Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis.

Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.

Ventilation-perfusion relationships in symptomatic asthma. Response to oxygen and clemastine.

Continuous distributions of ventilation-perfusion (VA/Q) ratios were measured in ten subjects with moderately severe symptomatic asthma. Six of the subjects had only minimal VA/Q inequality (mean log SD of bloodflow 0.5) despite having airways obstruction similar to that in the four subjects with marked VA/Q inequality (mean log SD of bloodflow 1.0). The six patients with minimal VA/Q inequality developed marked widening of their VA/Q distributions while breathing 100 percent oxygen (mean log SD bloodflow 1.1), and four of these patients maintained more modest widening after receiving an intravenous antihistamine, clemastine (mean log SD bloodflow 0.75). The four subjects with a wide control VA/Q distribution showed smaller changes while breathing pure oxygen and no change after receiving clemastine. FEV1 improved with clemastine treatment in the first four patients only. The results suggest that the majority of patients with moderately severe asthma have compensatory pulmonary vasoconstriction, causing better VA/Q matching which is responsive to hypoxia and, possibly, histamine. The data demonstrate a relationship between active compensatory vasoconstriction and airway sensitivity to antihistamine.

Duration of protection by inhaled salmeterol in exercise-induced asthma.

Beta-adrenoceptor agonists such as albuterol are very effective in preventing exercise-induced asthma (EIA) when they are given as an aerosol immediately before exercise. However, their duration of protection against EIA is usually less than 2 h. This may be due partly to their rapid clearance from the airways. Salmeterol is a highly lipophylic compound that is thought to bind to an exoreceptor near the beta-receptor. The objective of this study was to compare the protective effect of salmeterol with albuterol against EIA. Exercise was performed 0.5, 2.5, 4.5, and 6.5 hours after administration of the active drugs. Subjects attended the laboratory on four days within six weeks and cycled for 8 min breathing dry compressed air. We studied 17 asthmatic subjects (aged 19 to 49 years) with moderate to severe EIA. Salmeterol (50 micrograms) or albuterol (200 micrograms) was given from a metered dose inhaler via a spacer (Volumatic). On the control day, the mean work load +/- 1 SD was 174 +/- 47 W, ventilation (VE) was 77.9 percent +/- 11.2 percent of the target ventilation (60 percent maximum voluntary ventilation [MVV]), and heart rate was 170 +/- 14 beats per minute. This intensity was maintained for all tests. FEV1 was measured before and after exercise and was expressed as percent predicted and as percentage of the preexercise value (percentage of fall). Thirty minutes after treatment, both drugs were effective in inhibiting EIA--percentage of fall in FEV1, 17 +/- 12 after salmeterol; percentage of fall in FEV1, 15 +/- 15 after albuterol. At 2.5, 4.5, and 6.5 hours, the reduction in FEV1 was significantly less (p less than 0.01) after salmeterol compared with albuterol. At 6.5 hours, the percentage of fall in FEV1 was 20 +/- 10 after salmeterol and 36 +/- 12 after albuterol. Salmeterol also had a more prolonged action as a bronchodilator and values for FEV1 were significantly higher compared with those on albuterol at 4.5 and 6.5 hours. At 6.5 hours, the FEV1 percent predicted was 96 +/- 10 after salmeterol and 84 +/- 12 after albuterol (p less than 0.01). We conclude that the extent of protection against EIA and the bronchodilation induced by both drugs was similar, but that salmeterol has a longer duration of action compared with albuterol. The reason for its superior duration of action may be due to a slower clearance of the drug from the airways.

The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis.

