laboratory measurements, vital signs or ECG. Treatments produced similar improvements in lung function, ACQ scores and Mini AQLQ domains that were maintained throughout 12 months. CONCLUSIONS: Budesonide/formoterol in a single inhaler is as safe and effective in the long-term treatment of asthma as budesonide plus formoterol via separate inhalers. The lower number of withdrawals with budesonide/formoterol may reflect better adherence to treatment compared with budesonide plus formoterol.

Administration, Inhalation↗
PubMed1992

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Administration, Inhalation↗
PubMed2003

Noninvasive delivery of inhaled nitric oxide therapy for late pulmonary hypertension in newborn infants with congenital diaphragmatic hernia.

OBJECTIVE: To determine the incidence of late pulmonary hypertension (late PH) in congenital diaphragmatic hernia (CDH) and whether prolonged treatment with noninvasive inhaled NO therapy delivered through a nasal cannula (NC) would sustain pulmonary vasodilation during a period of transition from mechanical ventilation to spontaneous breathing. STUDY DESIGN: We collected data on all patients with a diagnosis of CDH admitted to the Children's Hospital, Denver, from January 1996 through December 2001. Patients who had suprasystemic pulmonary hypertension when inhaled NO was discontinued before extubation were treated with inhaled NO delivered with the nasal cannula. RESULTS: Newborn infants (n = 47) with CDH were treated during this time period. Short-term (<3 months) and long-term (>1 year) survival was 85% and 75%, respectively; 30 newborn infants were treated with inhaled NO (64%). Inhaled NO was successfully discontinued in 16 patients before extubation, and 10 (21%) were treated with inhaled NO through NC after extubation because of pulmonary hypertension and marked hypoxemia when trials off inhaled NO were performed. Nasopharyngeal NO concentrations were 5.4 +/- 0.5 ppm and 2.4 +/- 0.4 ppm with inhaled NO measured proximally in the delivery device at 10 and 5 ppm, respectively. CONCLUSIONS: Late PH occurs in a significant subset of newborn infants with CDH. Noninvasive inhaled NO treatment may reduce the duration of mechanical ventilation while safely treating late PH.

Administration, Inhalation↗
PubMed2000

Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury. METHODS: The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH). RESULTS: After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control). CONCLUSIONS: This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.

Administration, Inhalation↗
PubMed2002

Radical scavengers protect murine lungs from endotoxin-induced hyporesponsiveness to inhaled nitric oxide.

BACKGROUND: Sepsis is associated with an impaired pulmonary vasodilator response to inhaled nitric oxide (NO). A combination of NO and other inflammatory mediators appears to be responsible for endotoxin-induced pulmonary vascular hyporesponsiveness to inhaled NO. The authors investigated whether scavengers of reactive oxygen species could preserve inhaled NO responsiveness in endotoxin-challenged mice. METHODS: The vasorelaxation to inhaled NO was studied in isolated, perfused, and ventilated lungs obtained from mice 16 h after an intraperitoneal challenge with saline or 50 mg/kg Escherichia coli lipopolysaccharide. In some mice, challenge with saline or lipopolysaccharide was followed by intraperitoneal administration of N-acetylcysteine, dimethylthiourea, EUK-8, or polyethylene glycol-conjugated catalase. RESULTS: The pulmonary vasodilator response of U46619-preconstricted isolated lungs to ventilation with 0.4, 4, and 40 ppm inhaled NO in lipopolysaccharide-challenged mice was reduced to 32, 43, and 60%, respectively, of that observed in saline-challenged mice (P < 0.0001). Responsiveness to inhaled NO was partially preserved in lipopolysaccharide-challenged mice treated with a single dose of N-acetylcysteine (150 or 500 mg/kg) or 20 U/g polyethylene glycol-conjugated catalase (all P < 0.05 vs. lipopolysaccharide alone). Responsiveness to inhaled NO was fully preserved by treatment with either dimethylthiourea, EUK-8, two doses of N-acetylcysteine (150 mg/kg administered 3.5 h apart), or 100 U/g polyethylene glycol-conjugated catalase (all P < 0.01 vs. lipopolysaccharide alone). CONCLUSIONS: When administered to mice concurrently with lipopolysaccharide challenge, reactive oxygen species scavengers prevent impairment of pulmonary vasodilation to inhaled NO. Therapy with scavengers of reactive oxygen species may provide a means to preserve pulmonary vasodilation to inhaled NO in sepsis-associated acute lung injury.

