Comparison of airway reactivity induced by histamine, methacholine, and isocapnic hyperventilation in normal and asthmatic subjects

In an investigation of a rapid screening test for airway reactivity using isocapnic hyperventilation with room air and cold air the results of this test were compared with the airway response to histamine and methacholine challenge. Twelve non-atopic, non-smoking normal subjects and 11 subjects with stable asthma who had an FEV1 above 74% of the predicted value were studied. In the normal subjects isocapnic hyperventilation with room air (75 l/min; 22 degrees C (SEM 0.2 degrees); 10 mg H2O/l air) and isocapnic hyperventilation with cold air (77 l/min; -10 degrees C (0.9 degrees); 2.4 mg H2O/l air) produced no significant change in FEV1. In the asthmatic subjects, hyperventilation with room air (71 l/min; 22 degrees C (0.8 degrees); 10 mg H2O/l air) caused a mean fall in FEV1 of 11.7%; cold air hyperventilation (70 l/min; -10 degrees C (0.9 degrees); 2.4 mg H2O/l air) caused a mean fall in FEV1 of 20.4%. Cold air hyperventilation produced greater separation between normal and asthmatic subjects than room air. The provocative concentration of histamine required to reduce the FEV1 by 20% (PC20) correlated closely with the PC20 for methacholine (r = 0.95; p less than 0.001). Both tests separated normal from asthmatic subjects. PC20 for both histamine and methacholine correlated with the fall in FEV1 after cold air hyperventilation (r = 0.93, p less than 0.001; r = 0.87, p less than 0.001 respectively). We conclude that the results of a rapid screening test based on hyperventilation with cold air correlate well with a standard pharmacological challenge.     

Inhibition by sodium cromoglycate of bronchoconstriction stimulated by respiratory heat loss: comparison of pressurised aerosol and powder

The protective effect was examined of three doses (2, 10, and 20 mg) of sodium cromoglycate inhaled from a pressurised metered dose inhaler on the response to isocapnic hyperventilation of cold dry air in 10 asthmatic subjects. This was compared with the effect of cromoglycate powder (20 mg) inhaled from a Spincap and with placebo given on two occasions. The medications were inhaled on separate days, in random order and with the use of a double blind double dummy technique, 20 minutes before isocapnic hyperventilation of two fold increasing volumes of air (-15 degrees C, 0% humidity) to produce a 20% fall in the post-treatment FEV1. The response was expressed as the provocative dose of respiratory heat loss required to cause a fall in FEV1 of 15% (PD15, kcal/min). The mean baseline spirometric indices exceeded 85% of predicted normal values on each test day; both placebo treatments reduced the baseline FEV1 by comparison with all active treatments (p less than 0.0001). Comparison of the PD15 on the two placebo days confirmed excellent reproducibility. All doses of cromoglycate shifted the respiratory heat loss dose-response curve to the right of the placebo curve; PD15 after all active treatments exceeded PD15 after placebo (p less than 0.0001). There was no cromoglycate dose-response relationship between the three doses of aerosol (p greater than 0.05), or between any dose of aerosol and powder (p greater than 0.05). It is concluded that cromoglycate aerosol inhaled from a pressurised inhaler in a dose of 2 mg gives the same magnitude of protection against bronchoconstriction stimulated by airway cooling as 20 mg of pressurised aerosol or powder from a Spincap.     

Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis.

In a previous study on 27 patients with chronic bronchitis we found that only three developed bronchoconstriction in response to hyperventilation of cold, dry air despite an increased responsiveness to methacholine inhalation. We therefore investigated bronchial responsiveness to hyperventilation with cold, dry air and methacholine in 27 patients with stable asthma who had a similar range of baseline FEV1 values but who developed bronchoconstriction that could be reversed to give an FEV1 more than 70% of the predicted value. Baseline FEV1 was 0.88-3.98 l (37-114% predicted). All but one subject developed bronchoconstriction in response to hyperventilation. There was a linear relationship between baseline FEV1 and response to methacholine (r2 = 0.37, p less than 0.001) and the relationship was significantly different from that found in the bronchitic subjects (F2.50 = 24.94, p less than 0.001). In general, the response to methacholine was greater in the asthmatic than in the bronchitic subjects for any baseline FEV1. The results suggest that there are different mechanisms underlying the increased responsiveness to methacholine in asthma and chronic bronchitis.     

