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(Chest. 2006;130:1063-1071.)
© 2006 American College of Chest Physicians

Room Air Entrainment During ß-Agonist Delivery With Heliox*

Sunil Dhuper, MD; Sonia Choksi, MD; Simdararajan Selvaraj, MD; Gautam Jha, MD; Aziz Ahmed, MD; Harsh Babbar, MD; Baljit Walia, MD; Alpana Chandra, MD; Virginia Chung, MD and Chang Shim, MD

* From the Department of Medicine (Drs. Dhuper, Choksi, Selvaraj, Jha, Ahmed, Babbar, Walia, Chandra, and Chung), North Central Bronx Hospital, Bronx, NY; and the Department of Medicine (Dr. Shim), Jacobi Medical Center, Bronx, NY.

Correspondence to: Sunil Dhuper, MD, North Central Bronx Hospital, Medicine, 3424 Kossuth Ave, Bronx, NY 10467; e-mail: sunil.dhuper{at}nychhc.org

Abstract

Studies of the efficacy of heliox in patients with severe asthma have shown mixed results. Among the factors that are responsible for variable outcomes, the failure of heliox delivery systems to prevent room air entrainment (RAE) during ß-agonist delivery is probably the most critical. While keeping the rotameter flow rate (FR) of heliox mixed 70:30 to a nebulizer at 10 L/min, the FR of heliox from a second gas source to a T-connector (TC) was increased during the delivery of the ß-agonist with a conventional T-nebulizer delivery system (TNDS). A negative peak inspiratory flow (pneumotachometer reading) or a helium concentration of < 70% (quadralizer reading) were indicators of RAE. RAE was tested during spontaneous tidal breathing and acute asthma. A rotameter FR of 10 L/m to the nebulizer with no flow from a second gas source to a TC (conventional TNDS) resulted in a significant drop in helium concentration during tidal breathing (46.2%) and acute asthma (27.5%) due to RAE. This degree of helium dilution can negate the beneficial effects of heliox to lung mechanics almost completely. A rotameter FR of 10 L/m each to a nebulizer and a TC resulted in a helium concentration 69.8% during tidal breathing (no RAE), but 49% (significant RAE) during asthma events. A rotameter FR of 15 L/m (pressure regulator setting, 100 lbs per square inch) to a TC, while maintaining a rotameter FR of 10 L/m to a nebulizer prevented RAE during asthma (helium concentration, 69.9%). Conventional TNDS may be used to deliver the ß-agonist with heliox during asthma without RAE.

Key Words: ß-agonist delivery • heliox • nebulizer • room air entrainment

Helium is a biologically inert nontoxic gas with density that is significantly lower than ambient air.1 Compared to air, helium results in improved alveolar ventilation and better gas exchange.23456 The low density of helium also decreases the pressure gradient that is required to achieve a given flow rate (FR) through constricted airways that results in decreased resistive work of breathing, which may be clinically applicable to patients with severe airways obstruction.7891011 In addition, the low density and greater viscosity of heliox makes gas flow less turbulent, which improves the transport of aerosols to more peripheral airways through constricted airways in patients with bronchial asthma.12 In a study by Manthous et al,3 the decrease in resistive work of breathing with heliox use in asthma patients was demonstrated indirectly by a decrease in pulsus paradoxus and an improvement in peak expiratory FR. Improvement in lung function during acute asthma episodes with heliox use has also been reported by others,2413 although this has not been a universal finding.1415 From a practical standpoint, nebulizing albuterol with heliox serves the following two purposes: improved airflow based on the physical properties of the gas; and improved spirometry, presumably from the improved delivery of albuterol to its site of action in the lungs.16

Despite these demonstrated benefits, the role of heliox in asthma therapy remains controversial. In a metaanalysis17 on the role of heliox in asthma, the initial search (with MEDLINE, EMBASE, and CINAHL databases) produced 89 potentially relevant citations, of which 21 were reviewed in full text for possible inclusion. Of these studies, only seven were prospective controlled trials and were selected for inclusion. In four of seven studies, heliox was used to deliver nebulized therapy.13151618 The pooled data failed to demonstrate that nebulizer therapy was more effective than air/oxygen when pulmonary function tests were performed at 30 and 120 min. All studies allowed full room air entrainment (RAE) during ß-agonist delivery. To be effective in reducing airway resistance, concentrations of helium must be high, ideally > 70% of the inhaled gas mixture. Studies19 have demonstrated that relatively small dilutional decreases in the concentration of helium from 70 to 80% of inspired gas to ≤ 60% due to RAE can negate the beneficial effects of heliox to lung mechanics almost completely. In addition, the literature concerning the benefits of heliox therapy on drug nebulization has been conflicted, probably because of differences in the delivery systems utilized with less than optimal concentrations of helium being achieved.