Acetylcysteine↗
PubMed2003

Analgesic efficacy of inhaled morphine in patients after bunionectomy surgery.

BACKGROUND: The AERx Pain Management System (Aradigm Corporation, Hayward, CA) is a novel pulmonary delivery system for the systemic administration of morphine. The authors compared the relative analgesic efficacy and safety of the AERx Pain Management System with those of placebo and intravenous morphine in an orthopedic postsurgical pain model. METHODS: Eighty-nine male and female PS-1 to PS-3 patients underwent standardized bunionectomy surgery and received multiple doses of inhaled or intravenous placebo, inhaled morphine (one inhalation [2.2 mg] or three inhalations [6.6 mg]), or intravenous morphine (4 mg) in a blinded fashion. Open-label rescue morphine (2 mg) was also available as needed. Pain intensity, pain relief, and time to pain relief were measured after the first dose. Global evaluation, morphine consumption, vital signs, and adverse events were monitored for 8 h after treatment. Blinded study personnel performed all treatment administrations and pain assessments. RESULTS: Three inhalations of morphine and 4 mg intravenous morphine provided comparable single- and multiple-dose analgesia. One inhalation of morphine was statistically indistinguishable from placebo. Three inhalations of morphine and 4 mg intravenous morphine both consistently demonstrated significantly greater analgesic efficacy than did placebo and one inhalation of morphine. CONCLUSIONS: Comparable analgesic efficacy was demonstrated between a carefully matched dose of inhaled and intravenous morphine in a postsurgical pain model.

Administration, Inhalation↗
PubMed2007

Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure.

BACKGROUND: Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF. METHODS: In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2-1 microg.kg body weight.min) or by inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured. RESULTS: In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation. CONCLUSION: If these results can be confirmed in humans, inhalation of nebulized milrinone may present a novel, effective, safe, and pulmonary selective strategy for the treatment of pulmonary venous hypertension in CHF.

Administration, Inhalation↗
PubMed1990

The role of inhalation injury in burn trauma. A Canadian experience.

From 1977 to 1987, 1705 thermally injured patients were admitted to the Firefighters' Burn Center at the University of Alberta Hospitals. Thirteen hundred forty-four were male (78.8%) and 361 were female (21.2%), with a mean total burn surface area (TBSA) of 15.1 (SEM +/- 0.4%) and a range of 1% to 99% TBSA. Sixteen hundred thirty-five patients survived to be discharged from hospital, with an overall survival rate of 95.9%. One hundred twenty-four burn patients (7.3%) suffered concomitant inhalation injury diagnosed by bronchoscopy. Patients with inhalation injury suffered from larger TBSA (39.7% +/- 2.8% versus 12.2% +/- 0.3%; p less than 0.01) than those without inhalation injury. Inhalation injury increased the number of deaths from burn injury (34.7% versus 1.7%; p less than 0.01) independent of age and TBSA. Inhalation injury was associated with a threefold prolongation of hospital stay (23.7 +/- 0.7 versus 74.4 +/- 6.2 days; p less than 0.01) and was independent of age and TBSA. Multifactorial probit analysis was performed for both inhalation- and noninhalation-injured burned patients to allow TBSA and age adjusted rates of mortality for the burn population presented. The maximum detrimental effects of inhalation injury in burn patient outcome occurred when it coexisted with moderate (15% to 29% TBSA) to large (30% to 69% TBSA) thermal injuries. These data demonstrate that inhalation injury is an important comorbid factor in burn injury that increases the number of deaths substantially. Most importantly such injuries also independently prolong the duration of hospitalization in a highly unpredictable fashion as compared to patients with cutaneous burns only. As such our data illustrate the extreme importance of inhalation injury as a comorbid factor following thermal injury and reveal the present limitations for accurate quantification of the magnitude of respiratory tract injury accompanying thermal trauma.

