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PubMed2001

Effects after inhalation of (1-->3)-beta-D-glucan in healthy humans.

BACKGROUND AND AIM: This study was performed to assess the effects of an exposure to a pure (1-->3)-beta-D-glucan, a cell wall component of fungi, plants and certain bacteria. METHODS: Twenty-one healthy subjects inhaled saline or (1-->3)-beta-D-glucan suspended in saline in a random, double-blind, cross-over design. They were examined before exposure and 24 and 72h afterwards with spirometry, blood sampling and collection of induced sputum. Differential cell counts and eosinophilic cationic protein (ECP) were determined in blood and sputum, and myeloperoxidase (MPO), tumour necrosis factor-alpha (TNF-alpha), and interleukin (IL)-8 and IL-10 were determined in sputum supernatants. TNF-alpha was determined after cultivation of blood mononuclear cells. RESULTS: In sputum, inhalation of saline caused a significant increase in ECP and TNF-alpha. (1-->3)-beta-D-Glucan inhalation caused a further increase in these cytokines, although not statistically significantly different from the increase induced by inhalation of saline alone. In blood, the number of eosinophils was significantly decreased 72 h after the challenge with (1-->3)-beta-D-glucan. This effect was not found after the inhalation of saline alone. TNF-alpha production from stimulated blood mononuclear cells was significantly decreased 72 h after the (1-->3)-beta-D-glucan inhalation as compared with the increase induced by saline inhalation. CONCLUSIONS: The results suggest that (1-->3)-beta-D-glucan causes a different type of response as compared with inflammatory agents such as bacterial endotoxin that cause a neutrophil-dominated inflammatory response.

Adjuvants, Immunologic↗
PubMed2002

Towards an inhalative 13C breath test method.

Customary 13CO2 breath tests--and also 15N urine tests--always start with an oral administration of a test substrate. The test person swallows a stable isotope labelled diagnostic agent. This technique has been used to study several pathophysiological changes in gastrointestinal organs. However, to study pathophysiological changes of the bronchial and lung epithelium, the inhalative administration of a stable isotope labelled agent appeared more suitable to us. [1-13C]Hexadecanol and [1-13C]glucose were chosen. Inhaled [1-13C]hexadecanol did not yield 13CO2 in the exhaled air, but [1-13C]glucose did. To study the practicability of the [1-13C]glucose method and the reproducibility of the results, 18 inhalation tests were performed with healthy subjects. In 6 self-tests, the optimum inhalative dose of [13C]glucose was determined to be 205 mg. Using the APS aerosol provocation system with the nebulizer 'Medic Aid' (Erich Jaeger Würzburg), a 25% aqueous solution was inhaled. Then, breath samples were collected at 15 min. intervals and analysed for 13CO2. 75-120 min after the end of inhalation a well-reproducible maximum delta13C value of 6%o over baseline (DOB) was detected for 12 healthy probands. Speculating that the pulmonary resorption of the [13C]glucose is the rate-limiting step of elimination, decompensations in the epithelium ought to be reflected in changed [1-13C]glucose resorption rates and changed 13CO2 output. Therefore, we speculate that the inhalation of suitable 13C-labelled substrates will pave the way for a new group of 13CO2 breath tests aiding investigations of specific pathophysiological changes in the pulmonary tract, such as inflammations of certain sections and decompensations of cell functions.

Administration, Inhalation↗
PubMed2001

The performance of personal inhalable dust samplers in wood-products industry facilities.

Recent guidelines for particulate matter and aerosol measurements in the workplace describe sampling criteria for three progressively finer particle-size-selective fractions: inhalable, thoracic, and respirable. For substances like wood dust, for which health concerns usually center on particles that enter and deposit within the nasal passages, the inhalable fraction, which by definition includes particles ranging from 0 to 100 microm in diameter, is of greatest interest. There are a variety of commercially available personal samplers that can be used to measure inhalable dust in the workplace. At this time, however, most of these samplers have received only limited field testing in wood-products facility workplaces. This study compared the performance of three different personal inhalable dust samplers and a personal total dust sampler in several different wood-products industry facilities. Specifically, the study provided information on sampler precision and the relationship between results obtained with the various personal samplers. The personal samplers that were evaluated were the Institute of Occupational Medicine (IOM), the conical inhalable (CIS), and the multi-orifice (7-Hole) inhalable dust samplers and the closed-face filter cassette (CFFC) total dust sampler. Study results suggest that the CIS and CFFC may be more precise than the IOM and 7-hole samplers. Results also indicate that the relative performance of the inhalable samplers as compared to the total dust sampler may vary as a function of particle size distribution in the workplace.

