Pulmonary Arterial Hypertension Specific Therapy in Patients with Combined Post- and Precapillary Pulmonary Hypertension.

Background: Specific therapy for patients with PAH is associated with good outcomes. Little is known about the effect of this treatment in patients with Cpc-PH (PAPm ≥ 25 mmHg, PAWP > 15 mmHg, DPG ≥ 7 mmHg, and/or PVR > 3 WU). This study evaluates the outcome of treating patients with Cpc-PH using PAH specific therapy.

Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by H Magnetic Resonance Spectroscopy: A Feasibility Study.

Objectives: Lung cancer is one of the most lethal cancers. Currently, there are no biomarkers for early detection, monitoring treatment response, and detecting recurrent lung cancer. We undertook this study to determine if H magnetic resonance spectroscopy (MRS) of sputum and exhaled breath condensate (EBC), as a noninvasive tool, can identify metabolic biomarkers of lung cancer.

Directing therapy in pulmonary arterial hypertension using a target 6 min walk distance.

Background: The most effective approaches to escalating advanced therapies in pulmonary arterial hypertension (PAH) are controversial.

Objective: To compare outcomes before and after introducing a target 6 min walk distance (6MWD) treatment strategy in PAH using registry data.

Methods: From 2001 to 2005, WHO class II to IV patients were treated with bosentan or prostanoids.

Evaluating systemic lupus erythematosus patients for lung involvement.

Introduction: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS.

Methods: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan.

Vascular compromise and hemodynamics in pulmonary arterial hypertension: model predictions.

A previously validated computer model of the normal pulmonary circulation is adapted to simulate pulmonary arterial hypertension (PAH) in humans. Model predictions are used to explore the suitability of currently accepted criteria for diagnosing PAH by correlating hemodynamic data with the degree of vascular compromise (disease severity). Model predictions demonstrate a hyperbolic relationship between vascular compromise, mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR).

Treatment of pulmonary hypertension in patients with connective tissue disease and interstitial lung disease.

Background: Pulmonary hypertension (PH) in patients with connective tissue disease (CTD) can occur in isolation or concomitantly with interstitial lung disease (ILD). Targeted therapies for PH can mitigate clinical deterioration in CTD patients with isolated PH; however, the effect of these therapies in CTD patients with PH and ILD (CTD-PH-ILD) are poorly characterized.

Objective: To investigate outcomes following long-term treatment of PH in patients with CTD-PH-ILD.

Comparison of per cent predicted and percentile values for pulmonary function test interpretation.

Background: Pulmonary function tests (PFTs) are commonly interpreted as a fraction of predicted normal values, with an abnormal test often defined as less than 80% or greater than 120% of the predicted value. However, recommendations of the American Thoracic Society/European Respiratory Society suggest using a percentile-based approach to define an abnormal test (less than the fifth or greater than the 95th percentiles).

Objective: To compare PFT values obtained by the per cent predicted method with the percentile-based method for lung function parameters.

An atypical presentation of liver enzyme elevation resulting from bosentan use.

Hepatocellular enzyme elevation is a known side effect of both bosentan and atorvastatin. However, a rise in liver enzyme level not characteristic of either agent individually may represent a reaction to their combination or an atypical reaction to bosentan alone. The present case report describes a patient who had been taking atorvastatin for many years and was started on bosentan for chronic thromboembolic pulmonary hypertension.

Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy.

Background: Pulmonary arterial hypertension (PAH) remains a progressive disease despite improvement when using one of three medication classes: prostanoids, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Combination therapy has been proposed for patients with unsatisfactory response to monotherapy.

Objectives: To examine the effect of adding sildenafil to bosentan on 6 min walk distance (6MWD) and New York Heart Association (NYHA) classification in patients with PAH who achieved inadequate improvement with bosentan monotherapy.

Effect of maintenance azithromycin on established bronchiolitis obliterans syndrome in lung transplant patients.

Background: Bronchiolitis obliterans syndrome (BOS), the main cause of late mortality following lung transplantation, is defined as an irreversible decline in forced expiratory volume in 1 s (FEV1). Previous studies using azithromycin for BOS in lung transplant patients have demonstrated a potential reversibility of the decline in FEV1.

