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Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects.

The bronchoconstrictor activity of an aerosol of leukotriene E4(LTE4) was compared with that of histamine in 5 normal and in 6 asthmatic subjects to define the relative potency of LTE4 between the groups using 3 indices of airway response. The FEV1 and the flow rate measured at 30% of vital capacity from partial and maximal expiratory maneuvers (V30-P and V30-M) were measured. The geometric mean (GSEM) concentration of LTE4 required to reduce the V30-P by 30% was 0.30 (1.46) mM in the normal subjects, and 0.058 (1.63) in the asthmatic subjects; LTE4 was 39-fold more potent than histamine in the former and 14-fold in the latter group. Further, we observed that when normal and asthmatic subjects were compared at a degree of bronchoconstriction resulting in a 30% decrement in the V30-P after inhaling LTE4, there was a greater response in the asthmatic group than in the normal group of the accompanying change in the FEV1. The decrements in the FEV1 were not significantly different between the 2 groups after inhaling histamine. This study demonstrates that LTE4 is a potent bronchoconstrictor agonist in humans and suggests that airway responsiveness to this agonist differs substantially with the index of bronchoconstriction used for assessment of airway response.

Aerosols↗

Subacute effects of heavy marihuana smoking on pulmonary function in healthy men.

To evaluate the subacute effects of heavy marihuana smoking on the lung, pulmonary function was tested in 28 healthy young male experienced cannabis users, before and after 47 to 59 days of daily ad-libitum marihuana smoking (mean of 5.2 marihuana cigarettes per day per subject, 2.2 per cent delta9-tetrahydrocannabinol). Base-line pulmonary-function studies were nearly all within normal limits, but after 47 to 59 days of heavy smoking, statistically significant decreases in forced expired volume in one second (3 +/- 1 per cent, S.E.), maximal mid-expiratory flow rate (11 +/- 2 per cent), plethysmographic specific airway conductance (16 +/- 2 per cent) and diffusing capacity (8 +/- 2 per cent) were noted as compared with the base-line studies. The decreases in maximal mid-expiratory flow rate and specific airway conductance were correlated with the quantity of marihuana smoked. These findings suggest that customary social use of marihuana may not result in detectable functional respiratory impairment in healthy young men, whereas very heavy marihuana smoking for six to eight weeks causes mild but statistically significant airway obstruction.

Adult↗

Late pulmonary sequelae of bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS: We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS: Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS: Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known.

Adolescent↗

Severe acute asthma: a comparison of three methods of inhaling salbutamol.

The effects of salbutamol inhaled by three different methods were compared in groups of adult patients with severe acute asthma. 2 x 400 micrograms Rotacaps was the optimum dose of dry powder but about 40% of patients failed to respond to it. 5 mg salbutamol nebulized with IPPB resulted in a significant increase in peak expiratory flow rate when given before or after either Rotacaps or salbutamol nebulized without IPPB, whereas neither the dry powder nor the nebulized drug without IPPB resulted in significant change when given after salbutamol nebulized with IPPB. The extra benefit derived with IPPB is only slight and requires a device of appropriate characteristics. Occasional patients fail to respond to salbutamol inhaled by any means, generally those with the most severe airflow limitation.

Acute Disease↗

Overreactivity of the psyche or the soma? Interindividual associations between psychosomatic symptoms, anxiety, heart rate, and end-tidal partial carbon dioxide pressure.

