Nocturnal hypoxia in motor neuron disease is not predicted by standard respiratory function tests.

BACKGROUND: With increasing awareness of motor neuron disease (MND) in Australia, the approach to respiratory management of patients with this disease will more commonly face the respiratory physician. AIM: The aim of this study was to determine if standard respiratory function tests could determine the presence of nocturnal hypoxia (NH) in patients with MND. METHODS: Respiratory function tests were used to examine daytime respiratory function, and sleep studies were used to detect NH in 16 consecutive patients with MND and in 9 healthy control subjects. Demographic data, clinical parameters, respiratory function tests and sleep studies were obtained. Statistical analyses were carried out using t-tests and anova, where appropriate. RESULTS: NH was detected in 50% of patients with MND, with no hypoxic events detected in the control group. Standard respiratory function tests were not able to predict the presence of NH. CONCLUSION: There was no correlation between respiratory function tests and NH. This study emphasizes the inability of standard respiratory function tests to predict NH that may arise early in the course of MND.

The effect of nitrous oxide on the measurement of single-breath transfer factor.

One hour after a bone marrow biopsy and inhalation of Entonox gas (50% nitrous oxide (N2O) and 50% oxygen), a patient had a markedly reduced transfer factor of the lung for carbon monoxide (TL,CO). Three hours after Entonox, the patient had a normal TL,CO. Since carbon monoxide (CO) and N2O have similar spectral wavelengths, it was proposed that residual N2O in the lungs was interfering with the infra-red analysers used to detect CO concentrations. Experiments were performed to verify the "interference" effect and its duration. Five healthy volunteers performed serial triplicate TL,CO measurements over 3 h on two randomized days (Control vs N2O). The first triplicate TL,CO on each day served as a baseline measurement. Following the baseline measurement on the N2O day, each subject inhaled Entonox for 10 min. To serve as a control for the infrared effect, the identical protocol was repeated using a gas chromatography method for TL,CO determination. The infra-red method showed a marked reduction (> 50%) in TL,CO 30 min after N2O inhalation. This reduction did not return to baseline levels for at least 2 h. In comparison, the gas chromatography method showed no significant reduction in TL,CO. In a group of healthy nonsmoking subjects, N2O markedly affected the measurement of the transfer factor of the lungs for carbon monoxide using infra-red analysers. The time course over which the measurement was reduced was at least 2 h for a 10 min inhalation period. The effect was entirely due to a measurement error associated with infra-red technology.

Use of the Sensormedics MCT Accelerator in sputum induction.

Airway inflammation can be studied by obtaining sputum induced by inhalation of 3% saline. The Sensormedics MCT accelerator is an oral asymmetrical high frequency oscillator which safely enhances clearance of airway secretions. The aim of this study was to determine if use of the MCT Accelerator enhances sputum production in non-asthmatic non-atopic, atopic and asthmatic subjects. Fifteen subjects were studied over 3 days. On day 1 skin prick testing to common aeroallergens and methacholine bronchial reactivity were performed. On days 2 and 3, separated by 7 days, sputum was induced by inhalation of 3% saline alone for 30 mins or via the nebulizer port of the MCT Accelerator. The cellular profile and volume of sputum were analysed. The use of the MCT Accelerator did not alter the cellular profile of the induced sputum nor was there an increase in volume. In conclusion the induction of sputum by inhalation of 3% saline was not altered by use of the MCT Accelerator.

Evidence for opioid modulation and generation of prostaglandins in sulphur dioxide (SO)2-induced bronchoconstriction.