STUDY OBJECTIVE: To investigate the acute effect of mannitol on the clearance of mucus, and (1) the 24-h mucus retention, and (2) the mucus clearance rate and lung function 24 h after inhalation of a single dose of mannitol. DESIGN: Clearance of mucus was measured on 3 consecutive days using (99m)Tc-sulfur colloid radioaerosol and a gamma camera. INTERVENTIONS: Mannitol, 330 +/- 68 mg (mean+/- SD), was inhaled using a dry powder inhaler only on day 2. PATIENTS: Eight patients with bronchiectasis (age range, 29 to 70 years). MEASUREMENTS AND RESULTS: On each day, lung images were collected over 2 h and at 24 h. Key findings of the study are as follows: (1) the 24-h retention of mucus was reduced the day after mannitol had been inhaled, compared to the day without mannitol (day 1) in the whole right lung (57.6 +/- 6.2% vs 68.1 +/- 5.9%), central (47.5 +/- 6.7% vs 56.9 +/- 6.5%), intermediate (61.7 +/- 5.6% vs 73.8 +/- 5.5%), and peripheral regions (70.9 +/- 4.3% vs 86.6 +/- 4.6%)(p < 0.02); and (2) mannitol helped patients clear mucus within 2 h that might otherwise take up to 24 h, from the whole right lung and defined regions. However, clearance over 60 min measured 24 h after mannitol inhalation was not significantly different to baseline clearance without mannitol (8.7 +/- 1.9% on day 1 vs 9.7 +/- 3.7% 24 h after mannitol; p > 0.8). The patients maintained the same lung function the day before and after mannitol had been inhaled: FEV(1) (percent predicted), 79 +/- 5 on day 1 vs 80 +/- 5 on day 3; and forced expiratory flow, midexpiratory phase (percent predicted), 50 +/- 6 on day 1 vs 51 +/- 6 on day 3; p > 0.6). CONCLUSIONS: Mannitol inhalation acutely increases clearance of mucus, and this effect extends beyond the acute study period, resulting in decreased mucus retention at 24 h.

The distribution of ventilation-perfusion ratios in the lungs of a dysmature foal.

The distribution of ventilation-perfusion (VA/Q) ratios, before and after 100 per cent oxygen, was studied in an induced-premature foal at 4 h and again at eleven days of age, using the multiple inert gas elimination technique. The major finding was an absence of low VA/Q ratios when breathing air, indicating that low PaO2 in the neonatal period was totally attributable to the right-to-left shunt. At 4 h of age the PaO2 was 5.48 kPa and the right-to-left shunt represented 33.4 per cent of the cardiac output. At eleven days of age the PaO2 was 9.76 kPa and right-to-left shunt was 10.1 per cent of cardiac output. At both ages there was a separate high mode where ventilation was greatly in excess of blood flow but at neither age were units with low VA/Q ratios present. Oxygen breathing for 40 mins did not increase the right-to-left shunt, but at eleven days right-to-left shunt decreased when 100 per cent oxygen was administered.

Adult domiciliary oxygen therapy: position statement of the Thoracic Society of Australia and New Zealand.

Evidence shows that patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of 55 mm Hg or less will have longer life expectancy if given supplemental oxygen to keep the PaO2 above 60 mm Hg, preferably for longer than 15 hours a day, including sleep. There is some evidence for improved quality of life. It is reasonable to offer this therapy for other lung diseases which cause chronic hypoxaemia, and there are also less well defined indications for supplemental oxygen during exercise, sleep and air travel.

A tidally breathing model of ventilation, perfusion and volume in normal and diseased lungs.

BACKGROUND: To simulate the short-term dynamics of soluble gas exchange (e.g. CO2 rebreathing), model structure, ventilation-perfusion (VA/Q) and ventilation-volume (VA/VA) parameters must be selected correctly. Some diseases affect mainly the VA/Q distribution while others affect both VA/Q and VA/VA distributions. Results from the multiple inert gas elimination technique (MIGET) and multiple breath nitrogen washout (MBNW) can be used to select VA/Q and VA/VA parameters, but no method exists for combining VA/Q and VA/VA parameters in a multicompartment lung model. METHODS: We define a tidally breathing lung model containing shunt and up to eight alveolar compartments. Quantitative and qualitative understanding of the diseases is used to reduce the number of model compartments to achieve a unique solution. The reduced model is fitted simultaneously to inert gas retentions calculated from published VA/Q distributions and normalized MBNWs obtained from similar subjects. Normal lungs and representative cases of emphysema and embolism are studied. RESULTS: The normal, emphysematous and embolism models simplify to one, three and two alveolar compartments, respectively. CONCLUSIONS: The models reproduce their respective MIGET and MBNW patient results well, and predict disease-specific steady-state and dynamic soluble and insoluble gas responses.