Dust↗
PubMed2006

The effect of repeated inhalation on the distribution of uranium in rats.

For the assessment of doses after inhalation of airborne uranium compounds by workers, the International Commission on Radiological Protection (ICRP) developed compartmental models that are used to calculate reference dose coefficients and retention and excretion functions. It is assumed that each acute intake has no effect on the biokinetics of later intakes. Consequently, retention and excretion after multiple or chronic exposure are predicted using the same models as after acute exposure. This assumption was tested here on rats exposed to repeated inhalation of uranium dioxide (UO2). First, excretion and organ retention were determined after a single inhalation of UO2. The follow-up of incorporated activity was used to design a biokinetic model for uranium inhaled by rats. Second, the biokinetics of uranium were monitored in two experiments of repeated inhalations of uranium dioxide under different intake patterns. For these two experiments, the organs' retention and excretion after repeated UO2 inhalation were predicted using the biokinetic model and compared to the experimental measurement. Under the two sets of experimental conditions considered, the prediction of the biokinetic model based on acute exposure data was consistent with the biokinetics observed after repeated UO2 inhalations, with the possible exception of retention in the skeleton.

Animals↗
PubMed1999

A placebo-controlled experimental study of steroid inhalation therapy in ammonia-induced lung injury.

BACKGROUND: The use of corticosteroids in toxic lung injury caused by exposure to an irritating gas such as ammonia has not been adequately studied. OBJECTIVE: To evaluate the effects of budesonide inhalation in a rabbit model of toxic lung injury induced by ammonia. DESIGN: Randomized, blind placebo-controlled laboratory investigation employing 16 New Zealand White rabbits. Lung injury was induced by inhalation of a defined amount of aerosolized ammonia. Thirty minutes later, the rabbits were randomized to receive either inhalation therapy with 0.5 mg budesonide or placebo. After another 2 hours, a second treatment inhalation, identical to the first one, was administered. RESULTS: Airway pressures, hemodynamics, and gas exchange were measured at baseline, 5, and 15 minutes after ammonia administration and every 30 minutes during a 6-hour period after the first blind inhalation of corticosteroids or placebo. The ammonia inhalation resulted in an acute severe lung injury, detected after 15 minutes as a decrease in Pao2 from 23.3 (+/- 3.6) to 11.0 (+/- 3.6) kPa (p < 0.005) and an increase in peak airway pressure from 13 (+/- 2) to 17 (+/- 2) cm H2O (p < 0.005). During the 6-hour observation period, the blood gas parameters improved gradually in all rabbits. In comparison with placebo, budesonide did not result in improved gas exchange or reduced airway pressure levels during the observation period. CONCLUSION: In this animal model corticosteroid inhalation therapy had no effect on ammonia-induced lung injury.

Administration, Inhalation↗
PubMed2002

A survey of attitudes among drug user treatment providers toward the treatment of inhalant users.

This study assessed the attitudes of drug user treatment program directors towards the problem of inhalant "abuse." In 2000, surveys were mailed to directors asking about treatment success and prognosis for inhalant users, level of neurological damage incurred by users, availability of treatment resources, their program's policies toward admission of users, and staff training needs for inhalant use. Two open-ended questions queried their assessment of barriers to treatment and subjective feelings about the topic of inhalant use. Five hundred and fifty responses were received. Findings show that program directors perceive a great deal of neurological damage incurred through inhalant use and have a general pessimism about treatment effectiveness and recovery. The respondents also felt that there were insufficient resources for inhalant user treatment and that special staff training in the area was needed. The majority of the directors indicated that they have or would treat inhalant users. Implications for future research and policy change are discussed.

Administration, Inhalation↗
PubMed2004

Differences in characteristics of heroin inhalers and heroin injectors at admission to treatment: a preliminary study using a large database of client records.

