Global strategy for asthma management and prevention

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

/pdf/infectious-diseases-society-of-america-american-thoracic-1cn65eiqga.pdf

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Asthma is a serious health problem throughout the world During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively However, recommendations for asthma care need to be adapted to local conditions, resources and services Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines The 2006 report contains important new themes First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised

https://erj.ersjournals.com/content/erj/31/1/143.full.pdf

Global strategy for asthma management and prevention: GINA executive summary.

Introduction Acute Inflammation and Brief Symptoms Mechanisms: Experimentally Induced Allergic Reactions Clinical Consequences and Treatment Chronic Inflammation Site of the Inflammation in Asthma Cell Survival in Airway Tissues Characteristics of Chronic Inflammation Chronic Inflammation in the Different Forms of Asthma Clinic Consequences Treatment of Exacerbations Onset and Duration of Treatment Remodeling of the Airways Characteristics of Airways Remodeling in Asthma Clinical Consequences Radiographic Findings Treatment and Prevention of Airways Remodeling Conclusions

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.5.9903102

Asthma. From bronchoconstriction to airways inflammation and remodeling.

Background: The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.Purpose: The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.Methods: A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.Results: The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge ...

/pdf/an-official-american-thoracic-society-european-respiratory-18b801porh.pdf

An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice.

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

Clinical implications of the immunomodulatory effects of macrolides.

Alveolar macrophages (AMs) may play a critical role in cigarette smoke (CS)-related pulmonary diseases. This study was designed to determine whether CS induces apoptosis of AMs. In in vitro studies, mouse, rat, and human AMs and human blood monocyte-derived macrophages cultured with aqueous whole CS extracts underwent apoptosis that was detected by light and electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. The gas phase of CSE did not cause apoptosis. The CS-induced apoptosis was associated with increased oxidative stress, Bax protein accumulation, mitochondrial dysfunction, and mitochondrial cytochrome c release but was independent of p53, Fas, and caspase activation. This apoptosis was inhibited by antioxidants such as glutathione, ascorbic acid, and alpha-tocopherol. In in vivo studies where rats were exposed to the smoke from 10 cigarettes over 5 h in an exposure chamber, approximately 3% of AMs obtained by bronchoalveolar lavage after 24 h showed apoptosis. These results suggest that acute CS exposure is capable of inducing apoptosis of AMs.

https://www.physiology.org/doi/pdf/10.1152/ajplung.2001.281.6.L1392

Acute cigarette smoke exposure induces apoptosis of alveolar macrophages.

The Effects of Macrolides on Inflammatory Cells

Neutrophils constitutively undergo apoptosis at both normal and inflamed sites: an important process that limits the toxic potential of the neutrophil. However, the signal pathway for neutrophil apoptosis is currently unknown. In this study, we evaluated the role of p38-mitogen-activated protein kinase (MAPK) in the spontaneous apoptosis of neutrophils in vitro. We found that p38-MAPK was constitutively tyrosine phosphorylated and activated during spontaneous apoptosis of neutrophils. Inhibition of p38-MAPK by SB203580 and an antisense oligonucleotide delayed apoptosis by approximately 24 h. The antioxidants catalase and N-acetylcysteine delayed neutrophil apoptosis, but failed to inhibit phosphorylation and activation of p38-MAPK. Granulocyte-macrophage CSF and anti-Fas Ab, which altered the rate of apoptosis, did not affect phosphorylation and activation of p38-MAPK. These results suggest that the constitutive phosphorylation and activation of p38-MAPK are involved in the program of spontaneous apoptosis in neutrophils.

Jun Tamaoki

Papers

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

Clinical implications of the immunomodulatory effects of macrolides.

Acute cigarette smoke exposure induces apoptosis of alveolar macrophages.

The Effects of Macrolides on Inflammatory Cells

Role of p38-Mitogen-Activated Protein Kinase in Spontaneous Apoptosis of Human Neutrophils