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Dyspnea prevalence, trajectories, and measurement in critical care and at life's end.

Dyspnea is a multidimensional response to an asphyxial threat that heralds respiratory failure. A clinician's ability to treat dyspnea warrants understanding the prevalence, burden, trajectories, and measurement across chronic conditions and exacerbations. This review focuses on two contexts: the intensive care unit and the near death stage of illness.

RECENT FINDINGS: Dyspnea is the most distressing symptom experienced by critically ill patients at risk for dying. New longitudinal studies reveal varying dyspnea trajectories over time and by diagnosis. Patients with noncancer diagnoses, particularly chronic obstructive pulmonary disease, experience severe dyspnea for months before death, whereas patients with cancer even without apparent cardiorespiratory disease have an escalation of dyspnea near death. The sickest patients and those who are cognitively impaired or unconscious are not represented because self-report measures are used. Thus, dyspnea is underrepresented in most end-of-life cohorts. In most data, the Numeric Rating Scale for the intensity of breathlessness, while unidimensional, is the most valid measure for palliative care because of its simplicity. Use of the Respiratory Distress Observation Scale in future studies will permit the inclusion of patients who are unable to self-report dyspnea.

SUMMARY: In summary, new evidence is demonstrating the high prevalence and distress associated with dyspnea among critically ill patients and patients near death.

Deposition of Inhaled Particles in the Lungs.

Inhaled medication is the first-line treatment of diseases such as asthma or chronic obstructive pulmonary disease. Its effectiveness is related to the amount of drug deposited beyond the oropharyngeal region, the place where the deposit occurs and its distribution (uniform or not). It is also important to consider the size of the inhaled particles, the breathing conditions, the geometry of the airways and the mucociliary clearance mechanisms.

Currently, mathematical models are being applied to describe the deposition of inhaled drugs based on the size of the particles, the inspiratory flow and the anatomical distribution of the bronchial tree. The deposition of particles in the small airways gets maximum attention from pharmaceutical companies and is of great interest as it is related with a better control in patients receiving these drugs.

Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects.

Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects.

Br J Clin Pharmacol. 2012 Mar 30;

Authors: Aul R, Armstrong J, Duvoix A, Lomas D, Hayes B, Miller BE, Jagger C, Singh D

Abstract
Aims: Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFkB dependent cytokine production. We investigated LPS inhalation in healthy smokers as a model of COPD bacterial exacerbations. We studied safety, reproducibility, the translocation of the NFκB subunit p65 in sputum cells and changes in systemic biomarkers of inflammation. Methods: 12 smokers inhaled 5 and 30 µg LPS; safety was monitored over 24 hours. IL-6, CRP, CCL-18, SP-D, CC-16 and β-defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 hours. Sputum was induced at baseline, 6 and 24 hrs for cell counts and p65 expression. Repeated challenges were performed after a 2 week interval in 10 smokers. Results: LPS inhalation was well tolerated. Significant increases occurred in sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 hours after 30µg which was reproducible; r(i ) (intraclass correlation coefficient) = 0.88. LPS increased sputum cell nuclear p65 translocation and phospho-p65 expression. All of the serum biomarkers increased following challenge but with different temporal patterns. Discussion: Inhaled LPS challenge in smokers causes pulmonary and systemic inflammation that involves NFκB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

PMID: 22469312 [PubMed - as supplied by publisher]

Inflammatory mediators in exhaled breath condensate of healthy donors and exacerbated COPD patients.

Samples of exhaled breath condensate (EBC) provide a convenient and non-invasive method to study inflammation in lung diseases. The aim of the present study was to evaluate and compare the inflammatory protein mediator levels in EBC from healthy donors (HD) and from patients with exacerbation of chronic obstructive pulmonary disease (COPD) using an EBC collection device with and without a coating of albumin as a carrier.

We studied 13 HD and 26 patients with exacerbation of COPD. The concentrations of myeloperoxidase (MPO), IFNγ and secretory leukocyte protease inhibitor (SLPI) in EBC were measured by immunoassays. The EBC samples from HD and COPD patients showed higher concentrations of MPO when samples were recovered with an albumin-coated device. Furthermore, levels of MPO in COPD patients were significantly higher than in HD. An inverse correlation was observed between MPO and spirometric parameters (FVC and FEV1). Almost all samples collected with the albumin-coated device showed higher amounts of IFNγ and SLPI than those collected with the uncoated device. The levels of SLPI in COPD patients were significantly higher than in HD. A direct correlation was observed between FVC% predicted and SLPI.

We concluded that coating the collection device with albumin increased the sensitivity of the technique, at least for measurements of MPO, SLPI and IFNγ. Furthermore, the higher levels of MPO and SLPI and lower levels of IFNγ in EBC from COPD patients could reflect the immunological status and the response of lung parenchyma to treatment during the exacerbation of the illness.

Indacaterol : a new long-acting β(2)-agonist in the management of chronic obstructive pulmonary disease.

Introduction: Bronchodilators represent the mainstay of symptomatic treatment for chronic obstructive pulmonary disease (COPD). The principal bronchodilator agents are β(2)-agonists, anticholinergics and methylxanthines, used singly or in combination.

Indacaterol is a novel long-acting β(2)-agonist for maintenance bronchodilator treatment of airflow obstruction in patients with COPD, approved in December 2009 by the European Medicines Association, and recently by the US Food and Drug Administration. It is administered once daily and is delivered by means of a single-dose dry powder inhaler (SDDPI). In Europe, the recommended dose is 150 μg and the maximum dose is 300 μg, while in the US the recommended dose is 75 μg. Indacaterol shows evidence of a rapid onset of bronchodilation, and its bronchodilatory duration is sustained.

Areas covered: Numerous clinical studies have assessed the therapeutic effects of indacaterol in various physiologic parameters, as well as symptoms, disease progression, exacerbation rates, quality of life, safety and tolerability. This review summarises published evidence regarding the efficacy, tolerability and safety of indacaterol in regard to lung function and symptoms of COPD patients.

Expert opinion: Indacaterol, the novel once-daily β(2)-agonist, has rapid and sustained bronchodilatory effect, showing excellent efficacy, tolerability and safety, as shown by all clinical trials so far.

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