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PubMed1980

Role of H1- and H2-receptors in airway reactions to histamine in conscious sheep.

We investigated the role of histamine H1- and H2-receptors in the control of airway function in six conscious sheep. In five of these, inhalation of histamine (combined H1- and H2-receptor stimulation) caused an increase in pulmonary resistance (RL) and functional residual capacity and had a variable effect on distribution of ventilation as measured by N2-clearance delay. Pretreatment with the H1-antagonist, chlorpheniramine, prevented these functional effects of histamine challenge, whereas pretreatment with the H2-antagonist, metiamide, potentiated the effects of histamine on RL and caused a uniform increase in N2-clearance delay. Pretreatment with both chlorpheniramine and metiamide prevented the effects of histamine on all parameters indicating effective blockade of H1- and H2-receptors at the dosages used. In one sheep, an increase in RL and N2-clearance delay in response to histamine was only observed after metiamide pretreatment. With or without pretreatment, histamine failed to alter the static pressure-volume curve of the lung. We conclude that in conscious sheep a) inhalation of histamine produces bronchoconstriction and pulmonary hyperinflation without changing lung elastic recoil, b) the observed effects of histamine are mediated by H1-receptors, and H2-receptors have a modulating role, and c) variable effects of histamine on RL and distribution of ventilation may be related to differences in the distribution of H1- and H2-receptors in central and peripheral airways.

Aerosols↗

PubMed1994

Lung function testing--useless in ventilated newborns?

Several methods have been used for lung function testing in the ventilated newborn. The interest in the field has been stimulated by the recent appearance of commercially available equipment for assessment of mechanical parameters and of functional residual capacity in this group. Nevertheless, lung function testing is rarely used as a clinical routine, even such simple variables as tidal volume and minute ventilation. Among the many possible reasons for this condition, the fragile nature of the infants and the hands-off policy usually exercised, the difficulties in measuring flow accurately, and the complexity of the present methods deserve special attention. In order to change this situation more work needs to be done to elucidate basal physiology of the ventilated lung and the relationships between ventilator settings, lung function and side-effects in different conditions. If then sufficiently simple, safe and accurate methods to assess the most important functions can be offered, lung function testing would be likely to become a useful component of routine care in future neonatal intensive care.

Humans↗

PubMed1994

[The prognostic relevance of preoperative pulmonary function tests].

At Leipzig University, preoperative pulmonary function testing has been performed for about 3 years in order to detect and classify patients at high pulmonary risk. During the postoperative period, the risk of developing pulmonary complications is particularly high due to factors influencing respiratory mechanics such as the supine position, pain, residual effects of narcotic drugs, etc. It has often been emphasised that an underlying ventilatory disturbance such as obstructive lung disease or smoking may enhance the postoperative pulmonary risk, although the extent of the influence of preoperative pulmonary diseases on the postoperative complication rate is still controversial. The prediction of postoperative lung function from preoperative spirometric values is complicated by factors such as patient cooperation, pulmonary complications secondary to aspiration, infection, peritonitis, etc., and by differing and therefore non-comparable postoperative care. For this reason, the criteria for assessing pulmonary risk vary widely. METHODS. We examined 339 patients (mean age 59.3 years) preoperatively by quiet and forced spirometry; in most cases we also measured airway resistance and functional residual capacity. We estimated the postoperative lung function using the quadrant scheme of Miller and compared this risk class with our spirometric diagnosis and the postoperative clinical course. RESULTS. According to our results, Miller's classification seems inadequately differentiated for patients with mild to moderate ventilatory disturbances. A relatively high percentage of these patients were considered to have normal postoperative lung function. Some patients with severely diminished pulmonary function were classified as having sufficient postoperative lung function. The number and severity of pulmonary complications also corresponded better with the spirometric diagnosis, which was made using all spirometric parameters and not only vital capacity (VC) and 1-s forced expiratory volume (FEV1). We found that the percentage of primary respiratory complications increased with deterioration of the preoperative spirometric values. To provide a prognostic model combining both the advantages of using only a few parameters (FEV1, VC) and appropriate risk assessment, we propose a modification of the Miller scheme consisting of five risk classes. The analysis of the respiratory therapy regimen was unsatisfactory because of discrepancies between the predicted pulmonary risk, the use of respiratory therapy, and the occurrence of pulmonary complications. CONCLUSIONS. For minimising perioperative pulmonary complications, respiratory care (prophylaxis and therapy) adequate for the functional risk of the patient is necessary. We assume that intensive pre- and postoperative respiratory care and therapy in patients with underlying reductions in ventilatory function can help to avoid or reduce respiratory complications. The modification of Miller's scheme proposed after evaluating the postoperative course of our patients provides a differentiated prognostic model that allows the establishment of an appropriate and economical therapeutic regimen of perioperative pulmonary care.