BACKGROUND: Inhalation of sulphur dioxide (SO2) provokes bronchoconstriction in asthmatic subjects. Cholinergic mechanisms contribute, but other mechanisms remain undefined. The effect of morphine, an opioid agonist, on the cholinergic component of SO2-induced bronchoconstriction was investigated, and the effect of indomethacin, a cyclooxygenase inhibitor, on SO2-induced bronchoconstriction and tachyphylaxis was studied. METHODS: In the first study 16 asthmatic subjects inhaled either ipratropium bromide or placebo 60 minutes before an SO2 challenge on days 1 and 2. On day 3 an SO2 challenge was performed immediately after intravenous morphine. In the second study 15 asthmatic subjects took either placebo or indomethacin for three days before each study day when two SO2 challenges were performed 30 minutes apart. The response was measured as the cumulative dose causing a 35% fall in specific airways conductance (sGaw; PDsGaw35). RESULTS: Ipratropium bromide significantly inhibited SO2 responsiveness, reducing PDsGaw35 by 0.89 (95% CI 0.46 to 1.31) doubling doses. This effect persisted after correction for bronchodilatation induced by ipratropium bromide. The effect of ipratropium bromide and morphine on SO2 responsiveness also correlated (r2 = 0.71). In the second study SO2 tachyphylaxis developed with PDsGaw35 on repeated testing, being reduced by 0.62 (95% CI 0.17 to 1.07) doubling doses. Indomethacin attenuated baseline SO2 responsiveness, increasing PDsGaw35 by 0.5 (95% CI 0.06 to 0.93) doubling doses. CONCLUSIONS: These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2.

Comparison of sulphur dioxide and metabisulphite airway reactivity in subjects with asthma.

BACKGROUND: In asthmatic subjects bronchoconstriction is induced by inhalation of the common food preservatives sulphur dioxide (SO2) and metabisulphite (MBS). SO2 and MBS challenges share many similarities, but it is not known whether they are equivalent. In this study of subjects with mild clinical asthma equivalence was assessed by comparing SO2 and MBS reactivity by estimating the total dose of SO2 inhaled during SO2 and MBS challenges, and by calculating SO2 uptake during both challenges. In addition, as the MBS solutions inhaled were acidic and hyperosmolar, the effect of these factors on MBS responsiveness was investigated. METHODS: Fifteen subjects were challenged on separate days with doubling (0.5 to 8.0 ppm) concentrations of SO2 gas inhaled during three minute periods of isocapnic hyperventilation and MBS administered in doses ranging from 0.1 to 12.8 mumol using the Wright protocol. On two other days SO2 and MBS challenges were preceded by a challenge with phosphate buffered saline (PBS) solutions of pH and osmolarity similar to MBS solutions. Response was measured as the dose or concentration causing a 20% fall in FEV1 (PD20 or PC20). RESULTS: All subjects reacted to MBS and 14 responded to SO2. Geometric mean histamine PD20 was 1.61 mumol (95% confidence interval 0.72 to 3.60). MBS and SO2 airway responsiveness were not significantly related. Estimates of the mean concentration of SO2 inhaled during SO2 and MBS challenges differed, as did estimates of the mean SO2 uptake during both challenges. MBS and SO2 reactivity were not affected by prior challenge with PBS solutions. CONCLUSIONS: SO2 and MBS challenges are not comparable. MBS reactivity was not affected by the hyperosmolar, acidic nature of its solutions.

The relationship of inhaled sulfur dioxide reactivity to ingested metabisulfite sensitivity in patients with asthma.

When ingested in acid solution, the preservative sodium metabisulfite (MB) provokes asthma within minutes of ingestion in a proportion of asthmatic subjects. Freshly prepared acid solutions of MB liberate significant quantities of gaseous SO2. In order to test the hypothesis that asthma provoked by ingestion of acidified solutions of MB was due to supersensitivity to SO2 inhaled during swallowing, 3 groups of 10 subjects were studied. Groups 1 and 2 were asthmatics. Group 1 subjects were reactors and Group 2 were nonreactors to ingested MB. Group 3 subjects were nonasthmatic control subjects. Subjects were challenged, on separate days, with 50 mg of MB in citric acid and SO2 gas, via a steady-state system, at increasing concentrations (0.5, 1.5, 3, 5 ppm). The mean percent fall in peak expiratory flow rates after ingestion of MB for Group 1 was 35 +/- 14, Group 2 was 6 +/- 6, and Group 3 was 5 +/- 3. The mean SO2 provocation concentration (Pc20.SO2) for Group 1 was 1.19 +/- 0.78 ppm, for Group 2 it was 2.25 +/- 1.42 ppm, and for Group 3 it was greater than 5 ppm. The means for Pc20.SO2 of Groups 1 and 2 were not statistically different (p = 0.075), although the possibility of a Type 2 error is recognized. Five MB-sensitive subjects were subsequently challenged with the MB solution by mouthwash and nasogastric tube. Asthma was provoked in all 5 subjects by mouthwash but not by gastric challenge.(ABSTRACT TRUNCATED AT 250 WORDS)