Since most studies have failed to use an appropriate delivery system that prevents the entrainment of room air during ß-agonist delivery with heliox,235131415161718202122232425 it can be speculated that inconclusive results pertaining to the efficacy of heliox therapy in patients with asthma from the pooled data in two systemic reviews1726 may be attributed to various degrees of RAE during its use. The extent of RAE and helium dilution has not been measured in any of the previous studies. We hypothesized that a significant dilution of the helium concentration occurs during asthma episodes, and the concentration drops to < 60% to negate its potential salutary effects on reducing turbulent gas flow, hence enhancing drug delivery. We designed this study to determine the extent of RAE with the conventional open T-nebulizer delivery system, a system that is used in most clinical trials to assess the efficacy of heliox therapy in asthma patients. Another objective of this study was to determine whether a high flow of heliox from a second gas source through the open end of the T-connector (TC) could prevent RAE during ß-agonist delivery.

Materials and Methods

This study was carried out to investigate the extent of RAE during delivery of aerosolized albuterol with premixed 70:30 heliox gas in a spontaneous breathing in vitro lung model employing a conventional open T-nebulizer delivery system, as demonstrated in Figure 1 . The corresponding delivery system for clinical use is demonstrated in Figure 2 . As demonstrated in Figure 2, tubing from a second gas source is connected to the open side arm of the TC via a step-down adapter that is readily available in the prepackaged 100% non-rebreather (Cardinal Health; McGraw Park, IL).


Figure 1
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  		Figure 1. Schematic diagram of the study setup. One heliox tank delivered the gas to a nebulizer connected to the T-tube, and another heliox tank delivered it directly to the T-tube. A quadralizer and an oxygen analyzer were located close to the lung module proximal to the second T-tube. A pneumotachometer was attached to the vent arm of the second T-tube.

 

Figure 2
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  		Figure 2. Schematic diagram of the clinical heliox delivery system. Two sources of heliox deliver it to the T-connector, one through a nebulizer and another through a step-down adapter.

 
A double-sided test lung (Michigan Instruments; Grand Rapids, MI) was used to simulate spontaneous breathing. One side of the test lung was attached to the ventilator (model 7200 ventilator; Puritan Bennett; Pleasanton, CA), and that side of the test lung lifted the contralateral side to simulate spontaneous breathing. The delivery system was evaluated for RAE with heliox (premixed 70:30 ratio of helium/oxygen) under the following two sets of ventilatory conditions: an in vitro model mimicking normal adult tidal breathing (model A); and a second model mimicking acute asthma (model B). Adult tidal breathing guidelines have been recently published by the American Thoracic Society and have been adapted in several studies2728293031

Several other studies32 on resting breathing patterns in humans while breathing through a mouthpiece with a nose clip have demonstrated similar readings during spirometry. We have used the same guidelines to set the ventilatory parameters in this study (tidal volume, 600 mL; respiratory rate, 12 breaths/min; inspiratory/expiratory ratio, 1:2 [model A]). The ventilatory settings for model B were a tidal volume of 500 mL, a respiratory rate of 20 breaths/min, and an inspiratory flow that was adjusted to maintain an inspiratory/expiratory ratio of 1:4. The ventilatory settings for acute asthma were based on the results of several studies of breathing patterns during induced bronchoconstriction. A study33 in a dog model demonstrated that the breathing pattern response to bronchoconstriction consisted of increased frequency of breathing, decreased tidal volume, and decreased total inspiratory time. A study34 in asthmatic patients demonstrated that methacholine and histamine challenges result in more rapid and shallow breathing, as observed by the increased frequency of breathing, decreased tidal volume, and increased breathing frequency/tidal volume ratio. Other studies of respiratory profile in symptomatic asthma patients have shown increased minute ventilation, increased tidal volume/inspiratory time ratio, and decreased inspiratory duty cycle.35 In addition, in model B a fixed orifice resistor producing a resistive pressure of 20 cm H2O/L/s was placed between the filter and the coaxial circuit.