Adult↗

PubMed1999

Lung transplantation in very young infants.

INTRODUCTION: Established successes with adult lung transplantation have laid the foundation for extension of this therapeutic modality to infants and children dying of end-stage pulmonary disease. The purpose of this report is to convey our experience with 19 infants undergoing lung transplantation before the age of 6 months. METHODS: Six patients with predominantly pulmonary vascular disease and 13 patients with primarily pulmonary parenchymal disease have undergone bilateral sequential lung transplantation at our institution since 1990. Mean age at transplant was 104 +/- 44 days, and mean weight was 4.9 +/- 1.6 kg. RESULTS: Although early mortality (32%, 6/19) was higher than that previously reported for older pediatric age groups, long-term survival was similar (44% at a maximum follow-up of 6 years). Although anastomotic complications and infections occurred at a rate approximating that seen in older pediatric age groups, episodes of acute rejection appear to occur with decreased frequency. Similarly, at a mean follow-up of 3 years, only 2 (15%) of 13 long-term survivors have evidence of bronchiolitis obliterans. The functional residual capacity, as measured on infant pulmonary function tests, has gradually increased as the children have grown, suggesting that lung growth is occurring. CONCLUSIONS: Bilateral lung transplantation is a viable alternative in infants dying of end-stage pulmonary disease. Efforts directed toward avoiding the complications that lead to early posttransplant mortality combined with the seemingly lower incidence of early and late rejection may provide long-term results better than those in other age groups.

Actuarial Analysis↗

PubMed1985

Lung injury in guinea pigs caused by multiple exposures to submicron zinc oxide mixed with sulfur dioxide in a humidified furnace.

Sulfur dioxide, water vapor, and ultrafine particles rich in oxides of zinc and other surface-deposited trace elements are important products of coal combustion. In order to study the toxicity of zinc oxide generated under conditions simulating combustion, guinea pigs were exposed in a nose-only apparatus for 3 h on 6 consecutive days to 6 mg/m3 of submicron zinc oxide particles (count median diameter of 0.05 micron, sigma g 2.0), which were generated in a humid furnace and mixed with 1 ppm sulfur dioxide. The exposures caused increases in lung weight and [3H] thymidine labeling index of terminal bronchiolar cell nuclei and inflammation of the proximal portion of the alveolar duct. The lung weights and labeling index had returned to normal and inflammatory changes had nearly resolved by 72 h after the last exposure. Total lung capacity, vital capacity, functional residual volume, alveolar volume, and diffusing capacity for carbon monoxide were decreased following exposure and had not returned to normal by 72 h after the last exposure. Large airways were not affected by the repeated exposures, as indicated by normal morphology of trachea and bronchi, unchanged secretory cell concentration, and unaltered epithelial permeability to horseradish peroxidase. These results are essentially identical to changes we reported in guinea pigs exposed to zinc oxide alone, suggesting that surface-deposited sulfur compounds, which are important determinants of the response to a single exposure to these ultrafine particles, become less important as exposure progresses.

Animals↗

PubMed1975

Influence of body position on pulmonary diffusing capacity in yound and old men.

Steady-state diffusing capacity (DLCOSS2), studied in healthy nonsmokers, was significantly higher in five old men when seated than when supine, but was unchanged in five young men. However, "corrected" for the increased ventilation, it decreased in the young--but not in the old--when erect compared with when supine. The change of DLCOSS2 in the young during the first 20 min when seated was related to a change of the fractional dead space ventilation (VD/VT)mThe old showed less venous admixture when seated than when supine, whereas VD/VT and regional ventilation-perfusion index of the lung bases was the same in both positions. The decrease in venous admixture was probably due to the closing capacity (CC) being less than the functional residual capacity (FRC) when seated. The elimination of closed off regions when seated made more pulmonary capillaries available for diffusion.

