Development of an effective sample transfer device for biomarker detection in nasal secretions.

Nasal secretions (NS) reflect inflammatory activity of the nasal mucosa and thus can be utilized for disease diagnosis and determining treatment effects in Allergic rhinitis (AR). However, non-standardized collection of samples can affect the measured concentration of inflammatory biomarker in NS. In this study, we aimed to develop and evaluate new devices capable of standardizing the collection, storage, and preprocessing methods of NS samples. First, we chose the best swab as polyester (PE) and selected a stimulation method, twirling for 10 s at 1 Hz, to efficiently release AR biomarkers from a PE swab. Storage of sample solutions at -20 °C was optimal for the stability of biomarkers for the detection of AR. The new swab sample transfer device showed excellent concentration recovery efficiency (90-100%) for tryptase (Trp) and eosinophil cationic protein (ECP) without crosstalk between the two biomarkers. Finally, we compared the concentration of Trp in human NS samples of AR patients (n = 6) pre-processed by the new device with that by centrifuge as a standard method. As a result, the concentrations of Trp in NS were very similar in both groups. Therefore, this device can be utilized as an effective sample transfer and pre-processing device for point-of-care testing of AR.

Home and day-care microenvironment exposure to Blomia tropicalis allergens and their associations with salivary eosinophilic cationic protein (ECP) among preschool children in Singapore.

To date, exposure studies linking dust-mite allergens with asthma and allergic morbidities have typically relied on sampling from representative locations in the home for exposure assessment. We determine the effects of differing microenvironments allergen exposures on asthma and asthma severity among 25 case and 31 control preschool children in Singapore. Blo t 5 allergen levels in various niches from the children's home and day-care microenvironments as well as their Blo t 5 time-weighted concentrations were determined. Eosinophilic cationic protein (ECP) levels from the children's saliva as markers for airway inflammation were obtained. Salivary ECP levels were higher in children with asthma than those without and the strength of association increased with higher salivary ECP levels. Although there was no relationship between time-weighted Blo t 5 concentrations with salivary ECP levels among the controls, a positive statistically significant relationship was noted among cases, demonstrating the effects of cumulative exposure on asthma severity. Avoidance measures to reduce Blo t 5 allergen exposure should include all microenvironments that asthmatic children are exposed throughout the day.

Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Relationship of mannitol challenge to methacholine challenge and inflammatory markers in persistent asthmatics receiving inhaled corticosteroids.

BACKGROUND: Mannitol is a novel osmotic indirect bronchial challenge agent used to aid asthma diagnosis and management and is thought to reflect underlying inflammatory processes in asthma. Our objective was to evaluate relationships between mannitol airway hyperresponsiveness (AHR) and other measures of airway inflammation as well as direct-acting methacholine challenge in persistent asthmatics receiving inhaled corticosteroids. METHODS: We analysed screening data of mild to moderate persistent asthmatics, all receiving inhaled corticosteroids (ICS), who had mannitol and/or methacholine challenges, fractional exhaled nitric oxide (FeNO), and salivary eosinophilic cationic protein (ECP) performed as part of the same screen. Mannitol AHR was grouped by PD(10) (cumulative provocative dose required to produce a 10 % fall in FEV(1)): mild (315-635 mg), moderate (75-315 mg), and severe (0-75 mg). FeNO groups were low (<25 ppb), medium (25-50 ppb), and high (> 50 ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20 % fall in FEV(1)) groups were mild (2-8 mg/ml), moderate (0.5-2 mg/ml), and severe (0-0.5 mg/ml). RESULTS: Mannitol PD(10) groups were significantly different overall for FeNO (p = 0.023): 43 % higher in the severe vs. the mild group. There was a significant overall difference for methacholine PC(20) (p = 0.006): a 2.1 doubling dilution difference between severe vs. mild mannitol groups. FeNO groups were significantly different overall for mannitol PD(10) (p = 0.01) and methacholine PC(20) (p = 0.029). Methacholine PC(20) groups were significantly different overall for mannitol PD(10) (p < 0.001) and FeNO (p = 0.005). No significant differences were found across any groups for salivary ECP, FEV(1) % predicted, or ICS dose. Mannitol PD(10), methacholine PC(20), and FeNO as continuous variables all correlated with each other. CONCLUSIONS: Mannitol challenge reflects underlying inflammation using FeNO and direct AHR using methacholine. Thus, mannitol may be a useful screening tool for the assessment of asthmatic patients receiving inhaled corticosteroids.

