Chronic Obstructive Pulmonary Disease (COPD) and Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) are Risk Factors for Cryptococcosis

Cryptococcosis is a fungal infection of global importance affecting the central nervous system and other organs such as the lungs. The severity of cryptococcosis is largely dependent on the integrity of the host immune system. The protection to cryptococcosis is associated with Th1 immune response while Th2 results in susceptibility to Cryptococcus infection. Asthma is a chronic inflammatory disease commonly coordinated by Th2 immune response. The airway inflammation in Chronic Obstructive Pulmonary Disease (COPD) patients is characterized by increased neutrophils, macrophages, proteases, IL-6, IL-8, and Th1 cytokines. Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) patients present phenotype that shares Th1 (COPD) and Th2 (asthma). There are several risk factors associated with Cryptococcus infection, including smoking, that cause airway remodeling and dysregulated and damaging airway inflammation.

Association Between Endoscopic, Radiologic and Patient-reported Chronic Rhinosinusitis with Nasal Polyps

Objectives: Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) and with Nasal Polyps (CRSwNP) affect 10% and 1-4% of the general population respectively. Early detection and treatment of CRSwNP might prevent recalcitrant disease forms. The aim of this prospective controlled study was to evaluate association between endoscopic, radiologic, and self-reported CRSwNP, and a family history in defining CRSwNP. Methods: This study involved 73 CRS patients aged 18 years or over undergoing CRS-surgical consultation at the Tampere University Hospital. Data of sinus Computed Tomography (CT) scans and nasal endoscopy was obtained from patient records. Sixty controls ±allergic rhinitis underwent clinical examination. All subjects filled a questionnaire. Associations were analyzed by Chi square and adjusted regression models. The predictive performance of various parameters was assessed using the Area Under the Receiver Operating Characteristic curve (AUROC). Results: A total of 33% of CRSwNP patients reported not having Nasal Polyps (NPs), while 18% of CRSsNP patients reported having NPs (p < 0.001). Radiologic Nasal Polyp (NP) score differentiated CRSwNP from CRSsNP with an AUROC of 0.95 (95% CI 0.91-1.00). The AUROC value for Lund-Mackay (LM) score was 0.84 (0.75-0.94). Positive family history of NP did not differ significantly between CRS and control groups. Family history of allergy or asthma was given with certainty, whereas CRS patients had uncertainty of reporting NPs in family compared to controls (adjusted OR=6.02, 95% CI 1.98-18.30, p = 0.002). Conclusion: Our findings suggest that in situations where nasal endoscopy cannot be performed, early detection of CRSwNP could result from information obtained from sinus CT scans and patients, in comparison to family history which has lower predictive value. However validation studies with larger sample sizes are still needed.

Food Allergy Knowledge and Attitudes Among School Teachers in Jazan, Saudi Arabia

Background: Food allergy topic has become more widely discussed in developed countries, but with less interest in Middle Eastern Arabian Countries. Objectives: The main objective of this paper is to assess the knowledge and perception of schoolteachers about food allergy. Methods: A cross sectional study was conducted among a sample of 360 school teachers between May 2013 and February 2014 in province of Jazan in Saudi Arabia, using a validated web-based self-administered survey. Results: The results revealed that almost (59.7%) of the schoolteachers had a medium insufficient knowledge about food allergy; only 17.3% had good knowledge about food allergy. Female teachers had higher knowledge scores (58.5 ± 17.2) as compared to male (51.8 ± 16.0) with statistically significant difference (p = 0.017). The majority of schoolteachers have a significantly poor knowledge in most of food allergy domains. More than half of responders either do not know or they disagree that the food allergy is a serious problem and can lead to death. Regression analysis revealed that participant’s level of knowledge is significantly associated with school teacher’s attitudes towards food allergy (OR = 0.06, 95% CI: 0.39 - 0.92, p = 0.01), practice (OR = 1.68, 95% CI: 1.11 - 2.56, p = 0.01), and years of experiences (OR = 1.8, 95% CI; 1.15 - 2.98, p = 0.011). Conclusion: Knowledge of food allergy among schoolteachers is not adequate, failing to recognize and treat fatal food allergy reactions necessitate an urgent need to set a school policy to improve the food allergy situation.

