Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine - MCh) or indirect (adenosine 5'-monophosphate - AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). OBJECTIVE: We designed a randomized, single-blind, cross-over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. METHODS: Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV(1)) value (PD(20)MCh); (ii) a provocative dose producing a 25% fall in the maximal mid-inspiratory flow (FIF(50)) from baseline (PD(25)MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV(1) value (PC(20)AMP) and (iv) a provocative concentration producing a 25% fall in the FIF(50) from baseline (PC(25)AMP) for AMP. RESULTS: All 113 patients with CVA responded to PD(20)MCh and 96% and 69% responded to PC(20)AMP, if we used PC(20)

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion.

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 +/- 14 in IRG-SS vs 11 +/- 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 +/- 15 in IRG-SS vs 76 +/- 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 +/- 0.06 in IRG-SS vs 0.09 +/- 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.

Protective effect of aminoguanidine in a murine model of pulmonary fibrosis induced by bleomycin.

Aminoguanidine is a drug known for more than a century, which has been attracting increasing interest in recent years due to the discovery of new pharmacological properties. This study investigated the effects of aminoguanidine on the fibrotic response induced by intratracheal administration of bleomycin to rats. Three groups of animals were studied: Group A (n = 19) corresponded to the control group. Group B (n = 20) received 10 IU/kg bleomycin intratracheal, and Group C (n = 12) received the same amount of bleomycin as Group B followed by 50 mg/kg/day aminoguanidine bicarbonate for 4 weeks. Aminoguanidine led to significant reductions in total hydroxyproline content of the lungs in Group C compared to Group B (Group A: 1.83+/-0.14 mg x Group B: 3.46+/-0.36 mg x Group C: 2.09+/-0.22 mg). Morphometric collagen studies carried out on histological sections stained with Sirius red F3BA showed that aminoguanidine promoted a significant reduction of the area occupied by collagen in the axial and septal zones of the lungs (Axial region = Group A: 4.29+/-1.31% x Group B: 19.30+/-4.86% x Group C: 8.52+/-1.96%; Septal region = Group A: 0.15+/-0.06% x Group B: 0.61+/-0.21% x Group C: 0.15+/-0.06%). These results suggest that aminoguanidine is a potential therapeutic agent for the treatment and prevention of pulmonary fibrosis which is associated with different clinical conditions.

Ventilation with high tidal volume induces inflammatory lung injury.

Mechanical ventilation with high tidal volumes (V(T)) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V(T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V(T) = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V(T) = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62 +/- 0.91 vs 1.69 +/- 0.48 and 1.44 +/- 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high V T induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-alpha in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response.

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume.

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2+/-90.9 and BAL, 118.2+/-82.1; IL-1 : plasma, 45.2+/-42.7 and BAL, 50.2+/-34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.

Pulmonary emphysema induced by passive smoking: an experimental study in rats.

We describe a short time model for inducing experimental emphysema in rats by chronic tobacco smoke inhalation. Three groups of male Wistar rats (6 months old) were studied: controls (N = 8), rats intoxicated for 45 days (s-45, N = 7) or for 90 days (s-90, N = 8). The exposed animals were intoxicated 3 times a day (10 cigarettes per exposure period), 5 days a week. Pulmonary damage was assessed by means of functional tests and quantitative pathological examination of the airways and lung parenchyma. The s-45 and s-90 animals were similar in terms of functional residual capacity (FRC) corrected for body weight (FRC/kg) but both groups of smoking rats exhibited significantly higher FRC/kg values than the controls (s-45 = 6.33; s-90 = 6.46; controls = 3.78; P < 0.05). When the two groups of smoking rats were pooled together and compared to controls, they showed decreased lung elastance (1.6 vs 2.19; P = 0.046) and increased mean linear intercept (Lm) (85.14 vs 66.44; P = 0.025). The s-90 animals presented higher inflammation and muscular hypertrophy at the level of the axial bronchus than the controls (P < 0.05). When smoking groups were pooled and compared to controls, they presented significantly higher inflammation at the lateral level (P = 0.028), as well as airway secretory hyperplasia (P = 0.024) and smooth muscle hypertrophy (P = 0.005) at the axial level. Due to its simplicity, low cost and short duration, this technique may be a useful model to obtain new information about airspace remodeling due to chronic tobacco consumption.

[Artificial respiration with extracorporeal membrane oxygenator in arteriovenous position without pump. Experimental study]. / Respiração artificial com oxigenador de membrana extracorpóreo em posição artério-venosa sem bomba. Estudo experimental.