Effect of intrapulmonary hematocrit maldistribution on O2, CO2, and inert gas exchange.

The potential effect of intrapulmonary variations in hematocrit on gas exchange has been studied in theoretical models of the lung containing maldistribution of both hematocrit (Hct) and ventilation-perfusion (VA/Q) ratio. Hematocrit inequality enhanced gas exchange when units of low VA/Q were given a low Hct, arterial PO2 rising by as much as 14 Torr and PCO2 falling by up to 2 Torr depending on the particular distributions of Hct and VA/Q, whereas gas exchange was depressed when units of low VA/Q had a high Hct. After measuring inert gas solubilities in both dog and human blood of different Hct, the effect of Hct inequality on inert gas exchange was similarly assessed. Solubility was found to increase with HCT for less soluble gases. Because of this, conditions for enhancement of inert and O2 exchange by HCt inequality coincided, and it was found that in general the effects on O2 and inert gas transfer were quantitatively internally consistent. Even when Hct inequality was extreme, the resulting perturbation of inert gas concentrations was sufficiently small that the main features of the recovered VA/Q distributions were unaltered.

Solubility of inert gases in homogenates of canine lung tissue.

The solubility of sulfur hexafluoride (SF6), ethane, cyclopropane, halothane, diethyl ether, and acetone in homogenates of dog lung tissue were measured and compared with values obtained in dog blood. The measurements were made to provide data for a method for determining distribution of ventilation, blood flow, and tissue volume (Physiologist 20: 95, 1977) and for reasons discussed, the blood was not washed from the tissue prior to homogenization. All gases except SF6 were significantly more soluble in blood than lung tissue, whereas SF6 was 3.7 times more soluble in tissue than blood. It was further found that SF6 is 5 times more soluble, and ethane is twice as soluble in tissue obtained from lungs containing blood than in tissue obtained from rinsed lungs, suggesting that measurements of parenchymal solubility made on tissue from sinsed lungs may be considerably in error for some lipid-soluble gases.

Changes in arterial blood gas tensions during unsteady-state exercise.

Arterial oxygen (Pao2) and carbon dioxide (Paco2) tensions and inspired minute ventilation were measured during the first 2 min of stair-climbing exercise in nine normal subjects. The subjects climbed a staircase at a rate of approximately 9 m vertical height every minute and arterial blood was drawn from an indwelling cannula at 15-s intervals. Large falls in Pao2 from a resting value of 92 +/- 2.0 (mean +/- SE) Torr to a lowest value of 65 +/- 3.4 Torr were recorded in the first 50 s of exercise while Paco2 oscillated around the resting value. Most subjects demonstrated an initial plateau of Pao2 for at least 7 s followed by a rapid fall and subsequent rise toward the resting level after 1 min. The falls in Pao2 measured were larger than those reported for laboratory exercise. The possible reasons for this discrepancy are discussed.

Arterial blood gas tension changes at the start of exercise in chronic obstructive pulmonary disease.