Anaphylaxis to Glatiramer Acetate

Glatiramer acetate (Copaxone, Teva Pharma) and interferon beta are the two only disease-modifying therapies for multiple sclerosis. Glatiramer acetate is known for frequently simulating mild, anaphylactoid reactions while true, IgEmediated allergic reactions have been hardly reported so far. Herein, we report two females suffering from multiple sclerosis who experienced rapidly aggravating hypersensitivity-reactions upon treatment with glatiramer acetate. Patient one experienced an asthma attack, patient two an exacerbation of her urticaria and angioedema. An IgE-mediated mechanism could be demonstrated by a positive intradermal test to a 1:1000 dilution in the first 31-year old and by a positive skin prick test to a 1:10 diluted skin prick test in the second 32-year old second woman.

Dynamics of Plasma and Granule Membrane in Murine Bone Marrow-Derived Mast Cells after Re-stimulation

Mast cells are derived from hematopoietic stem cells and play important roles in allergic responses. Mast cells are long-lived compared with other granular cell types. Since the response of the individual mast cell after FcεRI-induced degranulation is unclear, the aim of this study was to analyze morphological changes in individual mast cells after restimulation. To observe plasma and granule membrane dynamics, AcGFP-actb (β-actin) and DsRed-monomer (DRM)- CD63 fusion constructs were introduced into bone marrow-derived mast cells (BMMCs). Furthermore, AcGFP-CD63 and DRM-Cma1 (mMCP-5) were introduced into BMMCs. Re-stimulation resulted in increased β-hexosaminidase release and cytokine mRNA expression similar to those observed during initial stimulation. Moreover, expression of FcεRI on BMMCs 24 h after initial stimulation was similar to that measured before initial stimulation. Changes in morphology of the plasma membrane and colocalization of granules and plasma membrane were observed after initial stimulation. BMMCs returned to normal 120 min after the initial stimulation. These phenomena were also observed in BMMCs after re-stimulation. BMMC chymase content decreased 20 min after stimulation but returned to near normal 24 h after stimulation. These findings suggest that mast cell functions can be maintained and that these cells can be repeatedly degranulated after FcεRI-mediated stimulation.

Sputum Induction in Children and Adolescents with Problematic Severe Asthma: Success Rate, Safety and Tolerability

Background: In problematic severe asthma (PSA), inflammatory phenotypes can by identified by assessing cellularity in induced sputum (IS) samples. However, there have been few studies employing sputum induction (SI) in pediatric patients. Objectives: To assess the success rate, safety and tolerability of SI, as well as IS sample cellularity, in pediatric PSA patients. Methods: We conducted a cross-sectional study involving 44 pediatric PSA patients. We collected IS samples using inhalations of nebulized saline solution. On the basis of the post-bronchodilator forced expiratory volume in one second (FEV1, % of predicted), we administered nebulization with 4.5% hypertonic saline (for patients with an FEV1 ≥ 60%) or 0.9% isotonic saline (for those with an FEV1 < 60%). We classified IS samples as satisfactory if there was ≤ 20% squamous cell contamination and cell viability was > 50%. Results: The observed success rate was 75% (95% CI: 60-86). Most of the patients provided satisfactory samples, although multiple SI sessions were required in some cases (27%). In comparison with the IS samples containing > 20% squamous cells, those containing ≤ 20% showed significantly more neutrophils (P = 0.02) and eosinophils (P = 0.03). The most common adverse events were mild wheezing (in 14%) and salty taste (in 9%). In 8% of the sessions, there was a ≥ 20% decrease in FEV1. Conclusion: In our sample of pediatric patients with PSA, sputum induction was safe and generally well tolerated, suggesting that it could be useful in the assessment of inflammatory processes in such patients.

