Sputum induction as a research tool for sampling the airways of subjects with cystic fibrosis.

BACKGROUND: Sputum induction (SI) has proved to be a reliable non-invasive tool for sampling inflammatory airway contents in asthma, with distinct advantages over collection of expectorated sputum (ES) and bronchoalveolar lavage (BAL). A study was undertaken to evaluate the safety of SI and to assess if it might be an equally valuable outcome tool in patients with cystic fibrosis (CF). METHODS: The safety of the procedure was examined and sample volume, cell counts, cytokine concentrations, and bacterial culture results obtained by SI, spontaneous ES, and fibreoptic bronchoscopy were compared in 10 adults with CF. RESULTS: SI was well tolerated and was preferred to BAL by all subjects. The mean (SE) sample volume obtained by SI was significantly greater than ES (6.74 (1.46) ml v 1.85 (0.33) ml, p = 0.005). There was no significant difference in the number of cells per ml of sample collected. There was a difference in the mean (SD) percentage of non-epithelial, non-squamous cells collected (67 (28)%, 86 (21)%, and 99 (1)% for ES, SI, and BAL, respectively). These percentage counts were different between ES and both SI and BAL (p=0.03 and p=0.006, respectively). Cell differential counts (excluding squamous cells) from all collection methods were similar (mean (SD) 84 (9)%, 87 (7)%, and 88 (11)% polymorphonuclear cells for ES, SI, and BAL, respectively). The concentrations of interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha were the same in all three samples when corrected for dilution using urea concentration. The test specific detection rate for recovery of bacteriological pathogens was 79% for SI, 76% for ES, and 73% for BAL. CONCLUSION: SI offers safety advantages over BAL and may be a more representative airway outcome measurement in patients with CF.

Biomedical ethics and the withdrawal of advanced life support.

It is common for health care providers to deal with the complex and difficult issue of withdrawing advanced life support. The patient is always the key source of authority in these decisions. The most important ingredient in end-of-life decision making is effective communication. It is important to try to ascertain what the patient thought about quality-of-life values before surrogate decisions can be made on the patient's behalf. The concepts of beneficence, nonmaleficence, autonomy, and justice are the foundation of ethical decision making. Numerous legal precedents have laid the groundwork for end-of-life decision making. Most state courts have supported withholding and withdrawing life support from patients who will not regain a reasonable quality of life. The recent Patient Self-Determination Act encourages patients to fill out advance directives that state their desires. When continued intensive care is futile, advanced life support should be withdrawn. However, a narrow definition of futility in this situation is the key, since the concept of futility could lead to inappropriate decisions. It is best to consider a situation futile when the patient is terminally ill, the condition is irreversible, and death is imminent. During the withdrawal of advanced life support, terminal or rapid weaning is preferable to extubation. Combinations of opiates, benzodiazepines, and other agents help provide comfort to patients who are suffering.

Effect of recombinant human platelet-activating factor-acetylhydrolase on allergen-induced asthmatic responses.

Platelet-activating factor (PAF) is a potent lipid mediator associated with key features of asthma such as airway constriction, eosinophil infiltration, edema, and mucus accumulation. Regulation of PAF occurs primarily through degradation to biologically inactive lyso-PAF by cellular and secreted PAF-acetylhydrolase (PAF-AH). We evaluated the effect of human recombinant PAF-AH (rPAF-AH) on the dual phase asthmatic response in atopic subjects with mild asthma. Effects on induced sputum cell counts and differentials, eosinophilic cationic protein (ECP), and tryptase were evaluated. Enrolled subjects demonstrated a positive skin test and a dual asthmatic response to allergen inhalation challenge. Fourteen subjects received rPAF-AH (1 mg/kg) or placebo intravenously in a randomized, double blind, placebo-controlled, two-period crossover study. Treatment with rPAF-AH did not significantly reduce either the early- or late-asthmatic response. Sputum eosinophil cell counts were not affected by treatment, but there was a trend toward a reduction in sputum neutrophils. No significant change in sputum ECP and tryptase was observed between rPAF-AH and placebo. Thus, at the dose studied, the unique anti-PAF agent rPAF-AH demonstrated no significant effect on the allergen-induced dual-phase asthmatic response.

Mechanisms of hypoxemia.

The definitions of hypoxemia and hypoxia, and basic pulmonary anatomy and oxygen delivery are reviewed. Low ambient oxygen, hypoventilation, ventilation-perfusion mismatch, and right-to-left shunt, the four basic mechanisms of hypoxemia are described in detail with patient examples. For the sake of completion, a fifth mechanism of hypoxemia that is rarely seen in human disease is described. Because getting oxygen into the blood stream is only half the story, mechanisms of tissue hypoxia in the setting of adequate oxygen exchange from the lungs to the blood are discussed. An algorithm is proposed for diagnosing patients who present with hypoxia.

Update on clinical trials of cystic fibrosis.

This review attempts to summarize the important areas of cystic fibrosis (CF) clinical research. Some of the trials outlined are incomplete or the data are not yet published. Focus is given to gene therapy and to studies that probe our understanding of CF cellular biology by attempting to correct or bypass abnormal cystic fibrosis transmembrane regulator. Trials of more immediate clinical value include improvement of mucociliary transport and inhaled tobramycin. Finally, mention is made of the significant nonpulmonary treatments for CF including ursodeoxycholic acid for CF liver disease and intracytoplasmic sperm injection for male infertility.