Respiratory heat loss in exercise-induced asthma. Measurement and clinical application

The theoretical considerations of conditioning inspired air and the application of the respiratory heat loss (RHL) formula are discussed. An on-line method for measuring RHL is described together with the apparatus for generating frigid dry and warm humid air. Exercise-induced asthma (EIA) was studied using these methods. Thirteen asthmatic and 6 normal children and adolescents participated in the study. Each subject undertook two submaximal exercise tests consisting of 6 minutes' ergometric cycling against a fixed load. One test was done while breathing cold dry air (mean temperature -22 degrees C and 0% relative humidity) and the other while breathing warm humid air (mean temperature 36 degrees C and 100% relative humidity). All the other exercise parameters (e.g. heart rate, minute ventilation, oxygen uptake) were carefully matched between the two tests. In the cold dry air tests with a mean RHL of 1,43 kcal/min, all asthmatic subjects developed EIA with a mean fall in forced expiratory volume in the 1st second (FEV1) of 48% from baseline. In the warm humid air tests with negligible RHL (0,02 kcal/min) none of the asthmatics developed EIA (mean fall in FEV1 5%). The difference between the two tests was highly significant (P less than 0,001). Neither air condition caused bronchospasm in the normal subjects. A dose-response relationship was obtained between the degree of RHL and corresponding fall in FEV1.     

Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapnic dry air hyperventilation in patients with asthma.

BACKGROUND: It has been suggested that inhaled corticosteroids may provide greater protection against constrictor stimuli that act indirectly such as exercise than those that act directly such as histamine. METHODS: The effects of six weeks treatment with inhaled budesonide (800 micrograms twice daily) on bronchial reactivity to histamine, exercise, and eucapnic voluntary hyperventilation of dry air were compared in a double blind, placebo controlled, non-crossover study in 40 subjects with asthma. Change in bronchial reactivity to histamine and eucapnic hyperventilation over the six weeks was measured as change in the provocative dose of histamine or dry air causing a 20% fall in FEV1 (PD20 histamine and PV20 eucapnic hyperventilation (EVH) of dry air); this was not possible for exercise because of the development of refractoriness. To enable the change in response to all three stimuli to be compared, the response (percent fall in FEV1) to a fixed dose was measured for all three challenge tests. RESULTS: After budesonide there was an increase in PD20 histamine from 0.48 to 2.81 mumol and in PV20 EVH from 364 to 639 litres, and a significant correlation between the changes in PD20 histamine and PV20 EVH (r = 0.63). The median percentage fall in FEV1 in response to eucapnic hyperventilation, exercise, and histamine was similar before budesonide (25.5%, 26.6%, and 24.5%); the reduction in the percentage fall in FEV1 with budesonide was also similar for the three challenges (18.9%, 17.5%, and 16.6%), and all differed significantly from the changes following placebo. There was a significant correlation between change in percentage fall in FEV1 after budesonide with the three stimuli (histamine v exercise: r = 0.48; histamine v eucapnic hyperventilation: r = 0.46; exercise v eucapnic hyperventilation: r = 0.63). CONCLUSION: The similar magnitude of change in bronchial reactivity to all three stimuli after budesonide and the within subject correlation obtained between these changes suggest that corticosteroids act by a common mechanism to protect against eucapnic hyperventilation, exercise, and histamine.     

Forced oscillation technique and spirometry in cold air provocation tests.

BACKGROUND: Impedance measurements by the forced pseudo random noise oscillation technique can be used to study the mechanical characteristics of the respiratory system. The objective of this study was to analyse the changes in impedance to a cold air provocation test in patients with asthma, and to correlate these changes with those in the forced expiratory volume in one second (FEV1). METHODS: The response to isocapnic hyperventilation with cold air was assessed by respiratory impedance measurements and spirometry in 60 patients with bronchial asthma in whom the provocative dose of histamine resulting in a 20% fall in FEV1 (PD20) was < or = 8 mumol. RESULTS: Cold air provocation resulted in a mean(SD) fall in FEV1 from 3.75(0.85) litres to 3.10(0.90) litres. The mean(SD) decrease in FEV1 as a percentage of predicted was 15.4(3.8)%. The oscillatory resistance at 8 Hz increased from a mean(SD) of 0.367(0.108) kPa/l/s to 0.613(0.213) kPa/l/s and at 28 Hz the resistance increased from 0.348(0.089) to 0.403(0.099) kPa/l/s. Frequency dependence of resistance became significantly more negative. The reactance at 8 Hz decreased from a mean(SD) of -0.035 (0.041) kPa/l/s to -0.234(0.199) kPa/l/s, and the resonant frequency increased from 12.5(4.9) Hz to 25.7(9.1) Hz. Significant correlations were calculated between the decrease in FEV1 and changes in the various impedance parameters, especially between the decrease in FEV1 and the increase in resistance at 8 Hz (r = -0.66), and the decrease in FEV1 and the increase in the resonant frequency (r = -0.63). CONCLUSION: Cold air provocation in asthmatic subjects results in changes in the impedance of the respiratory system that correlate well with the changes in FEV1. These changes in impedance reflect ventilatory inhomogeneities in the peripheral compartment of the bronchial tree. These observations show the value of this technique in the evaluation of induced bronchoconstriction, as both a quantitative and a qualitative analysis of the response is possible.     

