Exposures influencing total IgA level in colostrum.

Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, P<0.001). Adjusting for maternal parity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced by colostrum collection time (P<0.0001) and country of collection (P<0.01). Mode of delivery influence did not appear to be significant in univariate comparisons, once adjusted for the above maternal characteristics it showed a significant influence on total IgA (P=0.01). We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

Perioperative allergy: clinical manifestations.

Adverse drug reactions or side effects are usually expected, dose dependent, and occur at therapeutic doses. Anaphylactic and anaphylactoid reactions are unexpected and dose independent and can occur at the first exposure to drugs used during anesthesia. Perioperative anaphylaxis is a severe and rapid clinical condition that can be lethal even in previously healthy patients. The initial diagnosis of anaphylaxis is presumptive. A precise identification of the drug responsible for the adverse reaction is more difficult to establish in the case of anaphylactoid reaction because the adverse reaction could result from additive side effects of different drugs injected simultaneously. The timing of the reaction in relation to events, e.g. induction, start of surgery, administration of other drugs, i.v. fluids, is essential for the diagnosis. Generally, reactions are predominant in the induction and recovery phases, and manifested mainly as cutaneous symptoms. Reactions to drugs coincide with the phases when they are administered. Reactions to antibiotics are more frequent in the induction phase, to neuromuscular agents in the initiation and maintenance phases and to non-steroidal anti-inflammatory agents in the recovery phase. The differential diagnosis of any adverse reaction during or following anesthesia should include the possibility of anaphylaxis.

Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia.

BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD) can be challenging, and it may be particularly difficult to distinguish primary ciliary disease from the secondary changes after infections. OBJECTIVES: The purpose of the study was to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a biopsy, could be used in a culture system for the diagnosis of PCD in difficult cases. METHODS AND MAIN RESULTS: Ciliary motion analysis (CMA) and transmission electron microscopy (TEM) were performed on 59 subjects with persistent or recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13 (22%) patients while the defect of the cilia was considered secondary to infections in 37 (63%) subjects. In the remaining nine (15%) patients the diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients. CONCLUSIONS: Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD.

Medicines used in respiratory diseases only seen in children.

Detailed literature searches were carried out in seven respiratory disease areas. Therapeutic evidence for efficacy of medicinal products was assessed using the Grades of Recommendation, Assessment and Evaluation (GRADE) methodology, as well as an assessment of safety and side-effects. Systemic corticosteroids may reduce the development of bronchopulmonary dysplasia but have serious side-effects. Antioxidants need further study to demonstrate whether they have long-term benefits. Treatments for acute bronchiolitis have shown little benefit but new antiviral and monoclonal antibodies need further assessment. Well-constructed studies are needed to confirm the value of inhaled corticosteroids and/or montelukast in the management of viral-induced wheeze. Corticosteroids are the treatment of choice in croup. Minimal or no information is available for the treatment of congenital lung abnormalities, bronchiolitis obliterans and interstitial lung disease.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Bronchiectasis in children with recurrent pneumonia: an immunopathological damage associated with secondary ciliary dysmotility.

The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51 children with recurrent pneumonia, high resolution computed tomography (HRCT) was carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure, beat frequency and motion pattern were evaluated and compared to those observed in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children. Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%). Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent motion in some fields was found in 44/51 patients (86.3%) and this also showed significant correlation with the HRCT score (p=0.005). The specificity and sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3% and 83.3% respectively. The positive predictive value was 93.5%, and negative predictive value was 50%. Ciliary dysmotility, in children with recurrent airways infections, correlates with the presence and severity of bronchiectasis. Whether ciliary dysmotility is a cause or a consequence of anatomical lesion is a matter of speculation. Very likely there is an amplification and self-maintaining mechanism between the two events which may lead to more serious disease.

IL-8 and pH values in exhaled condensate after antibiotics in cystic fibrosis children.