Role of Antibiotics and Infection-Host Interactions in the Prevalence of Respiratory Atopy: Experience and Perspective

We have witnessed a dramatic increase in the prevalence of respiratory allergies during the last decades. The role of infections in the prevalence of respiratory allergic diseases is attributed to the antagonism between: a) induction of T helper (Th) 1 immune response by human organism; and b) manipulation of the human immune response toward Th2 profile by common infective agents in order to increase their surviving opportunity. This review proposes an important role of massive antibiotics exposure during neonatal and early childhood on the increasing epidemiological trend. It is believed that the antibiotics exposure during early childhood has also provided better surviving opportunity for atopic individuals with an inadequate immune defense against common infections, deviating therefore the genetic background of general population toward Th2 profile. Taking this into account, we suggest that Th2 profile frequency (and consequently atopic phenotype prevalence) can be increased along an individual lifespan after initial massive antibiotic introduction, until the entire population is exposed to them during childhood. This hypothesis may explain findings on epidemiological surveys, which report a prevalent increase among adults in industrialized countries between 1970s and 2000s, while in recently- developed countries this trend begun only at the end of 1980s. These arguments may lead to the conclusion that infections will manipulate the human immunity along generations, whereas actual antibiotics can increase the prevalence of respiratory allergies among a population only along an individual longevity. These findings may be beneficial in the development of future strategies for management of respiratory allergic or infective pathologies.

Distinct Reactivity of Transient Receptor Potential Vanilloid Subtype 1 in a Murine Model of Atopic Dermatitis with Serious Scratching

Background: Abnormality in skin sensitivity may be responsible for unbearable itch in patients with atopic dermatitis (AD). Objectives: We evaluated reactivity of NC/Tnd mice, a model for human AD, against various experimental stimulations. Methods: Several behavioral tests were performed after external stimuli were applied to NC/Tnd mice. Transient receptor potential vanilloid subtype 1 (TRPV1) reactivity of neuronal cells collected from the dorsal root ganglions (DRG) was analyzed with a Ca++ influx test. Finally, we evaluated suppressive effect of capsaicin on atopic itch of NC/Tnd mice. Results: Pain responses to heat, acidic stimulation, and capsaicin injection, which are transduced through TRPV1, were decreased in NC/Tnd mice, when compared to two standard strains BALB/c and C57BL/6 mice. The reactivity of the primary neurons isolated from DRG to capsaicin was markedly reduced in NC/Tnd mice. Topical application of histamine evoked scratching in NC/Tnd mice as well as other two strains; however, the scratching intensities induced by nonhistamine pruritogens were significantly lower in NC/Tnd mice comparing to the two strains. In conventional NC/Tnd mice with AD, topical application of capsaicin reduced the scratching behavior. Conclusion: TRPV1 is associated with both pain and itch sensation; however, abnormalities in TRPV1 reactivity may involve in severe itch in NC/Tnd mice.

Evidence-based Medicine and Clinical Study Designs: Examples of Applications for Allergy Research

Evidence of the effect of clinical interventions in allergology, and in medicine as a whole, can be hierarchically grouped based on the research design producing the evidence. The most weight is given to systematic reviews and metaanalyses, and to randomised controlled trials. These trial designs are superior to non-randomised controlled trials and cohort studies, which in turn are superior to case-control studies. The least weight is given to case-studies and anecdotal evidence. Herein, the principles of evidence-based medicine and clinical study designs are reviewed in the context of examples from the allergology literature.

Erlotinib-induced Adverse Skin Reactions

Erlotinib is low molecular-weight quinazolin derivatives which selectively inhibit the epidermal growth factor receptor (EGF-R) tyrosine kinase activity of the intracellular domain, block autophosphorylation and the subsequent signaling cascades. EGF-R is expressed on basal keratinocytes, sebocytes, the outer root sheath of hairs, and endothelial cells in the skin, and plays important roles in the regulation of differentiation, proliferation, apoptosis, attachment and migration of keratinocytes, inflammation, and wound healing. Therefore, inhibition of EGF-R causes a number of cutaneous adverse reactions. Among them, severe skin lesions are very stressful, and impair quality of life of patients. Moreover, they even bring disadvantages such as drug withdrawal or interruption. Several review papers describe representative or common skin lesions which appear either during the first a few weeks or at later phases. Common skin manifestations include papular and pustular follicular eruptions (acneiform eruption), xerosis, paronychia, pruritus, and abnormalities of hairs; however, other than those eruptions, several unusual lesions are also induced. Early intervention of dermatologists and management of skin lesions are quite important, because discontinuance of the drug is unfavorable for patients with clinical benefits for cancers. In this brief review, various cutaneous manifestations seen in Japanese patients treated with erlotinib (Tarceva) are shown, and current management of representative severe conditions is also described.