Current research has all but refuted previous suggestions about the role of hyperventilation as a proximal, common cause of psychosomatic symptoms. As an alternative, it has been proposed that the experience of psychosomatic symptoms is primarily associated with psychological mechanisms, i.e., with enhanced tendencies of distressed individuals to focus their attention on bodily sensations and to evaluate these in a catastrophic manner. Although this hypothesis has received considerable empirical support, physiological influences on symptom reporting have not, as yet, been fully explored. In this study, contributions of psychological and physiological factors were studied among a group of 83 normal healthy male subjects by an assessment of the interindividual relationships between symptom experience in daily life, situational and dispositional anxiety, baseline end-tidal partial carbon dioxide pressure (PCO2), and heart rate. Trait anxiety and end-tidal PCO2 each contributed separately to the prediction of the psychosomatic symptom score. Trait anxiety explained nearly one third of the symptom variance, and an additional 4% was explained by PCO2. Psychological symptoms were more strongly associated with anxiety and somatic symptoms, more strongly with PCO2. Heart rate only tended to be correlated with symptom reporting. Analysis of covariance among subgroups of extreme-symptom reporters supported the correlational findings by demonstrating that the association between hyperventilation and symptom reporting remained intact when psychological influences were factored out. The findings suggest that reports of psychosomatic symptoms represent two distinct components: one that is primarily psychological (and is unrelated to physiological factors) and a second that reflects objective variance in physiological functioning. The influence of the first component is probably greater than that of the second.

Adult↗

The influence of flow rate on breathing circuit compliance and tidal volume delivered to patients in mechanical ventilation.

Assessment of the gas volume that actually reaches the airways during mechanical ventilation appears to be a difficult task because of the presence of the breathing circuit. Most ventilators measure tidal volume at ventilator level making the determination of circuit compliance a critical factor in estimating the actual tidal volume. Tubing compliance can be measured in several ways and its value, being strongly dependent on the compressibility of the gas, may significantly differ depending on the measurement procedure. This paper addresses the dependence of the circuit compliance on the flow rate, and a theoretical hypothesis on the pneumatic behaviour of the breathing circuit is formulated and experimentally validated, with several tests conducted in vitro on an infant analogue. The dependence of the compliance on the inspiratory flow is experimentally assessed, and differences of about 20% on the measured value in the common flow range utilized in infant ventilation have been found, with consequent estimation errors of the volume delivered. Experimental tests show that the correct value of the tidal volume actually delivered to the patient can be reliably estimated from measurements performed at the ventilator level if the circuit compliance is determined with the same flow rates that will be utilized in mechanical ventilation.

Animals↗

Theoretical basis for improvement following reduction pneumoplasty in emphysema.

Reduction pneumoplasty may improve flow rates, comfort, and exercise tolerance in severe emphysema. The basis for improvement has not been systematically addressed. The major disability of emphysema stems from impairment of maximal expiratory flow-volume performance of the lung (MEFV). This requires the chest wall to operate at high volumes, which in turn severely compromises inspiratory muscle function. Clinical benefit, then, requires that MEFV performance improve so that the operating lung volume is reduced. This study presents theory and illustrative calculations. Removing nonventilating lung (e.g., bullae) simply displaces the MEFV curve down the volume axis. Removing ventilating parenchyma reduces both volume and maximal expiratory flow at iso-lung recoil pressure, and shortens the curve on the volume axis. The critical beneficial effect in both cases is reduction of the volume for a given limiting flow, VL (Vmax). Removing a given fraction of lung from the ventilating compartment is nearly as effective as removing it from the nonventilating compartment. Lowering of operating volumes benefits the strength, efficiency, endurance, and reserve of the inspiratory muscles and thus extends the metabolic scope of the emphysematous patient.

Humans↗

Controlled exposures of volunteers with chronic obstructive pulmonary disease to sulfur dioxide.

Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO2) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposure, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO2 exposure. Older adults with COPD seem less reactive to a given concentration of SO2 than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO2 dose rates) and/or to lower airway reactivity in the COPD group.

Aged↗

Sauna to transiently improve pulmonary function in patients with obstructive lung disease.

The influence of sauna on pulmonary functioning in patients with an obstructive pulmonary disease was studied in 12 male patients by measuring forced vital capacity (FVC) and forced expiratory volume in one second on seven measure points the day of the sauna program. Despite the fact that body cooling and changes in osmolality of bronchial liquid can induce bronchoconstriction, we measured a significant improvement of the lung function parameters: FVC values were 3.22 +/- 0.89 and 3.6 +/- 0.99 before and after the sauna program, respectively. It is concluded that patients with an obstructive pulmonary disease can take part in sauna programs without eliciting bronchoconstriction; sauna even causes transient improvement of the lung function.

