Mark R. Elstad

Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: Are two applications better than one?

Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short‐term improvement, is often associated with long‐term relapse. Mitomycin‐C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3–6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application.

Platelet-Activating Factor (PAF): Signalling and Adhesion in Cell-Cell Interactions

Signalling by PAF is closely linked to adhesive interactions between cells of the inflammatory and vascular systems. It acts as a juxtacrine signal that alters the activity of beta 2 integrins on myeloid leukocytes (Figure 1), and works in concert with P-selectin at the surfaces of endothelial cells (Figure 2 and text). Observations in models of flow and in vivo support the original experiments using cultured endothelium under static conditions that indicated that PAF acts at this vascular interface. P-selectin modifies and integrates signals delivered through the PAF receptor on monocytes (Figure 4). Adhesion via P-selectin and engagement of beta 2 integrins modify signals leading to PAF synthesis (text and Figure 5). The intimate relationship between adhesive events and signalling by PAF may be a critical determinant in its roles in physiologic and pathologic responses.

Iron and iron-related proteins in the lower respiratory tract of patients with acute respiratory distress syndrome

ObjectiveAn increased oxidative stress in the lower respiratory tract of individuals with acute respiratory distress syndrome is considered to be one mechanism of lung injury in these patients. Cell and tissue damage resulting from an oxidative stress can ultimately be the consequence of a disruption of normal iron metabolism and an increased availability of catalytically active metal. Using bronchoalveolar lavage fluid, we quantified concentrations of iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. DesignA clinical study to quantify iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. PatientsWe studied 14 patients with acute respiratory distress syndrome and 28 healthy volunteers. Main ResultsComparable to previous investigation, protein, albumin, and cytokine concentrations in the bronchoalveolar lavage fluid were significantly increased in acute respiratory distress syndrome patients. The concentrations of total and nonheme iron were also increased in the lavage fluid of patients. Concentrations of hemoglobin, haptoglobin, transferrin, transferrin receptor, lactoferrin, and ferritin in the bronchoalveolar lavage fluid were all significantly increased in acute respiratory distress syndrome patients. ConclusionsWe conclude that bronchoalveolar lavage fluid indices reflect a disruption of normal iron metabolism in the lungs of acute respiratory distress syndrome patients. Increased concentrations of available iron in acute respiratory distress syndrome may participate in catalyzing oxidant generation destructive to the tissues of the lower respiratory tract. However, increased metal availability is also likely to elicit an increased expression of transferrin receptor, lactoferrin, and ferritin in the lower respiratory tract which will function to diminish this oxidative stress.

The interaction of leukocytes with platelets in blood coagulation.

&NA; The concept that leukocytes play an active role in hemostasis and thrombosis has only recently been accepted. Leukocytes may influence coagulation directly, by the production of procoagulant and anticoagulant molecules, or indirectly, by actions on vascular cells including platelets, endothelial cells, and other leukocytes. This review examines the role of leukocytes in coagulation with an emphasis on regulation of leukocyte function by interactions, with platelets. Activated platelets may serve both to localize leukocytes in areas of thrombosis and to modulate their function. Over the past year, several in vitro studies further defined molecular mechanisms by which leukocytes may regulate coagulation. Further, in vivo studies have provided support for the relevance of these mechanisms in pathophysiologic coagulation.

Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome

ObjectivePlatelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6). DesignBronchoalveolar lavage was performed during acute (<96 hrs from onset), plateau (6 to 12 days), and late (≥14 days) phases of ARDS. PatientsIntubated patients with ARDS or a risk factor for ARDS. Measurements and Main ResultsIn ARDS, total bronchoalveolar lavage PAF-AH activity was markedly increased in the acute phase (87 ± 89 mU/mL, n = 33) and then decreased in the plateau (23 ± 14 mU/mL, n = 10) and late phases (19 ± 14 mU/mL, n = 7) (p = .003). Total bronchoalveolar lavage PAF-AH activity during the acute phase of ARDS was also increased as compared with patients at risk for ARDS (16 ± 13 mU/mL, n = 6) and healthy controls (3 ± 3 mU/mL, n = 6) (p < .001). In contrast, plasma PAF-AH activities were the same in controls (3215 ± 858 mU/mL, n = 6), in patients at risk for ARDS (3606 ± 1607 mU/mL, n = 6), and during the acute phase of ARDS (3098 ± 2395 mU/mL, n = 33) (p = .18). PAF-AH mRNA was present in alveolar macrophages in the acute phase of ARDS (five of six) and in at-risk patients (two of three) but not in healthy controls. ConclusionsPAF-AH activity is increased in bronchoalveolar lavage fluid from patients with ARDS. Likely sources include leakage of plasma PAF-AH into alveoli or release of PAF-AH from injured cells; however, the presence of PAF-AH mRNA in alveolar macrophages suggests that PAF-AH may be actively synthesized in the lungs of patients with ARDS. PAF-AH activity in the lungs of ARDS patients may regulate inflammation caused by PAF and related oxidized phospholipids generated in the inflammatory response.