Eosinophil cationic protein: is it useful in asthma? A systematic review.

INTRODUCTION: Eosinophil cationic protein (ECP) has been widely investigated as a potential biomarker of airway inflammation. METHOD: A systematic review was performed using Medline with key terms eosinophil cationic protein and asthma, limiting the search to titles or abstracts. Out of 688 potential papers found, abstracts were reviewed based on the following criteria: (1) ECP was used as a biological marker, (2) asthma was the index disease studied, (3) it was a controlled clinical study and (4) ECP was assessed as a diagnostic, assessment or management tool. One hundred and sixty-nine articles satisfied the selection criteria and their full-text versions were reviewed. Only 53 papers were found to provide clinically useful information. RESULTS: ECP has been measured in serum, plasma, sputum, saliva and broncho-alveolar lavage fluids but serum and sputum are the most established. Levels of ECP in normal and asthmatic subjects in various body fluids were identified. ECP correlates well with airway inflammation but not airway hyper-responsiveness. It is raised in other atopic diseases and hence is not diagnostic for asthma. However, it has been shown to be useful in assessing asthma severity, compliance with anti-inflammatory asthma therapy and as a guide to tailing down inhaled corticosteroid therapy. Although there is some evidence that ECP levels are affected by age, smoking, circadian rhythm and seasonal variation, only smoking appears to be of clinical significance. DISCUSSION: Despite its limitations, ECP remains potentially useful in asthma management. Future research on ECP should focus on using serial measurements and combining it with other markers of asthma which may increase its clinical usefulness.

Sublingual desensitization in children with congenital malformations and latex allergy.

The frequency of latex allergy in children requiring multiple surgery ranges from 16.7% to 65%. The aim of this study was to investigate the safety and efficacy of latex desensitization in a group of 10 patients with a history of multiple surgical procedures and clinically manifested allergy to latex. We selected 10 children (female-male ratio = 5:5), aged 4-16 yr (mean +/- s.d.: 9 +/- 4), with a history of multiple surgical procedures, adverse reactions to latex and positive skin test to latex and/or specific immunoglobulin E (IgE). Latex allergy diagnosis was confirmed by specific provocation tests (cutaneous, sublingual, mucous, conjunctival tests). Rush (4-day) sublingual desensitization was performed with increasing doses of latex extract (ALK Abellò) under patients' tongue until the highest dose of 500 microg of latex. A maintenance therapy (10 drops of undiluted solution three times a week) was recommended. During the 2-yr follow-up mean values of specific IgG4 and IgE, eosinophilic cationic protein and total IgE did not show significant variations. Patients did not manifest any adverse effect during the rush phase and only two patients manifested mild local symptoms during the maintenance therapy. All the challenges showed a reduction in terms of percentage of positivity and mean scores. All the patients showed a reduction of the mean individual score (p < 0.001). Furthermore patients who needed dental examination or surgery underwent such procedures without the occurrence of symptoms. Our preliminary results show sublingual desensitization to latex can be an important therapeutic tool in the management of young allergic patients requiring multiple operations.

Occupational asthma due to acrylates in a graphic arts worker.

BACKGROUND: Acrylates are used in a wide variety of products such as solvents, adhesives, paints, printing ink, soft contact lenses, porcelain nails, and methacrylates (used by dentists and orthopedists). Currently there are various types of acrylic compounds: acrylates, cyanoacrylates (such as tissue adhesives and home glues), and methacrylates (prostheses and dental and orthopedic fillings). The sensitization mechanism is unknown, but the allergy is believed to be due to a non-IgE mediated phenomenon, since a late asthmatic response occurs. Various cases of acrylate-induced asthma have been reported, especially in dentists and persons using glues or paints containing this substance. MATERIAL AND METHODS: We present the case of a 52-year-old man who had been working in graphic arts for the previous 7 years. For the previous 2 years he had experienced persistent cough with a sensation of drowning, dyspnea that increased with moderate exertion, and nasal obstruction despite continuous treatment. The symptoms first appeared after an episode of acute respiratory difficulty associated with weight loss, pulmonary infiltrates, and eosinophilia. Peak expiratory flow (PEF) was measured during work and sick leave, and specific bronchial challenge with acrylates was performed in a bronchial chamber. RESULTS: The PEF improved on weekends and sick leave. The challenge test provoked a late asthmatic response and the non-specific bronchial hyperreactivity increased after the test. As well in the sputum samples there was a increase of eosinophil amount.