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Biomedical subjects

A L Coates

Publications and source records attributed to A L Coates.

At least 19 recordsLinked to original sources

Inhaled mannitol identifies methacholine-responsive children with active asthma.

Inhaled mannitol has been developed for bronchial challenge testing in adults. This study determined if mannitol could identify children with active asthma and responsive to methacholine, and whether mannitol challenge was faster to complete than methacholine challenge. Twenty-five children (aged 6-13 years) responsive to methacholine and 10 nonasthmatic children unresponsive to methacholine were studied. The methacholine challenge (Cockcroft protocol) was followed by a mannitol challenge on separate days. Twenty-one asthmatic children were positive to mannitol. Three taking inhaled corticosteroids with borderline methacholine responsiveness did not respond to mannitol, and one could not complete the mannitol challenge due to cough. The geometric mean (GM) and 95% confidence interval (CI) for PD(15) for mannitol was 39 mg (19, 78), and PC(20) for methacholine was 0.6 mg/mL (0.35-1.02) (r(p) = 0.75, p < 0.001, n = 21). Responses to mannitol were repeatable: GM PD(15) for the first challenge was 29 mg (CI: 17,50), and for the second challenge, 33 mg (CI: 20, 55) (P = 0.44, n = 9). Mannitol was faster to administer than methacholine (median (range)) 14 min (5-32) vs. 29 min (19-49), respectively (P < 0.001). Time to recover to baseline FEV(1) spontaneously and after bronchodilator administration was similar for both challenges. There were no significant falls in arterial oxygen saturations. During mannitol challenge, the mean (SD) fall in FEV(1) in nonasthmatic children was 3.1% (2.9). We conclude that mannitol identifies children with airway hyperresponsiveness and is faster to perform than the methacholine challenge.

Asthma↗

Severe bronchopulmonary dysplasia increases risk for later neurological and motor sequelae in preterm survivors.

Preterm children who develop severe chronic lung disease may be developmentally compromised by exposure to hypoxic episodes. This study aims to determine if children with severe bronchopulmonary dysplasia (BPD) who required home oxygen therapy were at greater risk for neurological and motor deficits at school age than preterm peers without BPD. This study evaluated 27 subjects with BPD and 27 preterm control infants matched for gestational age, birthweight, sex, and year of birth at a mean age of 9.9 years (2.0 SD) using standardized neuromotor outcome measures. Pair-matched comparisons and regression analyses were used to determine if subjects with BPD were at increased risk for neuromotor sequelae. Neurological abnormalities, including subtle neurological signs, cerebral palsy, microcephaly, and behavioral difficulties were highly prevalent in the BPD group (71% compared with 19% in control group, P<0.005). Over half the BPD cohort had difficulties in gross and/or fine motor skills. There were significant differences in postural stability between groups. Duration of hospitalization and home oxygen treatment, and decreased lung function at school age, markers of severity of illness, correlated with motor outcomes. The findings underline the importance of preventing the cardiorespiratory complications associated with chronic lung disease to minimize disability in preterm children. For children with severe BPD, better recognition and subsequent remediation of neuromotor impairments that manifest at school age may help maximize their functional potential.

Bronchopulmonary Dysplasia↗

Do sinusoidal models of respiration accurately reflect the respiratory events of patients breathing on nebulizers?

The amount of drug that is delivered by nebulization is a combination of the physical properties of the agent being nebulized, the performance of the nebulizer, and the pattern of breathing of the patient. To avoid biological variation, mechanical models of breathing are frequently employed during the evaluation of the performance of a device. For simplicity, many investigators use sinusoidal models of breathing to calculate the expected inhaled mass, although some use square waves and other more complex models. Most assume that the duration of inspiration (Ti) is half of the total respiratory time (Ttot). This study compared the calculated inhaled mass from which the expected pulmonary deposition was estimated from the actual pattern of breathing of 43 children with cystic fibrosis (CF) breathing from an unvented nebulizer with a low dead volume and appropriate particle size distribution with that from a sinusoidal pattern of breathing using the same tidal volume (VT) and respiratory rate. The respiratory duty cycle (Ti/Ttot) was 0.45 +/- 0.05, which meant that less time was spent during inspiration than that found in a pure sinusoidal pattern. The difference between the predicted deposition from the actual pattern of breathing and that calculated from the sinusoidal model was 12 +/- 7%, which correlated with the respiratory rate (r = 0.67, P < 0.001). The degree of lung disease did not influence the discrepancy between the two values. In general, the actual VTs and respiratory rates were less in the patients than those employed in mechanical models of pediatric breathing. Although some patients had respiratory patterns that could be represented accurately with a sinusoidal model, most did not, and there were wide variations from child to child. These results suggest that there are both systematic and random errors arising from the use of a sinusoidal waveform to mimic respiratory events in patients.

