Lipoid Pneumonia and Sarcoidosis.

INTRODUCTION: Lipoid pneumonia is a rare, underdiagnosed disorder, and its combined presentation with sarcoidosis is even more unusual. METHODS: This paper presents a case in which both lipoid pneumonia and sarcoidosis were present, and includes the relevant literature review on lipoid pneumonia. RESULTS: Lipoid pneumonia may be acute or chronic in its presentation, resulting from exogenous or endogenous factors, or classified as idiopathic, with its precise incidence unknown. Radiographic changes maybe variable, but typically include lower lobe consolidation. Pathologic changes consist of an inflammatory giant cell reaction around lipid-related empty vacuoles and giant cell granulomas. Treatment in the case of exogenous lipoid pneumonia consists of removal of the offending oil ingestion. However, in endogenous lipoid pneumonia, treatment is aimed at the underlying cause, as there is no standard treatment. Repeated bronchoalveolar lavage, corticosteroids, and surgical resection have been used as therapies. The course of the disease is usually not progressive.

Inflammatory response to acute hypoxia in humans.

BACKGROUND: In animal studies hypoxia is known to cause an inflammatory response, inducing multiple transcription factors and activating molecular processes at the cellular level. However, it is not known whether acute hypoxia causes similar inflammatory effects in humans, although such an assumption is commonly made. METHODS: The effects of acute hypoxic exposure were studied in 12 healthy adults: Each subject was studied on 2 different days. Group 1 (mean age 33 ± 5.5 years; 2 females, 4 males) was exposed either to a hypoxic gas mixture or room air for 30 min and Group 2 (mean age 26.5 ± 7.5 years; 3 females, 3 males) for 60 min. Measurements of circulating adhesion molecules (AMs), Clara cell secretory protein (CC16), hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C reactive protein (hsCRP) were made at baseline and at intervals following exposure for 240 min. RESULTS: No significant changes were seen in circulating AMs, CC16, TNF-α, IL-6 or hsCRP, although both HIF-1α and VEGF levels increased significantly (p < 0.05) after hypoxic exposure. CONCLUSIONS: Acute hypoxic exposure in normal man does not induce a measurable change in inflammatory or epithelial biomarkers, in contrast to studies at the cellular level in animals. However, acute hypoxic exposure does induce the expression of HIF-1α and VEGF. These results indicate that in humans acute hypoxic exposure for up to 60 min does not induce a generalized inflammatory response, indicating that the human response to hypoxia is more complex than inferred from animal/cellular studies.

A novel extracorporeal CO(2) removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD.

BACKGROUND: Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients. METHODS: This is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean. RESULTS: The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization. CONCLUSIONS: This single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.

Mechanisms of dyspnea.

The mechanisms and pathways of the sensation of dyspnea are incompletely understood, but recent studies have provided some clarification. Studies of patients with cord transection or polio, induced spinal anesthesia, or induced respiratory muscle paralysis indicate that activation of the respiratory muscles is not essential for the perception of dyspnea. Similarly, reflex chemostimulation by CO2 causes dyspnea, even in the presence of respiratory muscle paralysis or cord transection, indicating that reflex chemoreceptor stimulation per se is dyspnogenic. Sensory afferents in the vagus nerves have been considered to be closely associated with dyspnea, but the data were conflicting. However, recent studies have provided evidence of pulmonary vagal C-fiber involvement in the genesis of dyspnea, and recent animal data provide a basis to reconcile differences in responses to various C-fiber stimuli, based on the ganglionic origin of the C fibers. Brain imaging studies have provided information on central pathways subserving dyspnea: Dyspnea is associated with activation of the limbic system, especially the insular area. These findings permit a clearer understanding of the mechanisms of dyspnea: Afferent information from reflex stimulation of the peripheral sensors (chemoreceptors and/or vagal C fibers) is processed centrally in the limbic system and sensorimotor cortex and results in increased neural output to the respiratory muscles. A perturbation in the ventilatory response due to weakness, paralysis, or increased mechanical load generates afferent information from vagal receptors in the lungs (and possibly mechanoreceptors in the respiratory muscles) to the sensorimotor cortex and results in the sensation of dyspnea.

Blockade of airway sensory nerves and dyspnea in humans.

Evidence has accumulated from previous studies that vagal fibers in the lungs are involved in the genesis of dyspnea. In a series of human studies, based on our previous animal data (J Physiol 1998; 508:109-18; J Appl Physiol 1998; 84:417-24; J Appl Physiol 2003; 95:1315-24) we established that intravenous adenosine has a dyspnogenic effect (J Appl Physiol 2005; 98:180-5; Respir Res 2006; 7:139; Pulm Pharmacol Ther 2008; 21:208-13), strongly implicating a role for vagal C-fibers in the genesis of dyspnea. We have now analyzed the relative effects of blockade of vagal C-fibers by two methods and routes of delivery: by inhibition of the sodium channel and interruption of action potential conduction in the nerve by inhaled local anesthetic (lidocaine), and by blockade by systemic theophylline, a known, nonselective adenosine receptor antagonist. Both techniques significantly (p < 0.05) attenuated the dyspneic response to intravenous adenosine. However, the attenuation was significantly (p < 0.05) greater with pretreatment with systemic theophylline (mean change in response, DeltaAUC -44%) versus pretreatment with inhaled lidocaine (mean change in response, DeltaAUC -11.8%). These differences in the results of airway sensory nerve blockade probably reflect different populations of C fiber receptors and may explain conflicting results of previous studies of dyspnea and airway anesthesia.

Effects of airway anesthesia on dyspnea and ventilatory response to intravenous injection of adenosine in healthy human subjects.

