Exhaled nitric oxide after beta2-agonist inhalation and spirometry in asthma.

Exhaled nitric oxide (ENO) is used increasingly as a surrogate marker of airway inflammation in research protocols that may incorporate standard efficacy measures, such as spirometry before and after bronchodilator, which could affect ENO measurements. In seven healthy volunteers and 11 mild asthmatic subjects, we measured ENO before and serially for 1 h after spirometry. On two additional days in the subjects with asthma, we reexamined the effect of spirometry as before, followed by the serial measurement of ENO for 1 h after two puffs of salbutamol (100 microgram/puff) by metered-dose inhaler or matching placebo.

Has high-frequency ventilation been inappropriately discarded in adult acute respiratory distress syndrome?

Objectives: To review the basic physiologic principles that support the role for high-frequency ventilation (HFV) in acutely lung-injured patients, to critically assess clinical trial data in this area, and discuss why a metasummary is not feasible and a large-scale clinical trial is needed.

Data Sources: We searched a computerized database (MEDLINE) from 1976 to January 1997 using the text words "high-frequency ventilation" and "acute respiratory distress syndrome" to retrieve all relevant candidate articles.

Study Selection: We retrieved all English language clinical studies conducted in tertiary care centers that employed HFV in adult acute respiratory distress syndrome (ARDS) patients.

Transgene expression after adenovirus-mediated retransfection of rat lungs is increased and prolonged by transplant immunosuppression.

Objectives: Adenovirus-mediated gene therapy has been proposed as a potential treatment modality in lung transplantation. However, to date its utility has been limited by an inflammatory host immune response that not only limits the amount and duration of transgene expression but also obviates successful retransfection. Having previously shown that by administering triple-immunosuppression, as is routine in lung transplantation, we could increase and prolong transgene expression after initial transfection, we hypothesized that transgene expression after retransfection could also be increased and prolonged.

Prevention of rapid reperfusion-induced lung injury with prostaglandin E1 during the initial period of reperfusion.

We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperature ischemia. This is associated with an early increase in pulmonary artery pressure (Ppa) and can be prevented by a stepwise increase in flow rate during the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermic preservation, and whether this injury can be attenuated by a short-course of prostaglandin E1 (PGE1).

Rapid reperfusion causes stress failure in ischemic rat lungs.

Objective: Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion. METHODS.

Effect of high dose inhaled acetic acid on airway responsiveness in Fischer rats.

Background: Sudden, severe airway injury has been associated with an acute, and at times persisting, airway hyper-responsiveness with clinical features of asthma, termed reactive airways dysfunction syndrome (RADS). An attempt was made to develop a rat model of RADS by exposing inbred Fischer rats to inhaled 8 N acetic acid for 2 mins (13 N inhalation was lethal).

Methods: Lung resistance (RL) and lung elastance (EL) were measured in 14 eight- to 10-week old male rats.

Ventilator-induced injury: from barotrauma to biotrauma.

Mechanical ventilation is an indispensable tool in the management of respiratory and ventilatory failure. However, ventilation per se may also initiate or exacerbate lung injury, contributing to patient morbidity and mortality. In this review, we examine the current mechanisms of ventilator-induced injury including those that primarily involve physical disruption of the lung, as well as those more recently described that involve cell- and inflammatory-mediator-induced injury.

A computed tomography scan assessment of regional lung volume in acute lung injury. The CT Scan ARDS Study Group.

The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and compared between 21 patients with ALI and 10 healthy volunteers. Distribution of PEEP-induced alveolar recruitment along the anteroposterior and cephalocaudal axis and influence of the resting volume of nonaerated lower lobes were also assessed.

A significant proportion of exhaled nitric oxide arises in large airways in normal subjects.

Nitric oxide (NO) of endogenous origin is present in exhaled breath. An increase in exhaled NO concentration (ENO) has been described in bronchial asthma and ENO falls after inhaled steroid therapy. The sources of ENO may include pulmonary blood, the gas exchange region, conducting airways and the nasal cavity.

Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function.

Background: Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts.

Genetics of asthma: a primer.

Despite intense research, the morbidity and mortality of asthma remain relatively high. The key reason for this high morbidity and mortality is that the fundamental mechanisms predisposing individuals to the development of asthma are not understood. One approach to discovering fundamental mechanisms is to examine the genetic basis of the disease, with the hope that uncovering the molecular defects will lead to a greater understanding of asthma and improved therapy.