Objectives: To examine whether initiating azithromycin reverses decline in FEV1 in lung transplant recipients with established BOS of at least three months.

Ventilator advisory system employing load and tolerance strategy recommends appropriate pressure support ventilation settings: multisite validation study.

Background: Loads on the respiratory muscles, reflected by noninvasive measurement of the real-time power of breathing (POBn), and tolerance of these loads, reflected by spontaneous breathing frequency (f) and tidal volume (Vt), should be considered when evaluating patients with respiratory failure. Pressure support ventilation (PSV) should be applied so that muscle loads are not too high or too low. We propose a computerized, ventilator advisory system employing a load (POBn) and tolerance (f and Vt) strategy in a fuzzy logic algorithm to provide guidance for setting PSV.

Basic principles of control of breathing.

The metabolic demands of the body, including consumption of oxygen and removal of carbon dioxide, vary widely in health and disease. Ventilation must adjust to meet these demands and accommodate volitional and behavioral activities. Control of breathing depends on a complex and intricate feedback control system that integrates these automatic and volitional aspects of ventilation.

Effects of pulmonary and intercostal denervation on the response of breathing frequency to varying inspiratory flow.

In mechanically ventilated awake and sleeping humans, it has been shown that increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on respiratory output. Mechanoreceptors located in intercostal muscles or within the lung have been suggested as possible pathways that may mediate the excitatory effect of V'I. To test this, five patients with bilateral lung transplantation (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7 (QP) were studied.

Respiratory response to CO2 during pressure-support ventilation in conscious normal humans.

The respiratory response to CO2 during pressure-support ventilation (PSV) was studied in 16 conscious normal humans. The subjects breathed through a mouthpiece connected to a ventilator in PSV mode, with pressure set to the highest comfortable level for each subject (10.1 +/- 0.

Effects of inspiratory muscle unloading on the response of respiratory motor output to CO2.

Inspiratory muscle output is downregulated when the mechanical load is reduced in awake humans. It is not known whether this is related to reduction in PCO2 or to removal of load-related neural responses. To address this issue, we did Read CO2 rebreathing tests in 13 normal subjects with and without unloading and compared respiratory output at identical end-tidal PCO2 (PET(CO2)) levels.

Effects of non-REM sleep on the response of respiratory output to varying inspiratory flow.

It has been shown in mechanically ventilated awake normal humans that increasing inspiratory flow rate (VI) exerts an excitatory effect on respiratory output. It is not known if this effect persists during sleep. To test this, seven normal adults were studied during wakefulness and non-rapid eye movement (non-REM) sleep.

Effects of breathing route, temperature and volume of inspired gas, and airway anesthesia on the response of respiratory output to varying inspiratory flow.

The determinants of the response of the respiratory output to inspiratory flow rates (VI) were examined in awake normal subjects. Subjects were connected to a volume-cycle ventilator in the assist/control mode, and VI was increased in steps from 30 to 90 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered.

Effect of breathing pattern and level of ventilation on pulmonary fluid filtration in dog lung.

The effect of breathing pattern and level of ventilation on fluid filtration in the lung under edema forming conditions was studied in an in situ left upper lobe (LUL) canine preparation. LUL weight was continuously monitored. In Group 1, rate of edema formation (delta W/delta t) was measured In seven dogs at two vascular pressures (35 and 45 mm Hg) while the LUL was randomly ventilated under six conditions.

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans.

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans.

Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model.

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds.

Distensibility and pressure-flow relationship of the pulmonary circulation. I. Single-vessel model.

To ascertain the relative contributions of vascular distensibility and nonhomogeneous behavior within the pulmonary circulation to the distinctive nonlinear relationship between inflow pressure (Pin) and flow [pressure-flow (P-F) relationship] and between Pin and outflow pressure (Pout) at constant flow (Pin-Pout relationship), we developed a multibranched model in which the elastic behavior of, and forces acting on, individual branches can be varied independently. The response of the multibranched model is described in the companion article (J. Appl.