We have recently shown that intravenous injection of adenosine causes dyspnea and hyperventilation in man, and we suggested that stimulation of vagal C-fibers in the airways and lungs is involved. To test this hypothesis further, the present study was performed in healthy subjects (n=12; age 32.4+/-10.2 yrs, 7 females) to determine if the effect of adenosine could be attenuated by blocking the airway sensory receptors by inhalation of aerosolized lidocaine, a local anesthetic. In each subject, the effects of intravenous injection of adenosine (10mg) on dyspneic sensation, minute ventilation, airway resistance and heart rate were measured after the subject inhaled lidocaine or placebo aerosol on two separate days. After a latency of approximately 20s, adenosine injection evoked a distinct dyspneic sensation, increase in minute ventilation (VE), and transient bradycardia followed by tachycardia in all subjects. The increase in VE resulted primarily from a significant increase in tidal volume. The intensity of adenosine-induced dyspnea was markedly reduced after the lidocaine pretreatment compared to placebo. In a sharp contrast, the VE and heart rate responses to adenosine were not affected by lidocaine. These results lend further support to our previous studies indicating that the origin of the dyspnogenic action of intravenous adenosine is most likely vagal bronchopulmonary C-fiber sensory nerves.

Chronic eosinophilic pneumonia: a review.

Chronic eosinophilic pneumonia (CEP) is a disease of unknown cause. The hallmark of CEP is eosinophil accumulation in the lungs. While the triggering factor is unknown, eosinophil accumulation in the lungs is now believed to be secondary to the actions of eosinophil-specific chemoattractants, including eotaxin and regulated upon activation, normal T-cell expressed and secreted (RANTES), and IL-5 released from Th2 lymphocytes in the lungs. There is a female preponderance in CEP, with a peak incidence in the 5th decade; the onset is insidious with weight loss, cough, and dyspnea. An atopic history is common, but asthma is not a prerequisite for the development of CEP. Airways obstruction may develop during the course of CEP, but may also result from CEP. The chest x-ray usually shows bilateral peripheral shadows, which may be migratory. Peripheral eosinophilia is usual. Standard treatment of CEP is with oral steroids, usually with dramatic resolution of symptoms and radiographic changes; however, relapses are common when the daily steroid dose is reduced below 15 mg. Current data suggest that when treatment is stopped, relapse is common in the majority of patients (>80%) followed for a sufficiently long period of time. Some recent reports suggest that treatment with inhaled steroids may be of some value in this condition.

The pulmonary effects of intravenous adenosine in asthmatic subjects.

BACKGROUND: We have shown that intravenous adenosine in normal subjects does not cause bronchospasm, but causes dyspnea, most likely by an effect on vagal C fibers in the lungs [Burki et al. J Appl Physiol 2005; 98:180-5]. Since airways inflammation and bronchial hyperreactivity are features of asthma, it is possible that intravenous adenosine may be associated with an increased intensity of dyspnea, and may cause bronchospasm, as noted anecdotally in previous reports. METHODS: We compared the effects of placebo and 10 mg intravenous adenosine, in 6 normal and 6 asthmatic subjects. RESULTS: Placebo injection had no significant (p > 0.05) effect on the forced expiratory spirogram, heart rate, minute ventilation (Ve), or respiratory sensation. Similarly, adenosine injection caused no significant changes (p > 0.05) in the forced expiratory spirogram; however, there was a rapid development of dyspnea as signified visually on a modified Borg scale, and a significant (p < 0.05) tachycardia in each subject (Asthmatics +18%, Normals + 34%), and a significant (p < 0.05) increase in Ve (Asthmatics +93%, Normals +130%). The intensity of dyspnea was significantly greater (p < 0.05) in the asthmatic subjects. CONCLUSION: These data indicate that intravenous adenosine does not cause bronchospasm in asthmatic subjects, and supports the concept that adenosine-induced dyspnea is most likely secondary to stimulation of vagal C fibers in the lungs. The increased intensity of adenosine-induced dyspnea in the asthmatic subjects suggests that airways inflammation may have sensitized the vagal C fibers.

Intravenous adenosine and dyspnea in humans.

Intravenous adenosine for the treatment of supraventricular tachycardia is reported to cause bronchospasm and dyspnea and to increase ventilation in humans, but these effects have not been systematically studied. We therefore compared the effects of 10 mg of intravenous adenosine with placebo in 21 normal subjects under normoxic conditions and evaluated the temporal sequence of the effects of adenosine on ventilation, dyspnea, and heart rate. The study was repeated in 11 of these subjects during hyperoxia. In all subjects, adenosine resulted in the development of dyspnea, assessed by handgrip dynamometry, without any significant change (P > 0.1) in lung resistance as measured by the interrupter technique. There were significant increases (P < 0.05) in ventilation and heart rate in response to adenosine. The dyspneic response occurred slightly before the ventilatory or heart rate responses in every subject, but the timing of the dyspneic, ventilatory, and heart rate responses was not significantly different when the group data were analyzed (18.9 +/- 5.8, 20.3 +/- 5.5, and 19.7 +/- 4.5 s, respectively). During hyperoxia, adenosine resulted in similar effects, with no significant differences in the magnitude of the ventilatory response; however, compared with the normoxic state, the intensity of the dyspneic response was significantly (P < 0.05) reduced, whereas the heart rate response increased significantly (P < 0.05). These data indicate that intravenous adenosine-induced dyspnea is not associated with bronchospasm in normal subjects. The time latency of the response indicates that the dyspnea is probably not a consequence of peripheral chemoreceptor or brain stem respiratory center stimulation, suggesting that it is most likely secondary to stimulation of receptors in the lungs, most likely vagal C fibers.