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.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma.

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex-matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients' VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.

Association of polymorphisms in the mast cell chymase gene promoter region (-1903 g/A) and (TG)n(GA)m repeat downstream of the gene with bronchial asthma in children.

BACKGROUND: Mast cell chymase is a mediator of inflammation and remodeling in the asthmatic lung. Although various studies have examined the association between the -1903 G/A single nucleotide polymorphism (SNP)in the mast cell chymase gene (CMA1) and allergic phenotypes, the results have been inconsistent. A (TG)n(GA)m repeat polymorphism 254 base pairs downstream of CMA1 has been reported in adult asthmatics. We investigated the relationship between these CMA1 genetic variants and childhood asthma in Egyptian children. METHODS: A case-control study was undertaken in 15 children (6-10 years old) with bronchial asthma enrolled consecutively during exacerbation and 15 age-matched and sex-matched nonasthmatic control subjects. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism to search for polymorphisms in the CMA1 gene promoter region (-1903 G/A) and PCR amplification followed by sequencing to detect the (TG)n(GA)m repeat 254 base pairs downstream of the gene. RESULTS: Our data showed a positive association between the CMA1 -1903 G/A SNP and asthma in children. The G allele was detected in 70% of patients while the A allele was more frequent in the controls (83.3%). Concerning the (TG)n(GA)m repeat, allele 39 was only present in asthmatics while allele 37 was more common in controls. CONCLUSION: We report the association of the -1903 G/A CMA1 SNP and (TG)n(GA)m repeat polymorphism with bronchial asthma in a group of Egyptian children. These polymorphisms are possible determinants of asthma susceptibility and may be involved in regulating immunoglobulin E levels.

In utero exposure to cadmium pollution in Cairo and Giza governorates of Egypt.

Serum cadmium levels at delivery were measured in a consecutive sample of 100 mother-infant pairs in Egypt using venous blood from mothers and umbilical cord blood from neonates. The serum cadmium levels of mothers ranged from 0.4 to 2.2 microg/L (mean 0.73 microg/L) and of infants from 0.2 to 1.5 microg/L (mean 0.66 microg/L). Infant cadmium levels were about 70% of maternal levels in most pairs. Serum cadmium was significantly higher in mothers and babies passively exposed to tobacco smoke. Five-minute Apgar scores were negatively correlated with cord blood cadmium levels. The cadmium levels did not differ between subjects from Cairo and Giza or according to urban, suburban or rural areas. Thus, in utero exposure to cadmium was evident and wider-scale studies on its long-term effects are recommended.

In utero exposure to cadmium pollution in Cairo and Giza governorates of Egypt

Serum cadmium levels at delivery were measured in a consecutive sample of 100 mother-infant pairs in Egypt using venous blood from mothers and umbilical cord blood from neonates. The serum cadmium levels of mothers ranged from 0.4 to 2.2 microg/L [mean 0.73 microg/L] and of infants from 0.2 to 1.5 microg/L [mean 0.66 microg/L]. Infant cadmium levels were about 70% of maternal levels in most pairs. Serum cadmium was significantly higher in mothers and babies passively exposed to tobacco smoke. Five-minute Apgar scores were negatively correlated with cord blood cadmium levels. The cadmium levels did not differ between subjects from Cairo and Giza or according to urban, suburban or rural areas. Thus, in utero exposure to cadmium was evident and wider-scale studies on its long-term effects are recommended

Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and children.

BACKGROUND: The previously reported eotaxin overexpression in the lesional skin of atopic dermatitis (AD) led us to the assumption that circulating levels of eotaxin may be elevated too. We sought to investigate the plasma expression of eotaxin in children with skin allergy in relation to clinical activity and type of lesions. METHODS: Plasma eotaxin was assayed in 78 infants and children, of whom 16 had AD, 19 had acute urticaria (AU), and 43 were healthy matched subjects. Seven children in the group of AU were resampled for plasma eotaxin after clinical remission. RESULTS: The plasma eotaxin levels in AD (median=158 pg/ml, mean [SD]=168 [61] pg/ml) were significantly higher than the control values (median=60 pg/ml, mean [SD]=59.5 [18.5] pg/ml). Not only did patients with AU demonstrate elevated plasma eotaxin levels (median=126 pg/ml, mean [SD]=124 [33] pg/ml), but also a significant decline occurred on follow-up. The coexistence of angioedema with AU did not cause any further increase in plasma eotaxin expression. Plasma eotaxin levels were significantly higher in AD than in AU, probably reflecting the chronic nature of eczematous AD lesions. The plasma eotaxin levels did not correlate with serum total IgE, peripheral blood absolute eosinophil count, or age of the patients. However, there was a positive correlation between age and plasma eotaxin in the control group. CONCLUSION: Our findings imply that circulating levels of eotaxin increase in AD and during flares of AU, probably to serve in the recruitment and activation of eosinophils. It may also represent a biomarker of lesional activity.

Environmental exposure of the pediatric age groups in Cairo City and its suburbs to cadmium pollution.

