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.
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.
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.
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.
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.
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.
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.
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 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.
Herein, a case of improper epinephrine autoinjector injection into the thumb involving deep connective tissue and bone is reported. We additionally review knowledge, skills and habits of a cohort of autoinjector users of a hospitalbased dermatologic outpatient clinic.
Introduction: Studies conducted across Western Europe reported that bronchial asthma (BA) has an important impact on patients' lives quality. We present Albanian asthmatic patients’ views based on the questionnaire generated from the European Federation of Allergy and Airways Diseases Patients Associations (EFA). Materials and methodology: In this study participated 145 Caucasian patients consecutively and prospectively diagnosed with BA. Results: The vast majority of patients reported lifestyle' limitations because of uncontrolled BA, three-fourth of them reported restriction of physical activity, and 20% felt their professional perspectives were limited. Additionally, up to 80% of the subjects were not optimistic about achieving the guideline goals but they were optimistic regarding the availability of more qualitative medicines and improvement of healthcare level over the next years. Our patients indicated that optimal treatments should be fast-acting and long-lasting, should be working immediately and should stop the symptoms completely. Conclusions: These results demonstrate the high impact of uncontrolled asthma, despite its severity, on .patients’ lives in a developing country.
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.
Background: Skin testing is a mainstay in allergology, and its importance is increasing in several fields. The ability to choose the most suitable technique according to the clinical setting is an advantage for the medical team. Objectives: To describe in detail an alternative technique of the coetaneous allergy test (skin scrape test) conceived as a variation of the former skin scratch test; to evaluate its value as a tool for diagnosis of immune sensitization; and to compare its accuracy with the skin prick test. Methods: The skin scrape test and skin prick test were performed side by side with the same allergen extracts in 162 human subjects classified in two groups according to the known presence or absence of serum specific-IgE to these allergens. Results: The sensitivity of the skin scrape test to detect immediate reactions was 85.0%. The sensitivity of the skin prick test was 86.5%. The sensitivity of both techniques analyzed together as a unique procedure was 94.2%. The specificity of the skin scrape test was 90.1%.The specificity of the skin prick test was 72.9%.The specificity of both tests analyzed together as a unique procedure was 70.5%. Conclusions: The skin scrape test is an alternative and complementary technique for allergic skin testing, and it is able to detect IgE-specific immune sensitization without the disadvantages of the skin scratch test. The skin scrape test has similar outcomes to the skin prick test.
The ‘translationally controlled tumour protein’ TCTP was originally discovered 30 years ago by researchers interested in proteins regulated at the translational level. Cloning and sequencing confirmed the conservation of this protein among all eukaryotic kingdoms, but did not reveal any functional clue, and TCTP was listed in the databases as a ‘family’ of its own. The functional characterisation of this protein extended over more than a decade, leading to a plethora of individual functions and interactions that have been ascribed to this protein. A major addition to the functional characterisation of TCTP was the identification in 1995 of its histamine releasing factor (HRF) activity in allergic conditions, which for the first time described an extracellular activity for TCTP in human disease. This triggered a host of additional publications aimed at characterising this HRF activity, which are discussed in other articles of this issue. Another milestone in the elucidation of TCTP's function was the demonstration of its anti-apoptotic activity in 2001. Evidence is also accumulating for a role of TCTP in the cell cycle and in early development. This article provides an overview of the main cellular activities of TCTP. The second part will summarise our current knowledge on the mechanisms involved in regulating intracellular TCTP levels.
Histamine-Releasing Factor and TCTPIgE-mediated activation of mast cells and basophils underlies allergic diseases such as asthma.Since Thueson et al. first described an activity from cultured peripheral blood mononuclear cells that induced the release of histamine from basophils [1], histamine-releasing activities have been studied for more than 30 years.In addition to several cytokines and chemokines with this activity, an unrelated protein termed histamine-releasing factor (HRF) was purified and molecularly cloned by Susan Mac-Donald and her colleagues in 1995 [2].In this Mini Hot Topic, she describes her pioneering discoveries and others' findings on HRF functions and gives a historical perspective.HRF, also known as translationally controlled tumor protein (TCTP) and fortilin, is a highly conserved protein with both intracellular and extracellular functions [3].Secreted HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells.HRF-like activity is found in nasal, skin blister, and bronchoalveolar lavage fluids during the late-phase allergic reactions, which implicates HRF in allergic inflammation [4].Kyunglim Lee and his associates nicely summarize recent developments on the non-classical pathway-mediated secretion of HRF.On the other hand, TCTP has been characterized as a major tumor protein.TCTP is down-regulated upon tumor reversion.In addition, TCTP has a wide range of intracellular functions, including cell cycle progression, proliferation, and survival of a variety of cell types.These functions are related to its ability to work as a guanine nucleotide exchange factor for Rheb, a Ras superfamily protein and to interact with translational elongation factors eEF1A and eEF1B , antiapoptotic Bcl-2 family proteins, p53, tubulin, and Plk kinase.Ulrich-Axel Bommer elegantly covers recent findings on the molecular mechanisms of how TCTP performs its roles in the fundamental biological processes.Two colleagues and I review HRF-interacting molecules emphasizing recent observations on HRF-immunoglobulins interactions.Thus, this Mini Hot Topic covers most of the research area of HRF/TCTP in a timely manner.