A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma.

BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.     

Absence of refractoriness in asthmatic subjects after exercise with warm, humid inspirate.

Twelve asthmatic adults each completed two six minute treadmill runs separated by an interval of 20 minutes. Running speed was constant for each subject, and inspired air temperature averaged 5.5 degrees C (SD 1.5 degree) for both tests. Total minute ventilation and total respiratory heat loss showed no significant difference between the two runs. Forced expiratory volume in one second (FEV1) was measured before exercise and at five minute intervals throughout the recovery periods, during which subjects breathed room air at an average temperature of 17.8 degrees C (1.8 degree). Reduction in FEV1 from pre-exercise readings averaged 39.3% (13.3%) for the first run and 11.5% (7.3%) for the second. On another day the subjects underwent an identical procedure except that the first exercise period was performed with the saturated inspirate at 37.3 degrees C (1.7 degree). This run produced a mean FEV1 reduction of only 3.1% (7.3%). The ensuing run, during which the inspiratory temperature averaged 6.0 degrees C (2.0 degrees), led to a mean fall in FEV1 of 37.3% (17.3%). This was not significantly different from the value recorded for the first of the paired runs with cool air. We therefore have been unable to confirm that exercise with warm humid inspirate may induce refractoriness to exercise induced asthma. Our data are compatible with the theory that refractoriness may be due to depletion of mediators during an initial exercise induced asthma attack.     

Posture and nocturnal asthma.

To investigate whether the supine posture caused sustained bronchoconstriction and could thus contribute to the development of nocturnal asthma, nine patients with nocturnal asthma were studied on two consecutive days, lying supine for four hours on one day and sitting upright for four hours on the other, the order of the two postures being randomised. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were measured immediately before and after the four hours and over the subsequent hour. There was no significant difference between the erect and supine posture for PEF (248 v 248 l/min), FEV1 (1.31 v 1.22 l), or FVC (2.34 v 2.28 l) at the end of the four hours, nor did any significant change develop subsequently. Thus the supine posture is not associated with prolonged bronchoconstriction. As each patient had previously shown an average overnight fall in PEF of more than 20%, this study strongly suggests that the supine posture is not an important cause of overnight bronchoconstriction.     

The airway microvasculature and exercise induced asthma.

It has been proposed that exercise induced asthma is a result of "rapid expansion of the blood volume of peribronchial plexi" (McFadden ER, Lancet 1990;335:880-3). This hypothesis proposes that the development of exercise induced asthma depends on the thermal gradient in the airways at the end of hyperpnoea. The events that result in exercise induced asthma are vasoconstriction and airway cooling followed by reactive hyperaemia. We agree that the airway microcirculation has the potential for contributing to the pathophysiology of exercise induced asthma. We do, however, question whether reactive hyperaemia, in response to airway cooling, is the mechanism whereby hyperpnoea provokes airways obstruction in asthmatic patients. Further, we question whether vasoconstriction accompanies dry air breathing and whether an abnormal temperature gradient and rapid rewarming of the airways are prerequisites for exercise induced asthma. From published experiments we conclude that dry air breathing is associated with vasodilation and increase in airway blood flow rather than vasoconstriction and a decrease in blood flow to the airways. We propose that the stimulus for the increase in airway blood flow is an increase in osmolarity of the airway submucosa. This osmotic change is caused by the movement of water to the airway lumen in response to evaporative water loss during hyperpnoea. The increase in airway blood flow may occur directly or indirectly by the osmotic release of mediators. Exercise induced asthma is most likely to be due to the contraction of bronchial smooth muscle caused by the same mediators. Whether it is enhanced or inhibited by alterations in airway blood flow is not yet established in man.     

