Recently, heater/humidifier devices that use novel methods to condition breathing gases from an external source have been introduced. The addition of sufficient warmth and high levels of humidification to breathing gas has allowed for higher flow rates from nasal cannula devices to be applied to patients (i.e., high flow therapy). This article provides a review of the proposed mechanisms behind the efficacy of high flow therapy via nasal cannula, which include washout of nasopharyngeal dead space, attenuation of the inspiratory resistance associated with the nasopharynx, improvement in conductance and pulmonary compliance, mild distending pressure and reduction in energy expenditure for gas conditioning.

Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.

SUMMARY Introduction High-flow nasal cannula therapy (HFNC) has been shown to be more effective than continuous positive airway pressure (CPAP) in reducing intubations and ventilator days. HFNC likely provides mechanisms to support respiratory efficiency beyond application of distending pressure. We reason that HFNC washout of nasopharyngeal dead space impacts CO2 removal along with oxygenation. The aim of this study was to demonstrate the flow dependence of CO2 reduction and improved oxygenation during HFNC and the dependence on leak around the nasal prongs. Materials and Methods Neonatal piglets (n=13; 2-6kg) were injured with IV oleic acid and supported with HFNC at 2 through 8 L/minute. High and low leak around the nasal prongs was accomplished by using single and double prong cannulae, respectively. Measurement of hemodynamic, respiratory and blood gas parameters were made at each setting following 10 minutes for physiologic equilibration. Tracheal pressures were recorded by transmural catheters. Results With HFNC, CO2 trended downward in a flow dependent manner independent of leak. Oxygenation and tracheal pressures increased in a flow dependent manner with the greatest effect during double prong. At 8L/minute, tracheal pressures did not exceed 6±1 cmH2O. Conclusions HFNC improves gas exchange in a flow dependent manner; double prong had greater impact on O2; single prong had greater impact on CO2 elimination.

Thoracoabdominal asynchrony (TAA) has long been thought clinically useful in the assessment of airflow obstruction (AO) in infants. To test the hypothesis that the measurement of TAA is useful in the assessment of lung mechanics in infants with AO, we have used respiratory inductive plethysmography (RIP) to quantity TAA. We compared changes in TAA to changes in lung mechanics before and after aerosolized bronchodilator (BD) administration in 13 infants. Abdominal wall (AB) and rib cage (RC) motion were displayed on an X-Y recorder in a Lissajous figure. Asynchrony between RC and AB motion was quantified by comparing the width m of the Lissajous figure (difference between AB inspiratory and expiratory positions) at mid-RC excursion with the total AB excursion at its extremes (s). Phase angle phi ws computed as sin phi = m/s (or phi = 180 degrees - mu, where sin mu = m/s for phase angles greater than 90 degrees) and was taken as a measure of TAA. Lung resistance RL and elastance EL were calculated from esophageal pressure (Pes), mouth pressure, tidal volume, and tidal flow. All infants displayed TAA at baseline. After BD administration, TAA decreased in those infants in whom RL decreased. The percentage decrease in the phase angle from baseline after BD administration was significantly correlated with the decrease in peak-to-peak Pes (delta Pes) and the percentage decrease in RL and EL. We conclude that AO in infants leads to TAA through altered pleural pressure swings acting on the compliant chest wall. Changes in lung mechanics induced by bronchodilators are reflected in changes in TAA.(ABSTRACT TRUNCATED AT 250 WORDS)

This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury.

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Clara cell 10-kD protein (CC10) is a potent anti-inflammatory protein that is normally abundant in the respiratory tract. CC10 is deficient and oxidized in premature infants with poor clinical outcome (death or the development of bronchopulmonary dysplasia). The safety, pharmacokinetics, and anti-inflammatory activity of recombinant human CC10 (rhCC10) were evaluated in a randomized, placebo-controlled, doubleblinded, multicenter trial in premature infants with respiratory distress syndrome. A total of 22 infants (mean birth weight: 932 g; gestational age: 26.9 wk) received one intratracheal dose of placebo (n ϭ 7) or 1.5 mg/kg (n ϭ 8) or 5 mg/kg (n ϭ 7) rhCC10 within 4 h of surfactant treatment. Pharmacokinetic analyses demonstrated that the serum halflife was 11.6 (1.5 mg/kg group) and 9.9 h (5 mg/kg group). Excess circulating CC10 was eliminated via the urine within 48 h. rhCC10-treated infants showed significant reductions in total cell count (p Ͻ 0.0002), neutrophil counts (p Ͻ 0.001), and total protein concentrations (p Ͻ 0.01) and tended to have decreased IL-6 (p Ͻ 0.07) in tracheal aspirate fluid collected over the first 3 d of life. Infants in all three groups showed comparable growth. At 36 wk postmenstrual age, five of seven infants were still hospitalized and two of seven infants were receiving oxygen in the placebo group compared with two of seven hospitalized and one of seven receiving oxygen in the 1.5-mg/kg group and four of six hospitalized and three of six receiving oxygen in the 5-mg/kg group. A single intratracheal dose of rhCC10 was well tolerated and had significant anti-inflammatory effects in the lung. Multiple doses of rhCC10 will be investigated for efficacy in reducing pulmonary inflammation and ameliorating bronchopulmonary dysplasia in future studies. Bronchopulmonary dysplasia (BPD) affects 20 -60% of all premature, very low birth weight infants. It is associated with substantial morbidity and mortality as well as extremely high health care costs. Although the widespread use of exogenous surfactant and antenatal steroid therapy has reduced the overall severity of BPD, the prevalence of this condition has increased with improved survival of very low birth weight infants. BPD is a multifactorial disease process that is the end result of an immature, surfactant-deficient lung that has been exposed to hyperoxia, mechanical ventilation, and infection. These forces initiate a cascade of proinflammatory cytokines that lead to the development of significant inflammatory changes and chronic lung injury.Clara cell 10-kD protein (CC10) is also known as uteroglobin. It is a small homodimeric secretory protein that is produced by mucosal epithelial cells (1). In humans, Clara cells are the main site of CC10 production (located in the airways), and several other organs synthesize smaller amounts of mRNA encoding this protein (2-4). CC10 also circulates in the blood

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