Interleukin (IL)-8 is a major factor in inflammatory response and the IL-8 levels in exhaled breath condensate (EBC) may be used as a marker of airway inflammation. Airway acidification is implicated in the pathophysiology of obstructive airway diseases and pH EBC values have been used as a marker of airway acidification. The aim of our study is to investigate whether IL-8 and pH levels in EBC of cystic fibrosis (CF) children with respiratory exacerbations change after antibiotic treatment. Lung function, IL-8 and pH EBC values were measured in fifteen CF children (mean age 11 years) with acute exacerbation before (T0) and after two weeks (T1) of antibiotic treatment. IL-8 and pH values were compared by paired t-test. A p less than 0.05 was considered significant. IL-8 EBC levels decreased after antibiotic treatment (T0 0.36+/-0.03pg/ml vs T1 0.28+/-0.03pg/ml; p=0.03) and pH values increased (T0 7.36+/-0.09 vs T1 7.61+/-0.08; p=0.04). Results suggest possible application of EBC as a non-invasive tool to monitor efficacy of antibiotic treatment in CF patients.

Azithromycin may reduce cholestasis in primary sclerosing cholangitis: a case report and serendipitous observation.

The newer macrolides have been shown to exert additional anti-inflammatory effects. We report the possible effect of azithromycin on primary sclerosing cholangitis in a patient treated with the drug for severe asthma. A 45-year-old woman with Crohn?s disease and primary sclerosing cholangitis, also suffering from severe asthma, was treated with azithromycin 500 mg OD for 3 consecutive days a week because of the clinical suspicion of bronchiectasis and the severity of her asthma. When the therapy was discontinued, her urine again became darker, pruritus reappeared with the usual severity and laboratory parameters, evaluated after 6 weeks without azithromycin, also worsened. For these reasons macrolide treatment was re-established. Cholestasis-related symptoms and the dark colour of the urine were again reduced 6 weeks later and laboratory parameters were again reversed. We are therefore tempted to speculate that azithromycin may have an effect on primary sclerosing cholangitis on the basis of its anti-inflammatory properties.

Deficiency of INFgamma producing cells in adenoids of children exposed to passive smoke.

Exposure to passive smoke is a very common event associated with increased susceptibility to respiratory tract infections. Many related adverse effects result from the ability of cigarette smoke extracts to interfere with the immune system, but the mechanism is not yet completely understood. The aim of the present study is to evaluate the intracellular cytokine profile in adenoids and peripheral blood cells of children exposed to passive smoke. Children undergoing adenoidectomy exposed or not exposed to passive smoke were studied. The intracellular cytokine profile of lymphocyte subsets in adenoids and in peripheral blood were evaluated by flow cytometry analysis. Children exposed to tobacco smoke showed a significantly lower percentage of INF-gamma producing CD4+ and CD8+ cells in adenoids. Moreover a significant correlation was observed between the quantity of exposure and reduction in Th1 (CD4+INFgamma+ and CD8+INFgamma+) cells in adenoids. This reduction may be a contributing factor in the increasing susceptibility to respiratory tract infection in children exposed to tobacco smoke.

"Cyst-like" structures within the ciliary shafts in children with bronchiectasis.

"Cyst-like" structures within the ciliary shafts were considered in four adults as a primary defect involved in the development of bronchiectasis. In this study, the presence and the primary or secondary nature of this abnormality were assessed in children with bronchiectasis. High resolution computed tomography (HRCT) and nasal biopsies for motion analysis and transmission electron microscopy (TEM) evaluation of cilia were obtained in 45 children with recurrent lower airway infections and abnormal chest radiography. HRCT disclosed bronchiectasis in 35 out of 45 (77.8%) children and cyst-like structures were demonstrated with TEM in 29 out of 45 (64.4%) patients. Cyst-like structures were constantly associated with other ultrastructural abnormalities commonly observed in chronic inflammation, and were found both in subjects with primary and with secondary ciliary dyskinesia. When considering only patients with bronchiectasis, a significant correlation between prevalence of cyst-like structures and the severity of bronchiectasis was demonstrated. Follow-up (2-22 months) of seven patients demonstrated that in the five children with secondary dyskinesia, the ultrastructural defect completely disappeared and there was a small reduction in the abnormality in the two patients with primary dyskinesia. In contrast to one previous report, the reversibility of the defect suggests its secondary origin, which is most likely related to chronic airway inflammation.