Adult↗

PubMed1980

Pulmonary mechanics during exercise in subjects with chronic airflow obstruction.

A body plethysmograph was used to measure pulmonary mechanics in six subjects with chronic airflow obstruction during steady states at rest and during exercise at 200 and 400 kpm . min-1. The mean forced expired volume in 1 s was 1.32 liters (39.2% predicted). The flow rates during tidal breathing reached the maximum expiratory flow-volume (MEFV) curve in all but one subject, and on exercise they all reached the MEFV curve. Total lung capacity did not change significantly, but functional residual capacity increased to 104% of the control value (P less than 0.05) and residual volume increased to 113.3% of the control value (P less than 0.02). The MEFV curves did not change and tidal flow rates in excess of th MEFV curve were not seen. Dynamic compliance fell with increasing exercise to 52.8% (P less than 0.01) and static expiratory pulmonary compliance to 90.2% of the control value. Transpulmonary pressures during tidal breathing when expiratory flow reached the MEFV curve increased to progressively higher values as the work load increased. At low work loads there were several subjects with negative transpulmonary pressure when maximum flow rates were present. In patients with chronic airflow obstruction, little change occurs during exercise in pulmonary mechanics; the tidal flow patterns are dominated by the expired flow-volume curve, which is not changed by exercise; maximum flow occurs in some patients when transpulmonary pressure is still negative.

Adult↗

PubMed1981

Pulmonary mechanisms of the normal ferret.

Pulmonary mechanics were measured in normal anesthetized male Fitch ferrets (200-360 g). In eight transorally intubated ferrets, pressure-volume (PV) curves for the lung and chest wall were obtained with an esophageal balloon and body plethysmograph. The lung volumes and capacities expressed as a percentage of the total lung capacity (mean, 49.8 ml) were: vital capacity, 84.7%; inspiratory capacity, 63.7%; inspiratory reserve volume, 58.2%; functional residual capacity, 33.8%; expiratory reserve volume, 16.8%; residual volume, 15.3%; and tidal volume, 8.0%. The compliance of the lung (2.93 ml . cmH2O-1), chest wall (22.42 ml . cmH2O-1) and respiratory system (2.55 ml . cmH2O-1) were determined from the PV curves. The dynamic compliance (1.6 ml . cmH2O-1), pulmonary resistance (0.024 cmH2O . ml-1 . s), frequency of breathing (43.5 breaths . min-1), and minute ventilation (195 ml . min-1) were measured during spontaneous breathing. In a second group of 10 ferrets the total airway resistance (0.116 cmH2O . ml-1 . s) and specific conductance (0.915 ml . s-1 . cmH2O . ml-1) were measured during spontaneous nasal breathing. In general the pulmonary mechanics of the ferret were similar to those of the rabbit and dog, when the data were normalized for lung volume.

Airway Resistance↗

PubMed1989

Lung volumes after an increase in lung distension in pneumonectomized ferrets.

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3-6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2-3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3-5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.

Animals↗

PubMed2003

Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects.

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure Rrs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in Rrs between end tidal inspiration and TLC, re-narrowing as Rrs at FRC immediately after DI, as per cent Rrs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean Rrs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.

Adult↗

PubMed1980

The pre-operative chest film in relation to post-operative management--some effects of different projection, posture and lung inflation.

An essential feature in the assessment of chest films is the comparability of successive examinations. This is particularly important in post-operative care and there are several factors which make the conventional departmental chest film an inappropriate standard for assessment of post-operative chest films. Pre-operative chest films in patients undergoing cardiac surgery have, therefore, been taken in both upright and supine positions at full inspiration (total lung capacity) (TLC) and at resting expiration (functional residual capacity) (FRC) and then compared with those taken post-operatively. Significant differences in transverse cardiac diameter, cardio thoracic ratio, mediastinal width and vertical lung height were found in films taken with the patient supine, AP at inspiration or resting expiration, circumstances in which many chest films are taken in both post-operative and in intensive care patients. The taking of pre-operative films at lung volumes and in postures comparable with those occurring post-operatively is advocated.