Adolescent↗
PubMed1997

Inhaled nitric oxide reduces the utilization of extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn.

OBJECTIVE: To determine if the use of inhaled nitric oxide therapy reduces the need for extracorporeal membrane oxygenation (ECMO) in persistent pulmonary hypertension of the newborn. DESIGN: A matched cohort study with retrospective data extraction. SETTING: Pediatric and neonatal intensive care units at a medical school-affiliated children's hospital serving as a regional referral center for respiratory failure. PATIENTS: Records of all neonates transferred for rescue therapy for persistent pulmonary hypertension during the study period were analyzed, with inclusion in the study based on defined gas exchange parameters, and with exclusion from the study based on the presence of congenital heart disease, diaphragmatic hernia, or lethal chromosomal abnormality. Assignment to cohorts was based on availability of inhaled nitric oxide therapy: group 1 patients were admitted when inhaled nitric oxide was unavailable; group 2 patients were admitted when inhaled nitric oxide was available. INTERVENTIONS: Standard criteria (alveolar-arterial oxygen tension gradient of > 600 torr [> 80 kPa], or oxygenation index of > 40) were used to trigger initial evaluation for ECMO when these criteria were met for 2 hrs, and ECMO was initiated if these criteria continued to be met for 12 hrs, or if cardiovascular instability occurred. Ventilator management in all patients was directed to improve arterial oxygenation, such that ECMO criteria were no longer met. Patients in group 2 only were treated with inhaled nitric oxide after meeting ECMO evaluation criteria, and they continued to receive inhaled nitric oxide if a quantifiable improvement in gas exchange occurred. MEASUREMENTS AND MAIN RESULTS: Fifty patients qualified for inclusion in the analysis (29 patients in group 1, and 21 patients in group 2). In group 1, 21 (72%) patients met ECMO criteria, and 16 (76%) patients required ECMO therapy. In group 2, 16 (76%) patients met ECMO criteria, 15 patients received inhaled nitric oxide therapy, and only four (25%) patients required ECMO therapy (p = .003 compared with group 1). Treatment with inhaled nitric oxide resulted in an initial increase in PaO2, without adverse effects, in all of the treated patients. The reduction in ECMO utilization in group 2 was achieved with a higher rate of complication-free survival (survival without oxygen, requirement at 28 days, p = .018; survival without intracranial hemorrhage, p = .048), and a lower hospital cost per survivor (p = .021), compared with group 1 patients. CONCLUSION: In neonates with persistent pulmonary hypertension, therapy with inhaled nitric oxide reliably and safely improves oxygenation, thereby resulting in a decreased need for ECMO therapy, improved patient outcome, and lower hospital costs.

Administration, Inhalation↗
PubMed2000

The hemodynamic effects of inhaled nitric oxide and endogenous nitric oxide synthesis blockade in newborn piglets during infusion of heat-killed group B streptococci.