The applications of immunoglobulin preparation for intravenous injection (IVIg) for various intractable diseases are increasing. The two major clinical indications for IVIg are the replacement therapy and the anti-inflammation therapy for a variety of acute and chronic autoimmune diseases. One of the proposed mechanisms of IVIg activity is the modulation of cytokine expression and function; therefore, we analyzed the effect of IVIg on pathogen-associated molecular pattern (PAMP)-induced cytokine production by peripheral blood mononuclear cells (PBMCs). The production of tumor necrosis factor-α (TNF-α) as a result of stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid sodium salt (Poly I:C), or Pam3CysSerLys4 (Pam3) was significantly inhibited by sulfonated-IVIg (S-IVIg), or by F(ab')2. Assessed by one-color microarray analysis, the expressions of 229 genes were inhibited to 1/200 or less by F(ab')2. On the other hand, the expressions of 159 genes were increased by more than 100-fold by F(ab')2. According to these results, it was suggested that IVIg inhibits inflammatory PAMPs-induced cytokine production by PBMCs, due to the modulation of varieties of gene expression.
Atopic dermatitis is a multifactorial chronic disease that poses a great burden for patients and society. In recent decades the prevalence has increased substantially in many countries, notably in Western societies, and the causes for this increase are not completely understood. There are still many unanswered questions regarding atopic dermatitis with respect to aetiology, pathophysiology, co-morbidity as well as subgrouping and treatment of the disease. Establishment of the Danish Atopy Database (DAD), a cohort with ongoing inclusion of outpatients with atopic dermatitis from a tertiary referral centre, allows the study of these aspects of the disease. Herein we present our methodological considerations in regards to establishment of this cohort.
Numerous studies have demonstrated that TCTP/HRF is a unique cytokine, modulating the release of inflammatory mediators from various cell types including cells involved in allergic phenomena. Despite the absence of a leader sequence in its NH 2 -terminus, TCTP/HRF is regarded as a secreted protein found outside of cells as well as in fluids from allergic patients and parasitic organisms. Recent studies clarified several potential mechanisms leading to its secretion. For example, these studies showed that TCTP/HRF is exported from cells via a non-classical, endoplasmic reticulum (ER)/Golgi-independent mechanism associated with exosomal transport. TSAP6, a p53-inducible transmembrane protein, has been shown to enhance exosome production, and facilitate the secretion of TCTP/HRF into extracellular milieu. Additionally, H,K-ATPase also appears to play a role in the transport of TCTP/HRF, since inhibitors of H,K-ATPase also inhibit TCTP/HRF exit. The exact mechanisms involved in TCTP/HRF secretion has not yet emerged. Here we attempted to collate the available information in the current understanding of the mechanisms underlying the release of TCTP/HRF and of the factors that seem to influence these mechanisms.
Non-steroidal anti-inflammatory drugs are used daily by millions of patients worldwide for the management of various inflammatory diseases. Many well-documented adverse reactions are related to the use of these drugs. We report a fifty-four year-old woman with anaphylaxis after ingestion of ibuprofen liquid in a gelatin capsule. Eventually this was concluded to have resulted from hypersensitivity to the gelatin component of the capsule, which was likely IgE-mediated because of the positive skin test to gelatin. Gelatin allergy is only relevant for patients ingesting specific capsule formulation. The allergist/clinical immunologist must keep in mind the possibility of gelatin allergy.
Objective: Kawasaki disease (KD), an acute febrile disease that induces systemic vasculitis in infants, has been proposed by Awaya and Sahashi in 2003 to be epidemiologically linked with pollen exposure. In this report, seasonal variation patterns of the monthly development of KD in 5,917 patients (Pt.) in Kanagawa, Japan were compared with the monthly pollen release numbers (Nos.) from 1991 to 2002. Methodology: A correlation coefficient (c.c.) matrix was generated using regression analyses of the correlation of KD onset and pollen exposure in each month. The percent of Japanese cedar pollen Nos. was calculated from the pollen numbers (Po.Nos.) of all the species surveyed in March and April throughout the years. Results: Significant c.c. associations were revealed between Po.Nos. from all species in March and KD Pt.Nos. in August (0.88), November (0.72), May (0.68), and April (0.66). Significant c.c. associations were also found between Po.Nos. from all species in April and KD Pt.Nos. in August (0.70), and between Po.Nos from all species in February and KD Pt.Nos. in July (0.62). Mean c.c. values of 0.60 in March, 0.47 in October, 0.45 in July, 0.35 in April, and 0.31 in February between Po.Nos. and KD Pt.Nos. were shown. February, March and April contributed 4.7%, 40.6% and 38.8% of the annual Po.Nos., respectively, of which 93.8%, 84.3% and 10.9% were from cedar pollen, respectively. Conclusions: A positive association was demonstrated between the Po.Nos. from all species, particularly cedar Po.Nos. in March, and the KD Pt.Nos. in the following several months.
