Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Successful allogeneic peripheral blood stem cell transplantation in Wiskott-Aldrich Syndrome Patients: first report in Thailand.

Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody production, eczema, and thrombocytopenia. Stem cell transplantation is the only curative therapy. To evaluate the use of allogeneic peripheral stem cell transplantation (PBSCT) in this group of patients, we performed allogeneic PBSCT in two WAS patients (3 and 12 years old). The conditioning regimen consisted of busulfan 4 mg/kg/day for 4 days, and cyclophosphamide 50 mg/kg/day for 4 days. Graft-versus-host disease prophylaxis was consistent with cyclosporin A and methotrexate. Peripheral blood stem cells were collected from their brother donors (6 and 16 years old) by continuous flow leukapheresis after mobilization with granulocyte-colony-stimulating factor at a dose of 7.5 microg/kg/day for 5 days. Both recipients achieved neutrophils engraftment on days 11 and 12. The first patient achieved platelets engraftment on day 30. The second patient did not have platelet count below 20.0 x 10(9)/l during PBSCT procedure. Both did not develop acute or chronic graft-versus-host disease. At present, they are healthy after PBSCT. The follow up time after transplantation is 1,170 days and 269 days, respectively. Allogeneic PBSCT is economically feasible for WAS. The cost of PBSCT in Thailand is 20 to 30% less than bone marrow and cord blood stem cell transplantation. The cost of the transplant procedure for each patient in Thailand is US $ 12,000. This study is the first report of a successful stem cell transplantation in WAS patients in Thailand.

Fluticasone propionate and bronchial hyperresponsiveness in childhood asthma.

Bronchial asthma is now agreed as being a chronic inflammatory disease of the airways. Inhaled steroids are widely accepted as a preventive medication in asthmatic patients of all ages and severity. However, the optimal use of inhaled steroids and the important issue of safety and efficacy still remain of concern, particularly in children. Recently, fluticasone propionate (FP) has been developed for use as an inhaled preparation for the treatment of asthma. Because of its high topical potency and increased lipophilicity, it is claimed that FP has an improved risk/benefit compared with other inhaled steroids. In order to evaluate the use of FP in children, we have studied the efficacy of high dose FP (500 microg/day) in asthmatic children. Thirteen children (9 boys and 4 girls), aged 7-17 years (10.8 +/- 2.6), were instructed to use a pressurized metered-dose inhaler connected to a Volumetric spacer. The standard methacholine bronchial challenge test was used as a principal outcome parameter. The PD20, a cumulative dose of methacholine inducing a 20% decrease in FEV1, was measured pre- and post-treatment with inhaled FP. After 4 weeks of FP, PD20 significantly increased from 21.6 +/- 14.3 inhalation unit to 106.6 +/- 78.5 inhalation unit (4.9 fold, p = 0.004) reflecting the improvement of airway reactivity. All subjects improved clinically. These results demonstrate that the anti-inflammatory action of FP 500 microg a day for four weeks can markedly reduce bronchial hyperresponsiveness, the basic physiologic abnormality in bronchial asthma.

The kinetics of change in cytokine production by CD4 T cells during conventional allergen immunotherapy.

BACKGROUND: The effect of conventional allergen immunotherapy on allergen-specific T lymphocyte cytokine production is incompletely understood, particularly during the initial phase of treatment. OBJECTIVE: The purpose of this study was to prospectively follow the kinetics of change in CD4(+) T cell cytokine secretion during the course of conventional immunotherapy. METHODS: Six allergic individuals were treated with extracts of Dermatophagoides farinae/Dermatophagoides pteronyssinus or with rye grass pollen (Lolium perenne) allergen, but not both, by using an internally controlled conventional immunotherapy protocol. CD4(+) T cells from peripheral blood were examined in vitro at varying intervals after the initiation of immunotherapy by stimulation with D farinae or L perenne group I antigen. The quantity of IL-4 and IFN-gamma produced and its relationship to clinical improvement was determined. RESULTS: The ratio of allergen-specific IL-4/IFN-gamma production by CD4(+) T cells from 4 of 6 individuals receiving immunotherapy greatly increased during the period when the dose of allergen was increasing. However, after high-dose maintenance therapy was achieved, this ratio decreased in subjects responding clinically to, but not in those failing, immunotherapy. In addition, late-phase skin reactions and allergen-specific IgE levels in responding, but not in nonresponding, subjects diminished over the course of immunotherapy. CONCLUSION: Conventional immunotherapy may initially exacerbate allergic disease by increasing allergen-specific IL-4 and allergen-specific IgE production. Later clinical improvement is associated with a reduction in allergen-specific IL-4 production and in allergen-specific serum IgE.

Peak expiratory flow rate values of students in Bangkok.

BACKGROUND: As there are considerable variations in normal values of peak expiratory flow rate (PEFR) shown by studies from various population, a study is required to obtain normal values of PEFR in Thai children. OBJECTIVE: To determine the values of PEFR of students in Bangkok. METHODS: In a cross sectional study of PEFR measured with standard Wright peak flow meter, 501 normal students, aged 5 to 15 years, from five public schools in Bangkok were investigated. In the selection process of subjects, strict criteria of "normality" were applied and included history of medical illnesses, physical examination and nutritional status. RESULTS: The relationship between PEFR and height was approximately linear in both male and female children. Prediction equations for each sex were: Male children: PEFR (L/min) = [3.52 x Height (cm)] - 186.80 Female children: PEFR (L/min) = [3.48 x Height (cm)] - 204.11 The PEFR values of students in this study were different from the predicted values of PEFR in those of previous reports in Thai children. These discrepancies might be explained by a variety of study population and environmental factors. CONCLUSIONS: The relationship between PEFR and height of students in Bangkok is best described by a regression equation. The prediction graphs for each sex may be used to monitor PEFR values of children with obstructive airway diseases and to compare an individual's PEFR with those of others of the same height and sex.

Reduced prevalence of allergic disease in patients with multiple sclerosis is associated with enhanced IL-12 production.

BACKGROUND: We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined. OBJECTIVES: We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies. METHODS: Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was quantitated by a sensitive reverse transcription, competitive PCR. RESULTS: IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90+/-0.18 vs 1.24+/-0.19 log10 fmol/microL for individuals with allergies) (P = .02). Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant. CONCLUSIONS: IL-12 production in individuals with MS is much greater than in individuals with allergies. Because IL-12 induces TH1 cytokine synthesis and reduces the production of TH2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system.

Incorrect use of metered dose inhaler by pediatric residents.

Currently press-and-breath metered dose inhalers (MDIs) are widely prescribed but are often difficult for many patients to properly use. However many medical personnel cannot use the MDIs correctly. We administered a question and observed usage of a placebo metered dose inhaler with ad-on spacer (Nebuhaler) among 127 second year pediatric residents. Forty-eight per cent of the residents performed at least six of nine steps correctly. The two most common errors made by participants were not to place mouthpiece tightly between teeth and lips (64%) and failure to breath out to functional residual capacity before actuation (55.3%). Of the residents with improper timing of actuation (49%) all actuated the canister before starting inhalation. (5 seconds or longer time). We conclude that (1) pediatricians should have additional instruction in proper MDIs usage and practice with the asthmatic child and (2) routine assessment of MDIs technique should be instituted as standard practice care.