Cardiac Surgical Procedures↗

PubMed1980

Determining changes in airway caliber in asthma: the role of submaximal expiratory flow rates.

Sixteen patients with suspected reversible airway obstruction who had previously demonstrated an increase in specific airway conductance after isoproterenol, but who had not demonstrated an increase in forced expiratory flow were studied using a measurement of submaximal flow. Flow during tidal breathing (VTV) was measured spirometrically, and VTV increased in all 16 patients from a value of 0.61 L/sec before isoproterenol to 0.80 L/sec after isoproterenol. In addition, each of these 16 patients experienced a significant increase in vital capacity and a significant decompression of functional residual capacity after isoproterenol. If plethysmography is not available, the measurement of VTV may provide evidence of bronchodilatation. The mechanism responsible for the dichotomy between maximal and submaximal flow is the compression of airways by high positive pleural pressure which is present during maximal, but not submaximal maneuvers.

Adolescent↗

PubMed1989

Expected pressure-volume heterogeneity within the lung.

Using a model of the lung providing for pressure-volume (P-V) heterogeneity, we reproduced straight (allowing for some concavity or convexity) alveolar plateaus in the nitrogen washout curve with a slope identical to an experimentally measured one (1.2% N2/liter). In a two-unit lung, with one unit of high volume (H) at total lung capacity (TLC) and another of low volume (L) at TLC, three variables could be adjusted to produce the desired alveolar plateaus: the ratio of TLCL/TLCH; the ratio of functional residual capacity, FRCL/FRCH; and the ratio of the steepness constants of their sigmoid P-V curve, KL/KH. We searched for all possible combinations of the three variables that yielded the desired alveolar plateau. For any TLCL/TLCH ratio, there were two single-value solutions for the FRCL/FRCH ratio; thus, the family of solutions was represented by two surfaces in three-dimensional space. We extended the study to a smaller alveolar slope (0.6% N2/liter), assuming that the total slope (1.2% N2/liter) was partially caused by diffusion-convection interaction. We also studied a three-compartment lung as indicative of a multicompartmental lung. The results are discussed in relation to experimentally confirmed P-V heterogeneity. Granting our basic assumptions of P-V heterogeneity, the real physical lung characteristics may be a subsection of the range of theoretical solutions described herein.

Adult↗

PubMed2006

Multiple-breath washout in preschool children--FRC and ventilation inhomogeneity.

The open-circuit multiple-breath inert gas washout method is used to measure functional residual capacity and also to quantify ventilation distribution. The technique is readily applicable in preschool children as it requires quiet tidal breathing. Guidelines for data collection and interpretation in this age group will shortly be published by the European Respiratory Society and the American Thoracic Society.

Breath Tests↗

PubMed1995

Pressure-volume analysis of the lung with an exponential and linear-exponential model in asthma and COPD. Dutch CNSLD Study Group.

The prevalence of abnormalities in lung elasticity in patients with asthma or chronic obstructive pulmonary disease (COPD) is still unclear. This might be due to uncertainties concerning the method of analysis of quasistatic deflation lung pressure-volume curves. Pressure-volume curves were obtained in 99 patients with moderately severe asthma or COPD. These patients were a subgroup from a Dutch multicentre trial; the entire group was selected on the basis of a moderately lowered % predicted forced expiratory volume in one second (FEV1), and a provocative concentration of histamine producing a 20% decrease in FEV1 (PC20) < 8 mg.mL-1 obtained with the 2 min tidal breathing technique. The curves were fitted with an exponential (E) model and an exponential model which took the linear appearance in the mid vital capacity range into account (linear-exponential (LE)). The linear-exponential model showed a markedly better fit ability, yielding additional parameters, such as the compliance at functional residual capacity (FRC) level as slope of the linear part (b), and the volume at which the linear part changed into the exponential part of the curve (transition volume (Vtr)). Vtr (mean value Vtr/total lung capacity (TLC) = 0.79 (SD 0.07)) showed a close positive linear correlation with obstruction and hyperinflation variables, which might be due to airway closure, already starting at elevated lung volumes. The exponential shape factor K was closely correlated with b and mean values (K = 1.32 (SD 0.05) kPa-1; b = 2.96 (SD 1.16) L,kPa-1) and the relationship with age was comparable with data reported in healthy individuals. The shape factor of the linear-exponential fit showed no correlation with any elasticity related variable. Neither the elastic recoil at 90% TLC, as obtained from the linear-exponential fit, nor its relationship with age were significantly different from healthy individuals. We conclude that, for a more accurate description of the lung pressure-volume curve, a linear-exponential fit is preferable to an exponential model. However, the physiological relevance of the shape parameter (KLE) is still unclear. These results indicate that patients with moderately severe asthma or COPD had, on average, no appreciable loss of elastic lung recoil as compared with healthy individuals.