AIMS: To compare the characteristics of heroin injectors vs. inhalers at their first admission to publicly funded treatment in Texas. METHODS: The sample consisted of 9732 unique clients who entered publicly funded treatment programs in Texas between 1997 and 2001 and who had a primary problem with either injected or inhaled heroin, which they had used in the past 30 days. The records were analyzed using a generalized linear model of logistic regression with the outcomes modeled as binomial and multinomial distribution and a hierarchical linear model for continuous outcomes to compare heroin inhalers and injectors. FINDINGS: There were large statistically significant differences between injectors and inhalers. Inhalers were more likely to be older at first use of heroin, to have entered treatment sooner, to have minor children at home, to have higher annual incomes, to be first admissions to treatment, and to have a secondary drug problem with crack cocaine. They were also more likely to be Hispanic [odds ratio (OR) = 1.74] or African-American (OR = 12.32). CONCLUSIONS: Even though the race/ethnic differences in the Texas population and the type of heroin available for use in Texas differs from that studied elsewhere, many of the characteristics of heroin users are similar. Inhalers have more strengths in many areas, and these findings raise the possibility that there are factors, particularly among African-American participants in Texas, that lessen the risk of injecting heroin. Efforts should be directed to providing therapeutic interventions to discourage the transition to injecting and to encourage inhalers to enter treatment earlier rather than progressing on to injecting. This analysis is the first part of a larger study of heroin users in public and private treatment.

Administration, Inhalation↗
PubMed1991

Inhalation therapy: alternative systems--an overview.

Three possibilities exist, in principle, to apply medication by inhalation: (1) Inhalation from Pressurized Metered Dose Inhalers (2) Direct Inhalation of Dry Powder (3) Inhalation of Nebulized Aqueous Solutions. Chlorofluorocarbons that are necessary for pressurized metered dose inhalers have unwanted environmental properties. Therefore, alternative gases are being developed (HFA-134a and HFA 227) on the premise that pressurized metered dose aerosols in airways therapy have distinct advantages which are reflected in the high acceptance and application of these MDIs worldwide. Dry powder inhalation requires sophisticated devices to provide for exact dosing. For nebulizers the major problem was their size and consequently their restricted use. Multi-dose pocket-size systems are on the market for (1) and (2). For nebulization such a system is currently being introduced. A critical comparison of benefits and disadvantages of the existing drug delivery systems to the airways leads to the conclusion that all three modes will remain essential to cover the therapeutic needs for a wide variety of drugs and patient populations.

Administration, Inhalation↗
PubMed1995

Clinical comparisons of inhaler systems: what are the important aspects?

Inhaled medications are the mainstay of asthma treatment. This not only provides the greatest clinical effect in asthmatic patients, but does so with the least systemic side effects. A wide variety of inhaler systems exist, each of which has inherent advantages and disadvantages. These have to be considered when making a choice of inhaler system for a specific clinical circumstance, as no currently available system is ideal in every clinical situation. Three main types of inhaler systems currently exist and, of these, the pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are most frequently used. The advantages of pMDIs are their portability, ease of use (in a properly instructed and adequately co-ordinated patient), cheap cost of manufacture, and low inspiratory flow rates needed to achieve adequate drug deposition in the lung. The main disadvantages of pMDIs, such as oropharyngeal deposition of drug and improper use (in an uncoordinated patient), can be minimized by the use of a spacer device. In contrast, DPIs are easy to use (no co-ordination between actuation and inhalation is required by the patient) and portable, and for the DPI, Turbuhaler, are multiple dose and deposit twice the dose of drug in the lung in comparison with pMDIs. Moreover, the side effects, namely bronchoconstriction and cough, associated with the use of pMDIs are minimized or eliminated with the use of Turbuhaler. A potential disadvantage of DPI systems is that patients need to generate inspiratory flow rates of at least 30 L/min to obtain optimal drug delivery. This is, however, feasible in almost all patients, even in those patients with very severe airflow obstruction.

Administration, Inhalation↗
PubMed2004

Inhalation and dermal exposure among asphalt paving workers.

The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of inhalation and dermal exposure to pyrene. The effect of RAP content, as well as the fact that exposures were higher among paving workers than among millers and roadside construction workers, suggests that the PAC and pyrene exposures experienced by these paving workers were asphalt-related.

Construction Materials↗
PubMed2001

The toxicology of inhaled nitric oxide.

