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Chronic refractory dyspnoea - Evidence based management.

Aust Fam Physician. 2013 Mar;42(3):137-40

Authors: Wiseman R, Rowett D, Allcroft P, Abernethy A, Currow DC

Abstract
BACKGROUND: Chronic refractory dyspnoea is defined as breathlessness daily for 3 months at rest or on minimal exertion where contributing causes have been treated maximally. Prevalent aetiologies include chronic obstructive pulmonary disease, heart failure, advanced cancer and interstitial lung diseases.
OBJECTIVE: To distil from the peer reviewed literature (literature search and guidelines) evidence that can guide the safe, symptomatic management of chronic refractory dyspnoea.
DISCUSSION: Dyspnoea is mostly multifactorial. Each reversible cause should be managed (Level 4 evidence). Non-pharmacological interventions include walking aids, breathing training and, in chronic obstructive pulmonary disease, pulmonary rehabilitation (Level 1 evidence). Regular, low dose, sustained release oral morphine (Level 1 evidence) titrated to effect (with regular aperients) is effective and safe. Oxygen therapy for patients who are not hypoxaemic is no more effective than medical air. If a therapeutic trial is indicated, any symptomatic benefit is likely within the first 72 hours.

PMID: 23529525 [PubMed - in process]

Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases, both of which are characterized by airflow limitation. Although both represent distinct pathogenic entities, there can be significant clinical and physiologic overlap between the 2 disorders, creating potential management difficulties for clinicians. Although practice guidelines for both conditions outline diagnostic and management strategies, asthma and COPD are highly heterogeneous, and the symptoms of many patients remain poorly controlled despite adherence to current guidelines. Recent advances in phenotyping studies have elucidated heterogeneity in these airway diseases and might represent the best opportunity to enhance diagnosis, predict outcomes, and personalize treatments in patients with asthma and those with COPD. This review will focus on recent advances in describing phenotypic heterogeneity in asthma and COPD, including the evaluation of multiple clinical variables, molecular biomarkers, physiologic and radiologic data, and factors associated with disease progression and frequent exacerbations.

Basic and clinical immunology articles published in the Journal in 2012 were mostly related to the expanding area of primary immunodeficiencies (PIDs). Novel forms of PID were identified by using whole-exome sequencing or after careful examination of flow cytometric data, as in the reports of lymphocyte-specific protein tyrosine kinase, CD27, and CD21 deficiencies. Absent IgG and IgA memory B cells were described in patients with hyper-IgE syndrome, which is consistent with defective antibody response and suggests a potential benefit of immunoglobulin replacement. Impaired production of antibodies to polysaccharide antigens by the human B-cell subset analog to murine B-1 cells was reported in a child with selective polysaccharide antibody deficiency. Increased production of inflammatory cytokines by monocyte-derived cells on Toll-like receptor activation was reported in patients with X-linked agammaglobulinemia, underscoring the important role of Bruton tyrosine kinase in modulation of inflammation. The mechanisms explaining susceptibility to yeast infections and development of chronic mucocutaneous candidiasis were extensively studied. Universal newborn screening for T-cell deficiencies is being implemented in several states, resulting in the diagnosis of a higher number of immunodeficient newborns than previously estimated. The use of laboratory testing to distinguish PIDs from HIV infection was clarified. In the management of PIDs, refinement of indication and strategies to hematopoietic stem cell transplantation resulted in improved outcomes. The use of anti–IL-6 mAbs showed promise as an alternative treatment in patients with Schnitzler syndrome.

Objective: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma.Methods: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated.Results: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P  11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups.Conclusions: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.