W. Bruce Davis

Percutaneous Tracheostomy: Don't Beat Them, Join Them†

Objectives: The introduction of percutaneous tracheostomy (PercTrach) has resulted in tension over the scope of practice between otolaryngologists and pulmonary/critical care (PCC) specialists. We sought to determine the value of a collaborative approach to the performance of PercTrach at the bedside in the intensive care unit setting.

AMINOBENZOIC ACID COMPOUNDS AS HOCL TRAPS FOR ACTIVATED NEUTROPHILS

This study was designed to develop traps for hypochlorous acid (HOCl) which could be used to detect HOCl in the microenvironment of activated neutrophils. Reagent HOCl was found to react with para-aminobenzoic acid (PABA) in aqueous solution to produce a predominant metabolite detectable by high performance liquid chromatography (HPLC). Mass spectroscopy and nuclear magnetic resonance identified this metabolite as the ring addition product 3-chloro PABA. The related compound para-aminosalicylic acid (PAS) was also metabolized by HOCl to 3-chloro PAS. The formation of the 3-chloro metabolite was specific for reactions involving HOCl, since several other oxidants in chloride buffer failed to produce the metabolite. Human blood neutrophils activated by phorbol myristate acetate or zymosan in the presence of PABA (or PAS) used their HOCl to produce large amounts of the 3-chloro metabolite. The formation of 3-chloro PABA was inhibited by azide, catalase, and taurine, which is consistent with the production of the metabolite by the neutrophil myeloperoxidase (MPO) pathway. The reaction of HOCl with PABA and PAS was relatively slow as shown by competitive reactions with endogenous antioxidants like taurine, methionine, and glutathione. This was confirmed in reactions involving PABA/PAS and reagent HOCl or HOCl generated by the MPO enzyme system. In these in vitro systems, glutathione and serum completely inhibited the formation of the 3-chloro metabolite. In contrast, activated neutrophils metabolized PABA/PAS to the 3-chloro metabolite even in the presence of 1% serum. These findings demonstrate that PABA and PAS are specific trapping agents for HOCl produced by neutrophils in complex biological conditions.

Montelukast added to fluticasone propionate does not alter inflammation or outcomes

BACKGROUND Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation. OBJECTIVES To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists. METHODS Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation. RESULTS Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p<or=0.008). Both treatments significantly reduced submucosal mast cell, CD3+, CD4+, CD8+ and CD25+ cell counts. Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group. There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen. CONCLUSIONS Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting beta(2)-agonists without further improvement when montelukast is added to low-dose fluticasone propionate.

A 67-Year-Old Woman With Cough and Shortness of Breath

67-year-old woman was admitted to the hospital with complaints of cough and shortness of breath. She had immigrated to the United States from Pakistan 4 months earlier and subsequently developed the cough, which had worsened over the past months. Two weeks prior to admission she developed worsening dyspnea on exertion. The patient did not speak English, and her daughter did the translation. Her cough was mostly dry with occasional production of minimal whitish-brown sputum. She had received amoxicillinclavulanate and ciprofl oxacin for her symptoms by her primary care physician without any benefi t. She denied any complaints of persistent fever, night sweats, chest pain, skin rash, joint pains, hemoptysis, or weight loss. Her remaining medical history was signifi cant for hypertension, diabetes mellitus, and asthma. Her medications included amlodipine, metformin, glyburide, and albuterol metered-dose inhaler. She denied any history of tobacco or alcohol abuse; however, she had been exposed to biomass fuels as a child. There was no history of prior pulmonary infection or positive purifi ed protein derivative skin test.

Chapter 11 – Eosinophils

Publisher Summary This chapter highlights eosinophil structure and function and discusses the increasing evidence that eosinophils contribute to the pathogenesis of asthma. Eosinophil is a polymorphonuclear leukocyte produced in the bone marrow from totipotent stem cells. The presence of increased eosinophils in the blood, sputum, bronchoalveolar lavage (BAL) fluid, and bronchial wall of asthma patients is usually correlated with airway obstruction and bronchial hyperresponsiveness. Eosinophilic inflammation of the airways is more common in patients with asthma than in patients with chronic obstructive pulmonary disease (COPD). Eosinophil effector functions—particularly the release of toxic granule proteins and leukotrienes—are fundamental to the pathogenesis of asthma. Peripheral blood and sputum eosinophilia is significantly associated with both allergic and nonallergic asthma. Recent studies have focused on the complex cellular and molecular mechanisms that regulate the recruitment of eosinophils from the blood to the site of inflammation in the airways, and this understanding can lead to the development of several therapeutic agents that have the potential to improve asthma or a part of it by their effects on eosinophils.