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D P Johns

Publications and source records attributed to D P Johns.

At least 19 recordsLinked to original sources

European Community Respiratory Health Survey calibration project of dosimeter driving pressures.

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure. Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey. A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean+/-SD output of 7.0+/-0.8 mg x s(-1) and batch two, 6.3+/-0.7 mg x s(-1) (p<0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70-245 kPa, with most outside the quoted manufacturer's specification of 180+/-5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R2)=0.99, output=0.0377 x driving pressure-0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second. Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has been instigated by the organizing committee for the European Community Respiratory Health Survey II.

Aerosols↗

Reduced airway distensibility, fixed airflow limitation, and airway wall remodeling in asthma.

The airways of individuals with asthma are less distensible than normal and it has been assumed that this may be due to airway remodeling associated with chronic inflammation, although there are currently no available data directly relating these two aspects of asthma. We have therefore carried out a study of the relationship between airway distensibility (DeltaVD) and subepithelial reticular basement membrane (RBM) thickening as an index of airway remodeling, in a group of patients with relatively mild but symptomatic asthma. Our methods included a cross-sectional study of DeltaVD in patients with mild to moderate atopic asthma, with matched airway biopsy for structural components. We confirmed that DeltaVD was lower in patients with asthma than in normal individuals (19.8 +/- 1.1 versus 24.1 +/- 1.5; p < 0.05) and that RBM thickness was increased in patients with asthma (9.1 +/- 2.2 versus 7.7 +/- 1.2 microm; p < 0.01). There was a negative correlation between DeltaVD and RBM thickness in asthma (r = -0.37, p = 0.03) and positive correlations between percent predicted postbronchodilator large and small airway function (for percent predicted FEV(1 )versus DeltaVD, r = 0.59, p < 0.001). We conclude that, cross-sectionally, DeltaVD was related to airway remodeling (RBM thickening) and airflow limitation (percent predicted large and small airway function). Our findings support the hypothesis that DeltaVD is a physiologic test that is reflective of airway remodeling.

Adult↗

Airway distensibility in healthy and asthmatic subjects: effect of lung volume history.

Anatomic dead space (VD) is known to increase with end-inspiratory lung volume (EILV), and the gradient of the relationship has been proposed as an index of airway distensibility (DeltaVD). The aims of this study were to apply a rapid method for measuring DeltaVD and to determine whether it was affected by lung volume history. VD of 16 healthy and 16 mildly asthmatic subjects was measured at a number of known EILVs by using a tidal breathing, CO(2)-washout method. The effect of lung volume history was assessed by using three tidal breathing regimens: 1) three discrete EILVs (low/medium/high; LMH); 2) progressively decreasing EILVs from total lung capacity (TLC; TLC-RV); and 3) progressively increasing EILVs from residual volume (RV; RV-TLC). DeltaVD was lower in the asthmatic group for the LMH (25.3 +/- 2.24 vs. 21.2 +/- 1.66 ml/l, means +/- SE) and TLC-RV (24. 3 +/- 1.69 vs. 18.7 +/- 1.16 ml/l) regimens. There was a trend for a lower DeltaVD in the asthmatic group for the RV-TLC regimen (23.3 +/- 2.19 vs. 18.8 +/- 1.68 ml/l). There was no difference in DeltaVD between groups. In conclusion, mild asthmatic subjects have stiffer airways than normal subjects, and this is not obviously affected by lung volume history.

Adult↗

Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure.

Given that the apnea-ventilation cycle length during central sleep apnea (CSA) with congestive heart failure (CHF) is approximately 70 s, we hypothesized that rapidly responsive peripheral CO(2) ventilatory responses would be raised in CHF-CSA and would correlate with the severity of CSA. Sleep studies and single breath and rebreathe hypercapnic ventilatory responses (HCVR) were measured as markers of peripheral and central CO(2) ventilatory responses, respectively, in 51 subjects: 12 CHF with no apnea (CHF-N), 8 CHF with obstructive sleep apnea (CHF-OSA), 12 CHF-CSA, 11 CSA without CHF ("idiopathic" CSA; ICSA), and 8 normal subjects. Single breath HCVR was equally elevated in CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (0.58 +/- 0.09 [mean +/- SE] and 0. 58 +/- 0.07 versus 0.23 +/- 0.06, 0.25 +/- 0.04, and 0.27 +/- 0.02 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Similarly, rebreathe HCVR was elevated in both CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (5.80 +/- 1.12 and 3.53 +/- 0. 29 versus 2.00 +/- 0.25, 1.44 +/- 0.16, and 2.14 +/- 0.22 L/min/PET(CO(2)) mm Hg, respectively, p < 0.001). Furthermore, in the entire CHF group, single breath HCVR correlated with central apnea-hypopnea index (AHI) (r = 0.63, p < 0.001) and percentage central/total apneas (r = 0.52, p = 0.022). Rebreathe HCVR correlated with awake Pa(CO(2)) (r = -0.61, p < 0.001), but not with central AHI or percentage central/total apneas independent of its relationship with single breath HCVR. In conclusion, in subjects with CHF, raised central CO(2) ventilatory response predisposes to CSA promoting background hypocapnia and exposing the apnea threshold to fluctuations in ventilation, whereas raised and faster-acting peripheral CO(2) ventilatory response determines the periodicity and severity of CSA.

