The effect of submucosal edema on airways resistance.
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Airway Resistance↗
Biomedical subjects
P D Pare
Publications and source records attributed to P D Pare.
Reassessment of inflammation of airways in chronic bronchitis.
The term chronic bronchitis has been criticised because it is associated with hypersecretion of mucus rather than bronchial inflammation. This study was designed to establish the presence or absence of clinical chronic bronchitis and measure pulmonary function in 45 patients about to undergo resection of the lung. The condition in the cartilaginous and small airways and the severity of the emphysema were then measured in the resected specimen. The results from 20 patients who had clinical chronic bronchitis were compared with those in 25 patients who did not. The data show that patients with chronic bronchitis had greater inflammation (a) on mucosal surfaces (p less than 0.05) of all bronchi larger than 2 mm luminal diameter and (b) around glands (p less than 0.005) and gland ducts (p less than 0.05) in bronchi larger than 4 mm diameter. A variable degree of inflammation was present in the submucosa of smaller bronchi. The groups had equivalent proportions of mucous glands and Reid's indices in central airways, and no differences were noted in measurements of pulmonary function, condition of small airways, or emphysema. These data show that the term chronic bronchitis is justified by inflammation of cartilaginous airways and suggest that this abnormality may be the cause of the chronic productive cough.
Bronchi↗
Airways disease: evolution, pathology, and recognition.
Obstruction to airflow in the lung was studied in 150 patients who presented with coin lesions necessitating surgical resection of the lung. Pulmonary function tests were performed before surgery, and the structure of the lung or lobe was analysed by means of morphometric techniques. The evolution of obstructive airways disease appeared to be based on a progressive chronic inflammatory reaction in the respiratory and membranous bronchioles. This led to progressive airway obstruction and was associated with destruction of the lung surface. The early pulmonary vascular problems appeared to be related to progressive airways obstruction that may have increased pulmonary artery pressure by causing alveolar pressure to increase more than pleural pressure during the hyperventilation of exercise.
Adult↗
Bronchopulmonary anastomotic and noncoronary collateral blood flow in humans during cardiopulmonary bypass.
The sole source of blood returning to the left atrium during cardiopulmonary bypass, while the aorta is cross-clamped, is the bronchopulmonary anastomotic blood flow. In addition, there is noncoronary collateral blood flow which returns to the right atrium. Routinely, the bronchopulmonary anastomotic flow is drained from the left ventricle by a cannula and returned to the main circuitry via a cardiotomy reservoir. The noncoronary collateral flow may be vented similarly by introducing a cannula into the right atrium. Both the anastomotic and the noncoronary collateral flow can be measured with no further surgical intervention. We measured bronchopulmonary anastomotic flow in 40 patients undergoing coronary artery bypass surgery and the noncoronary collateral blood flow in 27 of these patients. Results from this study show that the bronchopulmonary anastomotic flow for the 40 patients was 140 +/- 182 ml/min (range 8 to 1,043 ml/min), representing 3.23 +/- 4.15 percent of the pump flow (equivalent to the cardiac output), and the noncoronary collateral flow in the 27 patients was 48 +/- 74 ml/min (range 0 to 261 ml/min), representing 1.11 +/- 1.67 percent of the pump flow.
Adult↗
Morphology of peripheral airways in current smokers and ex-smokers.
To investigate the effect of smoking status on pulmonary function and pathologic changes in the peripheral airways, we studied 97 patients who underwent thoracotomy for coin lesions. The patients were divided into 4 groups: nonsmokers (n = 9), current smokers (n = 51), and those who had ceased smoking for less than (n = 18) or more than (n = 19) 2 yr prior to surgery. We found that current smokers had evidence of air-flow obstruction with abnormal lung volumes when compared with nonsmokers. Ex-smokers had lung volumes similar to those of nonsmokers, but showed evidence of obstruction, with the FEV1/FVC between the values found for nonsmokers and current smokers. Examination of the small airways showed that the membranous bronchioles of current smokers and ex-smokers displayed only increased goblet cell metaplasia when compared with those in nonsmokers; the respiratory bronchioles of current and ex-smokers showed increases in intraluminal and airway wall inflammatory cells, wall fibrosis, and pigment deposition. We conclude that patients who currently smoke cigarettes have reduced lung function that is associated with abnormalities of airway structure. Although those who have stopped smoking have function that is closer to the nonsmoking group, there is no apparent difference in structural change between current and ex-smokers.
