Validation of inducible basophil biomarkers: Time, temperature and transportation.

BACKGROUND: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. METHODS: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. RESULTS: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. CONCLUSIONS: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Nonallergic rhinitis, with a focus on vasomotor rhinitis: clinical importance, differential diagnosis, and effective treatment recommendations.

The term "rhinitis" denotes nasal inflammation causing a combination of rhinorrhea, sneezing, congestion, nasal itch, and/or postnasal drainage. Allergic rhinitis is the most prevalent and most frequently recognized form of rhinitis. However, nonallergic rhinitis (NAR) is also very common, affecting millions of people. By contrast, NAR is less well understood and less often diagnosed. Nonallergic rhinitis includes a heterogeneous group of conditions, involving various triggers and distinct pathophysiologies. Nonallergic vasomotor rhinitis is the most common form of NAR and will be the primary focus of this review. Understanding and recognizing the presence of NAR in a patient is essential for the correct selection of medications and for successful treatment outcomes.

Differential effects of airway afferent nerve subtypes on cough and respiration in anesthetized guinea pigs.

The hypothesis that respiratory reflexes, such as cough, reflect the net and often opposing effects of activation of multiple afferent nerve subpopulations throughout the airways was evaluated. Laryngeal and tracheal mucosal challenge with either citric acid or mechanical probing reliably evoked coughing in anesthetized guinea pigs. No other stimulus reliably evoked coughing in these animals, regardless of route of administration and despite some profound effects on respiration. Selectively activating vagal C-fibers arising from the nodose ganglia with either adenosine or 2-methyl-5-HT evoked only tachypnea. Selectively activating vagal afferents arising from the jugular ganglia induced respiratory slowing and apnea. Nasal afferent nerve activation by capsaicin, citric acid, hypertonic saline, or histamine evoked only respiratory slowing. Histamine, which activates intrapulmonary rapidly adapting receptors but not airway or lung C-fibers or tracheal bronchial cough receptors induced bronchospasm and tachypnea, but no coughing. The results indicate that the reflexes initiated by stimuli thought to be selective for some afferent nerve subtypes will likely depend on the net and potentially opposing effects of multiple afferent nerve subpopulations throughout the airways. The data also provide further evidence that the afferent nerves regulating cough in anesthetized guinea pigs are distinct from either C-fibers or intrapulmonary rapidly adapting receptors.

Gastroesophageal reflux disease in children with asthma: treatment implications.

An association between asthma and gastroesophageal reflux disease (GERD) has long been recognized both mechanistically and epidemiologically. The clinical relevance of this interplay continues to be explored, with special interest given to the role of GERD in the worsening of asthma. The effect of GERD is most frequently contemplated in patients with asthma that is difficult to control. Medical and surgical anti-reflux trials attempting to alter asthma symptoms have reported mixed but generally underwhelming results, although asthma symptom scores are generally improved following effective treatment of GERD. Many of the pharmaceutical studies can be criticised for having too short a duration or for likely incomplete acid suppression. Few trials have specifically studied pediatric populations. Because GERD is a common condition, particularly in young children, the role reflux plays in the worsening of asthma symptoms and the potential benefit on asthma of anti-reflux therapy warrants further exploration. Whether or not treating symptomatic GERD reduces the symptoms and severity of asthma in children, GERD coexisting with asthma should be aggressively treated. GERD symptoms in most patients with or without asthma can be controlled medically with continuous use of proton pump inhibitors such as omeprazole and lansoprazole and to a lesser extent by histamine H(2) receptor antagonists such as famotidine and cimetidine.

Rhinitis and rhinologic headaches.

Rhinologic headache, a headache of nasal origin, generally has been attributed to past facial trauma causing nasal mucosa-septal contact points. Patients who have not knowingly experienced nasal trauma may have contact points caused by mucosal inflammation or anatomic abnormalities (septal spurs, septal deviation, and enlarged turbinates) and can develop rhinologic headaches. A population of 66 such patients was studied to classify the type of patient susceptible to such headaches and to examine the type of underlying inflammation or anatomic abnormality responsible for creating their mucosal contact points. Most patients were women with a mean age at the time of initial presentation of 40 years. VMR was the most frequent cause of nasal inflammation, either alone or in combination with allergic rhinitis. Generally, headache symptoms improved with treatment of the underlying nasal inflammation in the majority of patients.