Inhaled nitric oxide is a targeted pulmonary vasodilator that improves clinical outcomes for newborn patients with persistent pulmonary hypertension of the newborn, and may be effective in treating some premature patients with acute respiratory distress syndrome or lung disease of prematurity. Nitric oxide is now recognized as playing an important role in the regulation of diverse physiological processes. However, the pharmacological properties of inhaled nitric oxide are not easy to separate from its toxicological effects. For example, the intended effect of inhaled nitric oxide, vasodilation in the lung, is mediated, in part, by increased cellular cyclic GMP (cGMP). However, increased cGMP can also interfere with normal cellular proliferation. Nitric oxide has also been shown to cause DNA strand breaks and/or base alterations that are potentially mutagenic. Inhaled nitric oxide can rapidly react with oxygen in the lung to form nitrogen dioxide, which is a potent pulmonary irritant. Nitric oxide also reacts with superoxide anion to form peroxynitrite, a cytotoxic oxidant that can interfere with surfactant functioning. The overall effect of inhaled nitric oxide in potentiating or attenuating inflammation and oxidative damage in diseased lung is dependent on the dose administered. Furthermore, despite rapid inactivation by circulating hemoglobin, inhaled nitric oxide exerts effects outside the lung, including blocking platelet aggregation, causing methemoglobinemia, and possibly inducing extrapulmonary vasodilation. The toxicology of inhaled nitric oxide is not completely understood and must be considered in the design of protocols for its safe and effective clinical use.

Animals↗
PubMed2001

Occupational inhalant exposure and respiratory disorders among never-smokers referred to a hospital pulmonary function laboratory.

BACKGROUND: Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease. METHODS: We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants. RESULTS: Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%. CONCLUSIONS: Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.

Adolescent↗
PubMed1999

Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension.

UNLABELLED: Both inhaled nitric oxide (NO) and IV vasodilators decrease pulmonary hypertension, but the effects of combination therapy are unknown. We studied the response to inhaled NO (100 ppm) alone, IV vasodilator alone, and combined therapy during acute (U46619-induced) and chronic (monocrotaline-induced) pulmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator doses were 1.0, 3.2, 10, and 32 microg x kg(-1) x min(-1) sodium nitroprusside (SNP); 50, 100, 150, 200, and 300 microg x kg(-1) x min(-1) adenosine; or 25, 50, 150, 200, and 300 ng x kg(-1) x min(-1) prostacyclin. In the absence of IV vasodilator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmonary hypertension, the addition of inhaled NO to the largest dose of adenosine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. Because inhaled NO and SNP activate guanylyl cyclase and adenosine and prostacyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on guanylyl cyclase may produce additional selective pulmonary vasodilation. IMPLICATIONS: In therapy of pulmonary hypertension, inhaled nitric oxide should produce additional selective pulmonary vasodilation when combined with a vasodilator whose mechanism of action is not dependent on cyclic guanosine 3',5'-monophosphate.

Acute Disease↗
PubMed1992

Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension.

Patients with mitral valve disease can develop pulmonary artery hypertension that persists after mitral valve replacement. In 1987, nitric oxide (NO) was reported to be an important factor accounting for the biologic activity of endothelium-derived relaxing factor. Inhaled NO was subsequently reported to be a selective pulmonary vasodilator in animals and patients. Therefore we investigated the vasodilating effect of inhaled NO in patients with mild pulmonary artery hypertension after mitral valve replacement. Six patients who underwent mitral valve replacement for mitral stenosis presented with a mean pulmonary artery pressure greater than 25 mmHg within 24 h after surgery. During mechanical ventilation at FIO2 0.5, NO (36.8-38.4 ppm) was breathed for 10 min. Hemodynamic data were recorded before NO, after 10 min of NO inhalation, and 30 min after the end of NO inhalation. Statistically significant (P < 0.05) hemodynamic response to inhaled NO included a transient decrease in systolic (-10%), diastolic (-8%), and mean (-10%) pulmonary artery pressures; a decrease in pulmonary vascular resistance (-22%); an increase in mixed venous hemoglobin O2 saturation (+6%); and a decrease in arteriovenous O2 content difference (-7%). During NO inhalation, there was no change in systemic arterial or pulmonary wedge pressures. Methemoglobin levels remained < 1%. Inhalation of this concentration of NO for 10 min causes transient pulmonary artery vasodilation and hemodynamic improvement in patients with mild chronic pulmonary artery hypertension after mitral valve replacement.

Administration, Inhalation↗
PubMed1994

Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.

BACKGROUND: Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response. METHODS: Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days. RESULTS: Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 +/- 7 to 30 +/- 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 +/- 36 to 149 +/- 38 mmHg) and the venous admixture decreased (from 31.2 +/- 5.5 to 28.2 +/- 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm NO effectively reduced mean pulmonary artery pressure (38 +/- 7 vs. 31 +/- 6 mmHg) and increased arterial oxygen tension (79 +/- 10 vs. 114 +/- 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r = -0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r = -0.78). CONCLUSIONS: Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.

Administration, Inhalation↗
PubMed1998

Additive effect of nitric oxide inhalation on the oxygenation benefit of the prone position in the adult respiratory distress syndrome.