Adult↗

The effect of body position on maximal expiratory pressure and flow.

Positioning combined with coughing and huffing is frequently used to promote secretion clearance. Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) have been used as surrogate measures of cough and huff strength. This study investigated the effect of body position on MEP and PEFR. Repeated measures of MEP and PEFR were performed across seven randomised positions (standing, chair sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees, supine, side lying, and side lying with head down tilt 20 degrees) on 25 adults with normal respiratory function (NRF) and 11 adults with chronic airflow limitation (CAL). For the NRF group, MEP in standing (143+/-10cmH2O, mean+/-SEM) was significantly higher than MEP in chair sitting (133+/-10cmH2O) which in turn was significantly higher than in the remaining positions. The MEP in head down tilt (108+/-9cmH2O) was significantly lower than in all other positions. The PEFR in standing (571+/-24L/min) was significantly higher and head down tilt (486+/-23L/min) was significantly lower than in all other positions. For the CAL group, MEP in standing (134+/-18cmH2O) was significantly higher, while in head down tilt (96+/-15cmH2O) was significantly lower, than in most other positions. For the CAL group, PEFR in standing (284+/-40ml/sec) was significantly higher, while in head down tilt (219+/-38ml/sec) was significantly lower, than in most other positions. Body position has a significant effect on MEP and PEFR in NRF and CAL subjects, with the lowest values in the head down position. Thus, to maximise the strength of expiratory manoeuvres during treatments that use the head down position, patients should be encouraged to adopt a more upright position when coughing or huffing.

Adolescent↗

Effectiveness of the fold plication method in lung volume reduction surgery.

OBJECT: The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. PATIENTS AND METHODS: Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. RESULTS: There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). CONCLUSION: The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.

Aged↗

Exercise-induced respiratory resistance changes as measured with the airflow perturbation device.

Respiratory resistance (Rrs) changes during physical labor can modify the work of breathing and thus influence the time that the labor can be performed. Ideal in vivo human respiratory performance measurements should have fine temporal resolution and minimally impact the respiratory system itself. The airflow perturbation device (APD) provides respiratory resistance measurements in this manner. Pre-exercise Rrs was compared with post-exercise Rrs, continuously monitored for 6 min in 12 non-asthmatic subjects. Rrs following exercise at 70-75% VO2max was below pre-exercise levels for 40 s into recovery (p < 0.05) and inhalation resistance differed more markedly than exhalation resistance. The same post-exercise Rrs decline was found when Rrs measurements were compared to those taken during flow rates comparable to those found late in recovery. Results indicate that (1) Rrs indeed declines following exercise in non-asthmatic subjects, probably due to bronchial dilation, (2) Rrs changes can occur on short time scales, (3) Rrs changes are not related primarily to flow rate.

Adolescent↗

Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth.

Five dogs underwent left pneumonectomy at 10 wk of age, whereas four littermates underwent a sham operation. At 26 wk of age the postpneumonectomy dogs had total lung vital capacity (VC) and lung weight similar to controls, but maximum expiratory flow was reduced. Pressure capsules were glued to right lower (RLL) and right cardiac (RCL) lobes, and alveolar pressures (PA) were measured during forced expiration. In postpneumonectomy dogs RLL and RCL both emptied more slowly than in control dogs, and emptying was especially delayed in RCL, which underwent the most growth. When both lobes deflated together, PA in RCL and RLL were similar in control dogs, but in postpneumonectomy dogs PA in RCL exceeded that in RLL by approximately 3 cmH2O from 80 to 20% VC. Because the higher driving pressure in RCL compensated for the relatively high resistance of RCL, the pattern of lobar emptying was relatively uniform over these lung volumes. This result was compatible with interdependence of lobar maximum expiratory flows. In addition, at PA of 6-10 cmH2O in postpneumonectomy dogs, maximum emptying rates of RCL were less when RCL deflated alone than when RCL and RLL emptied together, again demonstrating interdependence of lobar maximum expiratory flow.