Refractory period following induced asthma: contributions of exercise and isocapnic hyperventilation.

To compare the refractory period that follows exercise and isocapnic hyperventilation, 10 asthmatic children performed two pairs of challenge tests in random order at least six hours apart. In pair A a hyperventilation challenge was followed by an exercise challenge and in pair B the order was reversed. Both pairs of tests were done while the children were breathing cold dry air. Tests were matched in terms of work load, ventilation, and end tidal carbon dioxide tension (PCO2). The mean percentage fall in FEV1 (delta FEV1) after the first challenge (hyperventilation) of pair A and the first challenge (exercise) of pair B were the same (30% (SEM 2%)) and 30% (4%) respectively). The mean delta FEV1 of the exercise test following hyperventilation in pair A and of hyperventilation following exercise in pair B was 22% (4%) and 18% (4%) respectively. Both these latter results were significantly lower than the respective delta FEV1 when the challenge was the first test of the pair. Although the mean refractoriness index (reduction in induced asthma in the second test of each pair compared with the first test) was greater when exercise was the first challenge, the difference was not significant.     

Comparison of four stainless steel heat exchangers for neonatal ECMO applications

Conventional neonatal extracorporeal membrane oxygenation (ECMO) circuits utilize a heat exchanger distal to the oxygenator to replace ambient heat loss and maintain patient normothermia. A secondary function of the ECMO heat exchanger is to act as an arterial line bubble trap to protect the patient against accidental air embolism. Using an asanguinous recirculating test circuit, we measured and compared heat transfer properties, pressure drop, air trapping capabilities, and priming characteristics of four commercially available stainless steel heat exchangers currently being used in neonatal ECMO circuits: Avecor ECMOtherm, Gish HE-3, Gish HE-4, and Electromedics D1079. Manufacturers' product specifications were also compared. The pressure drop across all four heat exchangers was less than 10 mmHg with flow rates up to 500 ml/min. The Gish HE-3 and HE-4 were the easiest to prime and de-air, while the Electromedics D1079 was the most difficult. The heat exchangers with integral bubble traps (D1079 and HE-4) have superior air trapping capabilities. The ECMOtherm provided moderate air trapping capabilities ( greater than 7.3 ml +/- 1.5 ml) at flow rates under 300 ml/min. The low prime HE-3 was the poorest at trapping air; less than 1 ml at a 400 ml/min pump flow rate. Thermal analysis indicated that the D1079 had the highest performance factor, though all four heat exchangers had similar heat transfer rates and were capable of warming perfusate from 34 degrees to 37 degrees C on a single pass at pump flow rates of 500 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Controlled-analysis of the effects of inhaled lignocaine in exercise-induced asthma.

To determine whether anaesthesia of the intrathoracic airways would attenuate the development of exercise-induced asthma, we studied eight symptomless asthmatic patients by cycle ergometry after saline or lignocaine pretreatment while they were breathing air at 24 degrees C with 9.1 mg of H2O/l. Pulmonary mechanics were measured before and after the administration of each agent, and again five minutes after cessation of exercise. Sufficient lignocaine was administered to abolish the gag reflex and the cough response to aerosols of citric acid. Before exercise there were no significant differences for any lung function variable between the saline and lignocaine results. Equally, there were no significant differences between these agents for minute ventilation (VE) during exercise (VE lignocaine = 71.0 +/- 7.4 (SEM) l/min; VE saline 67.2 +/- 8.1 l/min;), or in the severity of the subsequent bronchospastic response (for example, the FEV1 with saline was 22.6 +/- 2.9% decrease, and with lignocaine 23.6 +/- 8.5%). Thus these results do not support the idea that there are thermally sensitive neural receptors in intrathoracic airways that play a role in the pathogenesis of exercise-induced asthma.     

Efficacy of Intraoperative Cooling Methods

Background: Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods.

Methods: Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 [degree sign] Celsius, full-length mattress and cover), 2) forced air (10 [degree sign] Celsius, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 [degree sign] Celsius. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression.