Exhaled nitric oxide and bronchial reactivity during and after inhaled beclomethasone in mild asthma.

The measurement of exhaled nitric oxide (ENO) is recognized as a marker of airway inflammation. ENO was measured in 10 nonsteroid-treated asthmatics at recruitment, during 3 weeks of inhaled beclomethasone (1000 microg/day) and for 3 weeks after withdrawal. Baseline ENO was increased in asthma compared with nonasthmatics (85.

Decreased exhaled nitric oxide may be a marker of cardiopulmonary bypass-induced injury.

Background: Nitric oxide is an endothelium-derived vasodilator. Cardiopulmonary bypass may induce transient pulmonary endothelial dysfunction with decreased nitric oxide release that contributes to postoperative pulmonary hypertension and lung injury. Exhaled nitric oxide levels may reflect, in part, endogenous production from the pulmonary vascular endothelium.

Optimal inflation volume for hypothermic preservation of rat lungs.

Background: Recent studies have suggested that preservation of donor lungs with inflation provides better pulmonary function after transplantation, but hyperinflation of pulmonary grafts during storage increases reperfusion pulmonary edema. To elucidate the optimal inflation volume during the preservation period, and the possible role of barotrauma in lung injury after atelectatic storage, we examined the effects of inflation volume and reinflation protocols in hypothermically preserved rat lungs.

Methods: Adult rat lung blocks were preserved at 4 degrees C for 18 hours at various levels of inflation.

Exhaled nitric oxide in human lung transplantation. A noninvasive marker of acute rejection.

Acute allograft rejection in animals and humans has been associated with increased nitric oxide production in the graft. Exhaled nitric oxide (ENO) measurement is a noninvasive method of assessing inflammation in airway diseases, e.g.

Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous airway obliteration in an animal model of bronchiolitis obliterans.

Bronchiolitis obliterans, a form of chronic allograft rejection characterized by progressive fibrous obliteration of the airways, is the major obstacle limiting prolonged survival of lung transplant recipients. To date, no effective therapy against this fatal complication exists. Interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, inhibits various T cell and antigen-presenting cell functions.

Effect of inhaled furosemide in acute asthma.

We assessed the acute bronchodilator effect of nebulized furosemide when added to conventional therapy of acute emergency department (ED) asthma. Using a double-blind design, 42 patients with acute asthma were randomized to receive 2.5 mg nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution.

Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation.

Objectives: Increases in exhaled nitric oxide have been demonstrated to originate from the lungs of rats after septic lung injury. The aim of this study was to investigate whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) would prevent lipopolysaccharide (LPS)-induced increases in exhaled nitric oxide and whether this would have an effect on septic lung inflammation.

Design: Prospective, randomized, placebo-controlled animal laboratory investigation.

Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group.

Background: A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established.

Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension.

Recent data have suggested that the elastic properties of the chest wall (CW) may be compromised in patients with ARDS because of abdominal distension (4). We partitioned CW and lung (L) mechanics, assessed the role of abdominal distension, and verified whether the underlying disease responsible for ARDS affects the impairment of respiratory mechanics. Volume-pressure (V-P) curves (interrupter technique) were assessed in nine patients with surgical ARDS and nine patients with medical ARDS.

Genetics of asthma: the University of Toronto Program. University of Toronto Genetics of Asthma Research Group.

In 1991, we initiated a study to identify susceptibility gene(s) predisposing individuals to the development of asthma. Our strategy was to focus on the collection of inbred populations because (1) they are likely to exhibit greater homogeneity than outbred populations, potentially important in multigenic diseases, (2) there may be fewer genes explaining the asthma diathesis in families with a "founder effect," (3) it is possible to follow the pattern of inheritance more closely, and (4) environmental factors are likely to be more uniform in geographically isolated poulations. We have identified, and in some cases collected data on inbred and/or isolated populations in Brazil, China, Easter Island, Israel, and Tristan da Cunha.

Heat stress increases survival rates in lipopolysaccharide-stimulated rats.

Objective: To examine the hypothesis that heat stress applied after the administration of bacterial endotoxin is protective.

Design: Prospective, randomized, laboratory study.

Setting: University research laboratory.

Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.

Background: Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans.