Changes In Respiratory Resistance Research Articles

An in vitro technique to measure resistance to compression and kinking of endotracheal tubes.

During intraoperative care, ventilatory parameters including peak inflating pressure (PIP) and exhaled tidal volumes are continuously monitored to assess changes in respiratory resistance and compliance. Changes in these parameters, such as an increase in PIP or a decrease in the exhaled tidal volume, may indicate various pathologic processes that may require immediate attention to prevent inadequate ventilation resulting in hypoxemia or hypercarbia. A kinked endotracheal tube (ETT) may mimic other pathologic processes including bronchospasm, mainstem intubation, or ventilator malfunction. As newer ETTs are developed, a key factor in their design should be resistance to kinking or occlusion due to patient positioning. The current project developed and describes the process for using a repeatable in vitro mechanical test to determine resistance to kinking by an ETT. The mechanical testing procedure can be used to determine the compression force and distance required to kink an ETT under different conditions including temperature. The force required to induce devastating kink failure was lower during heated testing conditions. The addition of airflow through the ETTs during compression testing confirms the occurrence of airway obstruction at approximately the same time a mechanical kink is observed on the force-versus-distance curves. These procedures may be used to characterize and evaluate ETT designs under in vitro conditions mimicking those in the clinical practice.

The Effects of Endotracheal Tube and i-gel® Supraglottic Airway Device on Respiratory Impedance: A Prospective Observational Study.

BackgroundThe forced oscillation technique (FOT) is a non-invasive means of measuring respiratory resistance and reactance. We tested our hypothesis that endotracheal intubation would cause more substantial preoperative increases in FOT parameters than a supraglottic airway device (SGD).MethodsForty patients requiring general anesthesia and mechanical ventilation for transurethral bladder tumor resection underwent spirometry the day before surgery. Forced oscillation was measured using a MostGraph-01 device the day before surgery and immediately after removal of the airway adjunct. Changes in respiratory resistance and reactance were compared between those intubated and those who used SGD.ResultsThe trachea was intubated in 23 patients and SGD was used in the remaining 17 patients. Both airway adjuncts caused significant increases in preoperative respiratory resistance and reactance; however, the magnitude of the changes was significantly greater in the intubated patients.ConclusionsThe SGD appears to cause less pulmonary injury than tracheal intubation. Further study is needed to illuminate the influence of mechanical ventilation, and longer-term consequences and clinical significance of the changes we found in this study. Spontaneous ventilation through an SGD may be preferable in patients with severe respiratory disease.

Emphysema and airway disease affect within-breath changes in respiratory resistance in COPD patients.

Chronic obstructive pulmonary disease (COPD) is characterized by a mixture of emphysema and airway disease. The forced oscillation technique (FOT) has been applied to COPD patients to clarify changes in respiratory mechanics; dynamic changes in respiratory resistance (Rrs) during breathing (within-breath changes in Rrs, ΔRrs) are characteristic of COPD. However, the pathophysiological significance of these changes is unknown. The aim of this study was to assess how emphysema and airway disease influence ΔRrs in COPD patients. In this cross-sectional study, stable COPD patients were recruited and underwent respiratory impedance measurements with a commercially available FOT device. Rrs was recorded during tidal breathing and then analyzed as whole-breath Rrs (Rrs at 5 Hz, R5; Rrs at 20 Hz, R20; and their difference, R5-R20) or as ΔRrs, the difference between the expiratory and inspiratory Rrs (ΔR5, ΔR20 and ΔR5-R20). The percentage of the low attenuation area (LAA%) and airway wall area (WA%) was quantified by computed tomography analysis, and their contributions to ΔRrs were examined. Seventy-five COPD patients were recruited. LAA% was negatively correlated with ΔR5 and ΔR5-R20 (P = 0.0002 and P = 0.0033, respectively); meanwhile, WA% in B(10) was positively correlated with ΔR5 and ΔR5-R20 (P = 0.0057 and P < 0.0001, respectively). Multivariate analysis revealed that the contribution of both LAA% and WA% in B(10) to ΔRrs was independent of the severity of airflow limitations. This study shows that emphysema suppresses ΔRrs in COPD patients, while airway disease increases ΔRrs in these patients.

Adenoid Cystic Carcinoma in Trachea : Changes of Respiratory Resistance Before and After Intervention with Laser Ablation

Adenoid Cystic Carcinoma in Trachea : Changes of Respiratory Resistance Before and After Intervention with Laser Ablation

Airway obstruction, upper airway artifact and response to bronchodilator in asthmatic and healthy children.

The forced oscillation technique (FOT) may be affected by the upper airway artifact in children with airway obstruction. The aim was to test the impact of the artifact on FOT ability to diagnose asthma in children as recommended by current guidelines. The FOT was performed in 58 asthmatics and 27 controls before and after salbutamol. Respiratory resistance (Rrs) was measured at 8 Hz with a standard generator (SG), and a head generator (HG) that minimizes the upper airway artifact. The response to salbutamol was computed as change in respiratory resistance (Δ%Rrs) and admittance (Δ%Ars) that almost cancels the effect of the upper airway artifact. Rrs and Δ%Rrs were significantly larger in patients than controls by HG (respectively P < 0.001 and P = 0.002) but not SG, while Δ%Ars was larger in asthma than control by both (P < 0.04). Best discriminators between patients and controls were Rrs or Δ%Rrs by HG and Δ%Ars by SG. In asthmatic children, the upper airway artifact significantly impacts FOT measurements. The diagnostic value may be improved by minimization of the shunt, such as the computation of Δ%Ars.

Airway arginase expression and Nω-hydroxy-nor-arginine effect on methacholine-induced bronchoconstriction differentiate Lewis and Fischer rat strains

Innate airway hyperresponsiveness (AHR) is well modeled by two strains of rat, the hyperresponsive Fischer 344 rat and the normoresponsive Lewis rat. Arginase has been implicated in AHR associated with allergic asthma models. We addressed the role of arginase in innate AHR using the Fischer-Lewis model. In vivo arginase inhibition with N(ω)-hydroxy-nor-arginine (nor-NOHA) was evaluated on methacholine-induced bronchoconstriction in the Fischer and the Lewis rats. Arginase activity and mRNA expression were quantified in structural and resident cells of the proximal airway tree. The effect of nor-NOHA was evaluated on cultured tracheal smooth muscle proliferation. Fischer rats exhibited significantly greater changes in respiratory resistance and elastance in response to methacholine compared with Lewis rats. nor-NOHA reduced the methacholine-induced bronchoconstriction in the central airways of Lewis rats, while it did not change the innate AHR of Fischer rats. Lewis rats exhibited greater arginase activity in tracheal smooth muscle but a lower proliferation rate compared with Fischer rats. Smooth muscle proliferation was not affected by nor-NOHA in either strain of rats. The strain-specific arginase expression in the smooth muscle may contribute to the differences in sensitivity of the methacholine challenged airways of Lewis and Fischer rats to inhibition of arginase.

Visualized changes in respiratory resistance and reactance along a time axis in smokers: A cross-sectional study

Early detection of changes in respiratory function in smokers is important for the prevention of chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate any changes in the respiratory impedance of smokers with normal FEV1/FVC. We assessed and compared the impedance components, respiratory resistance, and reactance in both the inspiratory and expiratory phases of nonsmokers, smokers, and COPD patients. Approximately 60% of smokers showed elevated resistance and a negative shift in reactance, mainly in the expiratory phase, as observed in COPD patients. Smokers showed an increased gap between the maximum and minimum R5 and X5 values (R5sub, X5sub) in comparison with nonsmokers. Furthermore, R5-R20 was significantly higher in smokers than in nonsmokers. The expiratory-inspiratory gaps in resistance and reactance were also significantly higher in smokers than in nonsmokers. In smokers and COPD patients, the magnitude of expiratory X5 was more negative than that in nonsmokers. In smokers with V·50/V·25≥3, R5-R20 was significantly higher than those in smokers with V·50/V·25<3. Approximately 60% of smokers were shown to exhibit apparent impedance changes despite having normal FEV1/FVC values. Smoking-induced early remodeling of the small airways may be responsible for the observed changes in airway function of smokers. Further studies are necessary to determine if the change in respiratory impedance observed in smokers is an early indicator of COPD.

Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques

The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). The present study represents a preclinical animal study to determine whether these respiratory function techniques (LMS and IOS) are comparable in detecting changes in respiratory resistance derived from a direct pharmacological challenge.

Monitoring the Temporal Changes of Respiratory Resistance: A Novel Test for the Management of Asthma

Monitoring the Temporal Changes of Respiratory Resistance: A Novel Test for the Management of Asthma

Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry

In young children, it is difficult to obtain a reproducible flow-volume curve throughout all stages of bronchial challenge. The forced oscillation technique (FOT) is especially established in paediatrics because this method does not require forced or maximal manoeuvres and is less cooperation-dependent than conventional spirometry. To evaluate the association of spirometric and impulse oscillometric (IOS) indices in a short protocol for methacholine provocation. The primary endpoint was the methacholine dose that caused a 20% decrease in FEV(1) (PD(-20)FEV(1)) compared to baseline. Changes in respiratory resistance (Rrs5) and reactance (Xrs5) acquired by IOS were compared with FEV(1). Forty-eight children (5.3±0.9 years) were challenged. The mean maximal reduction in FEV(1) was 29.8%±14.7 (p<0.0001), the mean increase in Rsr5 was 55.3%±31.7, and the mean decrease in Xrs5 was 0.37kPasL(-1)±0.23 (p<0.001). An increase in Rrs5 of 45.2% and a decrease in Xrs5 of 0.69kPasL(-1) showed the optimal combination of sensitivity and specificity to detect a 20% reduction in FEV(1) (0.72 and 0.73; 0.80 and 0.76, respectively), and the area under the ROC curve was 0.76 and 0.81, respectively (p<0.005). In 28 patients with significant changes in FEV(1) and Rsr5, the PD(-20)FEV(1) was 0.48mg methacholine ±0.59 and the PD(+40)Rrs5 was 0.28mg methacholine ±0.45 (p=0.03). A short protocol for methacholine challenge testing is feasible in young children. IOS detected 70-80% of patients who responded in spirometry. During the challenge, the Rrs5 response preceded the FEV(1) response.

Dynamic change in respiratory resistance during inspiratory and expiratory phases of tidal breathing in patients with chronic obstructive pulmonary disease

Background and objectiveChronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation consisting of airway obstruction and parenchymal emphysema, with loss of elastic recoil. The forced oscillation technique can detect impairment of lung function by measuring lung impedance during normal tidal breathing. Respiratory resistance (Rrs) in COPD has been well-studied, but the differences in Rrs in the inspiratory and expiratory phases between mild and moderate COPD remain poorly understood. Since airway obstruction in COPD is known to change dynamically during tidal breathing and might affect Rrs, the differences in Rrs during tidal breathing between mild and moderate COPD were evaluated.MethodsMild (n = 13) and moderate (n = 13) COPD patients were recruited at Tokyo University Hospital (Tokyo, Japan). Rrs was measured using MostGraph-01 (Chest MI, Inc, Tokyo, Japan), which depicted Rrs in a frequency-and respiratory cycle-dependent manner in three-dimensional graphics. Rrs was evaluated at 4–35 Hz during tidal breathing.ResultsRrs changed dynamically during tidal breathing in COPD. The mean Rrs values were significantly greater in the moderate COPD group than in the mild group. The maximal and minimal Rrs values at higher frequencies in the respiratory cycle were significantly greater in moderate COPD. In inspiratory–expiratory breath analysis, the maximal and minimal Rrs values at 20 Hz and 35 Hz were significantly greater in the moderate group, whereas at 4 Hz they did not differ significantly between the groups.ConclusionRrs changed dynamically during tidal breathing in patients with COPD. The Rrs values at higher frequencies were greater in moderate COPD than in mild COPD. Rrs at higher frequencies might reflect the degree of airway obstruction in tidal breathing in patients with COPD and might be a useful marker for evaluation of airway obstruction at an early stage of COPD.

Mechanical effects of obesity on airway responsiveness in otherwise healthy humans

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index (r2=0.32, P<0.001) and waist circumference (r2=0.25, P<0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance (r2=0.19, P<0.001) and reactance (r2=0.40, P<0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity (r2=0.56, P<0.001) and total lung capacity (r2=0.59, P<0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.

Medialization of paralyzed vocal fold does not increase respiratory resistance measured by impulse oscillometry

Injection laryngoplasty restores voice in subjects with unilateral vocal fold paralysis, but knowledge of its effects on airflow dynamics is limited. Impulse oscillometry (IOS) is a non-invasive technique to investigate airway resistance. It is easily performed during normal breathing. A prospective study was conducted in order to investigate the effects of autologous fascia injection on airflow dynamics. IOS, flow-volume spirometry, acoustic analysis of voice, voice handicap index (VHI) questionnaire and subjective dyspnoea score were recorded before and 5-11 months after the operation. There was no significant change in respiratory resistance (Rres) or other variables of IOS. FEV1/FVC decreased from 0.80 to 0.77 (P = 0.02), but other variables of spirometry did not change significantly. Acoustic properties of voice (noise-to-harmonics ratio, shimmer, jitter, maximal phonation time) and VHI improved significantly. No change in dyspnoea occurred. In conclusion, medializing of a paralysed vocal fold improves voice, but does not have a clinically significant adverse effect on breathing. Flow-volume spirometry is more sensitive than IOS to changes in airflow dynamics after medialization.

Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure

Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH(2)O (high CPAP), at a CPAP of 0 cmH(2)O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.

Exercise-induced respiratory resistance changes as measured with the airflow perturbation device

Respiratory resistance (Rrs) changes during physical labor can modify the work of breathing and thus influence the time that the labor can be performed. Ideal in vivo human respiratory performance measurements should have fine temporal resolution and minimally impact the respiratory system itself. The airflow perturbation device (APD) provides respiratory resistance measurements in this manner. Pre-exercise Rrs was compared with post-exercise Rrs continuously monitored for 6 min in 12 non-asthmatic subjects. Rrs following exercise at was below pre-exercise levels for 40 s into recovery (p < 0.05) and inhalation resistance differed more markedly than exhalation resistance. The same post-exercise Rrs decline was found when Rrs measurements were compared to those taken during flow rates comparable to those found late in recovery. Results indicate that (1) Rrs indeed declines following exercise in non-asthmatic subjects, probably due to bronchial dilation, (2) Rrs changes can occur on short time scales, (3) Rrs changes are not related primarily to flow rate.

Modulation of airway responsiveness by anionic and cationic polyelectrolyte substances

To elucidate the effects of anionic and cationic polyelectrolyte substance on bronchoconstriction, we examined the serial changes in respiratory resistance (Rrs) in ovalbumin-sensitized guinea pigs after antigen exposure with or without preinhalation of low-molecular-weight heparin, poly- l-glutamic acid, poly- l-lysine and dextran, and with or without oral intake of dalteparin. Both immediate and late responses after antigen exposure were significantly decreased after pretreatment with inhaled low-molecular-weight heparin and poly- l-glutamic acid compared with saline alone. The late response was significantly decreased after pretreatment with oral dalteparin. Both low-molecular-weight heparin and poly- l-glutamic acid significantly decreased the airway response to methacholine in sensitized guinea pigs. In sensitized guinea pigs, the airway response to methacholine was significantly increased after pretreatment with inhaled poly- l-lysine. Pretreatment with inhaled low-molecular-weight heparin before poly- l-lysine exposure significantly suppressed the airway hyperresponsiveness after inhaled poly- l-lysine. These findings indicated that the “cationic–anionic interaction” plays an important role in airway responsiveness.

Changes in orofacial muscle activity in response to changes in respiratory resistance.

Increased resistance in the upper airway is known to be a contributing factor to deviant facial growth patterns. These patterns are the result of a prolonged presence of unbalanced oropharyngeal muscle activity. We hypothesized that mechanically increasing airway resistance would enhance the activity of the muscles facilitating respiration, and we attempted to demonstrate that the increased muscle activity is modulated by mechanoreceptors in the pharyngeal airway. The response of oropharyngeal muscles to increased airway resistance during spontaneous breathing was observed in 11 rabbits. Electromyographic signals from the ala nasi, orbicularis oris superior, genioglossus, mylohyoid muscles, and the diaphragm were recorded by fine-wire electrodes. Pressure changes were monitored by pressure transducers at the side branch of the cannule close to openings for the nose and the trachea. The study consisted of 2 experimental sessions. First, to evoke the response of muscles to the inspiratory resistance, increasing stepwise polyethylene tubes of various diameters were attached to the nasal and tracheal opening and the diameter of the tubes was gradually reduced. Muscle activity changes in response to the increased resistance were recorded during spontaneous nasal or tracheal breathing. Second, to examine muscle responses to negative pressure to the pharyngeal airway, irrespective of breathing activity, the pharynx was isolated as a closed circuit by a stoma constructed at a more caudal side in the trachea. Muscle responses to the negative pressure generated by a syringe in the pharyngeal segment were measured. Nasal breathing induced a greater muscle activity than did tracheal breathing, in general, at P <.05. When resistance was gradually increased, nasal breathing resulted in a greater increase in muscle activity than did tracheal breathing (P <.05), except in the diaphragm. Application of negative pressure to the isolated pharyngeal airway segment increased the muscle activity significantly (P <.05). We conclude that an increased airway resistance may facilitate oropharyngeal muscle activity through mechanoreceptors in the oropharyngeal airway.

Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on guinea pig respiratory mechanics

This study characterized the in vitro pharmacological properties of a newly developed endothelin receptor antagonist, N-butanesulfonyl-[ N-(3,5-dimethylbenzoyl)- N-methyl-3-[4-(5-isoxazolyl)-phenyl]-( d)-alanyl]-( l)-valineamide sodium salt (IRL 3630A), and its in vivo effects on respiratory mechanics were determined. IRL 3630A showed highly balanced affinities to human endothelin ET A and ET B receptors, giving apparent K i values of 1.5 and 1.2 nM, respectively. This compound also potently antagonized the endothelin-1-induced intracellular Ca 2+ increases in both embryonic bovine tracheal (EBTr) cells expressing endothelin ET A receptors and human Girardi heart (hGH) cells expressing endothelin ET B receptors. In guinea pig isolated tracheas having both endothelin ET A and ET B receptors, IRL 3630A greatly inhibited endothelin-1-induced contraction (p A 2=7.1), which was partially or scarcely suppressed by the endothelin ET A receptor antagonist cyclo[-( d)-Trp-( d)-Asp-( l)-Pro-( d)-Val-( l)-Leu-] (BQ-123) or the endothelin ET B receptor antagonist N-(3,5-dimethylbenzoyl)- N-methyl-3-(4-phenyl)-( d)-phenylalanyl-( l)-tryptophan (IRL 2500), respectively. Bolus i.v. injections of IRL 3630A administered into anaesthetized guinea pigs at 10 and 30 μg/kg inhibited endothelin-1 (1.3 μg/kg)-induced changes in respiratory resistance and compliance in a dose dependent manner, whereas both sodium 2-benzo[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5-trimethoxy-benzyl)-but-2-enoate (an endothelin ET A receptor antagonist: PD 156707) and IRL 2500 at doses of up to 30 μg/kg did not affect endothelin-1-induced changes in respiratory mechanics, reflecting the in vitro results. IRL 3630A is thus an effective bifunctional endothelin receptor antagonist, and will be useful in clarifying the role of endothelin in pulmonary diseases such as bronchial asthma.

The effect of cholecystokinin tetrapeptide on respiratory resistance in healthy volunteers

The effects of cholecystokinin tetrapeptide (CCK-4) on respiratory resistance were studied in 14 healthy volunteers by the registration of slow vital capacity and flow volume loop during forced respiration test. The administration of CCK-4 (50 micrograms) was performed in a double-blind and placebo-controlled design. Injections of CCK-4 induced prominent and time-limited paniclike symptoms in all healthy volunteers. Four volunteers (29%) experienced a panic attack. Subjective dyspnea was experienced by the majority of subjects at the peak of CCK-4 effect and seemed related to a diminution in vital capacity parameters; however, the forced respiration test did not reveal bronchoconstriction after CCK-4 challenge. Administration of CCK-4 also induced a short-lasting increase in heart rate and skin blood flow. This study suggests that dyspnea induced by CCK-4 is not related to changes in respiratory resistance.

Resistive‐load detection in healthy school‐aged children

The ability to detect changes in respiratory resistance, which may be important in acute and chronic adaptations to airways obstruction, has not been measured previously in children. Two methods were used to measure the resistive-load detection thresholds (the added resistance that produced a “just noticeable difference” in perception) in a group of 38 healthy children and adolescents aged 7–16 years. Total respiratory system resistance (Rrs), as measured by forced oscillation, was used as an index of each child's intrinsic baseline (pre-test) resistance. To determine thresholds, a computer program added various percentages of baseline resistance according to response (first method) and then in random order (second method). Thresholds by at least one of the two methods were detectable in 32 of the children (84%), and failure to detect a threshold was less common in older than in young children. Thresholds obtained by each method were significantly related to one another (r = 0.54, P < 0.05). Baseline resistance accounted for a marginally significant proportion of the variation in thresholds as assessed by the tracking method (R2 = 0.12, P < 0.10) and a large proportion of the variation in thresholds as assessed by the random method (R2 = 0.66, P < 0.0001). Thresholds expressed in terms of percent of baseline resistance were found to have mean values of 100.4–105.0%, regardless of gender or age. Results from a comparison group of adults (n = 10) indicated lower threshold by both procedures (mean values, 71.90–76.50%). We conclude that perceptual thresholds for added resistive loads are determined, in part, by growth-related changes in intrinsic resistance. Pediatr Pulmonol. 1996; 22:357–363. © 1996 Wiley-Liss, Inc.