PURPOSE: To test the hypothesis of respiratory support and to study the consequent hemodynamic alterations, we performed pumpless A-V ECMO using a 1.2m2 polipropylene hollow fiber membrane oxygenator, specially adapted from conventional model utilized in routine cardiac surgery. METHODS: Two canine groups of six dogs each were studied. Group 1 had normal lungs and group 2 acute respiratory failure induced by 0.035ml/kg intravenous oleic acid. The dogs were anesthetized and maintained in apnea with curare. Heparin was given in a single dose of 400U/kg. Gasimetric and hemodynamic parameters were monitored each 30 minutes during a 3 hour period. Then the oxygenator was discontinued and after 15 minutes a final arterial blood gas sample was taken for analysis. RESULTS: Blood samples at 3 hours have shown a mean PaO2 of 260.6mmHg in group 1 and 114.4mmHg in group 2 and PaCO2 of 54.3 and 56.2mmHg, respectively. After the oxygenator was discontinued PaCO2 levels increased to 161.6 and 193.7mmHg, respectively. The hemodynamic parameters shown few alterations. CONCLUSION: In both groups pumpless A-V ECMO was able to maintain gasimetric parameters within acceptable patterns and compatible with life, with few hemodynamic alterations. However, an adequate mean arterial blood pressure is needed to provide flow through membrane oxygenator.

[Applicability of the Torrington and Henderson scale]. / Aplicabilidade da escala de Torrington e Henderson.

PURPOSE: To validate the Torrington & Henderson preoperative risk assessment program in the population of surgical patients in an university hospital (Hospital São Paulo, UNIFESP, São Paulo, Brasil). MATERIAL AND METHODS: We evaluated 1162 patients who underwent to major thoracic, upper and under abdominal surgery using the Torrington & Henderson program. The patients were classified in low (785), moderate (317) and high risk (60). All patients were accompanied daily during the postoperative period by the same medical team which assessed the preoperative period, until discharged or died. RESULTS: The postoperative pulmonary complications were present in 6.1%, 23.3% and 35.0% in the low, moderate and high risk respectively. The relative risk to develop postoperative pulmonary complications was 3.8 higher in the patients with moderate risk and 5.7 higher in the patients with high risk. The mortality rate due to pulmonary complications was 1.7%, 6.3% and 11.7% respectively in the patients with low, moderate and high risk. The relative risk to the death was 3.7 higher in the patients with moderate risk and 6.9 in the high risk. CONCLUSION: We concluded that the Torrington & Henderson preoperative risk assessment program can identify in our population patients who will develop postoperative pulmonary complications.

Variable positive end-expiratory pressure can maintain oxygenation in experimental acute respiratory distress syndrome induced by oleic acid in dogs.

The use of positive end-expiratory pressure (PEEP) or lung recruitment maneuvers (RM) to improve oxygenation in acute respiratory distress syndrome (ARDS) is used but it may reduce cardiac output (CO). Intermittent PEEP may avoid these complications. Our objective was to determine if variable PEEP compared with constant PEEP is capable of maintaining arterial oxygenation and minimizing hemodynamic alterations with or without RM. Eighteen dogs with ARDS induced by oleic acid were randomized into three equal groups: group 1, low variable PEEP; group 2, high variable PEEP, and group 3, RM + high variable PEEP. All groups were submitted to constant PEEP, followed by variable PEEP (PEEP was increased from 5 to 10 cmH(2)O in group 1, and from 5 to 18 cmH(2)O in the other two groups). PaO(2) was higher in group 3 (356.2 +/- 65.4 mmHg) than in group 1 (92.7 +/- 29.7 mmHg) and group 2 (228.5 +/- 72.4 mmHg), P < 0.05. PaO(2) was maintained during variable PEEP except in group 2 (318.5 +/- 82.9 at constant PEEP to 228.5 +/- 72.4 at variable PEEP). There was a reduction in CO in group 3 after RM (3.9 +/- 1.1 before to 2.7 +/- 0.5 L*min(-1)*(m(2))(-1) after; P < 0.05), but there was not any difference between constant and variable PEEP periods (2.7 +/- 0.5 and 2.4 +/- 0.7 L*min(-1)*(m(2))(-1); P > 0.05. Variable PEEP is able to maintain PaO(2) when performed in combination with RM in dogs with ARDS. After RM, CO was reduced and there was no relevant difference between the variable and constant PEEP periods.

A prospective longitudinal study of clinical characteristics, laboratory findings, diagnostic spectrum and outcomes of specific therapy in adult patients with chronic cough in a general respiratory clinic.

Chronic cough with established diagnostic protocols has been well described in secondary and tertiary centres. Little information is available about adult patients to a general respiratory clinic where no such protocols exist. The objective of this study is to determine clinical characteristics, laboratory findings, diagnostic spectrum and outcomes of specific therapy in adult patients with chronic cough in a general respiratory clinic. In this prospective, longitudinal, descriptive study for patients with chronic cough defined as more than 8 weeks, we studied, according to a questionnaire, chest radiography, spirometry and reversibility, methacholine challenge and other measures. Treatment was prescribed on the basis of diagnosis informed by investigation results.We evaluated 147 patients (102 females) of a mean age of 48 years and complaining of cough an average of 24 weeks. On the basis of a successful response to treatment, the causes of cough were determined in 92% and the frequencies were asthma in 39%, COPD in 11%, chronic upper airway cough syndrome (CUACS) in 9%, gastro-oesophageal reflux disease (GERD) in 9% and no diagnosis in 8%. Cough was due to one condition in 82%. Our treatment success rate was 92%. The most frequent causes of chronic cough (asthma, COPD, CUACS and GERD) could be determined in a general respiratory clinic with a sequential approach. The frequencies are different from those in a tertiary cough clinic, but outcome of specific therapy is successful in our patients.