The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.

Background:Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity. Methods:In a randomized, sham procedure controlled, double-blind trial, 277 subjects were enrolled at 36 centers. Patients had emphysema, airflow obstruction, hyperinflation, and severe dyspnea. The primary effectiveness measure was a significant improvement in disease-related quality of life (St. George’s Respiratory Questionnaire) and changes in lobar lung volumes. The primary safety measure was a comparison of serious adverse events. Results:There were 6/121 (5.0%) responders in the treatment group at 6 months, significantly >1/134 (0.7%) in the control group [Bayesian credible intervals (BCI), 0.05%, 9.21%]. Lobar volume changes were significantly different with an average decrease in the treated lobes of −224 mL compared with −17 mL for the control group (BCI, −272, −143). The proportion of responders in St. George’s Respiratory Questionnaire was not greater in the treatment group. There were significantly more subjects with a serious adverse event in the treatment group (n=20 or 14.1%) compared with the control group (n=5 or 3.7%) (BCI, 4.0, 17.1), but most were neither procedure nor device related. Conclusions:This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results. Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies. Further studies need to focus on improved patient selection and a different treatment algorithm. Trial Registry:ClinicalTrials.gov NCT00475007.

Comparing nebulized water versus saline after laryngeal desiccation challenge in Sjögren's Syndrome

This study examined the effects of a laryngeal desiccation challenge and two nebulized hydration treatments on phonation threshold pressure (PTP), vocal effort, and throat dryness in patients with chronic airway dryness.

Incidence and Risk Factors for Intensive Care Unit–related Post-traumatic Stress Disorder in Veterans and Civilians

RATIONALE The incidence and risk factors of post-traumatic stress disorder (PTSD) related to the intensive care unit (ICU) experience have not been reported in a mixed veteran and civilian cohort. OBJECTIVES To describe the incidence and risk factors for ICU-related PTSD in veterans and civilians. METHODS This is a prospective, observational, multicenter cohort enrolling adult survivors of critical illness after respiratory failure and/or shock from three Veterans Affairs and one civilian hospital. After classifying those with/without preexisting PTSD (i.e., PTSD before hospitalization), we then assessed all subjects for ICU-related PTSD at 3 and 12 months post hospitalization. MEASUREMENTS AND MAIN RESULTS Of 255 survivors, 181 and 160 subjects were assessed for ICU-related PTSD at 3- and 12-month follow-up, respectively. A high probability of ICU-related PTSD was found in up to 10% of patients at either follow-up time point, whether assessed by PTSD Checklist Event-Specific Version (score ≥ 50) or item mapping using the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). In the multivariable regression, preexisting PTSD was independently associated with ICU-related PTSD at both 3 and 12 months (P < 0.001), as was preexisting depression (P < 0.03), but veteran status was not a consistent independent risk factor for ICU-related PTSD (3-month P = 0.01, 12-month P = 0.48). CONCLUSIONS This study found around 1 in 10 ICU survivors experienced ICU-related PTSD (i.e., PTSD anchored to their critical illness) in the year after hospitalization. Preexisting PTSD and depression were strongly associated with ICU-related PTSD.

Use of Silicone Stents in the Management of Subglottic Stenosis

The management of subglottic stenosis, an increasingly common clinical problem, is complex and challenging. Two surgical approaches have traditionally been used-segmental resection versus expansion of the stenosed segment with cartilage or bone grafts.13 Endoscopic therapies also play a major role in management of subglottic stenosis because segmental resection may be technically difficult in the absence of a stenosis-free subglottic space, surgery is not uniformly successful, and many patients are not suitable operative candidates. The endoscopic management of airway stenosis4 and the use of airway stents5 have been recently reviewed in detail.

Alveolar haemorrhage in a case of high altitude pulmonary oedema

A case of high altitude pulmonary oedema (HAPE) in a climber who made a rapid ascent on Mt McKinley (Denali), Alaska is described. The bronchoalveolar lavage (BAL) fluid contained increased numbers of red blood cells and an abundance of haemosiderin laden macrophages consistent with alveolar haemorrhage. The timing of this finding indicates that alveolar haemorrhage began early during the ascent, well before the onset of symptoms. Although evidence of alveolar haemorrhage has been reported at necropsy in individuals dying of HAPE, previous reports have not shown the same abundance of haemosiderin laden macrophages in the BAL fluid. These findings suggest that alveolar haemorrhage is an early event in HAPE.