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: a pilot study.

Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 +/- 1.1% at T0 and 3.5 +/- 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 +/- 0.5% at T0 and 1.5 +/- 1.0% at T1 (ns). Cys-LTs mean level was 14.24 +/- 4.53 pg/ml at T0 and 4.65 +/- 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 +/- 0.19 pg/ml at T0 and 2.41 +/- 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 +/- 3.18 pg/ml at T0 to 7.36 +/- 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.

Rhinitis in pre-school children: prevalence, association with allergic diseases and risk factors.

BACKGROUND: The aim of our study was to assess the prevalence of rhinitis, sneezing, runny or blocked nose apart from colds in a pre-school children population and to evaluate the risk factors and relationship with allergic diseases and sensitization. METHODS: Eighteen nursery schools were randomly selected. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire (WQ) was distributed and filled by parents of pre-school children (3-5 years). The allergic sensitization to common aeroallergens and foods was evaluated by skin prick test (SPT). chi2 tests were used to compare proportions between rhinitic and non-rhinitic children. RESULTS: One thousand four hundred and two (92%) valuable questionnaires were returned. Prevalence of rhinitis in the last 12 months was 16.8%. Rhinitic children compared to non-rhinitic children presented a significant increase of diagnosed asthma (20.8% vs. 6.2%, P<0.001), lifetime wheezing (43.2% vs. 21.6%, P<0.001), wheezing in the last 12 months (25.0% vs. 9.4%, P<0.001), atopic dermatitis (22.9% vs. 13.9%, P<0.001) and allergic sensitization (29.9% vs. 13.7%, P<0.001). Sensitization to grass pollen and house dust mites were significant risk factors for rhinitis (P<0.01). A family history of atopy, having pets at home, male gender and greater age were significant risk factors for rhinitis, but not smoking exposure, sharing a bedroom or breastfeeding. CONCLUSIONS: In pre-school children rhinitis has a strong association with wheezing symptoms, asthma and atopic dermatitis. Allergic sensitization is a risk factor for rhinitis and should be evaluated even in pre-school children.

Atelectasis: mechanisms, diagnosis and management.

The term atelectasis describes a state of collapsed and non-aerated region of the lung parenchyma, which is otherwise normal. This pathological condition is usually associated with several pulmonary and chest disorders and represents a manifestation of the underlying disease, not a disease per se. Atelectasis may occur in three ways: (i) airway obstruction; (ii) compression of parenchyma by extrathoracic, intrathoracic, chest wall processes; and (iii) increased surface tension in alveoli and bronchioli. Chest radiographs using both the anterior-posterior and lateral projections are mandatory to document the presence of atelectasis. Differentiation from lobar consolidation may be a clinical dilemma. The treatment of atelectasis varies depending on duration and severity of the causal disease from chest physiotherapy to postural drainage, bronchodilator and anti-inflammatory therapy. Persistent mucous plugs should be removed by bronchoscopy.

Association of a lymphotoxin alpha gene polymorphism and atopy in Italian families.