A nebulizer (Mistyneb; Cardinal Healthcare; Dublin, OH) was used as a standard nebulizer for all tests. All nebulizers provided by the manufacturer were from the same lot number. All nebulizers were from their saleable stock, and none were prototypes or otherwise prepared specifically for the study. The reproducibility between the nebulizers was assessed by measuring the airflow through dry nebulizers.3637 All experiments were performed with inspiratory gas at an ambient temperature of 25 to 27°C and a relative humidity of < 30%, as determined by thermohygrometer (Radio Shack; Fort Worth, TX). Pressure-compensated oxygen flowmeters (Rotameters; Timeter; St. Louis, MO) were connected to the heliox and oxygen tank pressure regulators, and were used to adjust the FR of gas to the nebulizer and the TC. All flowmeters were calibrated by the manufacturer at a 50-lbs per square inch (psi) inlet pressure and were used as per the manufacturer specifications. The appropriate calibration factor was applied to correct for the lower density of the premixed heliox gas to calculate the actual flow of the 70:30 premixed heliox gas.22383940 To avoid any erroneous flow readings, a pneumotachometer (Hans Rudolph; Kansas City, MO) was used to adjust the flow rate for heliox. The pneumotachometer used an algorithm to calculate the molecular weight-based density correction factor, and allowed accurate readings of gas flow and volume for a specific concentration of premixed heliox gas and oxygen. The accuracy of the measured volumes of heliox and the linearity of the pneumotachometer response were verified by a volumetric syringe containing premixed heliox gas.

While heliox gas (a premixed 70:30 helium/oxygen mixture) was delivered to the nebulizer at a fixed rotameter FR of 10 L/min; through a second gas source, heliox gas (a premixed 70:30 helium/oxygen mixture) was delivered to the open side arm of the TC. The flow to the nebulizer was not allowed to exceed 10 L /min during all experimental settings. When an attempt was made to deliver heliox gas at a higher FR to the nebulizer, the back pressure resulted in a disconnection of the tubing from the nebulizer at an FR of 13 L/min. The flow from the second gas source to the TC was incrementally adjusted until no RAE was observed. A quadralizer (model 224A; Raytech; North Vancouver, BC, Canada) was incorporated into the inspiratory limb of the circuit between the ventilator and the inspiratory filter, which allowed continuous monitoring of the concentration of four gases (oxygen, nitrogen, carbon dioxide, and helium). The helium concentration determined with the quadralizer was a directly measured value using the principles of the nondispersive infrared absorption, paramagnetic, and thermal conductivity properties of the gas. On all days, prior to the initiation of the experiments, the quadralizer was calibrated with room air (21% oxygen), 100% oxygen, a 50:50 heliox mixture, a 60:40 heliox mixture, a 70:30 heliox mixture, a 80:20 heliox mixture, and 100% helium. The quadralizer readings stabilized in less than 1 min, and the final readings for all experimental settings were obtained 5 min poststabilization. An oxygen analyzer (MaxO2; Maxtec; Salt Lake City, UT) was placed in series with a quadralizer to assess the oxygen concentration. Since a quadralizer is not readily available in most clinical settings, we decided to use a drop in the oxygen concentration (using an oxygen analyzer) to < 30% as an indicator of RAE. Both an oxygen analyzer and a quadralizer were used in our study to see whether there was a correlation between the helium readings calculated mathematically from the oxygen analyzer readings and those measured by the quadralizer.

A pneumotachometer was placed at the expiratory port that made continuous recording of the gas flow vs time. The RAE was determined by recording the gas flow vs time with a pneumotachometer, and the direct measurement of helium concentration with a quadralizer for all experimental flow settings of heliox as described in our earlier study.41 RAE was said to be present if the peak inspiratory gas flow recorded by the pneumotachometer during the inspiratory phase of the respiratory cycle was negative,41 and the helium concentration, as measured by the quadralizer, was < 70% during the delivery of the 70:30 heliox gas mixture.

Most conventional flowmeters in medical use are calibrated to measure the FR of gas at a pressure regulator setting of 50 psi. Most are limited by a maximum readable rotameter FR of 15 L/min. Therefore, under the two experimental conditions (models A and B), when the rotameter FR of 15 L/min to the TC measured with the conventional flowmeter was not adequate to prevent RAE, a FR of > 15 L/min was achieved by changing the pressure regulator setting to 100 psi while using the conventional medical-grade flowmeter, which was calibrated to provide FR readings for air at a pressure regulator setting of 50 psi. The corrected rotameter FR (RFlowc) [at a pressure setting of 100 psi] was calculated by the following formula38:

Formula
The relationship between pressure and flow outlined above is based on the Bernoulli equation, as follows:

Formula
Hence, the corrected rotameter FR for heliox was equal to the rotameter reading multiplied by 1.41 (which is a correction factor for change in the pressure regulator setting from 50 to 100 psi).

The actual FR for heliox was calculated by multiplying the rotameter FR or corrected rotameter FR (applicable only for the 100-psi setting) for heliox by the density correction factor for the low density of the heliox gas mixture of 70:30 (1.53). The correction factor for the heliox gas mixture of 70:30 was based on the ratios of the molecular weights of oxygen and heliox, and was calculated by the following formula39:

Formula
The density of heliox is calculated as follows:

Formula
The accuracy of the calculated FRs was confirmed by measurement of the actual FR with a pneumotachometer. The accuracy of the measured volumes and FRs of heliox and the linearity of the pneumotachometer response were verified by a volumetric syringe containing heliox gas premixed at 70:30. RAE was said to be completely eliminated if the pneumotachometer flow recording was positive, and the helium concentration was 70% (determined by the quadralizer) throughout the respiratory cycle.

Results

Table 1 outlines the results of RAE and the extent of helium dilution during ß-agonist delivery with heliox gas premixed at 70:30 using the open T-nebulizer delivery system during normal spontaneous breathing (model A). An incremental change in the flow of heliox to the TC from a second gas source, while keeping a constant flow of heliox to the nebulizer, resulted in a progressive decrease in RAE. This is demonstrated by a progressive decrease in the negative peak inspiratory flow, as indicated by the pneumotachometer reading, and a progressive increase in the helium concentration to approach nearly 70%, as measured by the quadralizer. At a rotameter FR of 10 L/min, both to the nebulizer and the TC with heliox, the RAE was completely eliminated. At these FRs, the peak inspiratory flow was positive throughout the respiratory cycle, and the helium concentration as measured by the quadralizer was 70%.


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  		Table 1. Spontaneous Normal Ventilation*

 
Table 2 shows the results when the same delivery system was tested for helium dilution during a ventilatory pattern that mimics acute asthma (model B). Similar to the findings observed with model A, the RAE progressively decreased in model B as the FR of heliox to the side arm of the TC was increased from a second gas source. However, changes in the negative peak inspiratory flow (measured by pneumotachometer) and the helium concentration (measured by quadralizer) for the same increase in the heliox FR to the TC were modest compared with results from model A. At a FR of 15 L/min (maximum readable rotameter reading with a conventional flowmeter) from the second gas source, there was a significant RAE, as indicated by the quadralizer helium concentration of 54.3% and a peak negative inspiratory FR of –19.1 L/min. An incremental change in the FR of heliox to the side arm of TC of > 15 L/min, which was achieved by changing the pressure regulator setting to 100 psi, resulted in a progressive decrease in the RAE. This was demonstrated by a decrease in the peak negative inspiratory flow readings (measured by pneumotachometer) and by an increase in the helium concentration approaching nearly 70% (measured by quadralizer). At a rotameter FR of 15 L/min (pressure regulator setting, 100 psi) to the to the TC from a second gas source (see Table 2 for actual FRs), the RAE was completely eliminated. The indicators of the elimination of RAE were the positive peak inspiratory flow and a helium concentration of nearly 70% (from a quadralizer reading) throughout the respiratory cycle.


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  		Table 2. Ventilation During Asthma*

 
Figure 3 shows a strong correlation between the actual helium concentration measured by a quadralizer and the predicted helium concentration derived from the oxygen concentration measured by the oxygen analyzer (Tables 2, 3). To calculate the predicted helium concentration, we first calculated the dilution factor using the mathematical equation given below:

Formula
We then calculated the helium concentration using the following formula:

Formula


Figure 3
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  		Figure 3. Helium concentration calculated by using an oxygen analyzer was plotted against that measured directly by a quadralizer. There is an excellent correlation between the two values.

 
Figure 4 shows that there is a strong correlation between the helium concentration (from a quadralizer reading) and the peak inspiratory reading (from a pneumotachometer reading) both during normal spontaneous breathing (r = 0.96) and in an asthma model (r = 0.90). As the pneumotachometer peak inspiratory reading becomes less negative and approaches zero, the helium concentration increases progressively to approach 70%.


Figure 4
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  		Figure 4. The peak inspiratory flow readings of the pneumotachometer are closely related to the helium concentration. The greater the peak inspiratory flow rate, the greater the drop in the helium concentration.

 
Discussion

ß-agonists and corticosteroids form the mainstay of treatment for patients with acute asthma. The role of heliox as an adjunct to conventional medical treatment has been studied with mixed results.23513141516171920 Most asthmatic patients get better after two to three sequential conventional treatments with ß-agonists.42 HeO2 may have a role in the treatment of acute severe asthma when a patient fails to respond to the conventional therapy and remains severely obstructed.2345891011 This conjecture is supported by a randomized controlled study43 in which 24 patients with mild-to-moderate asthma and 8 patients with severe asthma were assigned to receive a ß-agonist with heliox (79:21) vs with compressed air. No significant difference was observed for FVC, FEV1, and forced expiratory flow at 50% of FVC between the two groups in patients with mild-to-moderate asthma, but patients with severe asthma showed significant differences between heliox and air for all three parameters.43 A metaanalysis32 that evaluated the efficacy of heliox on respiratory mechanics concluded that heliox may offer mild-to-moderate benefits in patients with acute severe asthma within the first hour of use, but its advantages become less apparent beyond 1 h. All studies in the metaanalysis allowed full RAE. With the exception of two studies in literature, one by Carter et al14 and another by Kress et al,16 most investigators did not prevent RAE during ß-agonist delivery with heliox. We hypothesized that the significant dilution of the helium concentration occurs during asthma and the concentration drops to < 60% to negate its potential salutary effects on reducing turbulent gas flow and enhancing drug delivery.

In this study, we have demonstrated that there is significant RAE during normal spontaneous tidal breathing (helium concentration, 46.2%) and an acute asthma episode (helium concentration, 27.5%) when a ß-agonist is delivered with heliox using the conventional open T-nebulizer delivery system. The dilution is far greater during asthma episodes compared with normal tidal breathing due to the high inspiratory flow requirement during acute asthma episodes to maintain a high ratio of expiratory to inspiratory time, which allows a maximum time for exhalation in the setting of the predominantly expiratory airflow obstruction seen in asthma patients. Since the concentration of heliox in our study dropped to well below 60% during asthma episodes, which is a concentration below which the benefit of decreased airways resistance may be lost, one can question the validity of the conclusions that have been drawn regarding the efficacy of heliox in asthma patients either in individual trials251314151617181920 or in metaanalyses of pooled data.1726

Our reservation about the validity of the previous studies examining the role of heliox in asthma patients is supported by the results of two studies performed by Kress et al.16 Kress et al16 had performed a pilot study using a conventional open T-nebulizer delivery system to nebulize albuterol. The control patients had received three treatments with albuterol nebulized with oxygen, whereas study patients received three treatments nebulized with heliox. Following treatment 1, the medium percentage change in FEV1 was 15.7% in the control group and 14.5% in the heliox group; after treatment 2, the results were 22.2% and 18.4%, respectively; after treatment 3, the results were 24.1% and 23.7%, respectively. There were no differences in spirometry results between the heliox and oxygen groups. When the same study was repeated,16 taking precautions to prevent RAE, following treatment 1 the medium percentage change in FEV1 was 14.6% in the control group and 32.4% in the heliox group; after treatment 2, the results were 22.7% and 51.5%, respectively; after treatment 3, the results were 26.6% and 65.1%, respectively. There were significant differences in spirometry between the heliox and oxygen groups. Kress et al16 hypothesized that RAE decreased the effective concentration of heliox delivered to the patient with the conventional T-nebulizer delivery system and, as a result, did not demonstrate any beneficial results. Our findings support their hypothesis. This is the first study to make an accurate assessment of RAE and to demonstrate that the resultant diluted helium concentration drops well below the concentration that is required to derive any benefit from helium during ß-agonist delivery with heliox in asthma patients.