In a previously reported study of a group of normal subjects, large decreases in arterial O2 tension (PaO2) of as much as 37 mm Hg were measured during the first 90 sec of slow stair-climbing exercise (chosen as a common daily exertion). This study reports the changes in PaO2, arterial CO2 tension (PaCO2), and ventilation in 7 patients with chronic obstructive pulmonary disease and resting hypoxemia during the first 90 sec of similar exercise. The patient group showed significantly smaller unsteady-state decreases in PaO2 starting from a smaller resting value (patient group, 72 +/- 2.6 mm Hg, mean +/- SE; normal group, 92 +/- mm Hg; P less than 0.001) and decreasing to a similar smallest value (patient group, 58 +/- 3.8 mm Hg; normal group, 65 +/- 3.4 Hg; P greater than 0.05). PaCO2 tended to oscillate around the resting value in both the patient group and the normal group, and the rates of increase in ventilation in the 2 groups were similar. The physiologic processes that could limit the unsteady-state decrease in PaCO2 in the patient group are analyzed, the analysis suggesting that a slower rate of increase in tissue consumption of O2 is most likely to account for the smaller decrease in PaO2.

Effect of low dose nebulised morphine on exercise endurance in patients with chronic lung disease.

Low dose nebulised morphine may relieve dyspnoea through a direct effect on lung afferent nerves. To study this further 11 adult patients with advanced chronic lung disease (FEV1 range 0.4-1.41), whose exercise endurance was limited by dyspnoea, were entered into a double blind, randomised, crossover study in which low dose morphine or a placebo was inhaled. The effects were assessed by an endurance exercise test at 80% of maximum work load. One hour after a control endurance test patients inhaled 5 ml of morphine 1 mg/ml or isotonic saline for 12 minutes from a jet nebuliser. An endurance exercise test was repeated 15 minutes later and change in endurance time recorded. The two endurance tests were repeated on a separate day, before and after inhalation of the alternative solution. In all tests 100% oxygen was inhaled from a demand valve. The mean (SD) increase in endurance time was significantly greater after the subjects had inhaled morphine (64.6 (115) s, 35%) than after placebo (8.9 (55) s, 0.8%; p less than 0.01). The mean dose of morphine nebulised was 1.7 (0.66) mg, giving a mean inhaled dose of about 0.6 mg, on the assumption of 30% retention of the nebulised dose by each patient. No side effects were reported. Possibly small amounts of morphine delivered to the lungs act directly on lung afferent nerves to reduce dyspnoea.

The oxygen delivery characteristics of the Hudson Oxy-one face mask.

The inspired oxygen fraction (FIO2) delivered by the Hudson Oxy-one face mask was measured under changing conditions of ventilation, oxygen flow rate to mask, and mask fit. A single trained subject sat in a body plethysmograph to measure ventilation and breathed at a constant rate of 15 per minute at three different tidal volumes, of approximately 0.3, 0.6, and 1.2 litres, from the mouthpiece in the plethysmograph. The Oxy-one face mask was fitted to a plaster-of-Paris face model on the outside of the plethysmograph in a loose and then in a tight fashion. Oxygen concentration was continuously monitored from a point in the metal tube connecting the face model to the mouthpiece. The tightly fitting mask demonstrated an orderly reduction in FIO2 as ventilation increased and oxygen flow rate to the mask decreased. The mean FIO2 at a ventilation of 4.5 l.min-1 and 8 l.min-1 oxygen flow was 78% and this fell to 27% at a ventilation of 16 l.min-1 and oxygen flow of 2 l.min-1. The loosely fitting mask demonstrated larger SD of measurements and lower mean maximum FIO2 values of 46 to 49% and these fell in an irregular fashion to similar minimum values as ventilation increased and oxygen flow decreased. Although the precise definition of the FIO2 for each breath from the changing concentration during each inspiration was not possible, these results indicate that FIO2 changes in a predictable way as a function of ventilation and oxygen flow, if the mask is close fitting. This method could be conveniently used to study other oxygen delivery systems.

Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of Australia and New Zealand.