Aged↗
Eosinophilic pneumonia and atypical mycobacterial infection.
Chronic eosinophilic pneumonia is a relatively uncommon condition associated with fever, malaise, weight loss, dyspnea, and hypoxia. The chest radiograph displays peripheral air-space consolidation, often referred to as the negative of pulmonary edema. The characteristic pathologic findings in the lung include marked accumulation of eosinophils in the alveolar spaces, often with the formation of eosinophilic abscesses. We report the history and pathologic findings in a patient who fit the clinical, radiologic, and pathologic features of chronic eosinophilic pneumonia, but who went on to develop cavitary atypical mycobacterial infection and died. We believe that this case represents an unusual response to an atypical mycobacterial infection.
Aged↗
Bronchial response to histamine after inhaled propranolol and atropine in monkeys.
To investigate the nature of the variable response to inhaled histamine in monkeys, we performed dose-response curves in a group of 10 anesthetized Macaca mulatta monkeys before and after administration of propranolol and atropine in inhaled doses sufficient to produce significant beta-adrenergic and cholinergic blockade of airway smooth muscle. Animals were studied in a volume-displacement body plethysmograph and changes in pulmonary resistance (RL), dynamic compliance (Cdyn), frequency (f) and tidal volume (VT) were plotted against inhaled histamine concentration (0.016 to 64 mg/ml). Sensitivity to histamine was assessed by the concentrations producing a 50% increase in RL and a 50% decrease in Cdyn. A wide range of sensitivity (0.44 to 3.3 mg/ml for RL, 0.47 to 11.3 mg/ml for Cdyn) was found in this small group of animals, and this was not influenced by prior inhalation of propranolol. Atropine inhalation resulted in a marked decrease in sensitivity in all animals but did not reduce the variability of response.
Administration, Intranasal↗
Exponential analysis of the lung pressure-volume curve as a predictor of pulmonary emphysema.
To compare the predictive value of different pulmonary function tests in the diagnosis of morphologic emphysema, we performed measurements of subdivisions of lung volume, gas exchange, maximal expiratory flow rates, and static deflation pressure-volume curves on 55 subjects prior to surgery for removal of an isolated peripheral pulmonary lesion. Emphysema was graded on the resected lung specimen and the pressure-volume data were fitted to an exponential equation (V = A - Be-KP). By chi-square analysis, K was the best predictor of emphysema in individual subjects and it was the only test that distinguished subjects with moderate emphysema from subjects with mild or without emphysema, but K did not distinguish those with mild emphysema from those without emphysema. As a group those with mild emphysema were distinguishable from predicted normal with K and elastic recoil pressures at 90 and 60% of predicted total lung capacity. We conclude that minimal emphysema may be detected by exponential analysis of the lung pressure-volume curve.
Adult↗
Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro.
During a type I allergic reaction histamine, slow-reacting substance of anaphylaxis (SRS-A) and other mediator substances are elaborated from specific tissue sites. In allergic asthma these sites are in the lung and the mediator substances cause airway obstruction by contracting smooth muscle and altering mucociliary function. Unlike histamine, slow-reacting substances (SRSs) have been assessed very little for their roles in obstructive airways disease. This has been partly due to the fact that their chemical nature was unknown until recently and thus pure samples were not available for pharmacological studies. However, SRSs isolated from both immunological and non-immunological reactions have been identified as a combination of two related lipid substances--leukotriene C4 (LTC) and leukotriene D4 (LTD); thus it is now possible to use pure SRSs (leukotrienes) in pharmacological studies of airway smooth muscle. LTC and LTD have been shown to contract guinea pig tracheal and lung parenchymal strips but there is no evidence that these substances produce similar effects on human lung tissue. To clarify this, in vivo pharmacological studies were done to determine the actions of LTC and LTD on smooth muscle strips of human bronchus, pulmonary vein and artery, and lung parenchymal tissue containing smooth muscle components and pleura. As indicated in a preliminary report, all four types of tissues contracted in a dose-dependent fashion to the leukotrienes, although these substances only function as partial agonists.