Results: The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss 10 [nearly =] 10 W and decreased core temperature 0.8 +/- 0.3 [degree sign] Celsius/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, [nearly =] 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 [degree sign] Celsius/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 [degree sign] Celsius/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss [nearly =] 600-800 W and decreased core temperature 9.7 +/- 4.4 [degree sign] Celsius/h (r sup 2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of [nearly =] 2 [degree sign] Celsius.     

Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness.

The response to inhaled methacholine is increased in patients with chronic airflow obstruction, but it is not known whether this is due to true hyperresponsiveness or is a result of the airflow obstruction. In asthmatics the response to methacholine correlates with the bronchoconstriction produced by hyperventilation of cold dry air. We studied 27 patients with a history of smoking and chronic bronchitis with a range of severity of airflow obstruction. Bronchial responses to methacholine (expressed as the provocation concentration causing a fall in FEV1 of 20%-PC20) and isocapnic hyperventilation of cold dry air were measured. In 19 patients the PC20 was less than 8 mg/ml (that is, in the asthmatic range) but only three developed bronchoconstriction in response to hyperventilation. There was a linear correlation between the log PC20 and the FEV1 (r = 0.86, p less than 0.001). The results suggest that in patients with chronic airflow obstruction the response to methacholine is determined by the degree of airflow obstruction, and cannot be used in the diagnosis of asthma in the absence of additional information.     

Relationship between ambient temperature and heat flux in the scrotal skin

Excessive scrotal heating or cooling may lead to the cessation of spermatogenesis. Data regarding heat exchange rates in scrotal skin can be used to control testicular temperature within the appropriate range. Heat flux (HF) in the scrotal skin surface is generated based on the surrounding environment. This study aims to elucidate the HF of scrotal skin by varying ambient temperature. Twenty college students including seven varicoceles volunteered as the subjects (mean age: 22.95 +/- SD 1.96 years; height: 175.00 +/- 5.17 cm; weight: 68.40 +/- 8.65 kg; body mass index: 22.28 +/- 2.15), and participated in the experiments from September 11 to October 4, 2006. The environmental temperature was controlled at 20 degrees C and 25 degrees C in the first and second experiment respectively. The HF and skin temperature on both sides of the scrotal surface were measured for 60 min in the environmental chamber. The results revealed that the HF was 87.64 +/- 12.69 W/m(2) and 78.91 +/- 12.09 W/m(2) in the left and right side of the scrotum respectively. The scrotal skin temperature (SST) was 30.28 +/- 0.75 degrees C and 30.24 +/- 0.62 degrees C on the left and right side of the scrotum in the 20 degrees C environment respectively. In the 25 degrees C environment the HF was 53.54 +/- 8.86 W/m(2) and 45.25 +/- 8.32 W/m(2), and the SST was 32.29 +/- 0.61 degrees C and 32.07 +/- 0.36 degrees C on the left and right side of the scrotum respectively. The cooling source power to decrease testicular temperature is suggested at 290 W/m(2). This suggested value could be adopted a cooling device as clinical therapy for a heat stress patient to decrease testicular temperature affecting spermatogenesis.     

Clinical dose-response relationship of fluticasone propionate in adults with asthma

BACKGROUND: A study was undertaken to examine the dose-response relation of inhaled fluticasone in adolescents and adults with asthma. METHODS: A meta-analysis was carried out of randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two doses of fluticasone given twice daily. The main outcome measures were forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (amPEF), beta agonist use, and withdrawals due to exacerbations of asthma. RESULTS: Seven studies of 2431 adolescents and adults with moderate to severe asthma met the inclusion criteria for the meta-analysis. Four studies examined a dose of >500 microg/day. For all outcome measures there were no statistically significant differences between a dose of 200 v 500 microg/day, 500 v 1000 microg/day, and 200 v > or =500 microg/day, although the point estimates favoured the higher doses. The mean improvement for FEV1 and amPEF resulting from an increase in dose from 200 to > or =500 microg/day was 0.07 l (95% CI -0.01 to 0.14) and 5.9 l/min (95% CI -3.0 to 15.3), respectively. The odds ratio for withdrawals with 200 microg/day compared with > or =500 microg/day was 1.27 (95% CI 0.78 to 2.07). CONCLUSIONS: In adolescents and adults with asthma, most of the therapeutic benefit of fluticasone is achieved with a total daily dose of 200 microg/day with minimal further clinical benefit achieved with higher doses. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients may obtain a greater clinical benefit at higher doses.     