Adolescent↗

Long-term pulmonary sequelae of severe bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the long-term pulmonary sequelae of survivors of bronchopulmonary dysplasia (BPD) of sufficient severity to have required supplemental oxygen for at least 1 month after term. STUDY DESIGN: Fifteen patients with a mean age of 1.1 years were matched to preterm infants of similar gestational age and age at time of study. Pulmonary function testing included spirometry, plethysmographic lung volumes, carbon monoxide diffusion capacity, and in 9 of 15 subjects with BPD, measurement of lung static elastic recoil pressures. RESULTS: The subjects with BPD had a mean expiratory volume in 1 second (FEV1) of 64% +/- 21% predicted (4 had an FEV1 < 50% predicted) compared with 85% +/- 11% (P < .01) for the preterm children in the control group. Subjects with BPD had a significant degree of gas trapping with a residual volume to total lung capacity ratio of 37% +/- 13% compared with 25% +/- 4% for the control group (P < .01). An inverse relationship was seen between the FEV1 and the time on supplemental oxygen (r = -0.84, P < .0001), with 3 of the 4 children whose FEV1 was < 50% requiring oxygen for more than 900 days. Those with the greatest degree of airflow limitation and gas trapping had the greatest abnormalities in both shape and position of the pressure volume curves of the lung. CONCLUSION: Severe BPD may result in moderate to severe long-term abnormalities in pulmonary function tests.

Bronchopulmonary Dysplasia↗

A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers.

STUDY OBJECTIVE: To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis. DESIGN: Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer. Drug output was measured from changes in weight and concentration (assessed by changes in osmometry) within the nebulizer. Particle size distributions were determined by laser diffraction allowing the calculation of the amount of aerosol output in the respirable range (<5 microm). The nebulizers were first run until end-nebulization to establish total drug output and then for either 4 or 5 min to determine the rate of drug output (mg/min) before intermittent aerosol output. RESULTS: The total drug output without VI for both the unvented and the vented nebulizers was not significantly different, 55 (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson 1730 nebulizer but significantly increased the rate of total drug output and the rate of drug output in the respirable range for the vented Pari LC Jet Plus nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20, 9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). CONCLUSIONS: These findings indicate that the increase in the rate of drug output with VI for the vented nebulizer would result in shorter nebulization times and a relative decrease in drug loss during the expiratory phase.

Anti-Bacterial Agents↗

Exercise ability in survivors of severe bronchopulmonary dysplasia.

There is limited information concerning the exercise performance of long-term survivors of bronchopulmonary dysplasia (BPD), and much of what is available pertains to those with relatively mild disease. The present study was undertaken to describe exercise responses in patients with a history of severe BPD, defined as those patients with a clinical and radiographic diagnosis of BPD who required supplemental oxygen at least until they were 44 wk postconceptual age and who were discharged home on oxygen. Fifteen children with a history of severe BPD were matched for gestational age with 15 children who had previously had respiratory distress syndrome but who did not develop BPD (Prem). These Prem control children were subsequently compared with 13 healthy control children born at term (Control) who were of similar postnatal age. Participants underwent pulmonary function testing, progressive exercise testing on a cycle ergometer, and a steady-state exercise test with cardiac output determined by CO2-rebreathing. Despite the patients with BPD having a lower FEV1 than those in the Prem group, who had lower values than the Control group (BPD, 64 +/- 21%; Prem, 85 +/- 11%; Control, 95 +/- 8%), the exercise capacity did not differ between the BPD and the Prem and between the Prem and the Control groups (BPD, 84 +/- 15%; Prem, 81 +/- 17%; Control, 91 +/- 12%). However, the BPD patients used a greater percentage of their ventilatory reserve (VEmax/40 FEV1: BPD, 93 +/- 20%; Prem, 67 +/- 12%; Control, 59 +/- 13%). Of the four patients with BPD who had significant oxygen desaturation with exercise, three had the lowest values for FEV1. Cardiac output was appropriate for oxygen consumption in most patients.