Analysis of Variance↗

A critical evaluation of the Mefar dosimeter.

Multicentre studies of airway responsiveness (AR) are increasingly important tools in asthma epidemiology. Because comparisons of AR are made between centres it is essential that measurement techniques are accurate and standard. This study investigated the Mefar dosimeter which is currently used in the 35 centre European Community Respiratory Health Survey (ECRHS) with the next phase currently being planned. Significant differences were found in driving pressures and aerosol outputs between the three Mefar dosimeters in the laboratory. A linear relationship was also found between driving pressure and aerosol output (R2=0.96). These differences are important as they may lead to variations between centres of < or =35% in the drug dose delivered in AR measurement, which could potentially diminish the power of individual study centres to accurately detect national differences in AR. Dosimeter driving pressure and nebulizer output should be standardized in future studies of airway responsiveness. With relatively simple quality control measures in place it is believed that the Mefar dosimeter can produce reliable between-centre longitudinal data with an increase in the accuracy of these important studies.

Aerosols↗

A cost-analysis of two approaches to infection control in a lung function laboratory.

BACKGROUND: The Thoracic Society of Australia and New Zealand (TSANZ) guidelines for infection control in respiratory laboratories are based on a 'Universal Precautions' approach to patient care. This requires that one-way breathing valves, flow sensors, and other items, be cleaned and disinfected between patient use. However, this is impractical in a busy laboratory. The recent introduction of disposable barrier filters may provide a practical solution to this problem, although most consider this approach to be an expensive option. AIM: To compare the cost of implementing the TSANZ infection control guidelines with the cost of using disposable barrier filters. METHODS: Costs were based on the standard tests and equipment currently used in the lung function laboratory at The Alfred Hospital. We have assumed that a barrier filter offers the same degree of protection against cross-infection between patients as the TSANZ infection control guidelines. Time and motion studies were performed on the dismantling, cleaning, disinfecting, reassembling and re-calibrating of equipment. Conservative estimates were made as to the frequency of replacing pneumotachographs and rubber mouthpieces based on previous equipment turnover. Labour costs for a scientist to reprocess the equipment was based on $20.86/hour. The cost of employing a casual cleaner at an hourly rate of $14.07 to assist in reprocessing equipment was also investigated. The new high efficiency HyperFilter disposable barrier filter, costing $2.95 was used in this cost-analysis. RESULTS: The cost of reprocessing equipment required for spirometry alone was $17.58 per test if a scientist reprocesses the equipment, and $15.56 per test if a casual cleaner is employed to assist the scientist in performing these duties. In contrast, using a disposable filter would cost only $2.95 per test. Using a filter was considerably less expensive than following the TSANZ guidelines for all tests and equipment used in this cost-analysis. CONCLUSIONS: The TSANZ infection control guidelines are expensive and impractical to implement. However, disposable barrier filters provide a practical and inexpensive method of infection control.

Australia↗

Respiratory function in lambs after in utero treatment of lung hypoplasia by tracheal obstruction.

Tracheal obstruction (TO) stimulates growth of hypoplastic lungs in the fetus, but there is little knowledge of subsequent postnatal respiratory function. We have determined the effectiveness of TO in fetal sheep with existing lung hypoplasia in restoring postnatal respiratory function. Lung hypoplasia was induced by lung liquid drainage from 112 days of gestation to term ( approximately 148 days). We used an untreated group (ULH), a treated group (TLH) in which the trachea was obstructed for 10 days, and a control group. ULH lambs died within 4 h of birth. TLH lambs were hypoxic for the first week and were hypercapic at 2 days. Pulmonary diffusing capacity, gas volumes, and respiratory compliances were not different between control and TLH lambs. Minute ventilation was not different between the two groups; however, tidal volumes were lower and respiratory frequencies were higher in TLH lambs than in controls for 2 wk after birth. We conclude that 10 days of TO in the presence of initial lung hypoplasia prevents death at birth and returns most aspects of pulmonary function to normal by 1-2 wk after birth.