BACKGROUND: The response to inhaled nitric oxide and prone positioning was investigated in 47 patients with adult respiratory distress syndrome to test the hypothesis that inhalation of nitric oxide when in the prone position would result in additive improvement in oxygenation. METHODS: The authors prospectively studied patients of both genders who were 15 to 75 yr old and had adult respiratory distress syndrome confirmed by computed tomography (lung injury score, 3.1+/-1). RESULTS: Compared with baseline values in the supine position (T1), inhalation of 10 ppm nitric oxide for 1 h (T2) decreased the mean pulmonary artery pressure from 33+/-9 mmHg to 28+/-6 mmHg (P < 0.05; T2 vs. T1) and increased the ratio of the partial pressure of oxygen in arterial blood (PaO2) to inspired oxygen concentration (FiO2) from 115 (median first quartile [Q1] 97, median third quartile [Q3] 137) to 148 (Q1 132, Q3 196) (P < 0.05; T2 vs. T1). Cessation of nitric oxide brought the values back to baseline (T3). Two hours of prone positioning (T4) significantly increased the PaO2:FiO2 ratio (T4 vs. T3). However, after an additional hour of nitric oxide inhalation in the prone position (T5), a significant decrease of the venous admixture (from 33+/-6% to 25+/-6%; P < 0.05) and an increase of the PaO2:FiO2 ratio (from 165 [Q1 129, Q3 216] to 199 [Q1 178, Q3 316] [P < 0.05; T5 vs. T4]) were observed. CONCLUSIONS: In patients with isolated severe adult respiratory distress syndrome, inhalation of nitric oxide in the prone position significantly improved oxygenation compared with nitric oxide inhalation in the supine position or in the prone position without nitric oxide. The combination of the prone position with nitric oxide inhalation in the treatment of severe adult respiratory distress syndrome should be considered.

Adolescent↗
PubMed1999

Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide.

BACKGROUND: In animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (NO). This impairment is prevented by treatment with inhibitors of NO synthase 2 (NOS2), including glucocorticoids and L-arginine analogs. However, because these inhibitors are not specific for NOS2, the role of this enzyme in the impairment of NO responsiveness by lipopolysaccharide remains incompletely defined. METHODS: To investigate the role of NOS2 in the development of lipopolysaccharide-induced impairment of NO responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm NO in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and NOS2-deficient mice. The authors also evaluated the effects of breathing NO for 16 h on pulmonary vascular responsiveness during subsequent ventilation with NO. RESULTS: In wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm NO (reduced 79% and 45%, respectively, P < 0.001), but not to 40 ppm. In contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled NO in NOS2-deficient mice. Breathing 20 ppm NO for 16 h decreased the vasodilator response to subsequent ventilation with NO in lipopolysaccharide-pretreated NOS2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated NOS2-deficient or untreated wild-type mice. CONCLUSIONS: In response to endotoxin challenge, NO, either endogenously produced by NOS2 in wild-type mice or added to the air inhaled by NOS2-deficient mice, is necessary to impair vascular responsiveness to inhaled NO. Prolonged NO breathing, without endotoxin, does not impair vasodilation in response to subsequent NO inhalation. These results suggest that NO, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled NO in a murine sepsis model.

Administration, Inhalation↗
PubMed1987

The influence of inhalation injury and pneumonia on burn mortality.

In order to assess the specific effects of inhalation injury and pneumonia on mortality in burn patients, the records of 1058 patients treated at a single institution over a five-year period, 1980-1984, were reviewed. Of these patients, 373 (35%) had inhalation injury diagnosed by bronchoscopy and/or ventilation perfusion lung scan. Of the 373 patients, 141 (38%) had subsequent pneumonia. Among the patients without inhalation injury, pneumonia occurred in 60 of 685 (8.8%). A multiple logistic equation was developed to estimate expected mortality at any age and burn size for patients without either inhalation injury or pneumonia, with either alone, or with both. Subtraction of the expected mortality without either inhalation injury or pneumonia from the expected mortality in the presence of either or both permitted the estimation of additional mortality attributable to these complications. Inhalation injury alone increased mortality by a maximum of 20% and pneumonia by a maximum of 40%, with a maximum increase of approximately 60% when both were present. The influence on mortality was maximal in the midrange of expected mortality without these complications for any age group. These data indicate that inhalation injury and pneumonia have significant, independent, additive effects on burn mortality and that these effects vary with age and burn size in a predictable manner.

Adolescent↗