Anthropometry↗

Redefining end of test (EOT) criteria for pulmonary function testing in children.

In order for an individual FVC maneuver to be considered acceptable according to the 1994 American Thoracic Society (ATS) standards it must meet end of test (EOT) criteria of a minimum expiration time of 6 s with minimal volume change (0.03 L) over 1 s. We have found that while these criteria are often not met in children, most of the tests do meet the ATS criteria for reproducibility with repeated efforts. We, therefore, sought to develop new EOT criteria that would be more appropriate for children and in keeping with the findings for reproducibility. Using an exponential curve fitting of the volume time tracing, we determined a theoretical curve that closely approximated the actual curve (mean difference between actual and derived FEV1 0.01 +/- 0.04 L). The theoretical FVC (FVCFULL) at the point where the curve reached its asymptote was then determined using the fitted curve. Since this point could be difficult to reach for some patients, 95% of FVCFULL (FVC95) was proposed as the new EOT in children. Data from 382 patients were reviewed. Their ages ranged from 5 to 18 yr and their FEV1s from 21 to 120% of predicted. Only 19% of the patients met current ATS EOT requirements despite the fact that 91% met the reproducibility criteria for both FEV1 and FVC. However, 90% of them reached their FVC95. When this was broken down by age, 37% of those < or = 7 yr failed to reach FVC95 whereas only 4% of the older children failed to do so. It is proposed that patients be coached to obtain maximal effort and that the curves be individually fitted to an exponential equation to determine whether the patient has achieved EOT as defined by FVC95.

Adolescent↗

A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) Respirator Solution.

The two most common albuterol preparations used for nebulization are: (1) Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.5 mg/2.5 mL). The two preparations were compared using both a Hudson 1720 "T" up-draft Neb-U-Mist jet nebulizer and a Hudson 1730 "T" up-draft Neb-U-Mist II jet nebulizer (Hudson; Temecula, Calif), which were driven by a compressor (Pulmo-Aide; Devilbiss; Somerset, Pa) and by dry compressed air at 6 and 8 L/min. Particle size distribution was measured with a particle sizer (Malvern 2600; Malvern Instruments; Malvern, UK) and drug output for the nebulizer was calculated from the differences in predrug and postdrug volume and concentration. Drug availability was defined as the amount of drug carried in particles less than 5 microns in diameter. Drug availability was greater with the albuterol respiratory solution, due to the surface activity of the preservative benzalkonium chloride, for both nebulizers but particularly for the 1720. Differences in drug availability between nebulizers exceeded fourfold depending on the preparation, the nebulizer, and the nebulizing flow. These differences could not have been predicted from the manufacturer's specifications. The results suggest that prediction of drug availability must be based on measurements with the specific preparation and the specific nebulizer used.

Aerosols↗

The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols.

The use of inhaled antibiotics in the treatment of cystic fibrosis has become widespread despite controversy in the literature as to the appropriate dosing regimen and its effectiveness. This study compared two tobramycin (T) preparations (one with and one without the addition of albuterol) using two different jet nebulizers in order to determine if drug output would be affected. Using calibrated flows from a dry compressed gas source of 6 and 8 L/min as well as a specific compressor (Pulmo-Aide), the Hudson 1720 nebulizer was compared with the newer disposable Hudson 1730. The albuterol preparation used in this study was the Ventolin (albuterol) Respirator Solution (VRS). The nebulizers were charged with (1) 2 mL T (80 mg/2 mL) with 0.5 mL VRS (5 mg/mL) and normal saline solution to make the total nebulizer charge of 3 or 4 mL, or (2) 2 mL T and either 1 or 2 mL normal saline solution. A laser diffraction analyzer (Malvern 2600) was used to determine the aerosol particle size distribution. From the distribution, the respirable fraction, which is the fraction of aerosol that could enter and remain in the lungs, was calculated. For all solutions and each particular flow, the Hudson 1730 had a larger respirable fraction of T. The addition of VRS lowered the surface tension of the solution in the nebulizer and resulted in a greater output of T. This effect was most apparent for the 3-mL volume fills of the Hudson 1720. The greatest differences were between the 3-mL nebulizer charges of T using the Hudson 1720 driven by a flow of 6 L/min, which produced 8 mg of T in the respirable fraction, compared with 35 mg produced by the Hudson 1730 driven by a flow of 8 L/min. These results suggest that different nebulizers, different nebulizer solutions, and different techniques of nebulization may result in very different amounts of T aerosol output in the respirable fraction.

