How to confirm occupational asthma

A methodological overview is provided on the important question of how to confirm occupational asthma in routine work. Recent knowledge gained in immunology and occupational allergy has been utilized, supplemented by an overview of recent publications on the diagnosis and pathophysiology of occupational asthma. The aim of the paper is to facilitate decision making for an investigator dealing with individual cases of occupational asthma. Moreover, by presenting stepping-stones in the diagnostic cascade, the author hopes to encourage the less experienced to conduct a comprehensive and cause-oriented diagnostic procedure. Methods which are being worked on at present (standardization) are discussed in more detail. Finally, the research goals in the understanding, confirmation, and prevention of occupational asthma are listed.     

Improvement of fruit allergenic extracts for immunoblotting experiments

A method based on ion-exchange column chromatography to enhance the protein content of fruit allergenic extracts was found to help make the subsequent SDS-PAGE immunoblotting assays possible; otherwise, they were difficult to achieve due to the high carbohydrate content. Fractionated extracts of apple, pear, and peach (peel and pulp) were obtained by anion-exchange chromatography (Q-Sepharose^TM column), providing clear electrophoretic patterns which allowed IgE detection by enzymatic assays of the transferred membranes. This chromatographic method produced in one single step an enriched extract directly from the standard crude aqueous one, with an increment in the protein content of more than sixfold, on average; thus, it proved to be more suitable than the usual chemical fractionation procedures.     

Pulmonary tuberculosis in patients treated with inhaled beclomethasone

Inhaled beclomethasone dipropionate (BDP) has been used with few side effects in the treatment of bronchial asthma for 2 decades. Until now the manifestation of tuberculosis (TB) in patients on inhaled BDP has not been reported. Eight patients with allergic asthma, of a total of 548 asthmatics (1.46%) seen over a 2-year period, developed active TB following the use of inhaled BDP. All were sputum-positive for acid-fast bacilli (AFB) on smear and/or culture, all responded well to a combination of anti-TB drugs, and none showed evidence of immunological or pituitary-adrenal suppression. Two patients agreed to a repeat administration of BDP; both developed TB again within 2 weeks and are again on anti-TB treatment.     

Increased sensitization in urban vs. rural environment – Rural protection or an urban living effect?

In a population-based longitudinal cohort study, we tested the hypothesis that children growing up in a high-traffic polluted urban area (UA) in the Athens' basin have higher prevalence of allergies and sensitization when compared with those growing up in a Greek provincial rural area (RA). We recruited 478 and 342 children aged 8-10 living in the UA and the RA, respectively. Respiratory health was assessed by a parent-completed questionnaire in three phases: 1995-96 (phase 1), 1999-2000 (phase 2), 2003-04 (phase 3) and skin-prick testing to common indoor and outdoor aeroallergens was performed at phases 1 and 2. Reported asthma and eczema did not differ between the two areas, whereas reported hay fever was persistently more prevalent in the UA than in the RA (16.5%, 17.0%, 18.2% vs. 7.0%, 8.3%, 9.6%, respectively). Sensitization was more prevalent in the UA at both phases (19.0% vs. 12.1% in phase 1, 20.0% vs. 14.1% in phase 2). Residential area contributed independently to sensitization to >or=1 aeroallergens (OR: 0.29; 95% CI: 0.13-0.66; p = 0.003) and to polysensitization (OR: 0.28; 95% CI: 0.10-0.82; p = 0.020) in phase 1. These associations were independent of farming practices. No significant contributions were found in phase 2. Our results suggest that long-term exposure to urban environment is associated with a higher prevalence of hay fever but not of asthma or eczema. The negative association between rural living and the risk of atopy during childhood, which is independent of farming practices, implies that it is mainly driven by an urban living effect.     

Placental p,p''-dichlorodiphenyldichloroethylene and cord blood immune markers

Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection

BACKGROUND: Carbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation. OBJECTIVE: This study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI). METHODS: CO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI. RESULTS: Nasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 +/- 0.15 ppm, n = 6 and 1.62 +/- 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 +/- 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased. CONCLUSION: The present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation.     

Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?

BACKGROUND: The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. METHODS: Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. RESULTS: All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. CONCLUSION: A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests 'localized allergy' may exist in the absence of systemic atopic markers.     

The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition

BACKGROUND: Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development. OBJECTIVE: To determine if changes in breast milk omega-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk. METHOD: In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) (n = 40) or 4 g olive oil capsules (n = 43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) were quantitated by ELISA or time resolved fluorescence (TRF). RESULTS: Omega-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher (P < 0.001) in breast milk from women supplemented with fish oil (n = 33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n = 40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower (P = 0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P = 0.046) and 22:5n-3 (P = 0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 (P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups. CONCLUSION: Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. omega-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.