Global strategy for asthma management and prevention

Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

Interleukin-10 and the interleukin-10 receptor.

Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma

Objectives: Lao Juan (LJ, 劳倦) is a syndrome described in Chinese medicine (CM) that manifests with : Lao Juan (LJ, 劳倦) is a syndrome described in Chinese medicine (CM) that manifests with fatigue, fever, spontaneous sweating, indigestion, work-induced pain, weakness of the limbs, and shortness of breath. fatigue, fever, spontaneous sweating, indigestion, work-induced pain, weakness of the limbs, and shortness of breath. The present study was conducted to examine the reliability and validity of a Lao Juan Questionnaire (LJQ). The present study was conducted to examine the reliability and validity of a Lao Juan Questionnaire (LJQ). Methods: A total of 151 outpatients and 73 normal subjects were asked to complete the LJQ. Seventy-three normal subjects A total of 151 outpatients and 73 normal subjects were asked to complete the LJQ. Seventy-three normal subjects were additionally asked to complete the Chalder Fatigue Scale (CFS). Twelve clinicians determined whether the were additionally asked to complete the Chalder Fatigue Scale (CFS). Twelve clinicians determined whether the 151 outpatients exhibited LJ or not. The internal consistency and construct validity for the LJQ were estimated using 151 outpatients exhibited LJ or not. The internal consistency and construct validity for the LJQ were estimated using data from the outpatient subjects. The CFS data were used to examine the concurrent validity of the LJQ. Total LJQ data from the outpatient subjects. The CFS data were used to examine the concurrent validity of the LJQ. Total LJQ scores and the clinicians' diagnoses of the outpatients were used to perform receiver operating characteristics (ROC) scores and the clinicians' diagnoses of the outpatients were used to perform receiver operating characteristics (ROC) curve analyses and to defi ne an optimum cut-off score for the LJQ. curve analyses and to defi ne an optimum cut-off score for the LJQ. Results: The 19-item LJQ had satisfactory internal : The 19-item LJQ had satisfactory internal consistency (α=0.828) and concurrent validity, with signifi cant correlations between the LJQ and the CFS subscales. consistency (α=0.828) and concurrent validity, with signifi cant correlations between the LJQ and the CFS subscales. In the test of construct validity using principal component analysis, a total of six factors were extracted, and the overall In the test of construct validity using principal component analysis, a total of six factors were extracted, and the overall variance explained by all factors was 59.5%. In ROC curve analyses, the sensitivity, specifi city, and area under the variance explained by all factors was 59.5%. In ROC curve analyses, the sensitivity, specifi city, and area under the curve were 76.0%, 59.2%, and 0.709, respectively. The optimum cut-off score was defi ned as six points. curve were 76.0%, 59.2%, and 0.709, respectively. The optimum cut-off score was defi ned as six points. Conclusions: Our results suggest that the LJQ is a reliable and valid instrument for evaluating LJ. Our results suggest that the LJQ is a reliable and valid instrument for evaluating LJ. KEYWORDS Chinese medicine, chronic fatigue syndrome, Chinese medicine-pattern Chinese medicine, chronic fatigue syndrome, Chinese medicine-pattern

Development and Validation of A

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.

In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.

This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.

The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.

Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.

The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

/pdf/allergic-rhinitis-and-its-impact-on-asthma-aria-2008-update-13eqfzaw4u.pdf

Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis. The method included the processing of freshly expectorated sputum separated from saliva, treatment with a fixed proportion of dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making cytospins, and collecting the supernatant. The reproducibility of measurements, calculated by the intraclass correlation coefficient, was high for all indices measured with the exception of total cell counts and proportion of lymphocytes. Asthmatics, in comparison with healthy subjects and smokers with bronchitis, had a higher proportion of sputum eosinophils (median percent 5.2 versus 0.5 and 0.3), metachromatic cells (0.3 versus 0.07 and 0.08), ECP (1,040 micrograms/L versus 288 and 352), MBP (1,176 micrograms/L versus 304 and 160), and EDN (1,512 micrograms/L versus 448 and 272). Asthmatics differed from healthy subjects, but not from smokers with bronchitis, in the proportion of neutrophils (46.9% versus 24.1%), albumin (704 versus 288 micrograms/mL), and fibrinogen (2,080 versus 440 ng/mL). Smokers with bronchitis showed a trend for a higher neutrophil count and levels of albumin and fibrinogen than healthy subjects. The proportion of sputum eosinophils correlated positively with ECP, MBP, EDN, albumin and fibrinogen levels, and metachromatic cell counts correlated with tryptase. In asthmatics, IL-5 correlated with eosinophil counts. There was a significant negative correlation between sputum indices and expiratory flows and methacholine PC20. Thus, the methods of measuring cell and fluid phase markers in induced sputum used in this study are reproducible and valid. They can therefore be used to reliably measure these indices of airway inflammation.

Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.

BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the sample was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. RESULTS: Adequate samples from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. CONCLUSION: Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.

https://thorax.bmj.com/content/thoraxjnl/47/1/25.full.pdf

Use of induced sputum cell counts to investigate airway inflammation in asthma.

Summary
Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV1 fall) in four, and equivocal late asthmatic responses (5–11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.

Allergen‐induced increase in non‐allergic bronchial reactivity

Bronchial responsiveness is the term used to describe the tendency of the airways to bronchoconstrict to specific stimuli such as allergens and isocyanates, which select a limited population of apparently sensitized subjects, and to nonspecific (nonallergic) stimuli, which affect most asthmatic persons. Specific bronchial responsiveness to allergic stimuli is difficult to quantitate because commonly available allergen extracts are not well standardized for the number and concentration of components. Nonspecific responsiveness can be quantitated by inhalation tests with histamine or methacholine, by exercise, or by isocapnic hyperventilation of cold air, and may be increased in asthma and other conditions such as chronic obstructive bronchitis and cystic fibrosis. In this article we will discuss the measurement of nonspecific bronchial responsiveness by inhalation tests with histamine or methacholine and its relationship to the occurrence and severity of asthma.

https://www.jacionline.org/article/0091-6749(81)90132-9/pdf

Jerry Dolovich

Papers

Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.

Use of induced sputum cell counts to investigate airway inflammation in asthma.

Allergen‐induced increase in non‐allergic bronchial reactivity

Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance

Chronic cough: eosinophilic bronchitis without asthma.