Administration, Inhalation↗

Noninvasive determination of cardiac output in patients with severe airflow limitation.

The noninvasive measurement of cardiac output (Q) by the Indirect Fick CO2-rebreathing technique requires mixed venous P CO2 (P CO2) to be determined by the rebreathing maneuver, and Pa CO2 to be estimated from end-tidal P CO2 (PET CO2). Previous work has suggested that although P CO2 can be determined, Pa CO2 cannot be accurately estimated in patients with significant airflow limitation. Nineteen patients with cystic fibrosis who had severe airflow limitation (%FEV1, 29.3 +/- 7.12 SD) were studied during steady-state exercise at 50% of their measured maximal work capacity. Estimated Pa CO2 was slightly lower than Pa CO2 measured from blood samples obtained from an indwelling arterial catheter (measured: 45.2 +/- 4.92; estimate: 42.7 +/- 5.68 mm Hg). To calculate arterial blood content, the values derived from Pa CO2, pH, hemoglobin (Hb), and O2 saturation were compared with those derived from PET CO2 and O2 saturation, where (1) pH was assumed to be 7.40 and Hb was measured, and (2) pH was assumed to be 7.40 and Hb was assumed to be 15 g/dl (measured mean pH, 7.34; Hb, 14.4 g/dl). No difference in arterial CO2 content was seen between the three methods (measured: 47.53 +/- 5.17; estimate 1: 49.57 +/- 6.58; estimate 2: 49.12 +/- 6.61 ml/100 ml). As pH and Hb can also affect mixed venous CO2 content, the effect on Q was also assessed. Both estimates fit closely with measured Q (r2=0.77 and 0.76), with intercepts not different from zero and slopes not different from 1, and coefficients of variation of 13.5 and 14.6%. When viewed with regard to the confidence intervals for Q as a function of O2 consumption, Q was altered to a minor extent. We conclude that the use of PET CO2 to estimate Pa CO2 can give reasonable values for Q determined noninvasively in patients with severe airflow limitation.

Adult↗

Do tidal expiratory flow patterns reflect lung mechanics in infants?

It has been suggested that during tidal breathing, the time to maximal expiratory flow, as a proportion of total expiratory time (Tme/TE), can be used as an index of airways obstruction. However, the relationship of Tme/TE to lung mechanics in infants is unclear. We examined this relationship in 42 premature infants (21 intubated and 21 not intubated) by comparing direct measures of pulmonary mechanics (lung resistance, dynamic lung compliance, and lung impedance) with Tme/TE measured over the same sample of tidal breathing. Tme/TE was positively correlated with lung compliance, expressed as a percent of the predicted value, in both intubated (r = 0.69, p < 0.005) and nonintubated (r = 0.64, p < 0.02) infants. There was no significant association between Tme/TE and lung resistance, expressed as a percent of the predicted value, in intubated (r = 0.32) and nonintubated (r = 0.23) infants. Tme/TE also showed, in nonintubated infants, a positive association with lung impedance, expressed as a percent of the predicted value, on the basis of the predictive values for compliance and resistance at the infant's unique respiratory rate, but this was significant only because of the influence of compliance on Tme/TE. These findings suggest that, in infants, the relationship between pulmonary mechanics and Tme/TE is complex, with Tme/TE being influenced by the elastic rather than the flow-resistive properties of the lungs.

Airway Resistance↗