Airway Resistance↗
The effect of inhalation of nebulized steroid on the acid aspiration syndrome.
The effects of acid aspiration on lung mechanics, gas exchange, haemodynamics and lung water, and their modification by nebulized dexamethasone were studied in 10 dogs. Each dog received 0.1 N HCl pH of 1.0 (15 ml/l vital capacity), instilled down the tracheal tube. PEEP 0.98 kPa (10 cm H2O) was introduced 20 minutes after aspiration and was continued until the completion of experiment. Treated animals (N = 5) received dexamethasone 5 mg . kg-1 by continuous nebulization over a two hour period starting 20 minutes after aspiration. Untreated (N = 5) animals received nebulized saline. Measurements were taken before aspiration and at 20 minutes 2.5 and 5.0 hours after aspiration. Red blood cells labelled with 51Cr were injected before sacrifice. After sacrifice multiple lung samples were taken for measurement of pulmonary extravascular water (PEW) by the gravimetric technique. Acid aspiration caused significant changes in lung volumes, PaO2, and intrapulmonary shunt. Pulmonary extravascular water was 6.16 +/- 0.93 ml/g dry tissue in treated and 6.47 +/- 0.60 ml/g dry tissue in untreated animals. These results indicate the presence of severe pulmonary oedema. There were no significant differences in any measured parameter between treated and untreated animals. We conclude that nebulized dexamethasone is of no value in treatment of the acute changes induced by acid aspiration.
Animals↗
Measurements of airway edema in allergic bronchoconstriction in the guinea pig.
We tested the hypothesis that acute bronchoconstriction in the guinea pig was associated with airway edema by measuring extravascular water in the airways and lung parenchyma. Thirty guinea pigs were immunized with egg albumin and 30 nonimmunized guinea pigs served as controls. An aerosolized challenge with egg albumin produced acute respiratory distress in the immunized but not in the control animals. The animals were killed (6 per group) immediately and 1, 3, 6, and 24 h after the challenge, and the extravascular water content of the airways and parenchyma was measured. We found that airway extravascular water varied from 3.90 +/- 0.58 to 3.12 +/- 0.25 g/g dry tissue in the control group and from 3.61 +/- 0.41 to 3.79 +/- 0.33 g/g dry tissue in the experimental group. A two-way analysis of variance showed no difference between the groups. Similar results were found in parenchymal samples. We concluded that allergic bronchoconstriction in the guinea pig is not associated with airway edema.
Airway Obstruction↗
Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys.
In four Ascaris-sensitive rhesus monkeys, we measured the fractional absorption of 3H-histamine (3HH) and airway response, as pulmonary resistance (R1), to standard histamine aerosols containing tracer amounts of 3HH for control runs (Run 1) and runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of radioactivity in the plasma volume as a function of delivered dose during histamine exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as compared with Run 1 (0.009% delivered dose/min). Whereas histamine inhalation led to insignificant (less than 25%) increases in R1 over control in Run 1. R1 increased by 247% over control after histamine inhalation in Run 2. Thus, both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model. These data are consistent with the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction is one of the factors contributing to airway hyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.
Airway Resistance↗
Airway sensitivity to slow-reacting substance of anaphylaxis, histamine, and antigen in Ascaris sensitive monkeys.
The effects of Ascaris suum antigen, histamine, and slow-reacting substance of anaphylaxis (SRS-A) on the respiratory system were compared in 3 anesthetized rhesus monkeys. The agents were administered by instillation into the trachea, and the animals were studied in a volume displacement body plethysmograph. Two of the animals showed skin and bronchial sensitivity to Ascaris suum antigen and responded to it with increased pulmonary resistance and decreased dynamic compliance. A similar response was seen in all 3 animals after instillation of histamine, but SRS-A at 2 concentrations produced a predominant effect of decreased dynamic compliance with lesser alterations in pulmonary resistance. The effects of SRS-A were slow in onset and prolonged, as compared to the abrupt and short-lived effects of Ascaris suum antigen and histamine. The predominant effect of SRS-A on dynamic compliance suggests a more peripheral site of action of this mediator. In 5 monkeys allergic to Ascaris, no SRS-A could be detected in the blood at one and 5 min after antigen challenge, using the bioassay techniques.