We have also demonstrated that while a rotameter FR of 10 L/min is maintained to the nebulizer with the use of heliox, the delivery of heliox to the side arm of the TC from a second gas source at FRs of 10 L/m (conventional pressure regulator setting of 50 psi) and 15 L/m (pressure regulator setting of 100 psi) during normal tidal breathing and acute asthma episodes, respectively, can eliminate RAE. Taking into account the density correction factor of a 70:30 heliox gas mixture (1.53), a net heliox FR of approximately 30.6 L/min during normal tidal breathing and approximately 48 L/min during an acute asthma episode is adequate to prevent RAE. Most conventional flowmeters have a maximum readable flow limit of 15 L/min. The delivery of a net FR of 48 L/min, especially when the FR to a nebulizer cannot exceed 10 L/min, would have necessitated the use of special flowmeters with a high delivery range. Quite unlike standard oxygen or air pressure regulators (range, 0 to 100 psi; Praxair; Danbury, CT), conventional pressure regulators for heliox have a higher range (0 to 200 psi; CONCOA; Virginia Beach, VA), and we were able to achieve high FRs (48 L/m) by changing the pressure regulator setting from 50 to 100 psi and applying a density correction factor for a heliox mixture of 70:30 (1.53). The ability to achieve the desired high FR with a conventional flowmeter makes our delivery system practical and cost-effective for routine use. Since most heliox delivery systems (ie, Flo-Mist; Smiths Medical; Waukesha, WI; prototype Heliox Delivery System; Aerogen, Inc; Sunnyvale, CA; and Datex-Ohmeda; Madison, WI; semi-closed system described by Henderson et al18) are either commercially unavailable or too expensive for the routine use of heliox, our delivery system offers an excellent alternative solution for ß-agonist delivery with heliox. Acute episodes of asthma require emergent treatment, and if heliox use is clinically indicated, we have suggested a user-friendly system that allows the instant delivery of the ß-agonist with heliox by attachment of a stepdown adapter with tubing (readily available) to the side arm of a TC. Training of the respiratory staff on the guidelines for the use of this delivery system would be necessary, as it would be for the use of any other heliox delivery system.

A strong correlation between the helium concentration (measured with the quadralizer) and the peak negative inspiratory flow (measured with the pneumotachometer) in this study demonstrates that we may accurately predict RAE with a pneumotachometer instead of a quadralizer in an in vitro setting. Similarly, we have demonstrated that RAE (helium dilution) can be predicted simply by using an oxygen analyzer. These findings are consistent with our prior data.41 The findings may be of relevance as the pneumotachometer or oxygen analyzer, both of which are more economical alternatives to a quadralizer, may be used for in vitro and possibly in vivo assessment of RAE with different heliox delivery systems in future studies.

The mandatory high FR of heliox gas from a second gas source may influence the inhaled mass of the ß-agonist.44 As the inhaled mass of the ß-agonist is critical to the outcome of patients with asthma, studies, both in vitro and in vivo, to assess ß-agonist delivery with the open T-nebulizer delivery system under the flow conditions that prevent RAE with this heliox delivery system would be warranted. We have performed an in vitro study using this delivery system and compared the inhaled mass of the ß-agonist during delivery with heliox and oxygen under matched flow conditions. The study demonstrates that the inhaled respirable mass of the ß-agonist with heliox at FRs that prevent RAE using the open T-nebulizer system is better than that with oxygen at matched FRs using the same system and is equal to delivery with oxygen using the conventional T-nebulizer delivery system.4546

Heliox is not used for the routine management of asthma, but for the cohort of patients (status asthmaticus) who are unresponsive to therapy with bronchodilators and might benefit from its use; the open T-nebulizer heliox delivery system described in this study is a practical and cost-effective system that may be used to deliver a ß-agonist with heliox without RAE. We have demonstrated the flaws of the most commonly used delivery system that is utilized during ß-agonist delivery in asthma patients and, in addition, demonstrated proper methodology for future studies and for clinicians who may choose to use it.

Footnotes

Abbreviations: FR = flow rate; psi = lbs per square inch; RAE = room air entrainment; TC = T-connector

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Received for publication October 26, 2005. Accepted for publication March 14, 2006.

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