Adolescent↗

PubMed1988

Drive and timing components of respiration in young children following induction of anaesthesia with halothane or ketamine.

Timing and drive components of respiration were studied in 18 young children following induction of anaesthesia with ketamine and were compared with results from ten children following induction of anaesthesia with halothane. During one minute of quiet breathing, signals from a pneumotachograph attached to the anaesthetic mask were analysed for tidal volume (Vt), respiratory frequency (f), minute volume (Ve), inspiratory and expiratory times (Ti, Te) and flow pattern. Following induction of anaesthesia with ketamine, children breathed more slowly and deeply than children receiving halothane, but there was no significant difference in Ve or in Vt/Ti, suggesting that respiratory drive was similar in the two groups of children. In the children receiving ketamine, Ti was more than twice as long, and thus the ratio Ti/Te was significantly increased, in comparison with the group receiving halothane. In addition to the prolonged Ti in the children induced with ketamine, there was a more rapid increase in volume in early inspiration than in late inspiration, which is an apneustic breathing pattern. There was a slower decrease in volume in early expiration, with occasional early expiratory breath holding lasting up to three seconds, in the ketamine-induced children. The unique breathing pattern demonstrated with ketamine, consisting of large Vt, increased Ti/Te ratio, apneustic inspiratory pattern, and expiratory braking, contributed to an increased mean lung volume above functional residual capacity, of 2.40 ml.kg-1 body weight, in comparison to 1.27 ml.kg-1 in the children receiving halothane.

Anesthesia, Inhalation↗

PubMed2001

Anatomic landmarks to estimate the length of the diaphragm from chest radiographs: effects of emphysema and lung volume reduction surgery.

STUDY OBJECTIVES: To define anatomic landmarks that can be used to predict insertions of the diaphragm on chest radiographs and to estimate diaphragm length. DESIGN: Prospective clinical trial with a parallel group design. SETTING: Laboratory investigations in normal volunteers recruited by advertisement and in emphysema outpatients being evaluated for elective bilateral lung volume reduction surgery (LVRS). PATIENTS: Twenty-six normal subjects classified into young and older age groups, with a third group of 13 emphysema patients matched for age and sex with the older group. MEASUREMENTS: Identification and between-group comparisons were made of anatomic landmarks on anteroposterior and lateral chest radiographs obtained at total lung capacity. Predicted landmarks were generated from normal subjects. Within-subject and between-group comparisons were made of diaphragm length index (DLI) based on observed anatomic landmarks (DLIobs) and diaphragm length index based on predicted anatomic landmarks (DLIpred) at functional residual capacity. RESULTS: Anatomic landmarks were not different between the three groups or between male and female subjects, and were not different before and after LVRS in emphysema patients. No difference was found between DLIobs and DLIpred in normal subjects and emphysema patients, but both were smaller in emphysema patients than in normal subjects and increased after LVRS in emphysema patients. CONCLUSION: This study validates the use of anatomic landmarks to estimate DLI. Using these landmarks simplifies the determination of diaphragmatic lengths and could be a useful tool for the evaluation of the functional capacity of the diaphragm, and possibly as a prognostic indicator of patients who are candidates for LVRS.

Adult↗

PubMed2006

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects.

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.

Administration, Inhalation↗