Aging↗

Postnatal development of respiratory function in lambs studied serially between birth and 8 weeks.

We have quantified developmental changes in major aspects of respiratory function in 12 pentobarbitone-sedated lambs by making repeated measurements during the first 8 postnatal weeks, between term birth and post-weaning. Pulmonary diffusing capacity for CO increased with age due to increases in both the diffusing capacity of the alveolar capillary membrane (Dm) and pulmonary capillary blood volume (Vc). Total lung capacity measured at a lung inflation pressure of 30 cmH2O decreased from 74.4 +/- 3.2 ml/kg at 3 days to 47.2 +/- 2.9 ml/kg at 8 weeks. Static respiratory system compliance, measured between FRC and TLC fell rapidly during the first 3 weeks, then remained unchanged; the early postnatal fall was largely due to a reduction in chest wall compliance as lung compliance was constant. FRC declined from 32.3 +/- 1.7 ml/kg at 3 days to 25.1 +/- 1.5 ml/kg at 2 weeks, then fell to 21.4 +/- 1.2 ml/kg by 8 weeks. Specific pulmonary conductance (conductance/FRC) during mid-inspiration and mid-expiration did not change with age (0.195 +/- 0.012 and 0.194 +/- 0.019 L x sec(-1) x cmH2O(-1) x L(-1)-FRC, respectively). Breathing frequency, and weight-adjusted tidal volume and minute ventilation declined after birth until 4 weeks after which they did not change. This study has shown that, using basic methodology, serial assessments of respiratory function can be obtained in sedated lambs from soon after birth. The age-related increase seen in pulmonary diffusing capacity is due to increases in both Dm and Vc, which are consistent with continuing alveolarisation. Our data on age-related changes in pulmonary function and volumes provide a reference for future studies on the effect of altered prenatal lung development on postnatal lung function in sheep.

Aging↗

Effect of breathing circuit resistance on the measurement of ventilatory function.

BACKGROUND: The American Thoracic Society (ATS) has set the acceptable resistance for spirometers at less than 1.5 cm H2O/l/s over the flow range 0-14 l/s and for monitoring devices at less than 2.5 cm H2O/l/s (0-14 l/s). The aims of this study were to determine the resistance characteristics of commonly used spirometers and monitoring devices and the effect of resistance on ventilatory function. METHODS: The resistance of five spirometers (Vitalograph wedge bellows, Morgan rolling seal, Stead Wells water sealed, Fleisch pneumotachograph, Lilly pneumotachograph) and three monitoring devices (Spiro 1, Ferraris, mini-Wright) was measured from the back pressure developed over a range of known flows (1.6-13.1 l/s). Peak expiratory flow (PEF), forced expiratory flow in one second (FEV1), forced vital capacity (FVC), and mid forced expiratory flow (FEF25-75%) were measured on six subjects with normal lung function and 13 subjects with respiratory disorders using a pneumotachograph. Ventilatory function was then repeated with four different sized resistors (approximately 1-11 cmH2O/l/s) inserted between the mouthpiece and pneumotachograph. RESULTS: All five diagnostic spirometers and two of the three monitoring devices passed the ATS upper limit for resistance. PEF, FEV1 and FVC showed significant (p < 0.05) inverse correlations with added resistance with no significant difference between the normal and patient groups. At a resistance of 1.5 cm H2O/l/s the mean percentage falls (95% confidence interval) were: PEF 6.9% (5.4 to 8.3); FEV1 1.9% (1.0 to 2.8), and FVC 1.5% (0.8 to 2.3). CONCLUSIONS: The ATS resistance specification for diagnostic spirometers appears to be appropriate. However, the specification for monitoring devices may be too conservative. PEF was found to be the most sensitive index to added resistance.

Adult↗

Nebulizer calibration using lithium chloride: an accurate, reproducible and user-friendly method.