Effect of positive ionisation of inspired air on the response of asthmatic children to exercise.

To evaluate the effect of positive ionisation of inspired air on bronchial reactivity, 12 asthmatic children were twice challenged by exercise in random order. During one test positively ionised air (5-10 X 10(5) ions/cm) was breathed. All challenges were matched in terms of basal lung function and exercise tests were matched in terms of ventilation and respiratory heat loss. Exercise induced asthma was significantly aggravated by exposure to positively ionised air, the postexercise fall in FEV1 (delta FEV1) being 24.7% (SEM and 5.3%) and 35.3% (5%) after the control and ionised air tests respectively (p less than 0.04). It is concluded that positive ionisation aggravates the bronchial response to exercise.     

Comparison of the effects of inhaled ipratropium bromide and salbutamol on the bronchoconstrictor response to hypocapnic hyperventilation in normal subjects.

A double blind, placebo controlled comparison was made of the effects of nebulised ipratropium bromide (0.05 and 0.5 mg) and salbutamol (0.25 and 2.5 mg) on lung function and the airway response to hyperventilation in eight normal subjects. Both agents at both doses caused similar baseline bronchodilatation, confirming the presence of resting bronchomotor tone. The overall mean increases as percentages of control were 33% in specific airway conductance (sGaw), 10% in maximal flow after expiration of 50% of vital capacity, and 3.7% in FEV1. Hypocapnia (mean end tidal carbon dioxide tension 2.2 kPa) was produced by three minutes of voluntary hyperventilation and resulted in a mean fall in sGaw of 0.49 s-1 kPa-1 (20%). After inhalation of 0.25 mg salbutamol hypocapnic hyperventilation still produced a mean fall in sGaw of 0.55 s-1 kPa-1, whereas salbutamol 2.5 mg reduced this response to 0.15 s-1 kPa-1 (6%). After both doses of ipratropium the decrease in sGaw caused by hyperventilation was similar to the control. This suggests that bronchoconstriction in response to hypocapnic hyperventilation in normal subjects is not mediated via a cholinergic reflex.     

Hyperventilation and asymptomatic chronic asthma

BACKGROUND: We have consistently argued that mild asthma is an important underlying aetiological factor in patients with severe symptomatic hyperventilation. While hyperventilation has been demonstrated in acute asthma, there have been few studies in mild chronic asthma, and mechanisms are uncertain. METHODS: Twenty three currently asymptomatic chronically asthmatic patients (occasional use of bronchodilators, normal lung function, hyperresponsive to methacholine) were studied and 17 matched normal subjects acted as controls. Ventilation, pattern of breathing, arterial carbon dioxide and oxygen tensions (PaCO(2), PaO(2)), end tidal PCO(2) (PETCO(2)), standard lung function, airway responsiveness to methacholine, airway inflammation assessed by eosinophils in induced sputum, and psychiatric morbidity (Spielberger STAI-Y and Beck Depression Inventory) were measured. RESULTS: Despite the absence of current asthmatic symptoms, no clinical evidence of hyperventilation, and normal lung function in the patients with asthma, PaCO(2) and PETCO(2) were significantly (p<0.01) lower in the patients than in the control group (mean (SD) PaCO(2) 4.96 (0.43) kPa for patients versus 5.27 (0.38) kPa for controls (mean difference 0.31 kPa, 95% confidence interval (CI) 0.06 to 0.56, p<0.02)). PETCO(2) was very similar to PaCO(2) in both groups (mean (SD) PETCO(2) 4.89 (0.47) kPa for the patients and 5.28 (0.40) for the controls (mean difference 0.39 kPa, 95% CI 0.12 to 0.66, p<0.01)). There was no significant difference in ventilation or respiratory pattern between the two groups. The reduced PaCO(2) in the asthmatic patients correlated significantly with the concentration of methacholine provoking a fall in FEV(1) of more than 20% (PC(20)) (r = 0.56, p<0.01) but not with any aspect of lung function, eosinophil count, or anxiety/depression. CONCLUSION: Mild asymptomatic asthma is not associated with clinically significant hyperventilation but is associated with a significant reduction in both arterial and end tidal PCO(2) which relates to airway hyperresponsiveness rather than to the degree of airway obstruction or mucosal inflammation. Anxiety and depression appear not to be implicated.