In a trial to assess the exposure of subjects in the pediatric age group to cadmium (Cd) pollution, serum Cd was estimated by atomic absorption spectrometry in 405 subjects, birth-18 years old, from Cairo City and its suburbs. Serum Cd mean concentrations were: 0.92 microg/l in 32 neonates (birth-4 weeks); 1.33 microg/l in 70 infants (4 weeks-2 years); 1.11 microg/l in 100 children in the preschool period (2-6 years); 1.34 microg/l in 103 primary school children (6-12 years); and 1.24 microg/l in 100 adolescents (12-18 years). In neonates, serum Cd was higher in babies with weights and heights that remained below the 5th percentile for age. Breast-fed infants had a serum Cd geometric mean level (1.25 microg/l) that was not in accordance to that of their mothers' milk (0.52 microg/l, P < 0.001), suggesting alternative routes of exposure. Environmental tobacco-smoke exposure was the most important determinant of Cd status in the school-aged children, the geometric mean being 1.42 microg/l in passive smokers vs. 1.2 microg/l in non-exposed children (P < 0.05). Moreover, adolescents who were active smokers had a significantly higher serum Cd level (1.7 microg/l) as compared to non-smokers (1.2 microg/l). Gender did influence the Cd status in adolescents, being higher among males, probably related to smoking, or to the difference in lifestyle of adolescents according to gender in the community. Alpha-1-microglobulinuria was accompanied by a higher serum Cd concentration in the group of adolescents only, suggesting a subclinical renal effect after several years of cumulative exposure. The residential classification, whether urban or suburban, did not influence the serum Cd status; neither did the present or past history of bronchial asthma. These findings certainly justify further evaluation of the problem of Cd pollution among Cairene individuals, knowing the long-term consequences of exposure to it. Systematic efforts for the proper disposal of Cd wastes and prevention of smoking in public places are recommended.

Anti-centromere antibodies as a marker of Raynaud's phenomenon in pediatric rheumatologic diseases.

To examine the possible relationship between anti-centromere antibodies (ACA) and pediatric rheumatologic diseases, we investigated the presence of ACA (using enzyme immunoassay) in the sera of 45 children and adolescents with such diseases and compared the results with a group of 42 age- and gender-matched healthy subjects. ACA were present ( > or =10 U/ml) in three out of five patients (60%) with scleroderma (SCD), in seven out of 16 (43.8%) patients with systemic lupus erythematosus (SLE), in two out of five patients (40%) with mixed connective tissue disease (MCTD), in one out of four patients (25%) with dermatomyositis (DMS), and in two out of 14 patients (14.3%) with juvenile rheumatoid arthritis (JRA). ACA were also detected in a single patient with anti-phospholipid syndrome (APL) who had digital gangrene and hemiparesis, as well as in two healthy subjects. ACA positivity was related to the presence of Raynaud's phenomenon in the studied sample, as 86% of patients suffering from the phenomenon were ACA positive. ACA positivity was associated with older age, high blood pressure and high erythrocyte sedimentation rate (ESR) values, and lower hemoglobin and weight and height percentile values. It was also higher among anti-nuclear antibody-positive subjects. Raynaud's phenomenon and ACA positivity shared almost the same clinical and laboratory associations in the studied patients. Thus, ACA are probably among the markers of Raynaud's phenomenon in pediatric rheumatologic diseases. Their value as predictors of future development of the phenomenon needs further evaluation.

Response of Egyptian infants with protein calorie malnutrition to hepatitis B vaccination.

The response to recombinant hepatitis B vaccine was assessed in 31 seronegative infants (2-26 months old) with protein calorie malnutrition (PCM), compared with 13 seronegative age- and sex-matched healthy infants. Both groups received three 10 micrograms vaccine doses at 0, 1, and 6 months. At month 8, all healthy infants and 87 per cent (27 out of 31) of PCM infants were seroprotected. Thus, hepatitis B vaccination (Engerix-B, SmithKline Beecham Biologicals) can be used effectively in PCM for mass vaccination in developing communities.

Cockroach sensitivity in asthmatic Egyptian children.

Cockroach-specific IgE antibodies (CR-IgE) were assayed in the sera of 51 asthmatic and 33 healthy, nonallergic children. Cockroach IgE was detected in 43 asthmatic children (84%), seven of whom showed a high CR-IgE response (> or = 1.5 IU/ml). Only three of the healthy children (9%) had a positive response, and none of them were in the strongly positive category. The difference from the asthmatic group was statistically significant (P < 0.001). Children with clinically mild asthma had a significantly lower CR-IgE positivity rate than moderate and severe cases. The presence of other allergic manifestations or family history of atopy had no relationship to CR-IgE, nor did the residency, age, duration of illness, or total serum IgE levels. However, the CR-IgE titres were positively correlated with the absolute eosinophil counts. Thus, cockroach antigens are common inhalant allergens in Egyptian asthmatic children.

Antiperinuclear factor in the diagnosis of juvenile rheumatoid arthritis.

The antiperinuclear factor (APF) was estimated by immunofluorescent microscopy in the sera of 32 children and adolescents with juvenile rheumatoid arthritis (JRA) in comparison to a group of 16 children and adolescents with other rheumatologic disorders and a group of 20 age-matched healthy subjects. The APF was detected in 17 children with JRA (53%), in only one patient in the group of other rheumatologic disorders (6%), and in 2 healthy children (10%). Accordingly, APF had a sensitivity of 53%, a specificity of 92%, and a diagnostic efficiency of 74% in our series. APF was found to have a higher diagnostic gain in rheumatoid factor (RF) seronegative cases than did the RF in APF negative cases, meaning a higher sensitivity of APF as compared to the RF. The APF seropositivity was neither altered by the use of corticosteroids nor influenced by the age, gender, duration of illness, or number of joints affected. Three out of 5 patients with JRA had the APF detected in their synovial fluid; they were running rather a severe course of illness. The use of the APF could be an aid in the diagnosis of JRA.