Conventional gravimetric (weight loss) calibration of jet nebulizers overestimates their aerosol output by up to 80% due to unaccounted evaporative loss. We examined two methods of measuring true aerosol output from jet nebulizers. A new adaptation of a widely available clinical assay for lithium (determined by flame photometry, LiCl method) was compared to an existing electrochemical method based on fluoride detection (NaF method). The agreement between the two methods and the repeatability of each method were examined. Ten Mefar jet nebulizers were studied using a Mefar MK3 inhalation dosimeter. There was no significant difference between the two methods (p=0.76) with mean aerosol output of the 10 nebulizers being 7.40 mg x s(-1) (SD 1.06; range 5.86-9.36 mg x s(-1)) for the NaF method and 7.27 mg x s(-1) (SD 0.82; range 5.52-8.26 mg x s(-1)) for the LiCl method. The LiCl method had a coefficient of repeatability of 13 mg x s(-1) compared with 3.7 mg x s(-1) for the NaF method. The LiCl method accurately measured true aerosol output and was considerably easier to use. It was also more repeatable, and hence more precise, than the NaF method. Because the LiCl method uses an assay that is routinely available from hospital biochemistry laboratories, it is easy to use and, thus, can readily be adopted by busy respiratory function departments.

Aerosols↗

The effect of physiologic and mechanical aging on the performance of peak flowmeters.

PURPOSE: To investigate the effects of physiologic and mechanical aging on peak flowmeters. MATERIALS AND METHODS: Eight each of MiniWright (MW; Clement Clark; Harlow, UK), Personal-Best (PB; HealthScan Products; Cedar Grove, NJ), Vitalograph (V; Vitalograph Ltd; Buckingham, UK), and Breath-Taker (BT; Medical Development Australia; Melbourne, Australia) peak flowmeters were assessed for accuracy and repeatability before and after aging using a computer-driven syringe to deliver peak flows from 100 to 700 L/min. Four of each type of flowmeter were physiologically aged by normal subjects performing up to six peak flows daily for 1 year. The remaining four of each flowmeter were mechanically aged using an accelerated aging device to deliver 2,000 exponential waveforms with a peak flow of 600 L/min over a period of 3 h. RESULTS: The V and BT flowmeters were linear and accurate over the range 100 to 700 L/min, while the PB overread at high flows. The MW was alinear throughout. The SD of the difference between readings before and after aging ranged from 8.6 to 40.6 L/min (mean, 9.2). Comparing the slopes of the relationship of actual against reference peak expiratory flow (PEF) showed that 16 flowmeters--5 BTs, 6 MWs, 4 PBs, and 1 V had no significant change in slope after aging. Mechanical aging caused a consistent underreading in PEF at high flow rates. Physiologic aging showed a more variable pattern both within and between flowmeter types. The MW was the most affected by physiologic aging, producing overestimates of PEF by as much as 100 L/min at 500 L/min. CONCLUSIONS: We conclude that the effects of physiologic and mechanical aging are different, and that while mechanical aging may provide a guide to the effects of aging, studies using physiologic aging would be more appropriate.

Equipment Failure↗

Clinical spirometry.

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Forced Expiratory Volume↗

Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation.

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66-1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.

Adult↗

Differences in aerosol output and airways responsiveness between the DeVilbiss 40 and 45 hand held nebulisers.

BACKGROUND: The DeVilbiss 40 glass hand held nebulisers have been widely used for airways responsiveness testing in epidemiological surveys of asthma. These nebulisers have been superseded in some recent studies by the DeVilbiss 45 plastic hand held nebulisers with the assumption that they are interchangeable. This study compared the aerosol outputs of the DeVilbiss 40 and DeVilbiss 45 nebulisers and investigated whether there was any difference in the in vivo measurements of airways responsiveness when using the two nebuliser types. METHODS: The aerosol output of six DeVilbiss 40 and six DeVilbiss 45 nebulisers was calculated by weight loss per actuation, the usual method of calibrating nebuliser output, and compared with the true amount of aerosol obtained measured by a flouride tracer technique. Airways responsiveness was measured twice in 13 asthmatic patients under identical conditions by the Yan protocol using DeVilbiss 40 and 45 nebulisers in random order. RESULTS: Weight loss overestimated the true aerosol output of both types of nebulisers. Weight loss was similar for the DeVilbiss 40 and 45 nebulisers but the true aerosol output of the DeVilbiss 45 was nearly twice that of the DeVilbiss 40 nebuliser. The geometric mean PD20 values with the DeVilbiss 40 nebuliser was a mean 1.7 doubling doses of histamine higher than that obtained with the DeVilbiss 45 nebuliser. CONCLUSIONS: The DeVilbiss 40 and 45 nebulisers should not be used interchangeably for airways responsiveness testing merely because their outputs based on weight loss are similar. Artefactual differences in the prevalence rates of airways responsiveness could occur in longitudinal studies if a change was inadvertently made from using DeVilbiss 40 to DeVilbiss 45 nebulisers.

Adult↗