Phosphatidylglycerol-deficient lung surfactant has normal properties.

We have investigated the effects of substituting phosphatidylinositol (PI) for phosphatidylglycerol (PG) on the functional properties of rabbit lung surfactant. We gave oral 10% glucose solution for 3 days to 11 rabbits and 10% inositol to 12 others. Lung lavage surfactant phospholipids were normal in both groups, except that PG was low and PI was high in the inositol group. Fatty acyl group distributions did not differ, except for a slight decrease of oleic acid in the inositol group. Electron microscopic examination showed normal surfactant structure in both. The time course of surfactant adsorption to an air-water interface was similar in both groups. Minimum surface tension after film compression was 4.0 +/- 0.8 mN . m-1 in the glucose group and 2.9 +/- 1.3 mN . m-1 in the inositol group (mean +/- SE). Surface potential-surface pressure isotherms were identical to within 12 mV. Arterial blood gases breathing air and 100% O2 were the same in both groups, as were pressure-volume curves of excised lungs, with both air and saline filling. The results suggest that, if acidic phospholipids are necessary for maintaining normal surfactant structure and surface properties, normal pressure-volume relationships, and normal gas exchange, then PI may substitute for PG.

[Anatomo-pathological alterations of the lung in hemorrhagic shock studied with lungs fixed by classical method and when expanded (author's transl)]. / Alterações anátomo-patológicas do pulmäo no choque hemorrágico estudadas com o pulmão fixado de maneira clássica e em expansão.

The authors have studied lungs of 14 dogs that have been submitted to hemorrhagic shock. The right lung was fixed in the ordinary way and the left lung in expansion. They examine preparations of a 11 lobes of both lungs. Vacuolar degeneration of the cells of the terminal bronchioles and the respiratory bronchioles, hypertrophy of the cells of the alveolar sac of mild degree were constant findings. Alveolar edema of some intensity was observed in all preparations. Atelectasias of severe degree were only seen in preparations fixed in the ordinary way.

[Pulmonary function in dogs submitted to bilateral cervical vagotomy (author's transl)]. / Função pulmonar em cães submetidos a vagotomia cervical bilateral.

A study of the effects of cervical vagotomy on pulmonary function in two groups of dogs was done: the first group had been vagotomized and submitted to spontaneous breathing and the second had been vagotomized and submitted to mechanical ventilation. pH, partial pressure of carbonic acid in arterial blood (PaCO2), partial pressure of oxygen in arterial blood (PaO2), plasmatic bicarbonate (HCO-3), alveolar arterial oxygen difference (P(A-a)O2) while the patients breathed room air and 100% O2 and pulmonary shunting didn't change after vagotomy. There was no difference between these two groups. Hemodynamic parameters like oxygen content difference (C(a-v)O2) between arterial and venous blood, heart hate (FC), mean blood pressure (Pam) and capillary hydrostatic pressure (Pcp) didn't change after vagotomy. None of these parameters were different between the two groups.

Variable positive end-expiratory pressure can maintain oxygenation in experimental acute respiratory distress syndrome induced by oleic acid in dogs

The use of positive end-expiratory pressure (PEEP) or lung recruitment maneuvers (RM) to improve oxygenation in acute respiratory distress syndrome (ARDS) is used but it may reduce cardiac output (CO). Intermittent PEEP may avoid these complications. Our objective was to determine if variable PEEP compared with constant PEEP is capable of maintaining arterial oxygenation and minimizing hemodynamic alterations with or without RM. Eighteen dogs with ARDS induced by oleic acid were randomized into three equal groups: group 1, low variable PEEP; group 2, high variable PEEP, and group 3, RM + high variable PEEP. All groups were submitted to constant PEEP, followed by variable PEEP (PEEP was increased from 5 to 10 cmH2O in group 1, and from 5 to 18 cmH2O in the other two groups). PaO2 was higher in group 3 (356.2 ± 65.4 mmHg) than in group 1 (92.7 ± 29.7 mmHg) and group 2 (228.5 ± 72.4 mmHg), P < 0.05. PaO2 was maintained during variable PEEP except in group 2 (318.5 ± 82.9 at constant PEEP to 228.5 ± 72.4 at variable PEEP). There was a reduction in CO in group 3 after RM (3.9 ± 1.1 before to 2.7 ± 0.5 L·min-1·(m2)-1 after; P < 0.05), but there was not any difference between constant and variable PEEP periods (2.7 ± 0.5 and 2.4 ± 0.7 L·min-1·(m2)-1; P > 0.05. Variable PEEP is able to maintain PaO2 when performed in combination with RM in dogs with ARDS. After RM, CO was reduced and there was no relevant difference between the variable and constant PEEP periods.

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 ± 14 in IRG-SS vs 11 ± 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 ± 15 in IRG-SS vs 76 ± 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 ± 0.06 in IRG-SS vs 0.09 ± 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.