OBJECTIVE: To determine the effects of therapy with inhaled nitric oxide (NO) gas and partial or complete blockade of endogenous NO synthesis with N(omega)nitro-L-arginine (L-NA) on the hemodynamic responses to group B streptococci infusion in newborn piglets. DESIGN: Randomized, acute intervention study. SETTING: Animal research laboratory. SUBJECTS: Twenty-five anesthetized piglets younger than 3 days of age divided into five groups. INTERVENTIONS: Heat-killed group B streptococci (GBS) were infused systemically until a 50% increase in pulmonary artery pressure (PAP) was obtained, and the infusion was continued for another 2 hrs. The five groups were designed as follows: group 1, sepsis control: continuous GBS infusion, with two brief trials (10 mins) of inhaled NO given after the initial development of pulmonary hypertension and again 2 hrs later; group 2, continuous inhaled NO: NO was given at 40 ppm for 2 hrs during GBS infusion; group 3, high-dose L-NA pretreatment: 10 mg/kg L-NA bolus followed by 1 mg/kg/min before, and continuing throughout, GBS infusion; group 4, high-dose L-NA: same dose as in group 3, but given after the start of the GBS infusion with continuous inhaled NO at 40 ppm; and group 5, low-dose L-NA: 3 mg/kg bolus given after start of GBS infusion with continuous inhaled NO at 40 ppm. MEASUREMENTS AND MAIN RESULTS: The sepsis controls, group 1, had an increase in PAP, which took 15-45 mins to develop, from a mean of 3.4 (SD 0.7) to 5.9 (1.9) kPa (p < .05), at which time the cardiac index had decreased from 169 (28) to 146 (46) mL/kg/min (p < .05). Brief inhaled NO during the early phase decreased PAP to normal. Two hours later, PAP had increased to 6.1 (0.2) kPa and cardiac index had decreased to 88 (31) mL/kg/min. Inhaled NO after 2 hrs decreased PAP to 3.2 (0.5) kPa and increased cardiac index to 106 (44) ml/kg/min (p < .05). Continuous inhaled NO (group 2) ameliorated the deterioration in cardiac index, which at 2 hrs was 140 (30) mL/kg/min (significantly greater than in the sepsis controls) (p < .05). The L-NA-pretreated animals (group 3) had a greater increase in PAP and pulmonary vascular resistance index when GBS infusion was started. PAP increased from 3.0 (0.7) to 7.3 (1.5) kPa within 15 mins, and cardiac index simultaneously decreased to 68 (20) mL/kg/min. Cardiac index subsequently rapidly deteriorated to 48 (21) mL/kg/min, and only one of five animals survived for 2 hrs. Group 4 animals also developed a rapid deterioration in cardiac output, and only two of five survived for 2 hrs. Group 5 animals had results indistinguishable from group 2 animals. CONCLUSION: Pulmonary hypertension and shock resulting from GBS infusion in newborn piglets are much worse if endogenous NO production is completely inhibited. Continuous inhaled NO with or without low-dose L-NA inhibits the decrease in cardiac output.

Administration, Inhalation↗
PubMed2000

Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic pulmonary hypertension.

OBJECTIVE: To determine whether the combination of the phosphodiesterase 5 inhibitor zaprinast and inhaled nitric oxide (NO) decreases hypoxic pulmonary hypertension in the rat. DESIGN: Prospective, experimental study. SETTING: Animal laboratory of a university medical center. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Anesthetized rats were mechanically ventilated and instrumented for measurement of mean systemic arterial pressure, pulmonary arterial pressure, and cardiac output. In group 1, four acute hypoxic challenges (FIO2 = 0.17 for 5 mins) were performed: initial, during 40 ppm inhaled NO, immediately after discontinuation of 5 mins of inhaled NO, and final. In group 2 rats, an initial hypoxic challenge was performed and rats then received zaprinast (3 mg/kg bolus followed by 0.3 mg/kg/min infusion). Four hypoxic challenges analogous to group 1 were then performed during zaprinast administration. MEASUREMENTS AND MAIN RESULTS: Initial hypoxic challenge produced similar increases in pulmonary arterial pressure in both groups. In group 1, inhaled NO either only before or only during hypoxia decreased the pulmonary hypertensive response to hypoxia. In group 2, zaprinast administration did not alter hemodynamics. Zaprinast alone decreased the pulmonary hypertensive response to hypoxia. The combination of zaprinast and inhaled NO (either before or during hypoxia) abolished the pulmonary hypertensive response to hypoxia. CONCLUSIONS: Treatment with inhaled NO for 5 mins before but not during hypoxia is as effective as inhaled NO during hypoxia. Inhaled NO and zaprinast both decrease the pulmonary hypertensive response to hypoxia, and the combination abolishes the response. The combination of a phosphodiesterase 5 inhibitor and inhaled NO may have clinical applicability in the treatment of pulmonary hypertension.

Administration, Inhalation↗
PubMed2002

Effects of inhaled nitric oxide in a mouse model of sepsis-induced acute lung injury.

OBJECTIVE: Although inhaled nitric oxide transiently improves oxygenation in patients with acute lung injury, it has not affected clinical outcomes. As well, the effects of inhaled nitric oxide on the pathophysiologic features of acute lung injury have not been well defined. Therefore, we assessed the effects of inhaled nitric oxide on the degree of pulmonary inflammation and injury in a mouse model of sepsis-induced acute lung injury. DESIGN: Randomized, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Male C57Bl/6 mice. INTERVENTIONS: Sepsis was induced by cecal ligation and perforation. At the time of surgery, septic and naïve mice were randomized to exposure to either 40 ppm inhaled nitric oxide or room air for 24 hrs before they were killed. MEASUREMENTS AND MAIN RESULTS: Sepsis-induced acute lung injury was characterized by increased pulmonary myeloperoxidase (68 +/- 13 vs. 13 +/- 3 mU/mg protein in naïve mice, p <.01), pulmonary 8-isoprostane content (627 +/- 51 vs. 88 +/- 20 pg/mg protein in naïve mice, p <.01), and protein in bronchoalveolar lavage fluid (p <.05). Inhaled nitric oxide exposure in septic mice completely abrogated the septic increases in myeloperoxidase activity (p <.05) and pulmonary 8-isoprostane content (p <.05) but had no effect on bronchoalveolar lavage protein. The induction of sepsis also was associated with an increase in pulmonary inducible NO synthase activity (2.8 +/- 0.5 vs. 0.4 +/- 0.1 pmol small middle dotmin-1 small middle dotmg-1 protein in naïve mice, p <.05), and inhaled nitric oxide attenuated this increase in pulmonary inducible NO synthase activity (p <.05). CONCLUSIONS: Exposure to inhaled nitric oxide early in the course of sepsis-induced acute lung injury is associated with reduced pulmonary leukocyte infiltration and less oxidative injury. Decreased lung inflammation and injury with inhaled nitric oxide is associated with decreased pulmonary inducible NO synthase activity. Therefore, inhaled NO may have greater clinical benefit if administered earlier in the natural history of acute lung injury in patients.

Administration, Inhalation↗
PubMed2002

Reconstruction of the inhalation dose in the 30-km zone after the Chernobyl accident.

Due to lack of measurements of activity concentrations in air, the assessment of the inhalation dose of the population evacuated from the 30-km zone after the Chernobyl accident is not possible from continuous filter measurements. Since the evaluation of the inhalation dose in each settlement of the zone is of great interest for epidemiological purposes, an approach was chosen that utilizes the available data on ground deposition of 137Cs, a recently performed best estimate of the radionuclide vector and its spatial distribution as well as the radionuclide dependent deposition velocity. The derived inhalation dose values in the 30-km zone range between 3 mSv to 150 mSv effective dose for adults depending on the distance to the reactor site and the day of evacuation. For 1-y-old infants the values range between 10 to 700 mSv. In Chernobyl town, an effective inhalation dose of 25 mSv until evacuation day was assessed. Thyroid doses due to inhalation ranged from 0.02 to 1 Sv for adults, for 1-y-old infants from 0.02 to 6 Sv. The inhalation dose in each settlement of the 30-km zone is approximately 8-13 times higher than the external exposure in each settlement if evacuation of the settlement occurred at an early stage. For settlements with evacuation at a later stage (day 10 or later) the inhalation dose was about 50-70% higher than the external dose. The dominant contribution to the effective inhalation dose comes from 131I (about 40%) and tellurium and rubidium isotopes (about 20-30%). Despite high zirconium and cerium ground depositions, zirconium and cerium isotopes contribute rather little to the inhalation dose which is mainly due to the great particle sizes to which they are attached. The relative contribution of short-lived radionuclides is, despite higher activities than at greater distances, less than 5%.

Air Pollutants, Radioactive↗