Tumour necrosis factor (TNF) is a proinflammatory cytokine that increases human airway tissue responsiveness and is considered a candidate gene for asthma. Two common polymorphisms (LTalphaNcoI and TNFalpha-308) in the TNF gene complex were studied in 600 subjects from 131 Italian families with atopic asthmatic children. Skin prick test (SPT), total IgE levels, atopy (defined as increased IgE levels or SPT positivity or both), bronchial hyperresponsiveness, and clinical asthma were investigated. The observed distribution of the identical by descent alleles at the LTalphaNcoI locus was different from expected for SPT and atopy (p=0.015). The LTalphaNcoI genotype distribution for increased IgE levels was different between males and females (p=0.0011), and an association of the 2.2 genotype with increased IgE levels was observed in females (p=0.0032). The results indicate that the LTalpha gene, or a closely linked locus, is associated with atopy, and suggest a sex difference in the effect of the gene.

Candidate genes and a genome-wide search in Italian families with atopic asthmatic children.

To identify genetic factors for susceptibility to atopy and asthma in childhood, 1,083 subjects were identified, mainly from the Veneto region and Bolzano province in North-east Italy, of whom 817 were from 172 families with at least two affected people, 189 were sporadic cases, and 77 unrelated controls. All the subjects were characterized for clinical asthma (asthma), total serum IgE (IgE), skin prick test (SPT) reactivity to common aeroallergens and bronchial hyperresponsiveness (BHR) to methacoline test. Atopy was defined as SPT positivity and/or increased IgE levels. Several candidate genes were investigated, and genome-wide linkage analysis was been initiated. The high affinity IgE receptor beta chain (FcepsilonRIbeta) locus showed significant allele sharing in affected sib-pairs for BHR and for SPT positivity. Lymphotoxin alpha (Ltalpha) gene Ncol mutation showed a suggestive linkage with atopy, and the LTalphaNcol 2/2 genotype was found to be associated with increased total IgE levels in all females. No evidence for linkage or association of any phenotype to the tumour necrosis factor alpha (TNFalpha) - 308 mutation or to the interleukin 4 receptor alpha (IL-4Ralpha) Q576R mutation was found. BHR, asthma and increased IgE were found to be linked to X and Y long arm pseudoautosomal region (PAR2) markers. Initial data were also collected from linkage analysis with chromosome 12, 14, and 19, DNA markers. Non-parametric multipoint analysis provides preliminary evidence for linkage of asthma with D12S390, of atopy with D19S601, and of BHR with D14S617. These results suggest that several genetic factors contribute to different allergic asthma phenotypes in the population investigated.

Mite-antigen avoidance can reduce bronchial epithelial shedding in allergic asthmatic children.

BACKGROUND: Asthma is characterized by bronchial hyperresponsiveness (BHR), bronchial mucosa inflammation and airway epithelial damage. OBJECTIVE: This study was designed to evaluate the effect of mite avoidance on bronchial epithelial shedding in asthmatic children sensitized to Dermatophagoides. METHODS: The percentages of airway epithelial cells and eosinophil have been counted in samples obtained by hypertonic saline-induced sputum before and after a period of antigen avoidance in an Alpine environment (1756 m). The degree of bronchial hyperresponsiveness to methacholine was also evaluated. RESULTS: After avoidance the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P=0.012) and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P<0.05). Median (Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25] mg/ mL (P=0.038). After 3 weeks of re-exposure to mite the epithelial median (Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5 [0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS). CONCLUSION: Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity of the mite major antigens.

Optimum treatment of allergic rhinitis in children.

Allergic rhinitis is a very common disease, occurring in 10% of children and up to 20% of adolescents. The effects of the disease are frequently underestimated and not regarded as a serious health problem. However, if not properly treated, the disease is associated with harmful sequelae and poor quality of life. The treatment of allergic rhinitis in children depends on 3 therapeutic approaches: avoidance of provoking factors, pharmacological therapy and immunotherapy. Environmental control measures should be directed against allergens as well as against nonspecific irritating factors such as tobacco smoke. Conventional therapy depends on the appropriate selection and combination of antihistamines, mast cell stabilisers, decongestants and topical corticosteroids. Immunotherapy must not be used indiscriminately and should be prescribed only when clearly indicated. Compliance with the treatment regimen is an essential element of therapeutic success.