Administration, Topical↗
Structure and function of airways in Ascaris-sensitive monkeys.
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Airway Obstruction↗
Static lung mechanics of intact and excised rhesus monkey lungs and lobes.
Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight.
Animals↗
Airway mucosal permeability in the Ascaris suum-sensitive rhesus monkey.
The permeability of the airways to technetium 99m-labeled albumin was measured in Ascaris suum-sensitive rhesus monkeys. All 8 animals were skin-sensitive to Ascaris suum (AA) antigen, 4 being respiratory responders (R) and 4 nonresponders (NR) to aerosolized antigen. In the absence of antigen challenge there were no differences in the accumulation in the blood of radioactive material from the tracheobranchial tree between the R and NR animals. After a five-minute challenge with aerosolized AA, there was a threefold increase in the rate of accumulation of radioactive material in the blood over control for the R group with no effect noted in the NR group. Gel filtration data indicated that the radioactivity in the blood most likely represented low molecular weight albumin fragments, resulting from spontaneous degradation of Tc-albumin, that crossed the mucosa and partially bound to circulating albumin. It is concluded that hyperpermeability of the airway mucosa probably is not a factor that contributes to the selective responsiveness of the R group to aerosolized antigen, and that airway permeability is increased consequent to the allergic reaction mediating acute bronchoconstriction.
Aerosols↗
Effect of indomethacin and atropine in experimental asthma in conscious guinea pigs.
Pulmonary mechanics were measured in unanesthetized guinea pigs sensitized to horseradish peroxidase (HRP) before and during two aerosolized challenges of this antigen. During the first challenge the pulmonary resistance increased in all animals. Prior to second challenge the animals received either atropine (0.2 mg/kg) or indomethacin (10 mg/kg) intraperitoneally. We found that during the second challenge the indomethacin group had an increase in pulmonary resistance slightly greater or similar to that during the first exposure to the antigen, while the animals treated with atropine had a significantly diminished response (P less than 0.05). In five guinea pigs sensitized to HRP but challenged with a nonspecific aerosal made up of rabbit albumin, we found that pulmonary resistance increased in some animals and that this increase could be partially blocked by atropine. These results show that indomethacin has no effect on this model of allergic airways disease. They also confirm the importance of the vagus nerves in allergic bronchoconstriction and in addition show that nonspecific hyperirritability can be induced in some animals by immunization.
Aerosols↗
Lung mechanics following antigen challenge of Ascaris suum-sensitive rhesus monkeys.
Pulmonary resistance (RL) breathing air and a helium-oxygen mixture (He-O2) dynamic compliance (Cdyn), respiratory frequency (f), subdivisions of lung volume, and static deflation pressure-volume (PV) curves were measured before and after bronchial challenge with Ascaris suum antigen in six rhesus monkeys with varying skin reactivity to this antigen. The animals were lightly anesthetized with pentobarbital sodium, intubated, and studied in a volume displacement body plethysmograph, transpulmonary pressure being measured with an esophageal balloon technique. With the animals breathing spontaneously antigen was delivered with a De Vilbiss ultrasonic nebulizer and RL was determined by the method of electrical subtraction. With challenge, three monkeys showed no response and three persistently demonstrated significant bronchonconstriction (peak RL 700+/-100% control) with a decreased response to He-O2 suggesting combined central and peripheral airway narrowing. Responding monkeys also developed tachypnea (f 210+/-8% control) and a fall in Cdyn (18+/-6% control) but no significant changes in total lung capacity and its subdivisions, or in static PV curves were seen. We conclude that this primate model shows important similarities to and differences from human asthma.
Airway Resistance↗