Animals↗

Effect of aerosol particle size on bronchodilatation with nebulised terbutaline in asthmatic subjects.

The bronchodilatation achieved by the beta 2 agonist terbutaline sulphate given as nebulised aerosol from different devices has been measured in seven patients with mild asthma (mean FEV1 76% predicted) over two hours after inhalation. The subjects were studied on four occasions. On three visits they received 2.5 mg terbutaline delivered from three different types of nebuliser, selected on the basis of the size distribution of the aerosols generated; and on a fourth (control) visit no aerosol was given. The size distributions of the aerosols expressed in terms of their mass median diameter (MMD) were: A: MMD 1.8 microns; B: 4.6 microns; C: 10.3 microns. The aerosols were given under controlled conditions of respiratory rate and tidal volume to minimise intertreatment variation. Bronchodilator response was assessed by changes in FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), and maximal flow after expiration of 50% and 75% FVC (Vmax50, Vmax25) from baseline (before aerosol) and control run values. For each pulmonary function index all three aerosols gave significantly better improvement over baseline than was seen in the control (p less than 0.05) and had an equipotent effect on FEV1, FVC, and PEF. Aerosol A (MMD 1.8 microns) produced significantly greater improvements in Vmax50 and Vmax25 than did B or C (p less than 0.05). These results suggest that for beta 2 agonists small aerosols (MMD less than 2 microns) might be advantageous in the treatment of asthma.

Adult↗

Airflometer: new toy or worthwhile advance?

The Airflometer provides a useful index of expiratory flow rate and as such it is a worthwhile advance. It can provide an accurate index of FEV1 provided it is individually calibrated. Perhaps the only limitation is the lack of response of the instrument at low flow rates, for example, with an FEV1 of less than one litre. It is remarkably inexpensive.

Adult↗

Early lung function changes after short heavy exposure to chrysotile asbestos in non-smoking women.

Forced spirometry, including maximal flow-volume (MEFV) curves, were evaluated in 35 non-smoking asbestos female workers submitted to a short heavy chrysotile textile exposure and compared to a case by case matched population. Exposed women presented certain respiratory signs and symptoms; they also had significantly lower forced vital capacities and maximal flow rates at higher (PEF), mid (MEF50%) and lower lung volumes (MEF25%) than women not exposed to asbestos. Duration of exposure to asbestos showed a significant negative correlation with FVC, FEV1, PEF, MEF50% and MEF25%. It is concluded that short heavy exposure to chrysotile is deleterious, causing significant reduction in lung volumes. Moreover, a significant reduction in airflow rates was also apparent.

Adult↗

Respiratory effects of relocating to areas of differing air pollution levels.

We studied 110 children (59 boys and 51 girls, who were 10 yr of age at enrollment and 15 yr of age at follow-up) who had moved from communities participating in a 10-yr prospective study of respiratory health (The Children's Health Study [CHS]) to determine whether changes in air quality caused by relocation were associated with changes in annual lung function growth rates. The subjects were given health questionnaires and underwent spirometry in their homes across six western states, according to a protocol identical to evaluations performed annually on the CHS cohort in school. Changes in annual average exposure to particulate matter with a mean diameter of 10 microm (PM(10)) were associated with differences in annual lung function growth rates for FEV(1), maximal midexpiratory flow, and peak expiratory flow rate. As a group, subjects who had moved to areas of lower PM(10) showed increased growth in lung function and subjects who moved to communities with a higher PM(10) showed decreased growth in lung function. A stronger trend was found for subjects who had migrated at least 3 yr before the follow-up visit than for those who had moved in the previous 1 to 2 yr. We conclude that changes in air pollution exposure during adolescent growth years have a measurable and potentially important effect on lung function growth and performance.

Adolescent↗