Evidence shows that patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of 55 mm Hg or less will have longer life expectancy if given supplemental oxygen to keep the PaO2 above 60 mm Hg, preferably for longer than 15 hours a day, including sleep. There is some evidence for improved quality of life. It is reasonable to offer this therapy for other lung diseases which cause chronic hypoxaemia, and there are also less well defined indications for supplemental oxygen during exercise, sleep and air travel.

Pattern and time course of ventilation-perfusion inequality in exercise-induced asthma.

The relation between exercise-induced airway obstruction and changes in the gas exchange function of the lung was studied in 6 subjects with asthma. Continuous distributions of ventilation perfusion (VA/Q) ratios and spirometry were measured before and at intervals after an exercise challenge that caused a greater than 20% decrease in FEV1 or in peak expiratory flow rate (PEFR). Before exercise, all subjects had unimodal VA/Q distributions that were broader than normal (mean log SD of blood flow, 0.54) and all developed wider distributions 15 to 28 min after the start of the 8-min exercise challenge (mean log SD of blood flow, 1.02). Two subjects developed bimodal VA/Q distributions, but all distributions returned to baseline configuration within 58 min, usually before FEV1 and PEFR had returned to baseline values. There was no relation between the decrease in FEV1 or PEFR and the degree of VA/Q inequality. Aerosolized salbutamol resulted in improved spirometry and further narrowing of the VA/Q distributions in 3 subjects tested.

Fulminant psittacosis requiring mechanical ventilation and demonstrating serological cross-reactivity between Legionella longbeachae and Chlamydia psittaci.

Chlamydia psittaci infection typically causes a mild respiratory illness in humans. Severe respiratory failure requiring mechanical ventilation or intensive care therapy is an uncommon development. The aetiological agents causing severe community acquired pneumonia often remain undetermined. Serological tests may aid in diagnosis. We present two cases of fulminant psittacosis, one demonstrating early cross-reactivity with Legionella longbeachae.

Use of protected telescoping brush system in the management of bacterial pulmonary infection in intubated patients.

The diagnosis of pulmonary infection remains a major problem in the management of intubated patients with respiratory failure. We performed fibreoptic bronchoscopy and protected telescoping catheter brushing in 25 such patients, in order to assess the role of this technique in the diagnosis of bacterial pulmonary infection. All patients were intubated, demonstrated lung field opacities on chest radiograph and 23 had bacteria grown from tracheal aspirate culture. A single microorganism was recovered from plugged telescoping catheter (PTC) brush in eight patients, two or more organisms in nine patients and eight had a sterile culture. These results led to a specific management decision in 13 patients. All patients were ventilated with positive pressure and a pneumothorax, attributable to the procedure, developed in two. The difficulties in assessing the sensitivity and specificity of this technique in human studies are outlined. This procedure appears to have a useful role in the diagnosis of pneumonia in these patients and in further evaluating the importance of bacterial colonization of the airways and its relationship to parenchymal lung infection.

Lack of effect of high doses of inhaled morphine on exercise endurance in chronic obstructive pulmonary disease.

Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Small doses of inhaled opiates may have similar effects; however, recent studies have shown no benefit. We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic. Twenty and 40 mg doses and 0.9% saline were nebulized in a randomized, double-blind study of 16 patients with stable COPD. Patients performed 6 min walk tests immediately after the nebulized test solution (Walk 1) and again 60 min later (Walk 2). Arterial oxygen saturation (Sa,O2), modified Borg dyspnoea score and cardiac frequency were recorded during each walk. There was no difference between placebo and either dose of nebulized morphine on these measurements. The higher dose of nebulized morphine achieved a higher plasma concentration. The highest plasma concentration was measured immediately after nebulization, and this decreased steadily in the hour thereafter (p<0.002). There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine. We conclude that higher doses of nebulized morphine do not improve exercise endurance or relieve dyspnoea in patients with chronic obstructive pulmonary disease, and that morphine is rapidly absorbed systemically after inhalation.

Differences in airway closure between normal and asthmatic subjects measured with single-photon emission computed tomography and technegas.

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.